Assessed for eligibility n=419 Excluded n=187 ♦ In a previous hospital for > 24 h n=93 ♦ Not admitted to ICU n=88 ♦ Not tetanus n=6 Analysed n=104 At risk of HCAP, remained semi-recumben
Trang 1Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 90– 97
jo u rn al h om epa g e : h t tp :/ / w w w e l s e v i e r c o m / l o c a t e / t r s t m h
Huynh Thi Loana, Janet Parryb,c, Nguyen Thi Ngoc Ngaa, Lam Minh Yena,
Nguyen Thien Binha, Tran Thi Diem Thuya, Nguyen Minh Duonga, James I Campbellb,c, Louise Thwaitesb,c, Jeremy J Farrarb,c, Christopher M Parryb,c,∗
a Hospital for Tropical Diseases, 190 Ben Ham Tu, District 5, Ho Chi Minh City, Vietnam
b The Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, 190 Ben Ham Tu, District 5, Ho Chi Minh City Vietnam
c Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
a r t i c l e i n f o
Article history:
Received 16 April 2011
Received in revised form 7 October 2011
Accepted 7 October 2011
Keywords:
Tetanus
Healthcare-associated pneumonia
Body position
Semi-recumbent
Tracheostomy
Vietnam
a b s t r a c t
Healthcare-associatedpneumonia (HCAP)is acommoncomplication inpatients with severetetanus.Nursingtetanuspatientsinasemi-recumbentbodypositioncouldreduce theincidenceofHCAP.Inarandomisedcontrolledtrialwecomparedtheoccurrenceof HCAPinpatientswithseveretetanusnursedinasemi-recumbent(30◦)orsupineposition
Atotalof229adultsandchildren(aged≥1year)withseveretetanusadmittedtohospital
inVietnam,wererandomlyassignedtoasupine(n=112)orsemi-recumbent(n=117) position For patients maintaining their assigned positions and in hospital for>48h therewasnosignificantdifferencebetweenthetwogroupsinthefrequencyofclinically suspectedpneumonia[22/106(20.8%)vs26/104(25.0%);p=0.464],pneumoniarate/1000 intensivecareunitdays(13.9vs14.6;p=0.48)andpneumoniarate/1000ventilateddays (39.2vs38.1;p=0.72).Mortalityinthesupinepatientswas11/112(9.8%)comparedwith 17/117(14.5%)inthesemi-recumbentpatients(p=0.277).Theoverallcomplicationrate [57/112(50.9%)vs76/117(65.0%);p=0.03]andneedfortracheostomy[51/112(45.5%)vs 69/117(58.9%);p=0.04)wasgreaterinsemi-recumbentpatients.Semi-recumbentbody positioningdidnotpreventtheoccurrenceofHCAPinseveretetanuspatients.[Clinical Trials.govIdentifier:NCT01331252]
© 2011 Royal Society of Tropical Medicine and Hygiene Published by Elsevier Ltd
All rights reserved
1 Introduction
Tetanusisanimportantcauseofmorbidityand
mor-tality throughout the developing world Despite the
availabilityofaneffectivevaccine,anestimatedonemillion
casesoftetanusstilloccureachyear.1Theprincipalcauses
of death in tetanus are respiratory failure and
cardio-vasculardysfunctionsecondarytoautonomicinstability.2
∗ Corresponding author Present address: Oxford University Clinical
Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, District 5,
Ho Chi Minh City, Viet Nam Tel.: +84 8 9 241 761; fax: +84 8 9 238 904.
E-mail address: cparry@oucru.org (C.M Parry).
