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2.
J Aerosol Med Pulm Drug Deliv ; 34(4): 262-264, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34152840

RESUMO

Despite the various parenchymal presentation of coronavirus disease 2019 (COVID-19) pneumonia, the involvement of the vascular component, the reduction of perfusion in noninjured part of the lung and secondary right to left shunt play an important role in the genesis of the respiratory insufficiency. We present the case of a 72-year-old woman admitted to Livorno Hospital for severe respiratory insufficiency due to SARS-CoV-2 infection unresponsive to noninvasive in whom administration of nebulized phosphodiesterase 3 (PDE3) inhibitor enoximone was able to improve oxygenation avoiding tracheal intubation. Intravenous infusions of phosphodiesterase inhibitors are commonly used as pulmonary vasodilators in the management of pulmonary hypertension. This is the first case showing that inhaled route administration of PDE3 inhibitor enoximone could be important in the management of COVID-19 hypoxemia, to restore perfusion in noninjured part of the lung, improving oxygenation and avoiding risks of systemic infusion.


Assuntos
COVID-19/tratamento farmacológico , Enoximona/administração & dosagem , Hipóxia/tratamento farmacológico , Pulmão/irrigação sanguínea , Inibidores da Fosfodiesterase 3/administração & dosagem , Circulação Pulmonar/efeitos dos fármacos , Administração por Inalação , Aerossóis , Idoso , COVID-19/fisiopatologia , COVID-19/virologia , Feminino , Humanos , Hipóxia/fisiopatologia , Hipóxia/virologia , Nebulizadores e Vaporizadores , Resultado do Tratamento
3.
Exp Lung Res ; 47(3): 149-160, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33544007

RESUMO

BACKGROUND: Standard care in severe SARS-CoV-2 pneumonia complicated by severe dyspnea and respiratory failure, consists of symptom reduction, ultimately supported by mechanical ventilation. Patients with severe SARS-CoV-2, a prominent feature of COVID-19, show several similar symptoms to Critical Asthma Syndrome (CAS) patients, such as pulmonary edema, mucus plugging of distal airways, decreased tissue oxygenation, (emergent) exhaustion due to severe dyspnea and respiratory failure. Prior application of elective phosphodiesterase (PDE)3-inhibitors milrinone and enoximone in patients with CAS yielded rapid symptomatic relief and reverted the need for mechanical ventilation, due to their bronchodilator and anti-inflammatory properties. Based on these observations, we hypothesized that enoximone may be beneficial in the treatment of patients with severe SARS-CoV-2 pneumonia and prominent CAS-features. METHODS: In this case report enoximone was administered to four consecutive patients (1 M; 3 F; 46-70 y) with emergent respiratory failure due to SARS-CoV-2 pneumonia. Clinical outcome was compared with three controls who received standard care only. RESULTS: After an intravenous bolus of enoximone 20 mg followed by 10 mg/h via perfusor, a rapid symptomatic relief was observed: two out of four patients recovered within a few hours, the other two (with comorbid COPD GOLD II/III) responded within 24-36 h. Compared to the controls, in the enoximone-treated patients respiratory failure and further COVID-19-related deterioration was reverted and mechanical ventilation was prevented, leading to reduced hospital/ICU time. DISCUSSION: Our preliminary observations suggest that early intervention with the selective PDE3-inhibitor enoximone may help to revert respiratory failure as well as avert mechanical ventilation, and reduces ICU/hospital time in patients with severe SARS-CoV-2 pneumonia. Our findings warrant further research on the therapeutic potential of PDE3-inhibition, alone or in combination with other anti-COVID-19 strategies.


Assuntos
COVID-19/tratamento farmacológico , Enoximona/uso terapêutico , Inibidores da Fosfodiesterase 3/uso terapêutico , Respiração Artificial , SARS-CoV-2 , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/terapia
4.
Cochrane Database Syst Rev ; 11: CD009669, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33152122

