Profilaxis con levosimendán para la prevención del síndrome de gasto cardíaco bajo y la mortalidad en pacientes pediátricos sometidos a cirugía por una cardiopatía congénita
Appendices
Appendix 1. Search strategies
CENTRAL
#1 MeSH descriptor: [Heart Defects, Congenital] explode all trees
#2 MeSH descriptor: [Heart Diseases] explode all trees and with qualifier(s): [Congenital ‐ CN]
#3 (heart near/2 (defect* or abnormal* or malform*))
#4 (congenital near/2 (heart or cardiac or cardio*))
#5 deletion next syndrome*
#6 (alagille* near/2 syndrome*)
#7 (watson* near/2 syndrome*)
#8 (hepatofacioneurocardiovertebral near/2 syndrome*)
#9 cardiovertebral near/2 syndrome*
#10 (arteriohepatic near/2 dysplasia*)
#11 "hepatic ductular hypoplasia*"
#12 aort* near/3 coarctation*
#13 (arrhythmogenic near/3 ventricular)
#14 Barth next Syndrome
#15 ((heart* or cor) 2 triatria*)
#16 (subdivided near/3 atrium*)
#17 "coronary vessel anomal*"
#18 myocardial next bridging*
#19 "criss‐cross heart*"
#20 "crisscross heart*"
#21 "criss cross heart*"
#22 dextrocardia*
#23 (kartagener* near/2 (syndrome* or triad))
#24 siewert next syndrome*
#25 "polynesian bronchiectas?s"
#26 "primary ciliary dyskinesia"
#27 (paten* near/2 ductus near/2 arteriosus)
#28 (ebstein* near/2 (anomal* or malform*))
#29 ectopia next cordis
#30 (Eisenmenger* near/2 (complex or syndrome))
#31 ((heart or cardiac) near/2 "septal defect*")
#32 heterotaxy next syndrome*
#33 polysplenia next syndrome*
#34 asplenia next syndrome*
#35 ambiguus near/3 situs
#36 isomerism
#37 ivemark next syndrome
#38 visceral next heterotax*
#39 "hypoplastic left heart syndrome"
#40 isolated next noncompaction
#41 isolated next non‐compaction
#42 leopard next syndrome*
#43 cardiomyopathic* next lentiginosis
#44 lentigines next syndrome*
#45 levocardia
#46 marfan* next syndrome
#47 noonan next syndrome
#48 turner* next syndrome
#49 fallot* near/2 tetralogy
#50 (transpos* near/4 (arter* or vessel*))
#51 (tricuspid near/2 atresias)
#52 (fallot* near/2 trilogy)
#53 turner* next syndrome
#54 bonnevie‐ullrich next syndrome
#55 "bonnevie ullrich syndrome"
#56 "bonnevie‐ullrich status"
#57 "bonnevie ullrich status"
#58 "ullrich‐turner syndrome"
#59 (gonadal near/2 dysgenesis)
#60 "univentricular heart"
#61 "arterial switch"
#62 norwood*
#63 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48 or #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56 or #57 or #58 or #59 or #60 or #61 or #62
#64 levosimendan or levosimedan or or1259 or "or 1259" or simdax
#65 MeSH descriptor: [Cardiotonic Agents] this term only
#66 (inotropic near/2 (agent* or drug* or medicat* or act*))
#67 inodilator*
#68 (calcium near/2 sensiti*)
#69 #64 or #65 or #66 or #67 or #68
#70 #63 and #69
MEDLINE
1. exp Heart Defects, Congenital/
2. exp Heart Diseases/cn [Congenital]
3. (heart adj2 (defect* or abnormal* or malform*)).tw.
4. (congenital adj2 (heart or cardiac or cardio*)).tw.
5. deletion syndrome*.tw.
6. (alagille* adj2 syndrome*).tw.
7. (watson* adj2 syndrome*).tw.
8. (hepatofacioneurocardiovertebral adj2 syndrome*).tw.
9. (cardiovertebral adj2 syndrome*).tw.
10. (arteriohepatic adj2 dysplasia*).tw.
11. hepatic ductular hypoplasia*.tw.
12. (aort* adj3 coarctation*).tw.
13. (arrhythmogenic adj3 ventricular).tw.
14. Barth Syndrome.tw.
15. ((heart* or cor) adj2 triatria*).tw.
16. (subdivided adj3 atrium*).tw.
17. coronary vessel anomal*.tw.
18. myocardial bridging*.tw.
