Crisis adrenal neonatal secundaria a hipoplasia hipofisaria / Neonatal Adrenal Crisis Secondary to Pituitary Hypoplasia

Introducción: La insuficiencia adrenal hipotálamo hipofisaria usualmente se manifiesta secundaria a tumores y, cuando resulta congénita se asocia, con frecuencia, con otras deficiencias hormonales. La crisis adrenal suele presentarse en su debut y puede resultar potencialmente mortal. Objetivo: Examinar el caso de una paciente con insuficiencia adrenal central que debutó con una crisis adrenal congénita. Presentación del caso: Recién nacida a término, padres no consanguíneos, hospitalizada a los 9 días de vida por clínica de una semana con múltiples episodios eméticos y apnea. Ingresó con deshidratación severa, hipotensa y estuporosa. Además, se encontró acidosis metabólica severa, hipoglucemia persistente, hiponatremia e insuficiencia prerrenal. Ante la no mejoría de su estado hemodinámico, a pesar del uso de cristaloides y vasopresores, finalmente mejoró con la administración de dosis altas de hidrocortisona. El diagnóstico de deficiencia de cortisol de origen central se realizó con un test dinámico de insulina y la resonancia magnética nuclear hipofisaria. Conclusiones: La crisis adrenal se debe tener presente como diagnóstico diferencial en episodios agudos con inestabilidad hemodinámica persistente e hipoglucemia de difícil manejo. Adicionalmente, hay que considerar que existen otras causas menos comunes de insuficiencia adrenal en neonatos como la hipoplasia hipofisaria(AU)

Introduction: Hypothalamic-pituitary adrenal insufficiency usually manifests secondary to tumors and, when congenital, is often associated with other hormonal deficiencies. Adrenal crisis usually occurs at its onset and can be life threatening. Objective: To review the case of a patient with central adrenal insufficiency who had an onset with a congenital adrenal crisis. Case presentation: Term newborn, non-consanguineous parents, hospitalized at 9 days of life for a week-long clinical presentation with multiple emetic episodes and apnea. She was admitted with severe dehydration, hypotensive and stuporous. In addition, severe metabolic acidosis, persistent hypoglycemia, hyponatremia and prerenal failure were found. Given the lack of improvement of her hemodynamic status, despite the use of crystalloids and vasopressors, she finally improved with the administration of high doses of hydrocortisone. The diagnosis of cortisol deficiency of central origin was made with a dynamic insulin test and pituitary nuclear magnetic resonance imaging. Conclusions: Adrenal crisis should be kept in mind as a differential diagnosis in acute episodes with persistent hemodynamic instability and difficult-to-manage hypoglycemia. Additionally, other less common causes of adrenal insufficiency in neonates, such as pituitary hypoplasia, should be considered(AU)

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.

Continuous Intravenous Inotropes in Ward Units: Expanding Therapy Outside Intensive Care using a Safety-Oriented Protocol / Inotrópicos Intravenosos Contínuos em Unidades de Enfermaria: Expandindo o Tratamento Além da Unidade de Terapia Intensiva Utilizando um Protocolo Orientado em Segurança

Abstract Selected clinically stable patients with heart failure (HF) who require prolonged intravenous inotropic therapy may benefit from its continuity out of the intensive care unit (ICU). We aimed to report on the initial experience and safety of a structured protocol for inotropic therapy in non-intensive care units in 28 consecutive patients hospitalized with HF that were discharged from ICU. The utilization of low to moderate inotropic doses oriented by a safety-focused process of care may reconfigure their role as a transition therapy while awaiting definitive advanced therapies and enable early ICU discharge.

Resumo Pacientes selecionados com insuficiência cardíaca (IC), clinicamente estáveis que necessitam de terapia inotrópica intravenosa prolongada podem se beneficiar de sua continuidade fora da unidade de terapia intensiva (UTI). Nosso objetivo foi relatar a experiência inicial e a segurança de um protocolo estruturado para terapia inotrópica em unidades de terapia não-intensiva em 28 pacientes consecutivos hospitalizados com IC que receberam alta da UTI. A utilização de doses inotrópicas baixas a moderadas, orientadas por um processo de cuidado focado na segurança, pode reconfigurar seu papel como terapia de transição enquanto aguarda terapias avançadas definitivas e permite a alta precoce da UTI.

