Background
Methods
Search strategy
Study selection
Data extraction and study characteristics
Quality assessment
Data analysis and synthesis
Results
First Author | Journal | Year | Procedures | Control | Inclusion Criteria | Exclusion Criteria | Primary Outcome | Secondary Outcome |
---|---|---|---|---|---|---|---|---|
Arbeus M [38] | Journal of Cardiothoracic and Vascular Anesthesia | 2009 | Elective CABG | Placebo | Stable angina, LVEF (%) > 30%, Sinus rhythm. | Unspecified | Graft flow | Unspecified |
Couture P [39] | Canadian Journal of Anaesthesia | 2007 | Elective CABG | Placebo | Ischemic heart disease, LV diastolic dysfunction. | Mitral and aortic valvular disease, Atrial fibrillation or pacemaker, Contraindication to TEE. | LV diastolic dysfunction | Unspecified |
Doolan LA [40] | Journal of Cardiothoracic and Vascular Anesthesia | 1997 | Elective CABG and valvular surgery | Placebo | LVEF (%) ≤ 35%, Mean PAP ≥ 20 mmHg. | Supraventricular tachyarrhythmias, Platelet countless than 100 × 109/L (preoperative), Significant primary hepatic or renal disease. | Success or failure in weaning from bypass. | Hemodynamic variables |
Guo YJ [9] | Chinese Heart Journal | 2014 | Elective CABG | Placebo | CABG surgery, LVEF (%) < 35%, | Emergency surgery, Myocardial infarction, Ventricular arrhythmias, Requiring inotropic support. | Myocardial ischemia and/or MI incidence | Mean arterial pressure, Requirements for vasopressors, Death, Length of hospital stay, Serum potassium and creatinine Concentrations. |
Hadadzadeh M [41] | Acta medica Iranica | 2013 | Elective CABG (off-pump) | Placebo | Severe myocardium dysfunction (LVEF (%) < 35%) | Emergency CABG, Myocardial infarction, Ventricular arrhythmias, Requiring inotropic support. | Myocardial ischemia and/or MI incidence | Unspecified |
Hamada Y [42] | Japanese circulation journal | 1999 | Elective CABG and valvular surgery | Standard treatment | Unspecified | Unspecified | Hemodynamic variables | Unspecified |
Hayashida N [43] | Annals of Thoracic Surgery | 1999 | Elective CABG | Standard treatment | Isolated CABG surgery | Myocardial ischemia, Acute myocardial infarction | Cytokine production | Unspecified |
Jebeli M [44] | Cardiology Journal | 2010 | Elective CABG | Placebo | LVEF (%) < 35%, | Emergency CABG, Myocardial infarction, Ventricular arrhythmias, Requiring inotropic support. | Myocardial ischemia and/or MI incidence | Cardiac enzyme levels, Duration of inotropic support. |
Jo HR [45] | Korean Journal of Anesthesiology | 2010 | Elective CABG (off-pump) | Placebo | CABG surgery, Normal LV function. | LVEF or RVEF (%) < 40%, Valvular heart disease, Severe cerebral or renal dysfunction, Emergency surgery. | Right ventricular function and early outcomes | Unspecified |
Kwak YL [46] | European journal of cardio-thoracic surgery | 2004 | Elective CABG (off-pump) | Placebo | Unspecified | Renal or hepatic dysfunction, Thrombocytopenia, Coagulopathy. | Cardiac Index | Unspecified |
Lee JH [32] | Journal of korean medical science | 2006 | Elective CABG (off-pump) | Placebo | RVEF (%) < 35% | Hepatic or renal dysfunction, Thrombocytopenia or coagulopathy, Supraventricular tachyarrhythmias, Single coronary artery disease, History of receiving inotropic agents. | Right ventricular function and early outcomes | Unspecified |
Möllhoff T [47] | Anesthesiology | 1999 | Elective CABG | Placebo | Elective CABG | LVEF (%) < 50%, Gastrointestinal disorders, Diabetes | Splanchnic oxygenation, Systemic inflammation, Subsequent acute-phase response. | Unspecified |
Shi YF [48] | Journal of Thoracic and Cardiovascular Surgery | 2006 | Elective CABG | Placebo | Elective CABG | Had pacemaker or not in sinus rhythm | Biventricular filling properties | Unspecified |
