REVISTA
PAULISTA
DE
PEDIATRIA
www.rpped.com.br
ORIGINAL
ARTICLE
Cerebral
blood
flow
assessment
of
preterm
infants
during
respiratory
therapy
with
the
expiratory
flow
increase
technique
Mariana
Almada
Bassani
a,∗,
Jamil
Pedro
Siqueira
Caldas
a,
Abimael
Aranha
Netto
b,
Sérgio
Tadeu
Martins
Marba
baHospitaldaMulherProfessorDoutorJoséAristodemoPinotti,CentrodeAtenc¸ãoIntegralàSaúdedaMulher(Caism),
UniversidadeEstadualdeCampinas(Unicamp),Campinas,SP,Brazil
bDepartamentodePediatria,FaculdadedeCiênciasMédicas,UniversidadeEstadualdeCampinas(Unicamp),Campinas,SP,Brazil
Received16May2015;accepted16August2015 Availableonline26February2016
KEYWORDS
Newborn; Preterm; Physicaltherapy modalities;
Bloodflowvelocity; TranscranialDoppler ultrasonography
Abstract
Objective: Toassesstheimpactofrespiratorytherapywiththeexpiratoryflowincrease
tech-niqueoncerebralhemodynamicsofprematurenewborns.
Methods: Thisisaninterventionstudy,whichincluded40preterminfants(≤34weeks)aged
8---15daysoflife,clinicallystableinambientairoroxygencatheteruse.Childrenwithheart defects,diagnosisofbrainlesionand/orthoseusingvasoactivedrugswereexcluded. Ultrasono-graphicassessmentswithtranscranialDopplerflowmetrywereperformedbefore,duringand aftertheincreaseinexpiratoryflowsession,whichlasted5min.Cerebralbloodflowvelocity andresistanceandpulsatilityindicesinthepericallosalarterywereassessed.
Results: Respiratoryphysicaltherapy didnotsignificantlyalter flowvelocity atthesystolic
peak(p=0.50),theenddiastolicflowvelocity(p=0.17),themeanflowvelocity(p=0.07),the resistanceindex(p=0.41)andthepulsatilityindex(p=0.67)overtime.
Conclusions: The expiratory flow increase technique did not affect cerebralblood flow in
clinically-stablepreterminfants.
©2015SociedadedePediatriadeSãoPaulo.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(https://creativecommons.org/licenses/by/4.0/).
∗Correspondingauthor.
E-mail:[email protected](M.A.Bassani).
http://dx.doi.org/10.1016/j.rppede.2016.02.007
PALAVRAS-CHAVE
Recém-nascido; Prematuro; Modalidadesde fisioterapia; Velocidadedofluxo sanguíneo;
Ultrassonografia Doppler transcraniana
Avaliac¸ãodofluxosanguíneocerebralderecém-nascidosprematurosdurantea fisioterapiarespiratóriacomatécnicadoaumentodofluxoexpiratório
Resumo
Objetivo: Avaliararepercussãodafisioterapiarespiratóriacomatécnicadeaumentodofluxo
expiratóriosobreahemodinâmicacerebralderecém-nascidosprematuros.
Métodos: Estudodeintervenc¸ãonoqualforamincluídos40neonatosprematuros(≤34semanas)
com8---15diasdevida,clinicamenteestáveisemarambienteouemusodecateterdeoxigênio. Foramexcluídascrianc¸ascommalformac¸õescardíacas,diagnósticodelesãocerebrale/ouem uso dedrogasvasoativas. Examesde ultrassonografiacomavaliac¸ãopordopplerfluxometria cerebralforamfeitosantes,duranteedepoisdasessãodeaumentodofluxoexpiratório,que duroucincominutos.Foramavaliadasasvelocidadesdefluxosanguíneocerebraleosíndices deresistênciaepulsatilidadenaartériapericalosa.
Resultados: Afisioterapiarespiratórianãoalterousignificativamenteavelocidadedefluxono
picosistólico(p=0,50),avelocidadedefluxodiastólicofinal(p=0,17),avelocidademédiade fluxo(p=0,07),oíndicederesistência(p=0,41)eoíndicedepulsatilidade(p=0,67)aolongodo tempo.
Conclusões: Amanobradeaumentodofluxoexpiratórionãoafetouofluxosanguíneocerebral
emrecém-nascidosprematurosclinicamenteestáveis.
©2015SociedadedePediatriadeSãoPaulo.PublicadoporElsevierEditoraLtda.Esteéumartigo OpenAccesssobalicençaCCBY(https://creativecommons.org/licenses/by/4.0/deed.pt).