Effect of magnesium sulphate and milrinone on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a randomized study / Efeitos do sulfato de magnésio e da milrinona sobre o vasoespasmo cerebral após hemorragia subaracnoidea por aneurisma: estudo randômico

Abstract Background: Aneurysmal subarachnoid hemorrhage is an important cause of premature death and disability worldwide. Magnesium sulphate is shown to have a neuroprotective effect and it reverses cerebral vasospasm. Milrinone is also used in the treatment of cerebral vasospasm. The aim of the present study was to compare the effect of prophylactic magnesium sulphate and milrinone on the incidence of cerebral vasospasm after subarachnoid hemorrhage. Methods: The study included 90 patients with aneurysmal subarachnoid hemorrhage classified randomly (by simple randomization) into two groups: magnesium sulphate was given as an infusion of 500 mg.day-1 without loading dose for 21 days. Group B: milrinone was given as an infusion of 0.5 µg.kg-1.min-1 without loading dose for 21 days. The cerebral vasospasm was diagnosed by mean cerebral blood flow velocity in the involved cerebral artery (mean flow velocity ≥ 120 cm.s-1), neurological deterioration by Glasgow coma scale, or angiography (the decrease in diameter of the involved cerebral artery >25%). Results: The mean cerebral blood flow velocity decreased significantly in the magnesium group compared to milrinone group through Day 7, Day 14 and Day 21 (p < 0.001). The incidence of cerebral vasospasm decreased significantly with magnesium compared to milrinone (p = 0.007). The Glasgow coma scale significantly improved in the magnesium group compared to milrinone group through Day 7, Day 14 and Day 21 (p = 0.036, p = 0.012, p = 0.016, respectively). The incidence of hypotension was higher with milrinone than magnesium (p = 0.012). Conclusions: The incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage was significantly lower and Glasgow coma scale significantly better with magnesium when compared to milrinone. Milrinone was associated with a higher incidence of hypotension and requirement for dopamine and norepinephrine when compared to magnesium.

Resumo Justificativa: A hemorragia subaracnoidea por aneurisma é uma importante causa de morte prematura e de incapacidade em todo o mundo. O sulfato de magnésio mostra um efeito neuroprotetor e reverte o vasoespasmo cerebral. A milrinona também é usada no tratamento de vasoespasmo cerebral. O objetivo do presente estudo foi comparar o efeito profilático do sulfato de magnésio e da milrinona sobre a incidência de vasoespasmo cerebral após hemorragia subaracnoidea. Métodos: O estudo incluiu 90 pacientes com hemorragia subaracnoidea por aneurisma randomicamente distribuídos (randomização simples) em dois grupos: sulfato de magnésio foi administrado em infusão de 500 mg.dia-1 sem dose de ataque durante 21 dias. O Grupo B recebeu milrinona em infusão de 0,5 µg.kg-1·min-1 sem dose de ataque durante 21 dias. O vasoespasmo cerebral foi diagnosticado pela velocidade média do fluxo sanguíneo cerebral na artéria cerebral envolvida (velocidade média do fluxo ≥ 120 cm.s-1), a deterioração neurológica por escala de coma de Glasgow ou angiografia (diminuição do diâmetro da artéria cerebral envolvida > 25%). Resultados: A velocidade média do fluxo sanguíneo cerebral diminuiu significativamente no grupo magnésio em comparação com o grupo milrinona nos dias 7, 14 e 21 (p < 0,001). A incidência de vasoespasmo cerebral diminuiu significativamente com o magnésio em comparação com milrinona (p = 0,007). A escala de coma de Glasgow melhorou significativamente no grupo magnésio em comparação com o grupo milrinona nos dias 7, 14 e 21 (p = 0,036, p = 0,012, p = 0,016, respectivamente). A incidência de hipotensão foi maior com milrinona do que com magnésio (p = 0,012). Conclusões: A incidência de vasoespasmo cerebral após hemorragia subaracnoidea por aneurisma foi significativamente menor e a escala de coma de Glasgow significativamente melhor com magnésio em comparação com milrinona. A milrinona foi associada a uma maior incidência de hipotensão e necessidade de dopamina e norepinefrina em comparação com o magnésio.

Milrinona inhalada en hipertensión pulmonar: A propósito de un caso / Case Report: Inhaled milrinone in pulmonary hypertension

INTRODUCCIÓN: Pulmonary hypertension (PH) is a disease that is characterized for an elevated pressure in the pulmonary artery and an increased pulmonary vascular resistance (PVR). Inhaled milrinone has demonstrated acting as a selective pulmonary vasodilator, being a useful tool for the treatment of patients with PH in the perioperative. MATERIALS AND METHODS: We report a successful case of inhaled milrinone in PH in cardiovascular surgery. The patient signed the informed consent for this report. DISCUSSION: Patients with PH has increased risk of perioperative complications (mortality as far as 37-90%) The management with intravenous vasodilators is frequently limited because of secondary effects of vasodilation and hypotension affecting the myocardial perfusion pressure. Milrinone is an inodilator that acts as an inhibitor of the phosphodiesterase III. Wang et al., and posterior studies have demonstrated that administered by inhalation it acts as a selective pulmonary vasodilator and inotrope, with a minor systemic effect. CONCLUSION: Inhaled milrinone have demonstrated to be a useful drug to lower PH, PVR and to enhance inotropism without deleterious systemic effects. Wide availability, lower costs and ease of administration make you think as it could be an ideal tool for perioperative management in patients with PH. There are still more studies to define it´s potentials.