RESUMO

BACKGROUND: Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) are potentially life-threatening complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery. While there is solid evidence for the treatment of other cardiovascular diseases of acute onset, treatment strategies in haemodynamic instability due to CS and LCOS remains less robustly supported by the given scientific literature. Therefore, we have analysed the current body of evidence for the treatment of CS or LCOS with inotropic and/or vasodilating agents. This is the second update of a Cochrane review originally published in 2014. OBJECTIVES: Assessment of efficacy and safety of cardiac care with positive inotropic agents and vasodilator agents in CS or LCOS due to AMI, HF or after cardiac surgery. SEARCH METHODS: We conducted a search in CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in October 2019. We also searched four registers of ongoing trials and scanned reference lists and contacted experts in the field to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) enrolling patients with AMI, HF or cardiac surgery complicated by CS or LCOS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures according to Cochrane standards. MAIN RESULTS: We identified 19 eligible studies including 2385 individuals (mean or median age range 56 to 73 years) and three ongoing studies. We categorised studies into 11 comparisons, all against standard cardiac care and additional other drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo; enoximone versus dobutamine, piroximone or epinephrine-nitroglycerine; epinephrine versus norepinephrine or norepinephrine-dobutamine; dopexamine versus dopamine; milrinone versus dobutamine and dopamine-milrinone versus dopamine-dobutamine. All trials were published in peer-reviewed journals, and analyses were done by the intention-to-treat (ITT) principle. Eighteen of 19 trials were small with only a few included participants. An acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements occurred in nine of 19 trials. In general, confidence in the results of analysed studies was reduced due to relevant study limitations (risk of bias), imprecision or indirectness. Domains of concern, which showed a high risk in more than 50% of included studies, encompassed performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events. All comparisons revealed uncertainty on the effect of inotropic/vasodilating drugs on all-cause mortality with a low to very low quality of evidence. In detail, the findings were: levosimendan versus dobutamine (short-term mortality: RR 0.60, 95% CI 0.36 to 1.03; participants = 1701; low-quality evidence; long-term mortality: RR 0.84, 95% CI 0.63 to 1.13; participants = 1591; low-quality evidence); levosimendan versus placebo (short-term mortality: no data available; long-term mortality: RR 0.55, 95% CI 0.16 to 1.90; participants = 55; very low-quality evidence); levosimendan versus enoximone (short-term mortality: RR 0.50, 0.22 to 1.14; participants = 32; very low-quality evidence; long-term mortality: no data available); epinephrine versus norepinephrine-dobutamine (short-term mortality: RR 1.25; 95% CI 0.41 to 3.77; participants = 30; very low-quality evidence; long-term mortality: no data available); dopexamine versus dopamine (short-term mortality: no deaths in either intervention arm; participants = 70; very low-quality evidence; long-term mortality: no data available); enoximone versus dobutamine (short-term mortality RR 0.21; 95% CI 0.01 to 4.11; participants = 27; very low-quality evidence; long-term mortality: no data available); epinephrine versus norepinephrine (short-term mortality: RR 1.81, 0.89 to 3.68; participants = 57; very low-quality evidence; long-term mortality: no data available); and dopamine-milrinone versus dopamine-dobutamine (short-term mortality: RR 1.0, 95% CI 0.34 to 2.93; participants = 20; very low-quality evidence; long-term mortality: no data available). No information regarding all-cause mortality were available for the comparisons milrinone versus dobutamine, enoximone versus piroximone and enoximone versus epinephrine-nitroglycerine. AUTHORS' CONCLUSIONS: At present, there are no convincing data supporting any specific inotropic or vasodilating therapy to reduce mortality in haemodynamically unstable patients with CS or LCOS. Considering the limited evidence derived from the present data due to a high risk of bias and imprecision, it should be emphasised that there is an unmet need for large-scale, well-designed randomised trials on this topic to close the gap between daily practice in critical care of cardiovascular patients and the available evidence. In light of the uncertainties in the field, partially due to the underlying methodological flaws in existing studies, future RCTs should be carefully designed to potentially overcome given limitations and ultimately define the role of inotropic agents and vasodilator strategies in CS and LCOS.


Assuntos
Baixo Débito Cardíaco/tratamento farmacológico , Cardiotônicos/uso terapêutico , Infarto do Miocárdio/complicações , Choque Cardiogênico/tratamento farmacológico , Vasodilatadores/uso terapêutico , Idoso , Baixo Débito Cardíaco/etiologia , Baixo Débito Cardíaco/mortalidade , Causas de Morte , Dobutamina/uso terapêutico , Enoximona/uso terapêutico , Epinefrina/uso terapêutico , Humanos , Hidrazonas/uso terapêutico , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Óxido Nítrico/uso terapêutico , Placebos/uso terapêutico , Piridazinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Simendana/uso terapêutico
5.
EuroIntervention ; 15(7): 586-593, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31147306

RESUMO

AIMS: The haemodynamic effects of primary implantation of an intra-aortic balloon pump (IABP) versus inotropes in decompensated heart failure and low output (DHF-LO), but without an acute coronary syndrome, have not been investigated. We therefore aimed to investigate the effect of primary IABP implantation as compared to inotropes on haemodynamics in DHF-LO with no acute ischaemia. METHODS AND RESULTS: Patients (n=32) with DHF-LO despite IV diuretics were randomised to primary 50 mL IABP or inotropes (INO: enoximone or dobutamine). The primary endpoint was the improvement of organ perfusion assessed by ∆ mixed-venous oxygen saturation (SvO2) at 3 hours; secondary endpoints included ∆ cardiac power output (CPO), NT-proBNP proportional change, cumulative fluid balance and ∆ dyspnoea severity score, all at 48 hours. Data are presented as median (IQR). Patients were 60 (48-69) years old and 72% were male. Baseline SvO2 was 44 (39-53)%. ∆SvO2 was higher in the IABP group (+17 [+9; +24] vs. +5 [+2; +9]%, p<0.05). IABP patients had a higher ∆CPO, a greater relative reduction in NT-proBNP, a more negative cumulative fluid balance, and a greater reduction in dyspnoea severity score. There were no IABP-related serious adverse events (SAEs). Thirty-day mortality was 23% (IABP) vs. 44% (INO). CONCLUSIONS: Primary circulatory support by IABP showed a significant increase in improved organ perfusion assessed by SvO2.