Introduction
The controlofcerebralblood flow(CBF)involvescomplex neuralandmetabolicmechanisms,whicharestillimmature in preterm newborns (PTNB).1 Therefore, these children show a failure in the autoregulation of the CBF, which is directly dependent on blood pressure and has a pattern knownaspressurepassive.Theimmaturityofcerebralblood flow control occurs mainly in newborns with gestational age up to34 weeks, when the germinal matrix begins to involute.2 The subependymal matrix, which is located in the areaadjacent tothe lateral ventricles, is the siteof proliferationofneuronalandglialcells,2,3andishighly vas-cularizedbyirregularvesselswithfewstructuralsupporton itswalls.2,4
Due toclinical reasons,newborns in intensivecare are morelikelytohaveCBFfluctuations,whichincreasestherisk ofhemorrhagicandischemiccerebrovascularlesions,such asperi-intraventricularhemorrhage(PIVH)and periventric-ular leukomalacia (PVL), respectively. These neurological diseases may causepermanentmotor sequelae of varying degrees,dependingonthelesionextent,aswell as cogni-tive,behavioralandintellectualdisorders.1,3---5
CBF alterations are commonly associated with upper airway obstruction, severe respiratory diseases, apnea, hypoxia, hypercapnia, hypocapnia, ventilation with inter-mittentpositive pressure, asynchronywith theventilator, trachealaspirationandexpansionofcirculatingvolume,as well ascare routine, suchasdiaper changingand reposi-tioning of the endotracheal tube, excessive manipulation and agitated sleep.6---8 As observed, the vast majority of situations that are known to cause significant alterations in CBF in preterm newborns is relatedto respiratory dis-ordersresultingfrompulmonaryimmaturity,leadingtothe needforincreasedhospitalstayandventilatorysupportand,
consequently, increased risk of complications associated withmechanical ventilation and increased morbidity and mortality.
In this context, respiratory physiotherapy has become necessary and a routine in most neonatal intensive care units (NICU) worldwide.9 The main objectives of respira-tory physiotherapy are the prevention and treatment of bronchial obstruction due to accumulation of secretion, whichcontributestoreducingitsdeleteriouseffects,such ashyperinflation, atelectasis, changes in the ventilation-perfusionandincreasedrespiratoryeffort.10,11
Few studieshave investigatedtheinfluence of respira-tory physiotherapy on braininjuries in preterm newborns regardingCBFalterations.12---15 Todate,nostudy quantita-tivelydescribedthepatternofbrainhemodynamicbehavior inthispopulationbefore,duringandafterrespiratory phys-iotherapymaneuversareperformed.
Theobjectiveofthisstudywastoassesstheinfluenceof physiotherapyontheCBFinclinically-stablepreterm new-borns.
Method
preterm newborns, even without pulmonary involvement, have indication for respiratory physiotherapy; however, in the ones that require oxygen and/or who have pul-monaryand/or nasalsecretions,respiratoryphysiotherapy is intensified. We excluded all newborns with cardiac and/orneurologicalmalformations,diagnosisofbrainlesion (hemorrhagicorischemic)duringanyperiodof hospitaliza-tion and/or receiving vasoactive drugs. Written informed consent was obtained from the parents/tutors of each subject.
To calculate the sample size, a pilot study was per-formed,inwhich10pretermnewbornsunderwentidentical assessments tothose used for the data collection in this study(describedlater).ConsideringatypeIerrorof5%and atypeIIerrorof 20%,thesample sizewasdeterminedby thedifferencebetweenthemeansofpairedmeasurements forallstudiedvariables.Thus,asamplesizeof40newborns wasdetermined.
Gestationalage(GA)wasobtainedfromthedateofthe lastmenstrualperiod.Ifthisdatewasunknownoruncertain, theGAestimatedatanearlyultrasound(lessthanorequal to16weeks)and/or clinicalandneurologicalexamination ofthe newbornbyNew Ballard methodwasconsidered.16 Wedidnotconsiderthecorrectedage.
CBF assessment of wascarried out by transfontanellar Doppler ultrasonography, performed by the same neona-tologist,inordertoavoidobserver-relatedvariations.The SonoSiteTMsystem,M-Turbomodel,witha5MHztransducer
was used. The pericallosal artery, a branch of the ante-rior cerebral artery, adjacent to the knee of the corpus callosum was evaluated. This artery was chosen because itiswidely usedin scientificstudiesfor similartests,17 as wellasitseasyaccessthroughtheanteriorfontanelle.The followingwereassessed:meanflowvelocity(MFV),peak sys-tolicflowvelocity(PSV),end-diastolicflowvelocity(EDFV), indexofresistance(IR=PSV−EDFV/PSV)andpulsatilityindex (PI=PSV−EDFV/MFV).