Song JW [49] | Korean Journal of Anesthesiology | 2011 | Elective CABG (off-pump) | Placebo | E/e’ value > 15 | Concomitant systolic dysfunction, Mitral regurgitation ≥ Grade 2, Emergency operation. | Hemodynamics and short term outcomes | Unspecified |
Yamaguchi A [50] | Annals Of Thoracic And Cardiovascular Surgery | 2009 | Elective CABG and valvular surgery | Standard treatment | Elective CABG concomitant LVR, LV dysfunction (LVEF (%) < 30%), LVESVI > 100 ml/m2 | Unspecified | Left ventricular restoration | Unspecified |
Yamaura K [51] | Journal of Cardiothoracic and Vascular Anesthesia | 2001 | Elective CABG | Standard treatment | Cardiac Surgery | Unspecified | Gastric intramucosal pH, Systemic inflammation | Unspecified |
Study characteristics
Author | Group | Patients | Age | Sex | Time of administration | Milrinone dose | Length of infusion | Duration of follow-up | |
---|---|---|---|---|---|---|---|---|---|
(n) | (y) | (M/F) | Bolus | Infusion | |||||
Arbeus M [38] | MIL | 22 | 63 ± 10 | 20/2 | After release of aortic clamp | 50 μg/kg | None | Bolus only | Hospital Stay |
Ctrl | 22 | 62 ± 9 | 17/5 | ||||||
Couture P [39] | MIL | 25 | 67 ± 8 | 19/6 | After anesthesia induction | 50 μg/kg | 0.5 μg/kg/min | Until skin closure | Hospital Stay |
Ctrl | 25 | 70 ± 7 | 19/6 | ||||||
Doolan LA [40] | MIL | 15 | 65 ± 10.4 | 14/1 | 15 min before weaning from CPB | 50 μg/kg | 0.5 μg/kg/min | 4 h or longer | 30 day |
Ctrl | 15 | 67 ± 8.6 | 14/1 | ||||||
Guo YJ [9] | MIL | 31 | 56 ± 6 | 21/10 | After release of aortic clamp | 50 μg/kg | 0.5 μg/kg/min | 24 h | Hospital Stay |
Ctrl | 31 | 54 ± 6 | 20/11 | ||||||
Hadadzadeh M [41] | MIL | 40 | 62 ± 10.7 | 31/9 | After anesthesia induction | 50 μg/kg | 0.5 μg/kg/min | 24 h | ICU Stay |
Ctrl | 40 | 63 ± 9.6 | 26/14 | ||||||
Hamada Y [42] | MIL | 10 | 66.2 ± 8.1 | 6/4 | After release of aortic clamp | 50 μg/kg | None | Bolus only | Operating Room |
Ctrl | 10 | 62.4 ± 6.5 | 6/4 | ||||||
Hayashida N [43] | MIL | 12 | 63.3 ± 2.8 | 7/5 | After anesthesia induction | None | 0.5 μg/kg/min | 24 h | 72 h |
Ctrl | 12 | 62.7 ± 2.8 | 9/3 | ||||||
Jebeli M [44] | MIL | 35 | 56.9 ± 9.7 | 25/10 | After release of aortic clamp | 50 μg/kg | 0.5 μg/kg/min | 24 h | Hospital Stay |
Ctrl | 35 | 58.2 ± 8.4 | 28/7 | ||||||
Jo HR [45] | MIL | 20 | 67.0 ± 9.2 | 12/8 | After sternotomy | None | 0.5 μg/kg/min | Until skin closure | Hospital Stay |
Ctrl | 20 | 64.1 ± 9.9 | 11/9 | ||||||
Kwak YL [46] | MIL | 29 | 61.5 ± 8.2 | 21/8 | After IMA harvest | None | 0.5 μg/kg/min | End of anastomosis | Hospital Stay |
Ctrl | 33 | 60.4 ± 8.4 | 26/7 | ||||||
Lee JH [32] | MIL | 24 | 63 ± 8 | 20/4 | After sternotomy | None | 0.5 μg/kg/min | Until skin closure | Hospital Stay |
Ctrl | 26 | 62 ± 8 | 20/6 | ||||||
Möllhoff T [47] | MIL | 11 | 60 ± 8 | Not specified | After anesthesia induction | 30 μg/kg | 0.5 μg/kg/min | Unspecified | 1 Year |
Ctrl | 11 | 61 ± 6 | |||||||
Shi Y [53] | MIL | 25 | Not specified | Not specified | After anesthesia induction | 50 μg/kg | 0.5 μg/kg/min | Until skin closure | 6 month |
Ctrl | 24 | High: 75 μg/kg | High: 0.75 μg/kg/min | ||||||
Song JW [54] | MIL | 31 | 67.2 ± 7.6 | 14/17 | After harvesting the left | None | 0.5 μg/kg/min | 31 ± 7 min | Hospital Stay |
Ctrl | 31 | 65.7 ± 7.9 | 21/10 | internal mammary artery | |||||
Yamaguchi A [55] | MIL | 14 | 64.1 ± 8 | 13/1 | After induction of CPB | None | 0.5 μg/kg/min | 48 h | ICU Stay |
Ctrl | 14 | 65.2 ± 8.5 | 13/1 | ||||||
Yamaura K [56] | MIL | 10 | 66 ± 6 | 7/3 | After induction of CPB | None | 0.25 μg/kg/min | 1 h after in ICU | Hospital Stay |
Ctrl | 10 | 57 ± 16 | 6/4 |