Assuntos
Débito Cardíaco/fisiologia , Cardiotônicos/uso terapêutico , Dobutamina/uso terapêutico , Enoximona/uso terapêutico , Insuficiência Cardíaca/cirurgia , Hemodinâmica/fisiologia , Balão Intra-Aórtico/métodos , Idoso , Débito Cardíaco/efeitos dos fármacos , Feminino , Coração Auxiliar , Hemodinâmica/efeitos dos fármacos , Humanos , Balão Intra-Aórtico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Int J Cardiol ; 269: 51-55, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30037630

RESUMO

BACKGROUND: Perioperative administration of Enoximone has been shown to improve hemodynamics, organ function, and inflammatory response. Aim of the present study was to evaluate the effects of Enoximone after on-pump cardiac surgery. METHODS: A protocol for a multicenter observational study was reviewed and approved by local ethic committee. This preliminary report involves the first 29 patients enrolled, in whom Enoximone was perioperatively administered in the context of on-pump cardiac surgery. All patients enrolled were propensity-matched 1:1 with controls not receiving Enoximone, renal function was evaluated in terms of estimated glomerular filtration rate (eGFR) with the CKD-EPI equation. RESULTS: After propensity matching, the two cohorts of patients receiving Enoximone or not did not show any significant differences among baseline characteristics. Patients receiving Enoximone showed a progressive improvement of eGFR at each time-point of follow-up: roughly +4.3, +10.0, and +12.3 mL/min/1.73 m2 on postoperative days 2, 7, and 30; respectively. Consistently, maximum difference versus baseline was +12.6 mL/min/1.73 m2 (or +19.3%) among Enoximone patients vs +3.3 mL/min/1.73 m2 (or +4.4%) among controls (p = 0.02). Multivariable regression analysis (R2-adjusted 0.47) showed only age (ß -0.53; p = 0.01), preoperative eGFR (ß -0.39; p = 0.02), diabetes (ß 2.1; p = 0.01), cardio-pulmonary bypass duration (ß 0.08; p = 0.05), and Enoximone administration (ß -0.74; p = 0.05) to be independently correlated with delta eGFR variation on day 30. CONCLUSION: These preliminary results show that perioperative Enoximone administration improved renal function in patients undergoing on-pump cardiac surgery. Further studies are needed to confirm these findings.


Assuntos
Procedimentos Cirúrgicos Cardíacos/tendências , Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/cirurgia , Enoximona/uso terapêutico , Idoso , Procedimentos Cirúrgicos Cardíacos/métodos , Doenças Cardiovasculares/diagnóstico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
7.
Cochrane Database Syst Rev ; 1: CD009669, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29376560

RESUMO

BACKGROUND: Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) as complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery are life-threatening conditions. While there is a broad body of evidence for the treatment of people with acute coronary syndrome under stable haemodynamic conditions, the treatment strategies for people who become haemodynamically unstable or develop CS remain less clear. We have therefore summarised here the evidence on the treatment of people with CS or LCOS with different inotropic agents and vasodilative drugs. This is the first update of a Cochrane review originally published in 2014. OBJECTIVES: To assess efficacy and safety of cardiac care with positive inotropic agents and vasodilator strategies in people with CS or LCOS due to AMI, HF or cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in June 2017. We also searched four registers of ongoing trials and scanned reference lists and contacted experts in the field to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials in people with myocardial infarction, heart failure or cardiac surgery complicated by cardiogenic shock or LCOS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 13 eligible studies with 2001 participants (mean or median age range 58 to 73 years) and two ongoing studies. We categorised studies into eight comparisons, all against cardiac care and additional other active drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo, epinephrine versus norepinephrine-dobutamine, amrinone versus dobutamine, dopexamine versus dopamine, enoximone versus dopamine and nitric oxide versus placebo.All trials were published in peer-reviewed journals, and analysis was done by the intention-to-treat (ITT) principle. Twelve of 13 trials were small with few included participants. Acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements emerged in five of 13 trials. In general, confidence in the results of analysed studies was reduced due to serious study limitations, very serious imprecision or indirectness. Domains of concern, which show a high risk of more than 50%, include performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events.Levosimendan may reduce short-term mortality compared to a therapy with dobutamine (RR 0.60, 95% CI 0.37 to 0.95; 6 studies; 1776 participants; low-quality evidence; NNT: 16 (patients with moderate risk), NNT: 5 (patients with CS)). This initial short-term survival benefit with levosimendan vs. dobutamine is not confirmed on long-term follow up. There is uncertainty (due to lack of statistical power) as to the effect of levosimendan compared to therapy with placebo (RR 0.48, 95% CI 0.12 to 1.94; 2 studies; 55 participants, very low-quality evidence) or enoximone (RR 0.50, 95% CI 0.22 to 1.14; 1 study; 32 participants, very low-quality evidence).All comparisons comparing other positive inotropic, inodilative or vasodilative drugs presented uncertainty on their effect on short-term mortality with very low-quality evidence and based on only one RCT. These single studies compared epinephrine with norepinephrine-dobutamine (RR 1.25, 95% CI 0.41 to 3.77; 30 participants), amrinone with dobutamine (RR 0.33, 95% CI 0.04 to 2.85; 30 participants), dopexamine with dopamine (no in-hospital deaths from 70 participants), enoximone with dobutamine (two deaths from 40 participants) and nitric oxide with placebo (one death from three participants). AUTHORS' CONCLUSIONS: Apart from low quality of evidence data suggesting a short-term mortality benefit of levosimendan compared with dobutamine, at present there are no robust and convincing data to support a distinct inotropic or vasodilator drug-based therapy as a superior solution to reduce mortality in haemodynamically unstable people with cardiogenic shock or LCOS.Considering the limited evidence derived from the present data due to a generally high risk of bias and imprecision, it should be emphasised that there remains a great need for large, well-designed randomised trials on this topic to close the gap between daily practice in critical care medicine and the available evidence. It seems to be useful to apply the concept of 'early goal-directed therapy' in cardiogenic shock and LCOS with early haemodynamic stabilisation within predefined timelines. Future clinical trials should therefore investigate whether such a therapeutic concept would influence survival rates much more than looking for the 'best' drug for haemodynamic support.