INTRODUCCIÓN: La hipertensión pulmonar (HTP) es una enfermedad caracterizada por la elevación de las presiones de arteria pulmonar (PAP) y un aumento de la resistencia vascular pulmonar (RVP). La milrinona inhalada ha demostrado actuar como un vasodilatador pulmonar selectivo siendo una herramienta útil en el manejo de los pacientes con HTP en el perioperatorio. MATERIALES Y MÉTODOS: Reportamos un caso exitoso de milrinona inhalada en HTP en cirugía cardiovascular. La paciente firmó el consentimiento informado para este reporte. DISCUSIÓN: Pacientes con HTP tienen mayor riesgo de complicaciones perioperatorias (mortalidad hasta 37-90%). Su manejo con vasodilatadores intravenosos es frecuentemente limitado por sus efectos secundarios de vasodilatación e hipotensión, perjudicando la presión de perfusión miocárdica. La milrinona es un inodilatador que actúa como inhibidor de la fosfodiesterasa III. Wang et al., y estudios posteriores, han demostrado que administrada por vía inhalatoria actúa como un vasodilatador pulmonar selectivo e inótropo, con menor efecto sistémico. CONCLUSIÓN: La milrinona inhalada ha demostrado ser una herramienta útil para la disminución de la PAP, RVP y mejoría del inotropismo, sin efectos sistémicos deletéreos. Su amplia disponibilidad, menor costo y facilidad de administración, hacen pensar que podría ser una herramienta útil para el manejo perioperatorio de los pacientes con HTP. Hacen falta más trabajos para definir sus potencialidades.

Enterovirus 71 infection and neurological complications / 소아과

Since the outbreak of the enterovirus 71 (EV71) infection in Malaysia in 1997, large epidemics of EV71 have occurred in the Asia-Pacific region. Many children and infants have died from serious neurological complications during these epidemics, and EV71 infection has become a serious public health problem in these areas. EV71 infection causes hand, foot and mouth disease (HFMD) in children, and usually resolves spontaneously. However, EV71 occasionally involves the central nervous system (CNS), and induces diverse neurological complications such as brainstem encephalitis, aseptic meningitis, and acute flaccid paralysis. Among those complications, brainstem encephalitis is the most critical neurological manifestation because it can cause neurogenic pulmonary hemorrhage/edema leading to death. The characteristic clinical symptoms such as myoclonus and ataxia, cerebrospinal fluid (CSF) pleocytosis, and brainstem lesions on magnetic resonance imaging, in conjunction with the skin rash of HFMD and the isolation of EV71 from a stool, throat-swab, or CSF sample are typical findings indicating CNS involvement of EV71 infection. Treatment with intravenous immunoglobulin and milrinone are recommended in cases with severe neurological complications from EV71 infection, such as brainstem encephalitis. Despite the recent discovery of receptors for EV71 in human cells, such as the scavenger receptor B2 and P-selection glycoprotein ligand 1, it is not known why EV71 infection predominantly involves the brainstem. Recently, 3 companies in China have completed phase III clinical trials of EV71 vaccines. However, the promotion and approval of these vaccines in various countries are problems yet to be resolved.

Left Ventricular Noncompaction Complicated with Myocardial Infarction with Barth Syndrome in a Newborn

Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by a hypertrabeculation of the left ventricle. Patients may present with heart failure, arrhythmia, and thromboembolism. LVNC may be isolated or associated with congenital heart defects. The first discovered genetic cause of isolated LVNC was Barth syndrome (BTHS), an X-linked disorder caused by taffazin (TAZ) gene mutation. BTHS is characterized by cardiomyopathy, neutropenia, skeletal myopathy, and growth delay. A newborn male baby was referred to Soonchunhyang University Cheonan Hospital due to cyanosis and dyspnea. Based on findings of cardiomegaly, ST depression, and elevated cardiac enzyme, echocardiography was done, which revealed a hypocontractile, enlarged left ventricle with distinctive trabeculation in the apex. Heparinization for the treatment of myocardial infarction and continuous infusion of milrinone was started. During hospitalization, the TAZ gene mutation was detected in the patient, his mother, and elder sister. After 3 months, the patient was discharged with heart failure medication and aspirin.