19. criss‐cross heart*.tw.
20. crisscross heart*.tw.
21. criss cross heart*.tw.
22. dextrocardia*.tw.
23. (kartagener* adj2 (syndrome* or triad)).tw.
24. siewert syndrome*.tw.
25. polynesian bronchiectas?s.tw.
26. primary ciliary dyskinesia.tw.
27. (paten* adj2 ductus adj2 arteriosus).tw.
28. (ebstein* adj2 (anomal* or malform*)).tw.
29. ectopia cordis.tw.
30. (Eisenmenger* adj2 (complex or syndrome)).tw.
31. ((heart or cardiac) adj2 septal defect*).tw.
32. heterotaxy syndrome*.tw.
33. polysplenia syndrome*.tw.
34. asplenia syndrome*.tw.
35. (ambiguus adj3 situs).tw.
36. isomerism.tw.
37. ivemark syndrome.tw.
38. visceral heterotax*.tw.
39. hypoplastic left heart syndrome.tw.
40. isolated noncompaction.tw.
41. isolated non‐compaction.tw.
42. leopard syndrome*.tw.
43. cardiomyopathic* lentiginosis.tw.
44. lentigines syndrome*.tw.
45. levocardia.tw.
46. marfan* syndrome.tw.
47. noonan syndrome.tw.
48. turner* syndrome.tw.
49. (fallot* adj2 tetralogy).tw.
50. (transpos* adj4 (arter* or vessel*)).tw.
51. (tricuspid adj2 atresias).tw.
52. (fallot* adj2 trilogy).tw.
53. turner* syndrome.tw.
54. bonnevie‐ullrich syndrome.tw.
55. bonnevie ullrich syndrome.tw.
56. bonnevie‐ullrich status.tw.
57. bonnevie ullrich status.tw.
58. ullrich‐turner syndrome.tw.
59. (gonadal adj2 dysgenesis).tw.
60. univentricular heart.tw.
61. arterial switch.tw.
62. norwood*.tw.
63. or/1‐62
64. levosimendan.tw.
65. levosimedan.tw.
66. or1259.tw.
67. "or 1259".tw.
68. simdax.tw.
69. Cardiotonic Agents/
70. (inotropic adj2 (agent* or drug* or medicat* or act*)).tw.
71. inodilator*.tw.
72. (calcium adj2 sensiti*).tw.
73. or/64‐72
74. 63 and 73
75. randomized controlled trial.pt.
76. controlled clinical trial.pt.
77. randomized.ab.
78. placebo.ab.
79. drug therapy.fs.
80. randomly.ab.
81. trial.ab.
82. groups.ab.
83. 75 or 76 or 77 or 78 or 79 or 80 or 81 or 82
84. exp animals/ not humans.sh.
85. 83 not 84
86. 74 and 85
Embase
1. exp congenital heart malformation/
2. exp heart disease/cn [Congenital Disorder]
3. (heart adj2 (defect* or abnormal* or malform*)).tw.
4. (congenital adj2 (heart or cardiac or cardio*)).tw.
5. deletion syndrome*.tw.
6. (alagille* adj2 syndrome*).tw.
7. (watson* adj2 syndrome*).tw.
8. (hepatofacioneurocardiovertebral adj2 syndrome*).tw.
9. (cardiovertebral adj2 syndrome*).tw.
10. (arteriohepatic adj2 dysplasia*).tw.
11. hepatic ductular hypoplasia*.tw.
12. (aort* adj3 coarctation*).tw.
13. (arrhythmogenic adj3 ventricular).tw.
14. Barth Syndrome.tw.
15. ((heart* or cor) adj2 triatria*).tw.
16. (subdivided adj3 atrium*).tw.
17. coronary vessel anomal*.tw.
18. myocardial bridging*.tw.
19. criss‐cross heart*.tw.
20. crisscross heart*.tw.
21. criss cross heart*.tw.
22. dextrocardia*.tw.
23. (kartagener* adj2 (syndrome* or triad)).tw.
24. siewert syndrome*.tw.
25. polynesian bronchiectas?s.tw.
26. primary ciliary dyskinesia.tw.
27. (paten* adj2 ductus adj2 arteriosus).tw.
28. (ebstein* adj2 (anomal* or malform*)).tw.
29. ectopia cordis.tw.
30. (Eisenmenger* adj2 (complex or syndrome)).tw.
31. ((heart or cardiac) adj2 septal defect*).tw.
32. heterotaxy syndrome*.tw.