Theexaminationswerecarriedoutwiththenewbornin thesupinepositionwiththeheadin midlineposition,and kept at rest or reduced motor activity for approximately 10min,afterwhichthebrainultrasoundwasperformed to excludebrain lesions and,subsequently, the firstDoppler ultrasound examination (T0) was performed. After that,
the expiratory flow increase (EFI) maneuvers were per-formed for 5min. The examination was repeated on the second (T1) and fifth (T2) minutes of respiratory
phys-iotherapy and 10min after completion of the maneuvers (T3).Afterthetests,the newbornsreceivednursing care,
according to the service routine. The examinations were performed one hour before the following feeding to pre-ventvomiting and bonchoaspiration. Fasting patients and those fed by continuous infusion through infusion pump orparenteral nutritionwereassessedonehour beforethe subsequentnursingcareinordertonotinterruptthe new-born’srestingandsleeptime.Newbornsthatwererestless or tearful during the physiotherapy session were calmed with a 25% sucrose solution and/or non-nutritive sucking with pacifier or a gloved finger. All routine brain ultra-sonographicexaminations,performedafterthetestscarried out for this study, were systematically followed by the researchers.
Figure1 Respiratoryphysiotherapytechniqueofexpiratory flowincreaseinpretermnewborns.
The chosen physiotherapy technique was the slow EFI methodadaptedtoprematurepatients,whichwasapplied by the same therapist in a consistent and standardized manner.Thismaneuver consistsinslowlyapplyingaslight pressure on the patient’s chest with one hand, obliquely (cephalocaudalandanteroposteriorplanes),startingatthe end of the inspiratory plateau and ending at the end of expiration, which is prolonged. The hand must be pos-itionedbetweenthesternalnotchandthexiphoidprocess of the newborn’s sternum. The other hand of the thera-pist is placed onthe lastribs (without applyingpressure) asabridge,ofwhichcolumnsarethethumbandforefinger (or middle finger) (Fig.1). Thus,contact withthe child’s abdomen is avoided and the expansion of the lower ribs is limited, allowing better diaphragm excursion and pre-ventinganincreaseinintraabdominalpressure.2,18,19Inthis study,thisprocedure wasrepeatedfor 5min, witha brief pauseinthemiddleoftheperiodtoperformthe examina-tion.This respiratoryphysiotherapy techniquewaschosen becauseit is currently one ofthe most often usedin our service.
Maternalandneonatalsociodemographicvariableswere collected from medical records to characterize the sam-ple.Theabsolutefrequencyandpercentageofqualitative variablesanddescriptivestatisticsofquantitativevariables, withmeasuresofcentraltendency,positionanddispersion (mean,standarddeviationandminimumandmaximum val-ues)werecomputed.
Heartrateandoxygensaturationwerecontinuously mon-itoredinamulti-parametermonitor.Respiratoryfrequency was assessed by visual count. Blood pressure (BP) was measurednon-invasivelyusingtheautomatedoscillometric methodwithamulti-parametermonitor, preferablyinthe rightupperlimb.
wassetatp<0.05.The statisticalanalysiswascarriedout usingTheSASSystemforWindows,version9.2(2002---2008). TheProtocolforthisstudywasapprovedbyourhospital’s Institutional Research Committee and by the University’s local EhticsCommittee, under protocolsno. 24/2013 and 421.237,respectively.
Results
Forty-twonewbornswereenrolledinthisstudy,ofwhichtwo wereexcludedduetothepresenceofperiventricular leuko-malacia (PVL), observed in pre-discharge transfontanellar ultrasound.Thus,40newbornswereincluded,ofwhichmost ofthem(95%)werebreathingroomair,weremales(52.5%) andbornviaCesareansection(67.5%).Themeangestational andpostnatalagewas31.8±1.6weeks(range:28---34)and 10.9±1.9 days (range:8---15), respectively. The newborns hadameanbirthweightof1658±539g,rangingfrom830to 3840g. Fifteen newborns (37.5%) had birth weight<1500g. Most patients (70%, n=28) were considered adequate for gestationalage, while 27.5% (n=11) weresmall for gesta-tional age and only one (2.5%) was considered large for gestationalage.On examination,thepatients weighedon average1617±519g,rangingfrom840to3900g.Ofthe new-borns,10(25%)weretwins.Regardingthematernalhistory, 12(30%),four(10%)andseven(17.5)werebornto hyperten-sive,smokeranddiabeticmothers,respectively.Eight(20%) patients were born tomothers that had used magnesium sulfate and 33 (82.5%) to mothers who received antena-talcorticosteroids.Themostfrequentlyobservedneonatal morbiditieswereriskofovularinfection(n=20,50%), respi-ratorydistress(n=36,90%),useofsurfactant(n=20,50)and patentductusarteriosus(n=9,22.5%).