What do we take consideration in the patient who has an unpredicted severe portopulmonary hypertension in liver transplantation?: a case report / 대한마취과학회지

Severe portopulmonary hypertension (PPHT) is considered a contraindication for liver transplantation (LT) because of the associated high mortality and poor prognosis. We report the case of a 57-year-old cirrhotic woman with severe PPHT (mean pulmonary artery pressure [mPAP] > 65 mmHg), who underwent a successful living donor LT. Intra-operative use of inhaled iloprost, milrinone, dobutamine, and postoperative use of inhaled nitric oxide and oral sildenafil failed to lower the pulmonary artery pressure (PAP). The patient responded only to nitroglycerin and drainage of massive ascites. Meticulous intra-operative volume control, which included minimizing blood loss and subsequent transfusion, was carried out. The use of vasopressors, which may have elevated the PAP, was strictly restricted. Intra-operative PAP did not show an increase, and the hemodynamics was maintained within relatively normal range, compared to the preoperative state. The patient was discharged without any complications or related symptoms.

Safety and Efficacy of the Off-Label Use of Milrinone in Pediatric Patients with Heart Diseases

BACKGROUND AND OBJECTIVES: Milrinone is often used in children to treat acute heart failure and prevent low cardiac output syndrome after cardiac surgery. Due to the lack of studies on the long-term milrinone use in children, the objective of this study was to assess the safety and efficacy of the current patterns of milrinone use for > or =3 days in infants and children with heart diseases. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of patients aged or =3 days from January 2005 to December 2012. Patients' characteristics including age, sex, height, weight, and body surface area were recorded. The following parameters were analyzed to identify the clinical application of milrinone: initial infusion rate, maintenance continuous infusion rate, total duration of milrinone therapy, and concomitantly infused inotropes. The safety of milrinone was determined based on the occurrence of adverse events such as hypotension, arrhythmia, chest pain, headache, hypokalemia, and thrombocytopenia. RESULTS: We assessed 730 admissions (684 patients) during this period. Ventricular septal defects were the most common diagnosis (42.4%) in these patients. Milrinone was primarily used after cardiac surgery in 715 admissions (97.9%). The duration of milrinone treatment varied from 3 to 64.4 days (> or =7 days in 149 admissions). Ejection fraction and fractional shortening of the left ventricle improved in patients receiving milrinone after cardiac surgery. Dose reduction of milrinone due to hypotension occurred in only 4 admissions (0.5%). Although diverse arrhythmias occurred in 75 admissions (10.3%), modification of milrinone infusion to manage arrhythmia occurred in only 3 admissions (0.4%). Multivariate analysis indicated that the development of arrhythmia was not influenced by the pattern of milrinone use. CONCLUSION: Milrinone was generally administered for > or =3 days in children with heart diseases. The use of milrinone for > or =3 days was effective in preventing low cardiac output after cardiac surgery when combined with other inotropes, suggesting that milrinone could be safely employed in pediatric patients with heart diseases.

Effect of milrinone on the inflammatory response and NF-kB activation in renal ischemia-reperfusion injury in mice / 대한마취과학회지

BACKGROUND: Milrinone increases intracellular adenosine 3',5'-cyclic monophosphate concentration and enhances vascular relaxation. Nuclear factor-kappa B (NF-kB) plays a key role in inflammatory responses during ischemia-reperfusion (I/R) injury. We aimed to investigate the effect of milrinone on the inflammatory responses and NF-kB activation in renal I/R injury in mice. METHODS: Thirty C57BL/6 mice were allocated into 3 groups. In group S (n = 10), only right nephrectomy was done. In group C (n = 10), the left kidney was subjected to 30 min of ischemia after right nephrectomy. In group M (n = 10), milrinone (5 microg/kg) was administered before ischemia. After 24 hours of reperfusion, the serum creatinine was measured, kidney samples were obtained for histology, and expressions of NF-kB and proinflammatory cytokines were analyzed. RESULTS: In group C, the serum creatinine concentration was markedly elevated, compared with group S. Creatinine concentration in group M was also elevated, but it was significantly lower than that in group C. Histologic evidence of renal damage was severe in group C, but it was improved in group M. In groups C and M, expression of NF-kB, tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) mRNA increased significantly compared with group S (P < 0.05). But group M showed a lower expression of NF-kB, TNF-alpha, ICAM-1, MCP-1 and MIP-2 mRNA than group C (P < 0.05). CONCLUSIONS: Milrinone treatment attenuates the renal inflammatory response and activation of NF-kB, resulting in improvement of renal function and tissue injury.