Assuntos
Baixo Débito Cardíaco/tratamento farmacológico , Cardiotônicos/uso terapêutico , Infarto do Miocárdio/complicações , Choque Cardiogênico/tratamento farmacológico , Vasodilatadores/uso terapêutico , Idoso , Baixo Débito Cardíaco/etiologia , Baixo Débito Cardíaco/mortalidade , Causas de Morte , Dobutamina/uso terapêutico , Enoximona/uso terapêutico , Humanos , Hidrazonas/uso terapêutico , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Óxido Nítrico/uso terapêutico , Piridazinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Simendana
8.
JCI Insight ; 3(2)2018 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-29367458

RESUMO

Phosphodiesterase 3 (PDE3) and PDE4 regulate levels of cyclic AMP, which are critical in various cell types involved in allergic airway inflammation. Although PDE4 inhibition attenuates allergic airway inflammation, reported side effects preclude its application as an antiasthma drug in humans. Case reports showed that enoximone, which is a smooth muscle relaxant that inhibits PDE3, is beneficial and lifesaving in status asthmaticus and is well tolerated. However, clinical observations also showed antiinflammatory effects of PDE3 inhibition. In this study, we investigated the role of PDE3 in a house dust mite-driven (HDM-driven) allergic airway inflammation (AAI) model that is characterized by T helper 2 cell activation, eosinophilia, and reduced mucosal barrier function. Compared with wild-type (WT) littermates, mice with a targeted deletion of the PDE3A or PDE3B gene showed significantly reduced HDM-driven AAI. Therapeutic intervention in WT mice showed that all hallmarks of HDM-driven AAI were abrogated by the PDE3 inhibitors enoximone and milrinone. Importantly, we found that enoximone also reduced the upregulation of the CD11b integrin on mouse and human eosinophils in vitro, which is crucial for their recruitment during allergic inflammation. This study provides evidence for a hitherto unknown antiinflammatory role of PDE3 inhibition in allergic airway inflammation and offers a potentially novel treatment approach.


Assuntos
Asma/imunologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/metabolismo , Eosinófilos/imunologia , Inibidores da Fosfodiesterase 3/farmacologia , Alérgenos/imunologia , Animais , Asma/tratamento farmacológico , Asma/patologia , Biópsia , Antígeno CD11b/imunologia , Antígeno CD11b/metabolismo , Células Cultivadas , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/análise , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/imunologia , Modelos Animais de Doenças , Enoximona/farmacologia , Enoximona/uso terapêutico , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Humanos , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Milrinona/farmacologia , Milrinona/uso terapêutico , Uso Off-Label , Inibidores da Fosfodiesterase 3/uso terapêutico , Cultura Primária de Células , Pyroglyphidae/imunologia , Regulação para Cima/efeitos dos fármacos
9.
Pediatr Cardiol ; 37(7): 1297-301, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27377525