First Author | Preoperative EF (MIL Group) | Preoperative EF (Ctrl Group) | No. of Death (Death/Total, MIL Group) | No. of Death (Death/Total, Ctrl Group) | Cause of Death (MIL Group) | Cause of Death (Ctrl Group) | Adverse Effects (MIL Group) | Adverse Effects (Ctrl Group) | ||
---|---|---|---|---|---|---|---|---|---|---|
Arbeus [38] | 59 ± 12 | 63 ± 9 | 1 | 22 | 0 | 22 | Not specified | No death | No adverse events or side effects | |
Couture [39] | 51 ± 15 | 50 ± 13 | 2 | 25 | 0 | 25 | Multiple organ failure (2) | No death | Acute renal failure (2) | Acute renal failure (1) |
Doolan [40] | Not specified | Not specified | 0 | 15 | 0 | 15 | No death | No death | No adverse events or side effects | |
Guo [9] | 35 ± 4 | 35 ± 5 | 1 | 31 | 1 | 31 | Not specified | Not specified | Not specified | |
Hadadzadeh [41] | 29 ± 5.5 | 28.6 ± 5.6 | 1 | 40 | 1 | 40 | Cardiac shock | Cardiac shock | CVA, Renal failure (1) | CVA, Renal failure (3) |
Hamada [42] | Not specified | Not specified | 0 | 20 | 0 | 10 | No death | No death | No adverse events or side effects | |
Hayashida [43] | Not specified | Not specified | 0 | 12 | 0 | 12 | No death | No death | No serious adverse effects | Low output syndrome (1) |
Jebeli [44] | 31.8 ± 3.2 | 34.5 ± 1.4 | 0 | 35 | 2 | 35 | No death | Cardiogenic shock (2) | No adverse events or side effects | |
Jo [45] | 45 ± 14 | 51 ± 13 | 0 | 20 | 0 | 20 | No death | No death | Renal failure (1) | Renal failure (2) |
Kwak [46] | Not specified | Not specified | 0 | 29 | 0 | 33 | No death | No death | No adverse events or side effects | |
Lee [32] | 50 ± 17 | 57 ± 8 | 0 | 24 | 0 | 26 | No death | No death | No adverse events or side effects | |
Möllhoff [47] | Not specified | Not specified | 0 | 11 | 0 | 11 | No death | No death | No adverse events or side effects | |
Shi [53] | Not specified | Not specified | 1 | 25 | 1 | 24 | Not specified | Not specified | Not specified | |
Song [54] | 55.3 ± 15.3 | 51.5 ± 16.7 | 1 | 31 | 1 | 31 | Not specified | Not specified | Not specified | |
Yamaguchi [55] | 64.1 ± 8 | 65.2 ± 8.5 | 0 | 14 | 0 | 14 | No death | No death | Not specified | |
Yamaura [56] | Not specified | Not specified | 0 | 10 | 0 | 10 | No death | No death | No adverse events or side effects |
Quantitative data synthesis
Patients (Studies) Included | Milrinone: Events (%) | Control: Events (%) | RR | 95% CI | p for Effect | I2 (p for heterogeneity) | |
---|---|---|---|---|---|---|---|
Myocardical Infarction | 440 (30) | 5 (2.28%) | 25 (11.31%) | 0.23 | 0.10–0.54 | 0.0008 | 9% (0.35) |
Myocardial Ischemia | 212 (53) | 12 (11.32) | 41 (36.68) | 0.29 | 0.16–0.52 | < 0.0001 | 0% (0.55) |
Arrhythmias | 470 (47) | 16 (6.84) | 31 (13.14) | 0.53 | 0.31–0.91 | 0.02 | 0% (0.55) |
Stroke | 172 (2) | 2 (2.33) | 0 (0) | 3.00 | 0.32–27.88 | 0.33 | 0% (1.00) |
Renal Failure | 302 (17) | 9 (5.96) | 8 (5.30) | 1.25 | 0.45–2.81 | 0.80 | 0% (0.64) |
Meta-regression
Parameter | Regression | P value |
---|---|---|
Sample size | y = 0.0022x + 0.0603 | 0.9488 |
Mean number of grafts | y = −0.0368x + 0.2930 | 0.9926 |
Mean pump time | y = 0.0092x + 1.0395 | 0.6035 |
Mean AoXclamp time | y = −0.0091x + 0.9190 | 0.6505 |
Mean preop LVEF | y = 0.0160x - 0.4410 | 0.6420 |
Postop inotropes | y = −0.0629x + 1.3785 | 0.2812 |
Preop shock/MI | y = −0.0263x + 0.2877 | 0.7811 |
Postop IABP | y = −0.1269x - 0.7856 | 0.5557 |
Preop drugs | Regression | P value |
---|---|---|
ACE inhibitors | y = − 0.0713x + 1.3446 | 0.6860 |
Calcium channel inhibitors | y = − 0.0396x + 1.1287 | 0.6836 |
Diuretics | y = − 0.0066x + 0.0849 | 0.9734 |
Nitrates | y = 0.0997x - 0.6147 | 0.6246 |
β-receptor inhibitors | y = 0.0128x + 0.2710 | 0.8870 |