Effectiveness of milrinone for cardiogenic shock due to massive pulmonary aspiration: a case report / 대한마취과학회지

Pulmonary aspiration of gastric contents is one of the most frightening complications during anesthesia. Although pulmonary aspiration of gastric contents in general surgical patients is not common and resulting long-term morbidity and mortality are rare, severe hypoxemia and other sequelae of pulmonary aspiration continue to be reported. We report a case of massive aspiration of gastric contents during induction of general anesthesia, resulting in cardiac arrest due to severe pulmonary hypertension and myocardial infarction. Sustained cardiac arrest and shock that did not respond the conventional resuscitation was successfully treated using milrinone. The patient was discharged without complications in 20 days.

Enterovirus 71 Brainstem Encephalitis Presenting with Pulmonary Hemorrhage and Acute Heart Failure

Enterovirus 71 has been recognized as being highly central nervous system (CNS) involved and presents with diverse neurologic manifestations. Brainstem encephalitis is the most common neurologic manifestation of CNS involvement by enterovirus 71, and manifests myoclonus, ataxia, tremor, and autonomic dysfunction such as pulmonary hemorrhage. Here we report a 31-month-old girl with enterovirus 71 brainstem encephalitis presenting with pulmonary hemorrhage and acute heart failure. The patient was admitted to emergency department of our hospital due to high-grade fever, vomiting, myoclonus, and tremor 4 days after hand, foot and mouth disease. Four hours after admission, the patient presented with pulmonary hemorrhage and acute heart failure. CSF analysis demonstrated white blood cell 60/mm3, red blood cell 1/mm3, protein 43.0 mg/dL, and glucose 149 mg/dL. Despite aggressive management including intravenous immunoglobulin, milrinone and empirical antimicrobial therapy, the patient died due to uncontrolled pulmonary hemorrhage and shock in 15 hours after admission at emergency department. In stool specimen obtained from the patient, enterovirus 71 (subgenotype C4a) was detected. This case suggests that an early diagnosis of central nervous system involvement in patient with enterovirus 71 infection is vital because brainstem encephalitis resulting from enterovirus 71 infection can rapidly progress to the critical state of disease.

Additive effect of phosphodiesterase inhibitors in control of pulmonary hypertension after congenital cardiac surgery in children

Control of residual pulmonary arterial hypertension [PAH] after closure of left to right shunts in children is still a challenging issue. The purpose of this study was to compare the effect of two phosphodiesterase inhibitors in pediatric cardiac surgical patients. A total of 48 postoperative children were enrolled in the study between 2008 and 2010. Patients were stratified based upon choice of pulmonary vasodilator into three equal groups [n=16]; Milrinone group received intravenous milrinone [0.75 micro/kg/min], Sildenafil group received oral sildenafil [0.3 mg/kg every 3 hours] and the Combination group received both medications. Demographic variables and types of congenital anomalies were not different among the 3 groups. Patients in the Combination group had higher preoperative pulmonary artery to aortic [PA/AO] pressure ratios compared to other two groups [P=0.001]. Postoperatively, patients in Milrinone group incurred lower systolic PA and PA/AO pressures compared to Sildenafil group [P=0.014, 0.003], but it was the same in Sildenafil and Combination group [P=0.2; 0.330 respectively]. Pulmonary hypertensive crisis was noted in 6 patients in Sildenafil group, and 3 patients in Combination group [P=0.02]. Significant rise in PA pressure was noticed after discontinuation of drug in Milrinone group [P=0.001], which was not observed in the Combination group [P= 0.6]. No mortality was noticed in any of the groups. Intravenous milrinone is more effective than oral sildenafil in control of postoperative PAH and elimination of pulmonary hypertensive crisis. Combination of two drugs reduces the risk of rebound pulmonary arterial hypertension after discontinuation of milrinone