RESUMO

Phosphodiesterase 3 inhibitors have been used successfully in pediatric patients with acute or chronic myocardial dysfunction over the last two decades. Their protracted continuous intravenous administration is associated with risk of infectious and thromboembolic complications. Weaning intravenous medication and starting oral angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers can be challenging. We reviewed retrospectively hospital records of 48 patients receiving oral enoximone treatment in a single tertiary pediatric cardiac center between November 2005 and April 2014. Failure to wean from intravenous milrinone infusion and/or intolerance of ACE inhibitors and/or beta-blockers was indications for oral enoximone treatment. Age of the patients ranged between 0.5 and 191 months (median 7.5 months) at the time of starting enoximone treatment. There were 14 patients (29 %) with left ventricular dysfunction due to myocarditis or dilated cardiomyopathy and 34 patients (71 %) with myocardial dysfunction complicating congenital heart disease. Fifteen (44 %) of these 34 patients had left ventricular dysfunction, 13 (38 %) right ventricular dysfunction, and in 6 (18 %) both ventricles were failing. Duration of oral enoximone treatment was between 3 days and 34 months (median of 2.3 months). Myocardial functional recovery allowed for weaning of enoximone treatment in 15 patients (31 %) after 6 days-15 months (median 5 months). No adverse hemodynamic effects were noted. Blood stained gastric aspirates encountered in two patients resolved with concomitant milk administration. Based on our limited experience, oral enoximone is a well-tolerated and promising alternative to intravenous medication and/or other commonly used oral medications in selected pediatric patients with chronic heart failure.


Assuntos
Insuficiência Cardíaca , Antagonistas Adrenérgicos beta , Cardiotônicos , Criança , Enoximona , Hemodinâmica , Humanos , Milrinona , Disfunção Ventricular Esquerda
10.
BMJ Case Rep ; 20152015 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-26504095

RESUMO

A 42-year-old woman with end-stage renal failure was admitted to the intensive care unit following resuscitation from a pulseless electrical activity cardiac arrest after intravenous piperacillin/tazobactam. Persistent bradycardia and hypotension, unresponsive to epinephrine and norepinephrine, were suspected to have been exacerbated by chronic labetalol therapy for resistant arterial hypertension. As an alternative, the non-adrenergic inotrope, enoximone, was started. This, combined with thrombolysis for possible pulmonary embolism, heralded significant haemodynamic improvement, allowing weaning from inotropic support. A clear CT pulmonary angiogram 2 days post-arrest and significantly raised mast cell tryptase levels confirmed anaphylaxis rather than pulmonary embolism as the precipitating cause. We believe this to be the first case report of phosphodiesterase-III inhibitor use in the management of anaphylaxis complicated by α/ß-blockade, and discuss the mechanism behind this effect and comparison with the more commonly reported use of glucagon.


Assuntos
Anafilaxia/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Enoximona/uso terapêutico , Hipertensão/tratamento farmacológico , Hipotensão/tratamento farmacológico , Labetalol/uso terapêutico , Inibidores da Fosfodiesterase 3/uso terapêutico , Adulto , Anafilaxia/complicações , Anafilaxia/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Hipertensão/complicações , Hipotensão/etiologia
11.
Br J Anaesth ; 114(5): 746-56, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25652947

RESUMO

BACKGROUND: Inodilators are commonly used in critically ill patients, but their effect on survival has not been properly studied to date. The objective of this work was to conduct a network meta-analysis on the effects of inodilators on survival in adult cardiac surgery patients, and to compare and rank drugs that have not been adequately compared in head-to-head trials. METHODS: Relevant studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register of clinical trials (updated on May 1, 2014). The criteria for inclusion were: random allocation to treatment with at least one group receiving dobutamine, enoximone, levosimendan, or milrinone and at least another group receiving the above inodilators or placebo, performed in cardiac surgical patients. The endpoint was to identify differences in mortality at longest follow-up available. RESULTS: The 46 included trials were published between 1995 and 2014 and randomised 2647 patients. The Bayesian network meta-analysis found that only the use of levosimendan was associated with a decrease in mortality when compared with placebo (posterior mean of OR=0.48, 95% CrI 0.28 to 0.80). The posterior distribution of the probability for each inodilator to be the best and the worst drug showed that levosimendan is the best agent to improve survival after cardiac surgery. The sensitivity analyses performed did not produce different interpretative result. CONCLUSION: Levosimendan seems to be the most efficacious inodilator to improve survival in cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Vasodilatadores/farmacologia , Teorema de Bayes , Estado Terminal/mortalidade , Dobutamina/farmacologia , Enoximona/farmacologia , Humanos , Hidrazonas/farmacologia , Milrinona/farmacologia , Piridazinas/farmacologia , Simendana
12.
PLoS One ; 9(8): e103978, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25084171

