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Bancalari Uso Racional de Cafeina Concepcion Abu Dhabi 2016 PDF
Bancalari Uso Racional de Cafeina Concepcion Abu Dhabi 2016 PDF
cuando y cuanto
Eduardo Bancalari MD
University of Miami Miller School of Medicine
Concepcion 2016
Murat 1981
<
Total
0.01
0.1
Favors caffeine
10
Favors control
Adapted from: Henderson-Smart DJ, Steer P. Methylxanthine treatment for apnea in preterm infants. Cochrane
Database of Systematic Reviews 2001, Issue 3. Art No.: CD000140. DOI: 10.1002/14651858. CD 000140.
Henderson-Smart DJ, Steer PA. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.:
CD000273. DOI: 10.1002/14651858.CD000273.pub2.
Henderson-Smart DJ, Steer PA. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.:
CD000273. DOI: 10.1002/14651858.CD000273.pub2.
J Perinatology 2009
Reproduced from Bauer J, Maier, K, Linderkamp O with permission from Pediatrics 2001, Vol. 107, Pg 662,
Copyright 2001 by the AAP
CaffeineTherapyforApneaofPrematurity
Schmidt,Betal.NEngl JMed2006;354:21122121.
Table1.EffectsofCaffeineonCirculatoryParametersinPretermInfants
Before
1 Hour
2 Hours
0.18 0.04
0.15 0.03
0.14 0.02
0.14 0.02
0.12 0.04
0.12 0.02
0.37 0.14
0.32 0.12
0.35 0.13
0.23 0.10
0.16 0.07
0.16 0.06
196 53
179 43
173 52
45 9
47 9
45 5
2006infants500 1250gconsideredcandidatesfor
methylxanthinesduringthefirst10daysforapneaor
extubationwererandomlyassignedtocaffeineor
placebo
CAPTrial ShortTermOutcome
(20mgxkgloading+5 10mg/kgmaintenance)
Caffeine (n1006)
Placebo (n1000)
BWT
964
958
Death
5.2%
5.5%
NEC
6.3%
6.7%
OR
BPD 36 weeks
36.3%
46.9%
0.64 (0.52-0.78)
29.3%
38.1%
0.67 (0.54-0.82)
4.5%
12.6%
0.29 (0.20-0.43)
Brain injury by US
13%
14.3%
0.97 (0.74-1.28)
-23g
Adapted from Schmidt B. NEJM 2006; 354(20): 2112-2121
CAPTrial LongTermOutcome
(20mgxkgloading+5 10mg/kgmaintenance)
Caffeine(n1006)
Placebo (n1000)
BWT
937g
932g
Death
5.2%
5.5%
46.2%
0.008
Cerebral palsy
4.4%
7.3%
0.009
Cognitive delay
33.8%
38.3%
0.04
Outcome
Caffeine
Placebo
OR(95%CI)
Deathordisability
22%
25%
0.8(0.71.0)
Death
6.4%6.5%
1.0(0.71.4)
GMFCFlevel>1
2.4%3.8%0.6(0.41.1)
ScaleIQ<70
4.9%
5.1%
1.0(0.61.6)
Disablingbehavior
5.4%
7.1%
0.8(0.51.2)
CaffeineforApneaofPrematurityTrial:BenefitsMayVaryinSubgroups
DavisPGetal.JPediatr 2010;156:382387.
TrendsinCaffeineUseandAssociationbetweenClinicalOutcomes
andTimingofTherapyinVeryLowBirthWeightInfants
DobsonNRetal.JPediatr 2014;164:992998.
Earlycaffeinetherapyandclinicaloutcomes
Neonataloutcomes bytimingofcaffeineinitiation
Outcomes
Earlycaffeine Latecaffeine
(<DOL3)
(DOL3)
Oddsratio
(95%CI)
Adjustedodds
ratio
(95%CI)
Pvalue
Primaryoutcome
DeathorBPD
21(25%)
30(53%)
0.31(0.150.63)
0.26(0.090.70)
<0.01
5(6%)
3(5%)
1.15(0.265.03)
1.47(0.307.26)
0.640
17(24%)
27(51%)
0.30(0.140.64)
0.33(0.110.98)
0.04
PDArequiringtreatment
8(10%)
20(36%)
0.20(0.080.51)
0.28(0.100.73)
0.01
Pharmacologiconly
7(9%)
15(27%)
Surgical
1(1%)
5(9%)
22
Death
BPD
Secondaryoutcomes
Durationofventilation(mediandays)
PatelRMetal.JPerinatol 2013;33:134140.