The ability to be able to perform a tracheostomy and mechanicallyventilatepatientshascontributedtoa signif-icantreductioninmortalityduetorespiratoryfailure3–5
butleadstoanincreasein thefrequency of healthcare-associated pneumonia (HCAP).6,7 The management of patientswithpneumoniaiscomplicatedbydiagnostic dif-ficultiesandthedevelopmentofresistancetocommonly usedantimicrobialagents,problemsparticularlyacutein resource-limitedsettings.Simpleandinexpensive strate-giestoreducetherisk of HCAPin patientswithsevere tetanuswouldbevaluable
Positioningofmechanicallyventilatedpatientsinthe semi-recumbentpositionat30–45◦isnowgenerally rec-ommendedasapneumoniapreventativemeasure.8–10In
0035-9203/$ – see front matter © 2011 Royal Society of Tropical Medicine and Hygiene Published by Elsevier Ltd All rights reserved.
doi: 10.1016/j.trstmh.2011.10.010
Trang 2an unpublishedpilot study conducted by our group in
20patientswithseveretetanusattheHospitalfor
Trop-icalDiseases(HTD)inHoChiMinhCity,Vietnam,patients
wereunabletotolerateasemi-recumbent positionata
45◦anglebecauseofmusclerigidity.However,a30◦angle
wastoleratedbythepatientsanddidnotappeartocause
anyadverseeventssuchashypotension.Weinvestigated
thehypothesisthattheincidenceofHCAPinpatientswith
severetetanuscouldbereducedbynursingpatientsina
semi-recumbentpositionat30◦ratherthaninthesupine
position,aswasthecurrentwardpractice
2 Methods
2.1 Studypopulation
ThestudywasconductedattheHTD,HoChiMinhCity,
Vietnam.This500-bedinfectiousdiseasehospitalserves
thelocalcommunityandisaspecialistreferralcentrefor
thesurroundingprovincesforsevereinfectiousdiseases
suchastetanus.Thehospitaladmitted250–300casesof
tetanuseach yeartoa ward exclusivelydevotedto the
managementofpatientswithtetanus.Thewardcontained
a 14-bed intensive care unit (ICU) for adults, children
andneonateswithseverediseaseandaseparateareafor
patientswithnon-severediseaseandthoseintherecovery
phase
Consecutiveadultsandchildren(aged≥1year)
admit-tedtotheICUwithaclinicaldiagnosisofseveretetanus
wereeligible.Patientswereexcludediftheyhadbeenin
anotherhospitalformorethan24hpriortoadmissionto
HTD,iftheyhadaclinicaldiagnosisofpneumonia(defined
below)atthetimeofadmission,shockrefractoryto
vasoac-tivedrugsorvolumetherapy,recentICUstay(<30days),
recentabdominalsurgery(<7days)orwereagedunder
1year.Foreacheligiblepatient,anopaqueenvelope
con-tainingthenextstudynumberwasopenedcontaininga
randomallocationina1:1ratiotoeithersemi-recumbent
(30◦)orsupine(0◦)bodyposition.Therandomisationwas
byacomputer-generatedlistbyastaffmembernot
other-wiseinvolvedinthestudy.Theattendingphysicianswere
responsibleforenrollingtheparticipants,andrecording
theclinicaldataintheindividualstudynotes.Healthcare
personnelwereinstructednottochangethepositionofthe
patient,unlessformedicalrequirements.Thecorrectness
ofthepositionwascheckedtwicedailybyamemberofthe
studyteam.Semi-recumbentpatientswerelaidsupineif
thepatienthadacardiacarrest,orhypotensiondeveloped
forlongerthan30min.Allpatientsweresupineduring
tra-cheostomyandfor30minafterwards
2.2 Patientmanagement
Wounds,ifpresent,werecleanedanddebrided,equine
tetanus antitoxin was administered in a dose ranging
from 500 to 100 IU/kg depending on the extent of
the disease and penicillin or metronidazole was given
(penicillin 100000–200000IU/kg/day or metronidazole
1600mg/dayrectally)for7–10days,changingtoanoral
preparationwhenthepatientwaswellenough