33. polysplenia syndrome*.tw.
34. asplenia syndrome*.tw.
35. (ambiguus adj3 situs).tw.
36. isomerism.tw.
37. ivemark syndrome.tw.
38. visceral heterotax*.tw.
39. hypoplastic left heart syndrome.tw.
40. isolated noncompaction.tw.
41. isolated non‐compaction.tw.
42. leopard syndrome*.tw.
43. cardiomyopathic* lentiginosis.tw.
44. lentigines syndrome*.tw.
45. levocardia.tw.
46. marfan* syndrome.tw.
47. noonan syndrome.tw.
48. turner* syndrome.tw.
49. (fallot* adj2 tetralogy).tw.
50. (transpos* adj4 (arter* or vessel*)).tw.
51. (tricuspid adj2 atresias).tw.
52. (fallot* adj2 trilogy).tw.
53. turner* syndrome.tw.
54. bonnevie‐ullrich syndrome.tw.
55. bonnevie ullrich syndrome.tw.
56. bonnevie‐ullrich status.tw.
57. bonnevie ullrich status.tw.
58. ullrich‐turner syndrome.tw.
59. (gonadal adj2 dysgenesis).tw.
60. univentricular heart.tw.
61. arterial switch.tw.
62. norwood*.tw.
63. or/1‐62
64. levosimendan/
65. levosimendan.tw.
66. levosimedan.tw.
67. or1259.tw.
68. "or 1259".tw.
69. simdax.tw.
70. cardiotonic agent/
71. (inotropic adj2 (agent* or drug* or medicat* or act*)).tw.
72. inodilator*.tw.
73. (calcium adj2 sensiti*).tw.
74. or/64‐73
75. 63 and 74
76. random$.tw.
77. factorial$.tw.
78. crossover$.tw.
79. cross over$.tw.
80. cross‐over$.tw.
81. placebo$.tw.
82. (doubl$ adj blind$).tw.
83. (singl$ adj blind$).tw.
84. assign$.tw.
85. allocat$.tw.
86. volunteer$.tw.
87. crossover procedure/
88. double blind procedure/
89. randomized controlled trial/
90. single blind procedure/
91. 76 or 77 or 78 or 79 or 80 or 81 or 82 or 83 or 84 or 85 or 86 or 87 or 88 or 89 or 90
92. (animal/ or nonhuman/) not human/
93. 91 not 92
94. 75 and 93
Web of Science
# 15 #14 AND #13
# 14 TS=(random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross‐over*)
# 13 #12 AND #9
# 12 #11 OR #10
# 11 TS=("inotropic agent*" or "inotropic drug*" or "inotropic medicat*" or "inotropic act*" or inodilator* or "calcium sensiti*")
# 10 TS=(levosimendan or levosimedan or or1259 or "or 1259" or simdax)
# 9 #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1
# 8 TS=("turner* syndrome" or "bonnevie‐ullrich syndrome" or "bonnevie ullrich syndrome" or "bonnevie‐ullrich status" or "bonnevie ullrich status" or "ullrich‐turner syndrome" or "gonadal dysgenesis" or "univentricular heart" or "arterial switch" or norwood*)
# 7 TS=("leopard syndrome*" or "cardiomyopathic* lentiginosis" or "lentigines syndrome*" or levocardia or "marfan* syndrome" or "noonan syndrome" or "turner* syndrome" or "fallot* tetralogy" or "transpos* arter*" or "transpos* vessel*" or "tricuspid atresias" or "fallot* trilogy")
# 6 TS=("heart septal defect*" or "cardiac septal defect*" or "heterotaxy syndrome*" or "polysplenia syndrome*" or "asplenia syndrome*" or "ambiguus situs" or isomerism or "ivemark syndrome" or "visceral heterotax*" or "hypoplastic left heart syndrome" or "isolated noncompaction" or "isolated non‐compaction")
# 5 TS=(dextrocardia* or "kartagener* syndrome*" or "kartagener* triad" or "siewert syndrome*" or "polynesian bronchiectas?s" or "primary ciliary dyskinesia" or "paten* ductus arteriosus" or "ebstein* anomal*" or "ebstein* malform*" or "ectopia cordis" or "Eisenmenger* complex" or "Eisenmenger* syndrome")
# 4 TS=("hepatic ductular hypoplasia*" or "aort* coarctation*" or "arrhythmogenic ventricular" or "Barth Syndrome" or "heart* triatria*" or "cor triatria*" or "subdivided atrium*" or "coronary vessel anomal*" or "myocardial bridging*" or "criss‐cross heart*" or "crisscross heart*" or "criss cross heart*")
# 3 TS=("deletion syndrome*" or "alagille* syndrome*" or "watson* syndrome*" or hepatofacioneurocardiovertebral or "cardiovertebral syndrome*" or "arteriohepatic dysplasia*" or "hepatic ductular hypoplasia*" or "cardiovertebral syndrome" or "arteriohepatic dysplasia*")
# 2 TS=(congenital heart or congenital cardiac or congenital cardio*)
# 1 TS=(heart defect* or heart abnormal* or heart malform*)
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Forest plot of comparison: 1 Mortality, outcome: 1.1 Mortality.