RESUMO

AIM: To investigate the effects of inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. METHODS AND RESULTS: Thirty patients with cardiogenic shock were included. Patients received dobutamine, enoximone, or norepinephrine. We performed hemodynamic measurements at baseline and after titration of the inotropic agent until cardiac index (CI) ≥ 2.5 L.min-1.m(-2) or mixed-venous oxygen saturation (SvO2) ≥ 70% (dobutamine or enoximone), and mean arterial pressure (MAP) ≥ 70 mmHg (norepinephrine). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). All patients reached predefined therapeutic targets. The inotropes did not significantly change delta-T. Dobutamine did not change PCD. Enoximone increased PCD (9.1 [8.9-10.2] vs. 11.4 [8.4-13.9] mm.mm(-2); p<0.05), and norepinephrine tended to decrease PCD (9.8 [8.5-11.9] vs. 8.8 [8.2-9.6] mm.mm-2, p = 0.08). Fifteen patients (50%) died within 30 days after admission. Patients who had low final PCD (≤ 10.3 mm.mm-2; 64%) were more likely to die than patients who had preserved PCD (>10.3 mm.mm(-2); mortality 72% vs. 17%, p = 0.003). CONCLUSION: This study demonstrates the effects of commonly used inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Despite hemodynamic optimization, tissue perfusion was not sufficiently restored in most patients. In these patients, mortality was high. Interventions directed at improving microcirculation may eventually help bridging the gap between improved hemodynamics and dismal patient outcome in cardiogenic shock.


Assuntos
Dobutamina/farmacologia , Enoximona/farmacologia , Hemodinâmica/efeitos dos fármacos , Microcirculação/efeitos dos fármacos , Infarto do Miocárdio/complicações , Norepinefrina/farmacologia , Ressuscitação , Choque Cardiogênico/complicações , Idoso , Idoso de 80 Anos ou mais , Capilares/efeitos dos fármacos , Capilares/fisiopatologia , Dobutamina/administração & dosagem , Enoximona/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Norepinefrina/administração & dosagem , Perfusão , Circulação Pulmonar/efeitos dos fármacos , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Resultado do Tratamento
13.
J Int Med Res ; 42(3): 750-64, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24781725

RESUMO

OBJECTIVES: Levosimendan is an inotropic drug with organ-protective properties due to its activation of mitochondrial K(ATP) channels. This prospective, randomized, double-blind, placebo-controlled study investigated whether administration of levosimendan prior to cardiopulmonary bypass could reduce organ dysfunction and influence subsequent secondary endpoints. PATIENTS AND METHODS: Patients with left ventricular ejection fraction <30% scheduled for elective coronary artery bypass surgery (with or without valve surgery) received either levosimendan (12.5 mg, 0.1 µg kg(-1) per min; n = 17) or placebo (n = 16) central venous infusion, immediately after anaesthesia induction, as add-on medication to a goal-orientated treatment algorithm. RESULTS: A total of 33 patients completed the study. There were no statistically significant differences in Sequential Organ Failure Assessment scores, survival, haemodynamic parameters, time to extubation, time in intensive care unit, need for haemodialysis or health-related quality-of-life at 6 months post operation. The levosimendan group compared with the placebo group had significantly lower use of epinephrine (35% versus 81%) and nitroglycerine (6% versus 44%) 24 h postoperation, and significantly less frequent serious adverse events (13% versus 47%). CONCLUSIONS: These preliminary results show that timely perioperative levosimendan treatment is feasible, has a favourable safety profile safe and may help to prevent low cardiac output syndrome. However, organ function was not preserved. Further studies, using larger sample sizes, are required.


Assuntos
Cardiomiopatias/tratamento farmacológico , Cardiotônicos/uso terapêutico , Ponte de Artéria Coronária , Hidrazonas/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Piridazinas/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Cardiomiopatias/patologia , Cardiomiopatias/cirurgia , Método Duplo-Cego , Enoximona/uso terapêutico , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Isquemia Miocárdica/cirurgia , Norepinefrina/uso terapêutico , Estudos Prospectivos , Simendana , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Vasoconstritores/uso terapêutico , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/cirurgia
14.
Br J Anaesth ; 112(6): 1105-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24638233

RESUMO

This report describes the treatment of eight patients with status asthmaticus, six of whom were already maximally treated. They were consequently treated with enoximone, a selective phosphodiesterase III inhibitor, in their refractory phase. Bronchodilatation in these patients was immediate. No side-effects were observed. Enoximone appears to be a valuable addition to the treatment of status asthmaticus. I.V. administration bypasses inhalation incapability in severe asthma. It is likely to reduce or altogether prevent the need for resorting to secondary or tertiary high-tech therapy such as mechanical ventilation or anaesthetics, thus avoiding complications, as well as for transfers to specialized intensive care units. Not only do these aspects enable substantial cost savings, but they also may spare the patient a lot of anguish and a prolonged recovery.