Benzodi-azepines(diazepamormidazolam20–240mg/dayeither
asabolusorbyi.v.infusion)weregiventocontrol mus-cle spasmandhypertonia.Theindications forasurgical cuffedtracheostomywereacuteairwayobstructiondueto laryngealspasm,frequentspasmsinterferingwith respi-rationortofacilitatemechanicalventilation.Nopatients were orally intubated and no form of subglottic suc-tion or selective digestive tract decontamination was used Arterial blood gases and peripheral oxygen satu-rationsweremonitoredregularly.In severetetanus,the non-depolarizingneuromuscularblockingagent pipecuro-niumwasused,usingbolusdosestitratedagainstspasm Autonomic instability wastreated withincreased seda-tion,morphine (20–60mg/dayintramuscularly),calcium antagonists,digoxin,volumeexpansionorinotropes (nore-pinephrineordopamine)accordingtotheclinicalsituation Intermittententeralnutrition wasadministeredthrough
alargeborenasogastrictubeinthosepatientsunableto swallow.AnX-raywasusedtodeterminecorrect place-mentofthetubebeforefeedingcommenced.Patientswith
ahistoryofpreviousgastriculcerationcontinuedtoreceive theirregularmedication,andthose whodeveloped gas-trointestinalbleedingduringthecourseoftheiradmission werecommencedonstressulcerprophylaxiswitheither
anH2antagonistorsucralfate.Standardmeasuresfor gen-eralcriticalcareandpreventionofnosocomialpneumonia wereemployedandapressureareacareprotocolwas fol-lowedinallpatients.Closedsuctionwasusedforbronchial toilet.Onaveragethereweretwopatientsforeachnurse
intheICU
Admissionclinicalfeatures,thepresenceofunderlying disease,dailyprogress,theneedforatracheostomyand mechanicalventilation, durationandtypeofnasogastric intubation,typeofstressulcerprophylaxis,sedative treat-mentadministered,intercurrentinfectionsantimicrobial treatmentgiven,thecostofantimicrobialsgivenandthe durationofICUandhospitalstaywerecollected prospec-tivelyonadedicatedstudyform.Atthetimeofadmission
tothe ICU,blood wastaken for haematocrit,white cell count,plateletcountandcreatinineandachestX-ray per-formed.Thetetanusseverityscore(TSS)wasdetermined for the time of admission witha cut-off point TSS ≥8
as predictiveofdeath.11Olderagewasdefined asaged
>60years;prolongedventilationwasdefinedas mechani-calventilation>7days;hypotensionwasdefinedinadults
asasystolicbloodpressure≤80mmHgandinchildrenasa systolicbloodpressure≤70mmHg;thepresenceof auto-nomicinstabilitywasdiagnosedbytheattendingphysician
onthebasisofthepresenceoflabilityintheheartrate, bloodpressure,temperatureorexcessivesweating 2.3 Pneumoniasurveillance
Surveillanceforpneumoniaorotherinfectionwas con-ducteddailyuntildeathor72hafterthepatienthadleft theICU.Patientswithclinicallysuspectedpneumoniawere investigated withachest X-ray,whiteblood cellcount, blood culture and non-bronchoscopic bronchial lavage Clinicalpneumoniawasdefinedbythepresenceofnew andpersistentinfiltratesonchestX-ray,consideredlikely
tobe associated withpulmonaryinfection, and atleast twoofthefollowingthreecriteria:temperatureof≥38◦C,
Trang 3pres-enceofpurulenttrachealsecretions.Themicrobialcause
ofthepneumoniawasdeterminedbytheisolationofat
least one pathogenic microorganism in a blood culture
oratleastonepathogenicmicroorganismintheculture
ofthenon-bronchscopiclavagewiththebacterialgrowth
≥105colonyformingunits(CFU)/ml.Community-acquired
pneumoniawasdefinedaspneumoniadevelopingwithin
48hofadmissiontoanyhospitalandHCAPaspneumonia