No assessed CBF variable (PSV, EDFV, MFV, IR and PI) wassignificantly altered by the respiratory physiotherapy maneuversovertime(T0,T1,T2andT3)(Fig.2).
Hemoglobin oxygen saturation (p=0.99) and heart rate (p=0.07) did not change significantly with the respiratory physiotherapy over timeand werewithin nor-mal limits (Fig. 2). Systolic (SBP, 70.5±17.5), diastolic (DBP, 39.7±11.8) and mean blood pressure levels (MBP, 47.7±10.3), as well as respiratory rate (RR, 49.2±10.5) were also within the normal limits20 and, after the physiotherapy session, were similar to previous values at T0 (RR: 53.5±10.5rpm; SBP: 68.8±12.3mmHg; DBP:
38.2±10.3mmHg;MBP:46.1±7.5mmHg).
Discussion
This study showed, in an unprecedented manner, that respiratory physiotherapy using theEFI technique did not significantly change the CBF velocities, and did notseem to modify cerebral vascular resistance in clinically-stable preterm newborns. Some studies investigated the asso-ciation between respiratory therapy and the occurrence of cerebrovascular lesions.12---15 However, todate, we are unaware of the existence of studies that evaluated CBF velocityparametersinpretermnewbornsbefore,duringand aftersometypeofrespiratoryphysiotherapymaneuver.
In the late 1990s, Harding et al.15 observed a sig-nificant occurrence of encephaloclastic porencephaly in
50 PSV
p=0.50
p=0.07
p=0.17
p=0.67
p=0.41
P=.99
P=.35 40
30
20
10
0
–5
2.0
1.5
1.0
0.5
Flow velocity (cm/s)
0 5 10
Time (min)
Index
Oxygen saturation, %
EFI
15
–5
100
220
200
180
160
140
120 90
80
70
60
0 5 10
Time (min)
Heart rate (beats/min)
EFI
15
–5 0 5 10
Time (min) EFI
15
IR
EDFV MFV
PI
Sat O2 HR
A
B
C
Figure2 Influenceofphysiotherapyoncerebralbloodflow velocity(A),resistanceandpulsatilityindexes(B)andoxygen saturationandheartrate(C) ofpremature newborns(n=40). PSV,peaksystolicflowvelocity;MFV,meanflowvelocity;EDFV, end-diastolicflowvelocity; PI, pulsatilityindex; IR,index of resistance;SatO2,peripheraloxygensaturation;HR,heartrate;
EFI,expiratoryflowincreasetechnique.
Cerqueira-Netoetal.22studiedthecerebral hemodynam-ics of 20 adult patients with severe head trauma during respiratoryphysiotherapy(chestvibration,EFIand endotra-chealaspirationwithsalineinstillation).Thepatientswere sedated, received analgesics and neuromuscular blocker, were intubated and on invasive mechanical ventilation. Theintracranialpressure(ICP)ofthosepatientswas moni-toredbyanintraventricularcatheter.Theauthorsobserved thatphysiotherapymaneuversofthoracicvibrationandEFI did not result in significant effects on ICP, mean airway pressure(MAP)and cerebral perfusionpressure. However, endotrachealaspirationsignificantlyincreasedICPandMAP, whichreturnedtobaselinelevelswithin10min.Theauthors suggest that the increase in ICP may be associated with increasedMAPandwiththelimitationofcerebralbloodflow autoregulation,whichcanoccurinpatientswithseverehead trauma,23aswellasinpretermnewborns.1Anotherrelevant studyistheonebyMaynardetal.,24whoassessedthe pat-ternofCBFvelocityin themiddlecerebral arterybefore, duringandafterarapidthoraciccompression(usedfor pul-monaryfunctiontesting,butwhichcanbecomparabletothe rapidEFItechnique)in12pretermnewbornsandfull-term newborns. The authors observed a significant increase in EDFVandPIreductionduringthemaneuver,withreturnedto baselinevaluesimmediatelyafterthoracicrelease. Sneez-ingandsoftvocalizationsproducedchangessimilartothose observedduring rapidthoracic compression. Inthis study, some newborns had sneezing and/or coughing during the physiotherapysession,whichisexpected.Alimitationofthis studyisthefactthatwedidnottesttheisolatedinfluences ofcrying,coughing,sneezing,hiccupsandvocalizations.In addition,due totechnicaldifficulties,cerebralblood flow measurementswerenottakenattheexactmomentofchest compression.