Assuntos
Tratamento de Emergência/métodos , Enoximona/administração & dosagem , Inibidores da Fosfodiesterase 3/administração & dosagem , Estado Asmático/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Eur J Heart Fail ; 16(4): 435-43, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24464574

RESUMO

AIMS: Beta-blockers improve the prognosis in heart failure (HF), but their introduction may seem impossible in patients dependent on inotropic support. However, many of these patients can be titrated on beta-blockers, but there is little evidence of successful clinical strategies. METHODS AND RESULTS: We analysed the records of inotropy-dependent patients referred for assessment for heart transplantation. Thirty-six patients (45%) could not be weaned (NW) and underwent left ventricular assist device (LVAD) implantation or transplantation, or died. However, 44 (55%) were successfully weaned (SW). Neither the aetiology (ischaemic vs. non-ischaemic) nor cardiac indexes were different in the SW as compared with the NW group (2.27±0.5 vs. 2.15±0.6 L/min/m2). The NW patients had lower LVEF (15±5% vs. 19±5%, P=0.001), higher right atrial pressure (12±6 vs. 8±6 mmHg, P=0.02), and more severe mitral regurgitation (P<0.001) than the SW patients. At discharge, 35 of 44 SW patients were receiving beta-blockers. In 29 of them, a beta-blocker could only be initiated or continued during concomitant support with i.v. enoximone for a duration of 14.1±7.2 days. Patients discharged on a beta-blocker had an LVAD/transplantation-free cumulative survival of 71% during a follow-up of 2074±201 days (confidence interval 1679­2470). CONCLUSION: It takes time to put severely ill HF patients on beta-blockers and it may require bridging with inotropes which are independent of beta-adrenergic receptors. Whether such a strategy may result in a better clinical outcome warrants further research.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Adulto , Bisoprolol/uso terapêutico , Carbazóis/uso terapêutico , Carvedilol , Dobutamina/uso terapêutico , Ecocardiografia , Enoximona/uso terapêutico , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Propanolaminas/uso terapêutico , Estudos Retrospectivos , Taxa de Sobrevida , Desmame do Respirador
16.
Cochrane Database Syst Rev ; (1): CD009669, 2014 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-24385385

RESUMO

BACKGROUND: The recently published German-Austrian S3 Guideline for the treatment of infarct related cardiogenic shock (CS) revealed a lack of evidence for all recommended therapeutic measures. OBJECTIVES: To determine the effects in terms of efficacy, efficiency and safety of cardiac care with inotropic agents and vasodilator strategies versus placebo or against each other for haemodynamic stabilisation following surgical treatment, interventional therapy (angioplasty, stent implantation) and conservative treatment (that is no revascularization) on mortality and morbidity in patients with acute myocardial infarction (AMI) complicated by CS or low cardiac output syndrome (LCOS). SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), EMBASE (Ovid) and ISI Web of Science, registers of ongoing trials and proceedings of conferences in January 2013. Reference lists were scanned and experts in the field were contacted to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials in patients with AMI complicated by CS or LCOS. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the published protocol. All trials were analysed individually. Hazard ratios (HRs) and odds ratios with 95% confidence intervals (CI) were extracted but not pooled because of high heterogeneity between the control group interventions. MAIN RESULTS: Four eligible, very small studies were identified from a total of 4065 references. Three trials with high overall risk of bias compared levosimendan to standard treatment (enoximone or dobutamine) or placebo. Data from a total of 63 participants were included in our comparisons, 31 were treated with levosimendan and 32 served as controls. Levosimendan showed an imprecise survival benefit in comparison with enoximone based on a very small trial with 32 participants (HR 0.33; 95% CI 0.11 to 0.97). Results from the other similarly small trials were too imprecise to provide any meaningful information about the effect of levosimendan in comparison with dobutamine or placebo. Only small differences in haemodynamics, length of hospital stay and the frequency of major adverse cardiac events or adverse events overall were found between study groups.Only one small randomised controlled trial with three participants was found for vasodilator strategies (nitric oxide gas versus placebo) in AMI complicated by CS or LCOS. This study was too small to draw any conclusions on the effects on our key outcomes. AUTHORS' CONCLUSIONS: At present there are no robust and convincing data to support a distinct inotropic or vasodilator drug based therapy as a superior solution to reduce mortality in haemodynamically unstable patients with CS or low cardiac output complicating AMI.


Assuntos
Baixo Débito Cardíaco/tratamento farmacológico , Cardiotônicos/uso terapêutico , Infarto do Miocárdio/complicações , Choque Cardiogênico/tratamento farmacológico , Vasodilatadores/uso terapêutico , Baixo Débito Cardíaco/etiologia , Dobutamina/uso terapêutico , Enoximona/uso terapêutico , Humanos , Hidrazonas/uso terapêutico , Óxido Nítrico/uso terapêutico , Piridazinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Cardiogênico/etiologia , Simendana
18.
Int J Cardiol ; 167(5): 1961-6, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22633430