developingmorethan48hafteradmissiontoanyhospital
Thediagnosisofpneumoniawasconfirmedbyan
indepen-dentphysician,nototherwiseinvolvedinthedailyconduct
ofthestudy
2.4 Microbiologicalmethods
Blood,5–8ml(foradults)or2–5ml(forchildren),was
inoculatedintoBACTECplusaerobicbottles(Becton
Dick-inson,Sparks,MD,USA).Thesebottlescontainaresinto
adsorbantimicrobials.Thebottleswereincubatedat37◦C
in theBACTEC9050automated analyserfor 5days and
subculturedwhenthemachineindicatedapositivesignal
Patients were pre-oxygenated prior to the
non-bronchoscopic bronchial lavage.12 They were already
sedated by the tetanus therapy Secretions in the
tra-cheaandtracheostomywereremovedbysterilesuction
A standard50cm,14-gauge tracheal aspirationcatheter
(ArgyleSherwoodMedical,London,UK)wasattachedto
a 20ml syringefilled with20mlof sterilesaline(10ml
for children).The distal endwas lubricatedwithsterile
gel,introducedviathetracheostomytubeandadvanced
until significant resistancewas encountered Thesaline
wasinstilledover 10–15s, withdrawn1–2cm and then
immediatelyre-aspiratedandthecatheterwasremoved
Generally5–10mloffluidwasrecovered.Nofurther
aspi-ration wasattemptedduringremoval ofthecatheterto
avoidcontaminationwithtrachealsecretions
Sampleswereprocessedin thelaboratorywithin1h
ofcollection.A Gramstainand Ziehl–Neelsenstainwas
prepared from thelavage fluid, which was then mixed
withanequal volumeof freshly prepareddithiothreitol
(Sputasol;Oxoid,Basingstoke,UK).Themixturewasleft
atroomtemperaturefor10minduringwhichtimeitwas
shakenvigorouslyonthreeoccasions.Threeserialtenfold
dilutionsweremadebytransferring1mlofthemixture
to9mlofmaximumrecoverydiluent(Oxoid,Basingstoke,
UK).Analiquotof20loftheoriginalhomogenised
sam-pleandeachofthethreedilutionswasinoculatedonhalf
aplateeachofthefollowingmedia:5%sheepbloodagar,
heatedblood agar,aselectivepneumococcalagar
(incu-bated at 37◦C in 5% CO2 for up to48h),a MacConkey
agaranda furtherMacConkey agarcontaining4mg/l of
gentamicin(incubatedat37◦Cinairfor upto48h)(all
mediafromOxoid,Basingstoke,UK).Specificculturesfor
Legionella species and Mycobacteria spp were not
per-formed.After24and48hincubationcoloniesoneachof
theplateswerecountedandconvertedtoabacterial
con-centrationinCFU)/mloforiginallavagefluid
Isolated organismswereidentifiedby standard
labo-ratorymethodsusingAPIidentificationkits(Bio-Mérieux,
Basingstoke,UK)whennecessary.Thefollowingorganisms whenisolatedinthenon-bronchiallavagewereconsidered non-pathogenic:Streptococcusspp.exceptS.pneumoniae, coagulase negative staphylococci, Neisseria spp and Candida spp Antimicrobial susceptibility testing was performedbythemodifiedKirby-Bauermethodand inter-pretedaccordingto CLSI(formerlyNCCLS) guidelines.13
Theantimicrobialtherapyofthepatientswasadjustedin thelightofthemicrobiologyresults
2.5 Samplesizeandstatisticalanalysis Theaimofthestudywastoassessthefrequencyand rateofdevelopmentofclinicallysuspectedand microbi-ologicallyconfirmed HCAPin tetanuspatientsadmitted
totheICU nursedin a semi-recumbent orsupine body position.Thefrequencyofclinicallyandmicrobiologically confirmedHCAPwasdefinedasthenumberofcasesper
100patientsandtherateasthenumberofcasesper1000 ICUdaysandper1000ventilateddays.Patientsatriskof developingHCAPwerethosewhohadbeeninhospitalfor
atleast2dayswithoutdevelopingpneumonia.Analysisof admissionstothewardduring1998and1999hadshown thatapproximately85% ofpatientsadmittedtotheICU wereatrisk,and39%developedHCAP.Inordertoshow