Characteristics of circulatory disturbance and the treatment of severe hand-foot-and-mouth disease / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the characteristics of circulatory disturbance and treatment of severe hand-foot-and-mouth disease (HFMD).</p><p><b>METHOD</b>The clinical characteristics, laboratory findings, therapy and outcome of 22 severe HFMD patients were retrospectively analyzed.</p><p><b>RESULT</b>All the 22 severe HFMD patients came from the countryside. All these patients had encephalitis. Fifteen cases had myocardial injury. All had symptoms of sympathetic excitation and 17 cases had hypertension [(128 ± 16)/(81 ± 14) mm Hg (1 mm Hg = 0.133 kPa)]. Fourteen cases had exacerbation with rapid decline of blood pressure [(61 ± 12)/(33 ± 12) mm Hg]. In cardiorespiratory failure stage, 13 patients had neurogenic pulmonary edema accompanied by circulatory failure and 12 cases had a lower glasgow scores (less than 7). Myocardial injury and ECG change were found in some cases. Inotropic and pressor drugs were given in patients with circulatory collapse. Five cases received fluid resuscitation due to refractoriness to inotropic drugs. Nine patients received blood purification. Seventeen survived and 5 cases died due to circulatory failure.</p><p><b>CONCLUSION</b>Circulation failure of severe HFMD is the main cause of death. Early and appropriate circulation support is very important to reduce mortality.</p>

effect of aminophylline versus milrinone on ischemia-reperfusion myocardial injury during open heart surgery

Cardioplegic arrest during cardiopulmonary bypass [CPB] is essential for the majority of cardiac surgical procedures; Cardioplegia protects the myocardium by providing continuous or intermittent oxygen while simultaneously reducing cardiomyocyte oxygen demand, but it does not inherently increase the ischemic-reperfusion injury tolerance of the cardiomyocytes. Aminophylline and milrinone by their phosphodiesterase inhibitor and anti-inflammatory activity may decrease this type of injury. This study has been designed to compare between the protective effect of aminophylline and milrinone over the heart during open heart surgery for valve replacement with CPB. Sixty adult patients undergoing elective single valve replacement were randomized to receive aminophylline 5 mg/kg [n=20], milrinone 50 microg/kg [n=20], or normal saline as control group [n=20] through intravenous infusion 10 minutes before the aortic cross-clamping. The cardiac troponin I, inotrope score, duration of mechanical ventilation, and length of ICU stay and other hemodynamic variables were measured and recorded. There were no differences between the three groups with regard to clinical variables. Cardiac troponin I raised significantly after declamping in the three groups, however it was significantly lower in aminophylline and milrinone group compared to control group immediately after CPB and after 8 hours with no significant differences between aminophylline and milrinone group, inotrope score duration of mechanical ventilation and length of ICU stay showed no significant differences between the three groups. Administration of aminophylline or milrinone reduces the subclinical myocardial injury with no difference between both agents and with no effect on the hemodynamic parameters or short term clinical outcome in patients undergoing single valve replacement with CPB

The effect of milrinone on the intraoperative hemodynamics during off-pump coronary bypass surgery in patients with an elevated echocardiographic index of the ventricular filling pressure / 대한마취과학회지

BACKGROUND: Hemodynamic derangement during off-pump coronary artery bypass surgery (OPCAB) is mainly attributed to impaired filling and diastolic dysfunction. An elevated ratio of the mitral velocity to the early-diastolic velocity of the mitral annulus (E/e' > 15) is a relatively new indicator of diastolic function, and this was reported to be associated with impaired hemodynamics during OPCAB. We investigated the efficacy of milrinone on the perioperative hemodynamics and short term outcomes of patients with an E/e' > 15 and who underwent OPCAB. METHODS: The patients were randomly allocated into either group C (control, n = 31) or group M (n = 31) and they were treated with the same amount of either normal saline or milrinone (0.5 microg/kg/min) without bolus loading after completion of internal mammary artery harvest until the end of operation. Hemodynamic measurements were recorded after the induction of anesthesia (T1), 5 min after starting each distal anastomosis of the left anterior descending artery (T2), left circumflex artery (T3) and right coronary artery (T4), and 5 min after sternum closure (T5). RESULTS: The mixed venous oxygen saturation (SvO2) was lower through T2-T4 compared to the baseline value in both groups, while the degree of the decrease was significantly less in group M than that in group C. The other hemodynamic variables, the operative data and the postoperative outcomes were similar between the two groups. CONCLUSIONS: Intraoperative infusion of milrinone did not significantly improve the perioperative hemodynamics and the subsequent short term outcomes for the patients with preexisting diastolic dysfunction as represented by an elevated E/e' value, although it reduced the degree of decrease of the SvO2 during OPCAB.

