Enoximone in status asthmaticus

Schulz, Oscar; Wiesner, Olaf; Welte, Tobias; Bollmann, Benjamin-Alexander; Suhling, Hendrik; Hoeper, Marius M.; Busch, Markus

doi:10.1183/23120541.00367-2019

Cited by 4 publications

(10 citation statements)

References 9 publications

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“…The Enoximone in status asthmaticus letter [ 1 ] referenced our case series from the Netherlands wherein intravenous enoximone (Perfan, Carinopharm, Germany) reversed status asthmaticus in eight patients [ 2 ]. S chulz et al .…”

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confidence: 99%

(Oral) enoximone in asthma

Beute

2020

ERJ Open Res

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The Enoximone in status asthmaticus letter [1] referenced our case series from the Netherlands wherein intravenous enoximone (Perfan, Carinopharm, Germany) reversed status asthmaticus in eight patients [2]. SCHULZ et al. [1] end their letter with the statement that further research is called for; this correspondence is to indicate that research has been carried out and is still ongoing. Recently, SOBHY et al. [3] confirmed our case series with a successful clinical trial, which was performed in Egypt, using the phosphodiesterase (PDE)-3 inhibitor milrinone. We would like to report we are currently treating 12 children and 51 adults (outpatients) with oral enoximone (Perfan) in addition to standard therapy, in the context of investigational use, in search of effectiveness [4]. Enoximone very swiftly and markedly improved difficult-to-treat asthma, as well as reduced steroid and β 2-agonist drugs in 47 of the adult patients, and in 11 of the 12 children. Enoximone in oral form is used to reduce pulmonary arterial pressure by relaxing vascular smooth muscle and it has been used in paediatric post-operative heart failure since 2005 [5, 6]. Our average oral doses are 0.0625-0.125 mg•kg −1 , which is 1-6 mg per day for children and 5-15 mg per day for adults; some of them take the drug only two or three times per week. In the Netherlands physicians are allowed to treat their patients with drugs that are not indicated/registered for a particular disease, provided dosage, results and side-effects are closely monitored. We contacted the Dutch Inspection for Health Care and Youth regarding our add-on use of enoximone.

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confidence: 99%

(Oral) enoximone in asthma

Beute

2020

ERJ Open Res

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“…In this emergency setting, enoximone was given (at much lower doses than marketed) within the scope of regular patient care and based on previous successful case reports … 5,6,16 including our own experience in another indication (asthma) with a similar pathophysiologyall in line with good clinical practice (GCP). No prior ethical consent (MEC or IRB) was required.…”

Section: Ethical Considerationsmentioning

confidence: 99%

“…The algorithm for a safe, well-tolerated and effective dose and dosing regimen was based on our previous experience in near fatal asthma and status asthmaticus in the emergency department and on preoperative treatment of severe asthma patients. 5,6,16 In our COVID-19 patients with severe pneumonia, we used an intravenous bolus of 20 mg (0.25 mg/kg) enoximone followed by 10 mg/h (via perfusor) (0.125 mg/kg/h (i.e., approximately 2.1 mcg/kg/min)) for approximately 24-48 h, which is approximately 10-12-fold lower than the commonly applied (marketed) dose for cardiovascular indications (i.e., doses up to 2400 mg i.v./d).…”

Section: Dose and Dosing Regimen Of Enoximonementioning

confidence: 99%

“…Selective phosphodiesterase (PDE)3-inhibitors enoximone and milrinone previously showed clinical effectiveness in patients with CAS. [5][6][7] PDE3-inhibitors relax airway smooth muscle, 8,9 possess anti-inflammatory properties, [9][10][11] improve mucosal barrier function and prevent endothelial leakage caused by vaso-active mediators (e.g. bradykinin, histamine and leukotrienes).…”

Section: Introductionmentioning

confidence: 99%

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PDE3-inhibitor enoximone prevented mechanical ventilation in patients with SARS-CoV-2 pneumonia

Beute

Boermans

Benraad

et al. 2021

Experimental Lung Research

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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.

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“…anti-TNF-alpha, anti-IL6) [11] or the excessive pulmonary vascular leakage (e.g. Icatibant, a bradykinin antagonist or enoximone, a PDE3-inhibitor) [13,14].…”

mentioning

confidence: 99%