a50%reductioninthefrequencyofHCAPinthosepatients nursedinasemi-recumbentposition190at-riskpatients (95%confidencelevel,80%power)wouldberequired.We plannedto conductan analysis when 230patientshad beenrecruitedtothestudy.Asecondaryend-pointwasa comparisonofthemortalityineachgroupandthiswas per-formedonanintention-to-treatbasis.Patientseitherdied
inhospital,orweretakenbytherelativestodieathome whentherewasnofurthertreatmentpossibleandno like-lihoodofsurvivalintheviewoftheattendingphysician Thosetakenhometodiewererecordedasdeaths Categoricalvariableswerecomparedusingthe2test
orFisher’sexacttest.Non-parametricdatawascompared usingtheMann-WhitneyUtest.Riskfactorsforthe devel-opmentofHCAPanddeathwerecalculatedbyunivariate andmultivariatemethods.Analysiswasperformedusing SPSSversion18.0(SPSSInc.,Chicago,IL,USA)andEpiInfo v6(CDC,Atlanta,GA,USA)
3 Results 3.1 Studypopulation Therewere419admissions(excludingneonates)tothe tetanuswardbetweenAugust2000andMarch2002.Six patientswereimmediatelyexcludedastheydidnothave tetanus,88werenotsevereenoughtorequireadmission
totheICUand93hadbeeninaprevioushospitalfor>24h
Atotalof 232patientswereentered intothestudyand randomised(Figure1):115patientswererandomisedto
benursedinasupinepositionand117tobenursedina semi-recumbentposition.Threesupinepatientswere sub-sequentlyconsiderednottohavetetanusand excluded Theonlyimportantdifferenceinthecharacteristicsofthe twogroupsofpatients,atthetimeofadmission,wasthata significantlyhigherproportionofsemi-recumbentpatients
Trang 4Assessed for eligibility (n=419)
Excluded (n=187)
♦ In a previous hospital for > 24 h (n=93)
♦ Not admitted to ICU (n=88)
♦ Not tetanus (n=6)
Analysed (n=104)
At risk of HCAP, remained
semi-recumbent
26 (25%) developed HCAP
Lost to follow-up (n=0)
Died within 48 h of admission (n=6)
Changed to supine position (because of
hypotension) (n=7)
Allocated to semi-recumbent position
(n=117)
♦Received allocated intervention (n=117)
♦Did not receive allocated intervention
(n=0)
Lost to follow-up (n=0) Died within 48 h of admission (n=5) Self discharged (n=1)
Allocated to supine position (n=115)
♦Received allocated intervention (n=112)
♦Did not receive allocated intervention (not tetanus) (n=3)
Analysed (n=106)
At risk of HCAP, remained supine
22 (20.8%) developed HCAP
ALLOCATION
ANALYSIS FOLLOW-UP
Randomised (n=232)
ENROLMENT
Figure 1 CONSORT flow chart demonstrating recruitment of patients to the study HCAP: healthcare-associated pneumonia; ICU: intensive care unit.
hadpreviouslyreceivedanantimicrobial(Table1).There
wasnosignificantdifferenceintheTSSbetweenthetwo
groups
3.2 Pneumoniasurveillance
A clinical diagnosis of pneumonia was made in 55
patientsanda microbiologicaldiagnosisin45(Table2)
Ofthe55 patientswithpneumonia 53(96%) hada
tra-cheostomy at the time and 50 (91%) were receiving
mechanicalventilation.Therewasnosignificantdifference
intheoverallnumberofpatientswithaclinicalor
microbi-ologicaldiagnosisofpneumoniabetweeneachgroup.The
frequencyofpneumonia inthesupinegroupwaslower
thanwehadexpected,althoughtherangeoforganisms
iso-latedwastypicalofourpreviousexperienceontheward
(Table2)
Fivepatientsrandomised tothesupine positiondied
within48hofadmissionandonepatientself-discharged
ontheseconddayofadmission.Sixpatientsrandomisedto thesemi-recumbentpositiondiedwithin48hofadmission andsevenpatientshadtochangepositiontosupine,one becauseofacardiacarrestonday1andsixbecausethey developedhypotensionatsomepointbetweendays2and