Successful Opening of Ductus Arteriosus with Milrinone in a Newborn with Tetralogy of Fallot and Pulmonary Atresia

Tetralogy of Fallot (TOF) assumes its' most severe form when accompanied by pulmonary atresia (PA). Preserving the patent ductus arteriosus to maintain pulmonary blood flow is life-saving for patients with this congenital heart disease. Milrinone, a selective phosphodiesterase III inhibitor, is a potent vasodilator. Here, we report the successful use of milrinone for a newborn infant with TOF and PA for keeping the ductus arteriosus open and thereby maintaining pulmonary circulation. Milrinone is a useful drug because of its inotropic, lusitropic, and pulmonary vasodilating effects, in addition to its ability to keep the ductus arteriosus open and its relatively mild side-effects. Case series and comparative studies will be needed in the future to verify the effectiveness of this drug.

Comparação dos efeitos da dobutamina e da milrinona sobre a hemodinâmica e o transporte de oxigênio em pacientes submetidos à cirurgia cardíaca com baixo débito cardíaco após indução anestésica / Comparison of the effects of dobutamine and milrinone on hemodynamic parameters and oxygen supply in patients undergoing cardiac surgery with low cardiac output after anesthetic induction

JUSTIFICATIVA E OBJETIVOS: Diversas classes de fármacos inotrópicos, com efeitos hemodinâmicos diferentes, são utilizadas no tratamento do baixo débito cardíaco em pacientes com disfunção sistólica submetidos a procedimento cirúrgico cardíaco. O objetivo deste estudo foi comparar o efeito da dobutamina e da milrinona sobre a hemodinâmica e o transporte de oxigênio nessa população de pacientes. MÉTODO: Após aprovação do Comitê de Ética institucional e obtenção do consentimento escrito pós-informado, 20 pacientes submetidos à cirurgia cardíaca e com índice cardíaco < 2 L.min-1.m-2 pós-indução anestésica e instalação de cateter de artéria pulmonar foram distribuídos aleatoriamente para receber dobutamina 5 µg.kg-1.min-1 (n = 10) ou milrinona 0,5 µg.kg-1.min-1 (n = 10). Medidas hemodinâmicas foram obtidas pós-indução, 30 e 60 minutos após, e gasometrias arterial e venosa nos momentos basal e 60 minutos. Os dados foram comparados usando teste t de Student não pareado ou ANOVA de duas vias para medidas repetidas. RESULTADOS: A dobutamina e a milrinona promoveram aumentos significativos no índice cardíaco (56 por cento e 47 por cento) e no transporte de oxigênio (53 por cento e 45 por cento), redução nos índices de resistência vascular sistêmica (33 por cento e 36 por cento) e pulmonar (34 por cento e 19 por cento), respectivamente. Contudo, não foram observadas diferenças entre os fármacos. CONCLUSÕES: Ambos os fármacos inotrópicos foram igualmente efetivos em restaurar o fluxo tecidual sanguíneo e a oferta tecidual de oxigênio para valores adequados em pacientes com baixo débito cardíaco submetidos à cirurgia cardíaca.

BACKGROUND AND OBJECTIVES: Several classes of inotropic drugs with different hemodynamic effects are used in the treatment of low cardiac output in patients with diastolic dysfunction undergoing cardiac surgery. The objective of the present study was to compare the effects of dobutamine and milrinone on hemodynamic parameters and oxygen supply in this population of patients. METHODS: After approval by the Ethics Committee of the institution and signing of the informed consent, 20 patients undergoing cardiac surgery with cardiac index < 2 L.min-1.m2 after anesthetic induction and place ment of a pulmonary artery catheter were randomly divided to receive dobutamine 5 µg.kg-1. min-1 (n = 10), or milrinone 0.5 µg.kg-1.min-1 (n = 10). Hemodynamic parameters were measured after anesthetic induction and after 30 and 60 minutes, and arterial and venous blood gases were measured at baseline and 60 minutes. Non-paired Student t test or two-way ANOVA for repeated measurements was used to compare the data. RESULTS: Dobutamine and milrinone promoted significant increases in cardiac index (56 percent and 47 percent) and oxygen supply (53 percent and 45 percent), and reduction in systemic (33 percent and 36 percent) and pulmonary (34 percent and 19 percent) vascular resistance, respectively. However, statistically significant differences were not observed between both drugs. CONCLUSIONS: Both inotropic drugs were similarly effective in restoring tissue blood flow and oxygen supply to adequate levels in patients with low cardiac output undergoing cardiac surgery.