As currently the EFI technique is widely used in the NICU, we consider of great importance to quantitatively assess its effects on the CBF in premature newborns, as thismaneuverinvolves compression,evenslightandslow, ofamorecompliantchest.Itisnotknownwhetherthis sit-uation couldchange the intrathoracic pressure enough to affectvenousreturnand,thus,changeCBF.Wealso empha-sizethatthe techniqueusedin prematurenewborns does notinvolve the use of abdominalpressure, which, in the originaltechnicaldescription,shouldbeappliedinthe oppo-sitedirection tothat of thoracic pressure.18 It is possible thatthepressureontheabdomenmaysignificantlyincrease intra-abdominal pressureand, consequently,the intratho-racic pressure and ICP, but this possibility has yet to be demonstrated.Itisnoteworthythatthephysiotherapyteam inourserviceonlytreatspretermnewbornsafter72hoflife. ThereisgreatconcernaboutcausingCBFchangesinpreterm newborns,particularlythosewithlowerGAandbirthweight (<1.500g),duetothehemodynamicinstabilityinthe post-natal period,particularly within the first 72h,25---28 during which greater fluctuations of brain circulation occur due topressurepassiveautoregulation,27 andhenceincreasing theriskofhemorrhagic(HPIV)and/orischemic(PVL)1 cere-brovascularlesionsandtheircomplications.However,there isevidencethattheCBFisstillstabilizedduringthefirstand second weeksof life,29,30 which justifies the investigation oftherespiratoryphysiotherapy influenceinchildrenwith postnatalageof8---15days.Alimitationofthisstudyisthat
itdidnotconsiderthecorrectedgestationalageofpatients atthetimeoftheprocedure.Wechosetousechronological ageasariskfactorforchangeintheoutcome,asthatwas thecriterionforsubjectselection.Nevertheless,onlyfour patientshadcorrectedage>34weeksattheexamination.
Not all patients in this study had an absolute indica-tion for respiratory physiotherapy,asthe majority was in a clinically-stable situation and with no oxygen support. On theotherhand, thetherapywasindicatedfor oxygen-dependent patients and for those withpulmonary and/or nasal secretion. It is worth mentioning that no subject had contraindications for such intervention, which would not bring any harm to the patient. Therefore, the study population washeterogeneous regardingthe indication of pulmonarytherapy,butstableconsideringtheclinicalpoint ofview.
Furthermore,itisimportanttomentionthatthechildren werenotfollowedafterhospitaldischarge.Some patients weredischarged rightafter theassessment for thisstudy. Earlydischargeswereduetofavorableclinicaloutcomeor inter-hospitaltransfer,whichwasthecasefor18ofthe40 studiedchildren.Therefore,wehavenoinformationabout thepossibledevelopmentofsubsequentbrainlesions.
The knowledge of factors that could change the CBF of preterm newborns is important for the prevention and control of complications related to prematurity, such as cerebrovascularlesions.Asthevastmajorityofpremature newborns need respiratory physiotherapy, it is important to know the pattern of cerebral hemodynamics in these patients during the application of the most often used physiotherapytechniques. Thisinformationcancontribute to better care for the newborns, as well as better pre-vention, treatment and control of cerebral disorders and complications that affect them. Additionally, it may help physiotherapistsfor amore adequateand saferindication ofrespiratorytherapy.
ItcanbesaidthattheEFIisasafephysiotherapy tech-nique whenappliedin clinically-stablepretermnewborns, asitdidnotresultinsignificantchangesinCBF.Inthisstudy, weanalyzedclinically-stablenewbornsasafirststeptoward theassessment ofthetechniquesafety.The extrapolation oftheseresultsinclinically-unstableinfantsandonthefirst daysoflifeshouldbeviewedwithcautionandbecomesan interestingfieldfor furtherstudiesaddressing critically-ill pretermnewborns.
Funding
Thisstudydidnotreceivefunding.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgements
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