RESUMO

BACKGROUND: Perioperative administration of enoximone has been shown to improve hemodynamics, organ function, and inflammatory response. Aim of the present study is to evaluate the impact of enoximone on postoperative renal function after on-pump cardiac surgery. METHODS: A total of 3727 patients undergoing cardiac surgery at one Institution between May 2004 and November 2010 were reviewed. A propensity score was built and a 1:1 perfect matching was performed, providing two fairly comparable cohorts of 712 patients each, receiving or not enoximone after surgery. Renal function was evaluated by lower glomerular filtration rate (GFR) value reached postoperatively. RESULTS: Overall 30-day mortality rate was 4.3% (62/1424). Cumulative incidence of postoperative renal failure (RF) was 157/1424(11%), of which 99/1424(7%) needed renal replacement therapy. Mean lower postoperative GFR in patients who received or not enoximone was 63 ± 30.1 and 53.5 ± 26.1 ml/min/1.73 m(2) (p<0.0001), respectively. At multivariable analysis age (OR2.75, p=0.0004), diabetes (OR1.82, p=0.006), preoperative GFR (OR3.81, p<0.0001), preoperative cardiogenic shock (OR1.65, p=0.004), previous cardiac surgery (OR2.12, p=0.0002), type of intervention (OR1.96, p=0.005), and enoximone (OR0.38, p=0.001) were found to be independently associated with postoperative RF. Logistic regression analysis showed that the administration of enoximone (OR0.41, p=0.0001), and of no inotropes (OR0.27, p<0.0001) were protective vs. the occurrence of postoperative RF. CONCLUSION: Patients perioperatively receiving enoximone showed a statistically significant better renal function after cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Enoximona/administração & dosagem , Taxa de Filtração Glomerular/fisiologia , Rim/fisiologia , Assistência Perioperatória/métodos , Pontuação de Propensão , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/tendências , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vasodilatadores/administração & dosagem
19.
Congest Heart Fail ; 16(6): 265-70, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21091611

RESUMO

Few data exist on the safety of transferring patients to standard oral therapy for chronic heart failure (CHF) after acute management with inotropic agents. This study compares hemodynamic responses and cardiac dysrhythmic effects of continuous infusion of enoximone, dobutamine, or placebo in patients with moderate to severe CHF. The authors enrolled 136 patients who were randomly assigned to either open-label dobutamine or double-blind enoximone vs placebo. After 24 hours of treatment, the study was unblinded. Patients receiving placebo completed the study. Patients receiving enoximone or dobutamine received the infusion for an additional 24 hours and were then switched to standard oral therapy for 72 hours. Compared with placebo, both enoximone and dobutamine increased cardiac index and decreased pulmonary capillary wedge pressure (PCWP). Compared with dobutamine, enoximone significantly increased cardiac index after the first 24 hours of infusion and significantly decreased PCWP throughout the infusion period. There was no difference in the incidence of arrhythmias between enoximone and dobutamine. More patients (65%) tolerated the switch to oral therapy in the enoximone group compared with dobutamine (49%; P =.12). Enoximone is effective in improving the hemodynamics in patients with moderate to severe CHF and is tolerated at least as well as dobutamine.


Assuntos
Cardiotônicos/uso terapêutico , Dobutamina/uso terapêutico , Enoximona/uso terapêutico , Simpatomiméticos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Circulação Coronária , Proteínas Quinases Dependentes de AMP Cíclico , Proteínas Quinases Dependentes de GMP Cíclico , Progressão da Doença , Método Duplo-Cego , Eletrocardiografia Ambulatorial , Feminino , Indicadores Básicos de Saúde , Hemodinâmica , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pressão Propulsora Pulmonar , Estatística como Assunto , Volume Sistólico , Função Ventricular Esquerda
20.
Echocardiography ; 27(5): 544-51, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20374267

RESUMO

BACKGROUND: The aim of this study was to evaluate enoximone echocardiography (EE) for the identification of residual myocardial viability in postinfarction patients. Findings obtained during EE were compared with those acquired by myocardial uptake of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and functional follow-up results. METHODS: Twenty-five patients underwent EE and PET (18)F-FDG studies. An asynergic segment was considered as having contractile enhancement when the wall motion score decreased by > or = 1 grade during EE and was defined as viable if (18)F-FDG uptake score was > or = 2 grade on PET. RESULTS: Of 293 dysfunctional segments at baseline, 139 (47%) were viable by PET criteria; 117 (40%) had contractile enhancement induced by enoximone (P = 0.07). Agreement between EE and PET was found in 75% of involved segments (K = 0.46, P < 0.001). The majority of discrepancies (65%, P < 0.01) were mainly due to discordant segments in which PET revealed evidence of (18)F-FDG uptake but EE showed no change in wall motion. In 179 revascularized segments, negative predictive value for functional recovery of both tests reached the same value (89% for both), whereas positive predictive value was 82% for EE and 68% for PET, respectively (P < 0.05). Sensitivity was 85% for EE and 88% for PET (P = ns); specificity was 87% and 70%, respectively (P < 0.01). CONCLUSIONS: EE yields a fair concordance with PET study. Compared with PET, despite a similar negative accuracy, EE shows a greater specificity for prediction of function recovery after revascularization. (Echocardiography 2010;27:544-551).


Assuntos
Ecocardiografia/métodos , Enoximona , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Vasodilatadores , Idoso , Angiografia Coronária , Feminino , Fluordesoxiglucose F18 , Hemodinâmica , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Revascularização Miocárdica , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos
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