JUSTIFICATIVA Y OBJETIVOS: Diversas clases de fármacos inotrópicos con efectos hemodinámicos diferentes, se usan en el tratamiento del bajo débito cardíaco en pacientes con disfunción sistólica sometidos al procedimiento quirúrgico cardíaco. El objetivo de este estudio, fue comparar el efecto de la dobutamina y de la milrinona sobre la hemodinámica y el transporte de oxígeno en esa población de pacientes. MÉTODO: Después de la aprobación del Comité de Ética institucional y de la obtención del consentimiento informado, 20 pacientes sometidos a la cirugía cardíaca y con índice cardíaco < 2 L.min-1.m-2 postinducción anestésica e instalación de catéter de arteria pulmonar, fueron distribuidos aleatoriamente para recibir dobutamina 5 µg.kg-1. min-1 (n = 10) o milrinona 0,5 µg.kg-1.min-1 (n = 10). Medidas hemodinámicas se obtuvieron postinducción, entre 30 y 60 minutos después de las gasometrías arterial y venosa en los momentos basales y 60 minutos. Los datos se compararon usando el test t de Student no pareado o Anova de dos vías para medidas repetidas. RESULTADOS: La dobutamina y la milrinona produjeron aumentos significativos en el índice cardíaco (56 por ciento y 47 por ciento) y en el transporte de oxígeno (53 por ciento y 45 por ciento), una reducción en los índices de resistencia vascular sistémica (33 por ciento y 36 por ciento) y pulmonar (34 por ciento y 19 por ciento) respectivamente. Sin embargo, no fueron observadas diferencias entre los fármacos. CONCLUSIONES: Ambos fármacos inotrópicos fueron igualmente efectivos en la restauración del flujo tisular sanguíneo y en la oferta tisular de oxígeno para valores adecuados en pacientes con bajo débito cardíaco sometidos a la cirugía cardíaca.

effect of aminophylline versus milrinone on ischemia-reperfusion myocardial injury during open heart surgery

Cardioplegic arrest during cardiopulmonary bypass [CPB] is essential for the majority of cardiac surgical procedures; Cardioplegia protects the myocardium by providing continuous or intermittent oxygen while simultaneously reducing cardiomyocyte oxygen demand, but it does not inherently increase the ischemic-reperfusion injury tolerance of the cardiomyocytes. Aminophylline and milrinone by their phosphodiesterase inhibitor and anti-inflammatory activity may decrease this type of injury. This study has been designed to compare between the protective effect of aminophylline and milrinone during open heart surgery for valve replacement with CPB. Sixty adult patients undergoing elective single valve replacement were randomized to receive aminophylline 5 mg/kg [n=20], milrinone 50 -microg/kg [n=20], or normal saline as control group [n=20] through intravenous infusion 10 minutes before the aortic cross-clamping. The cardiac troponin I, inotrope score, duration of mechanical ventilation, and length of ICU stay and other hemodynamic variables were measured and recorded. There were no differences between the three groups with regard to clinical variables. Cardiac troponin I raised significantly after declamping in the three groups, however it was significantly lower in aminophylline and milrinone group compared to control group immediately after CBP and after 8 hours with no significant differences between aminophylline and milrinone group, inotrope score duration of mechanical ventilation and length of ICU stay showed no significant differences between the three groups. Administration of aminophylline or milrinone reduces the subclinical myocardial injury with no difference between both agents and with no effect on the hemodynamic parameters or short term clinical outcome in patients undergoing single valve replacement with CPB

The effect of milrinone infusion on right ventricular function during coronary anastomosis and early outcomes in patients undergoing off-pump coronary artery bypass surgery / 대한마취과학회지

BACKGROUND: During coronary anastomosis in off-pump coronary artery bypass surgery (OPCAB), hemodynamic alternations can be induced by impaired diastolic function of the right ventricle. This study was designed to examine the effect of milrinone on right ventricular function and early outcomes in patients undergoing OPCAB. METHODS: Forty patients undergoing OPCAB were randomly assigned in a double-blind manner to receive either milrinone (milrinone group, n = 20) or normal saline (control group, n = 20). Hemodynamic variables were measured after pericardiotomy (T1), 5 min after stabilizer application for anastomosis of the left anterior descending coronary artery (LAD, T2), the obtuse marginalis branch (OM, T3), the right coronary artery (RCA, T4), 5 min after sternal closure (T5), and after ICU arrival. The right ventricular ejection fraction (RVEF) and right ventricular volumetric parameters were also measured using the thermodilution technique. For evaluation of early outcomes, the 30-day operative mortality and morbidity risk models were used. RESULTS: There was no significant difference in hemodynamic variables, including mean arterial pressure, between the 2 groups, except for the cardiac index and RVEF. The cardiac index and RVEF were significantly greater at T3 in the milrinone group than in the control group. CONCLUSIONS: Continuous infusion of milrinone demonstrated a beneficial effect on cardiac output and right ventricular function in patients undergoing OPCAB, especially during anastomosis of the graft to the OM artery, and it had no adverse effect on early outcomes.