<0.01
TrendsinCaffeineUseandAssociationbetweenClinicalOutcomes
andTimingofTherapyinVeryLowBirthWeightInfants
TableIV. Clinicaloutcomes
PSmatchedpatients
Earlycaffeine
(n=14535)
Latecaffeine
(n=14535)
OR(99%CI)
Pvalue
BPDordeath
3681(27.6)
4591(34.0)
0.74(0.690.80)
<.001
BPDinsurvivors
3070(23.1)
4154(30.7)
0.68(0.630.73)
<.001
659(4.5)
542(3.7)
1.23(1.051.43)
<.001
TreatmentofPDA
1794(12.3)
2765(19.0)
0.60(0.550.65)
<.001
Lateonsetsepsis
3083(21.2)
3559(24.5)
0.81(0.760.88)
<.001
11(0,48)
17(0,64)
3(112)
6(025)
DOL7
6.3(25.1,12.9)
3.5(23.6,17.0)
<.001
DOL14
5.6(5.1,17.1)
6.5(5.0,18.9)
<.001
DOL28
13.6(4.8,23.6)
13.7(4.3,24.4)
.40
Outcomes
Primaryoutcomes,n(%)
Death
Secondaryoutcomes,n(%)
DurationofMV,d
Mean(5th95thpercentile)
Median(IQR)
<.001
DobsonNRetal.JPediatr 2014;164:992998.
Randomization
CAFFEINE GROUP
CONTROL GROUP
Equivalent volume
normal saline
bolus
Caffeine bolus 20
mg/kg
Maintenance
caffeine 5 mg/kg
Maintenance
volume placebo
Pre-extubation
placebo bolus
EXTUBATE
Re-intubated
< 24 hrs
EXTUBATE
Remains
extubated 24 hrs
Re-intubated
< 24 hrs
Highdosecaffeinecitrateforextubationofpreterminfants:
arandomised controlledtrial
Table2.Analysisof trialdata
20mg/kg
(n=113)
Extubationfailure
5mg/kg
(n=121)
RR(95% CI)
pValue
0.51(0.31to0.85)
<0.01
17(15%)
36(29.8%)
10
29
Durationofmechanicalventilation(days)
7.4(3.316.5)
9.0(0.577)
0.38
DurationofNCPAP(days)
10.1(2.321.2)
9.8(4.320.1)
0.56
Documentedapnoea
4(112)
7(222)
<0.01
Documentedapnoea (days)
0.6(0.12.1)
1.3(0.34.3)
0.02
Reventilated
Steer,Petal.ArchDisChildFetalNeonatalEd2004;89:F499F503.
Highdosecaffeinecitrateforextubationofpreterminfants:
arandomised controlledtrial
Table3.Adverseeffects
20mg/kg
(n=113)
5mg/kg
(n=121)
Tachycardia
Jitteriness
Totalinwhomcaffeinewaswithheld
9(8)
5(4)
0.24
Feedintolerance
40(35)
37(31)
0.44
Weightgain(g/kg/day)
12.2(6.515.2)
12.6(9.215.2)
0.35
Timetoregainbirthweight(days)
14.8(5.3)
12.9(5.0)
<0.01
Steer,Petal.ArchDisChildFetalNeonatalEd2004;89:F499F503.
pValue
Highdosecaffeinecitrateforextubationofpreterminfants:
arandomised controlledtrial
Table4.Majormorbidityanddeath
20mg/kg
(n=113)
5mg/kg
(n=121)
Proveninfection
52(46)
60(50)
Necrotisingenterocolitis
5(4)
21(23)
34(33)
0.68(0.43to1.09)
0.11
0.42(0.11to1.52)
0.22
Chroniclungdisease,28days
64(66)
80(74)
0.89(0.74to1.07)
0.22
Chroniclungdisease,36weeks
33(34)
51(48)
0.72(0.51to1.01)
0.06
RR(95% CI)
0.93(0.71to1.21)
pValue
0.59
Intraventricularhaemorrhage
Grades3or4
Retinopathyofprematurity
Stage3and4
Steer,Petal.ArchDisChildFetalNeonatalEd2004;89:F499F503.
0.11
Highdosecaffeinecitrateforextubationofpreterminfants:
arandomised controlledtrial
Table5.Outcomesat12monthscorrected forprematurity
20mg/kg
(n=87)
5mg/kg
(n= 86)
n=80
n=78
Generalquotient(GQ)
96.6(13.2)
92.2(17.3)
Majordisability
14
0.42(0.17to1.05)
0.05
Deathordisability
13
22
0.58(0.32to1.08)
0.08
Developmentalassessment
Steer,Petal.ArchDisChildFetalNeonatalEd2004;89:F499F503.
RR(95% CI)
pValue
0.08
CaffeineCitrateTreatmentforExtremelyPrematureInfantswithApnea:
PopulationPharmacokinetics,AbsoluteBioavailability,andImplicationsfor
TherapeuticDrugMonitoring
Caffeineinducesalveolarapoptosisinthehyperoxia
exposeddevelopingmouselung
CorrelationbetweenSerumCaffeineLevelsandChanges
inCytokineinaCohortofPretermInfants
Changeinplasmacytokineconcentrationsandserumcaffeinelevels
after1weekoftreatment
ChavezValdezRetal.JPediatr 2011;158:5754.