Forest plot of comparison: 2 Low cardiac output syndrome (LCOS), outcome: 2.1 LCOS.
Comparison 1 Mortality, Outcome 1 Mortality.
Comparison 2 Low cardiac output syndrome (LCOS), Outcome 1 LCOS.
Comparison 3 Length of ICU stay, Outcome 1 Length of ICU stay (days).
Comparison 3 Length of ICU stay, Outcome 2 Length of ICU stay (days).
Comparison 4 Length of hospital stay, Outcome 1 Length of hospital stay (days).
Comparison 5 Duration of mechanical ventilation, Outcome 1 Duration of mechanical ventilation (days).
Comparison 5 Duration of mechanical ventilation, Outcome 2 Duration of mechanical ventilation (days).
Comparison 6 Mechanical circulatory support or cardiac transplantation, Outcome 1 Mechanical circulatory support or cardiac transplantation.
| Prophylactic levosimendan compared to standard treatment in children following heart surgery | ||||||
| Patient or population: paediatric patients following heart surgery | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
| Risk with standard inotropes | Risk with levosimendan | |||||
| Mortality | Study population | RR 0.47 | 123 | ⊕⊕⊝⊝ | ||
| 57 per 1000 | 27 per 1000 | |||||
| Low cardiac output syndrome (LCOS) | Study population | RR 0.64 | 83 | ⊕⊕⊝⊝ | ||
| 367 per 1000 | 235 per 1000 | |||||
| Length of intensive care unit stay (Length of ICU stay) | The mean length of stay in the ICU in the control groups ranged from 2.05 to 11 days | The mean length of stay in ICU in the intervention groups was 0.33 days higher (1.16 lower to 1.82 higher) | ‐ | 188 | ⊕⊕⊝⊝ | |
| Length of hospital stay | The mean length of hospital stay in the control groups ranged from 15 to 15.8 days | The mean length of hospital stay in the intervention groups was 0.26 days higher | ‐ | 75 | ⊕⊕⊝⊝ | |
| Duration of mechanical ventilation | The mean duration of mechanical ventilation in the control groups ranged from 0.29 to 6.5 days | The mean duration of mechanical ventilation in the intervention groups was 0.04 days lower | ‐ | 208 | ⊕⊕⊝⊝ | |
| Mechanical circulatory support or cardiac transplantation | Study population | RR 1.49 | 60 | ⊕⊕⊝⊝ | ||
| 10 per 1000 | 14 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded for imprecision due to small sample size. 2 Downgraded for imprecision due to few number of events (less than 300). 3 Detection of outcome potentially dependent on study personnel: risk of detection bias in two studies due to unblinded setting. 4 Considerable inconsistency between study results. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mortality Show forest plot | 3 | 123 | Risk Ratio (M‐H, Random, 95% CI) | 0.47 [0.12, 1.82] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 LCOS Show forest plot | 2 | 83 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.39, 1.04] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Length of ICU stay (days) Show forest plot | 4 | 188 | Mean Difference (IV, Random, 95% CI) | 0.33 [‐1.16, 1.82] |
| 2 Length of ICU stay (days) Show forest plot | 4 | 188 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.05 [‐0.54, 0.44] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Length of hospital stay (days) Show forest plot | 2 | 75 | Mean Difference (IV, Random, 95% CI) | 0.26 [‐3.50, 4.03] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Duration of mechanical ventilation (days) Show forest plot | 5 | 208 | Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.08, 0.00] |
| 2 Duration of mechanical ventilation (days) Show forest plot | 5 | 208 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.08 [‐0.43, 0.27] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mechanical circulatory support or cardiac transplantation Show forest plot | 2 | 60 | Risk Ratio (M‐H, Random, 95% CI) | 1.49 [0.19, 11.37] |
