Zwölfer 1995.
| Study characteristics | ||
| Methods |
Study design: single‐centre, 2‐arm parallel group RCT (Austria) Recruitment period: 1.5 years Follow‐up: 4 h |
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| Participants | n = 53 (randomised), n = 12 (enrolled) Inclusion criteria: postoperative LCOS in patients of either sex and of NYHA classification II – III undergoing elective valve replacement Exclusion criteria: renal insufficiency (serum creatinine > 3.5 mg/dL); need for catecholamines to be weaned off cardiopulmonary bypass LCOS definition: CI < 2.5 L/min/m2; PCWP > 12 mmHg Characteristics: (enoximone/epinephrine‐nitroglycerin, mean ± SD) Age (years): 59.0 ± 8.4/66.2 ± 5.3 Sex (male, %): 33/33 Diabetes (%): 0/17 Hypertension (%): ‐ Smoker (%): ‐ Prior AMI/vascular intervention (%): ‐ MAP (mmHg): 82 ± 19/73 ± 9 HR (bpm): ‐ SBP (mmHg): ‐ DBP (mmHg): ‐ CI (L/min/m2): ‐ PCWP (mmHg): 25 ± 6/25 ± 6 LVEF (%): ‐ SVRI (dyne.s/cm5/m2)/SVR (dyne.s/cm5): ‐ Timetable: treatment for 4 h; observation at 0/15/30/60/90/120/240 min |
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| Interventions |
Enoximone (n = 6): bolus of 0.5 mg/kg over 10 min followed by an infusion of 5 µg/kg/min increased up to 20 µg/kg/min according to haemodynamic response (MAP 60 – 80 mmHg) for 4 h Epinephrine‐nitroglycerin (n = 6): epinephrine infusion starting with 0.05 µg/kg/min in combination with a nitroglycerin infusion of 0.5 µg/kg/min according to haemodynamic response (MAP 60 – 80 mmHg) for 4 h Concomitant medication: digitoxin, spironolactone, furosemide, verapamil, theophylline, captopril, nitrite, acetylsalicylate, etomidate, diazepam, fentanyl, pancuronium Concomitant intervention: mechanical ventilation Intervention before baseline: elective valve replacement |
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| Outcomes |
Primary: haemodynamic efficacy and safety of enoximone as first‐line monotherapy in comparison with standard treatment with epinephrine and nitroglycerin Secondary: myocardial oxygen consumption (modified pressure work index) Safety: adverse events |
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| Notes |
Funding: H.T. Dressler and H.A. Dietrich were associated with Marion Merrell Dow GmbH Contact: W. Zwölfer (Department of Cardiothoracic Anaesthesia and Intensive Care, University of Vienna, Vienna) Trial registration: ‐ Other: ‐ |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No information provided |
| Allocation concealment (selection bias) | Unclear risk | No information provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Not possible (different administration of study drugs) |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | No information provided |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No missing outcome data |
| Selective reporting (reporting bias) | Low risk | Pre‐planned endpoints were reported. |
| Other bias | Low risk | Cross‐over: no Baseline differences: no Influence of interim results on the conduct of the study: no Deviation from study protocol: no Inappropriate administration of an intervention: no Contra‐active or similar supporting pre‐randomisation intervention: yes (digitoxin, spironolactone, furosemide, verapamil, theophylline, captopril, nitrate, acetylsalicylate, etomidate, diazepam, fentanyl, pancuronium) |
| Adverse effects | High risk | Definitions of AEs given: no Monitoring of AEs: only partly Participants excluded from AE analysis: no Numerical data by intervention: yes |
ACE: angiotensin‐converting enzyme ADHF: acute decompensated heart failure AE: adverse effects AMI: acute myocardial infarction BNP: B‐type natriuretic peptide bpm: beats per minute CI: cardiac index CPO: cardiac power output CRRT: continuous renal replacement therapy CS: cardiogenic shock DBP: diastolic blood pressure ECG: electrocardiogram ESWS: end‐systolic wall stress Fas: Fas receptor h: hour HR: heart rate IABP: intra‐aortic balloon pump ICU: intensive care unit IL: interleucin IQR: intra‐quartile‐range i.v.: intravenous LCOS: low cardiac output syndrome LVEF: left ventricular ejection fraction MAP: mean arterial pressure min: minute NT‐pro‐BNP: N terminal pro brain natriuretic peptide NYHA: New York Heart Association PCI: percutaneous coronary intervention PCO2: partial pressure of carbon dioxide PCOP: pulmonary capillary occlusion pressure PCWP: pulmonary capillary wedge pressure PDE: Phosphodiesterase RCT: randomised controlled trial SBP: systolic blood pressure SD: standard deviation SEM: standard error of the mean sFas: soluble Fas receptor SOFA: Sepsis‐related organ failure assessment STEMI: ST‐segment elevation myocardial infarction SVR: systemic vascular resistance SVRI: systemic vascular resistance index TNF: tumor necrosis factor WMSI: wall motion score index