6.Therefore,106supinepatientsand104semi-recumbent patientswere eligiblefor analysisof thefrequency and rateofHCAP(Figure1;Table2).Thiswasmorethanthe intendedsamplesizeof190at-riskpatients.The propor-tion of patients with HCAP was 22/106 (20.8%) in the supinegroupand26/104(25.0%)inthesemi-recumbent group[odds ratio(OR)0.79, 95% CI0.39–1.57, p=0.46)
In thepatients treated with a tracheostomythe corre-spondingproportionswere22/49(44.9%)vs26/59(44.1%) (OR1.03,95%CI0.45–2.38,p=0.93)andforthepatients requiring mechanical ventilation the proportions were 21/37(56.8%)vs24/44(54.5%)(OR1.09,95%CI0.41–2.90,
p=0.84).Therewerealsonosignificantdifferencesinthe rates of HCAP/100 ICU days and HCAP/1000 ventilated
Trang 5Table 1
Comparison of the admission characteristics of all patients recruited into the study
Supine (n = 112)
Semi-recumbent (n = 117)
p-value
Entry site
Mean (range) tetanus severity score 2.31 (−6 to 25) 1.91 (−5 to 22) 0.582 Mean (range) white cell count (×10 9 /l) 9.5 (5.3–14.7) 8.4 (5.5–14.7) 0.503
Data are number (%) unless otherwise indicated.
Table 2
Clinical and microbiological pneumonia in 229 study patients
Supine Semi-recumbent Odds ratio (95% CI) p-value (n = 112) (n = 117)
Patients with clinical diagnosis of pneumonia 26 (23.2%) 29 (24.8%) 0.92 (0.48–1.76) 0.78 Patients with microbiological diagnosis of pneumonia 19 (17.0%) 26 (22.2%) 0.72 (0.35–1.45) 0.32 Organisms isolated a
Pseudomonas aeruginosa 8 11
Klebsiella spp 10 (1) 11 (1)
Streptococcus pneumoniae 3 3
Patients who developed HCAP 2 (>48 h after admission to hospital) 22/106 (20.8%) 26/104 (25.0%) 0.79 (0.39–1.57) 0.46 Patients with a tracheostomy who developed HCAP 22/49 (44.9%) 26/59 (44.1%) 1.03 (0.45–2.38) 0.93 Ventilated patients who developed HCAP 21/37 (56.8%) 24/44 (54.5%) 1.09 (0.41–2.90) 0.84
HCAP rate/1000 ventilated days 39.2 38.1 0.72 Mean (range) cost of antimicrobials for pneumonia treatment (US$/patient) 228 (56–611) 215 (9–933) 0.84 Data are number (%) unless otherwise indicated.
HCAP: healthcare-associated pneumonia; ICU: intensive care unit.
a Organisms isolated from blood, or from the non-bronchoscopic lavage (≥10 5 CFU/ml) Number in parentheses refers to the isolation of the organism from blood culture.
days.HCAPonlydevelopedinthepatientsmanagedwith
a tracheostomy.In this group ofpatients, by
multivari-ateanalysisthedevelopmentofclinicalpneumoniawas
independently associated witholderage(p=0.086) and
durationofmechanicalventilationformorethan7days
(p<0.001)
3.3 Outcomeandadverseevents
The proportion of patients who required a
tra-cheostomy, and theoverall frequency of complications,
was significantly greater by univariate analysis in the
patientsnursedinthesemi-recumbentpositioncompared
withthose nursedinthesupine position(Table3).The
mortalityinthepatientsrandomisedtothesupineposition
was11/112(9.8%)comparedwith17/117(14.5%)inthose
randomised to the semi-recumbent position (OR 0.64, 95%CI0.27–1.53,p=0.277).Otheroutcomevariableswere similarineachgroup.Independentriskfactorsassociated withafataloutcomebymultivariateanalysiswereanolder age(p<0.001),currentorpreviousinjecting drugabuse (p<0.001) and the occurrence of autonomic instability (p<0.001).Inthe36patientswithaTSS≥8,themortality was19(52.8%)comparedwith9(4.7%)inthe193patients withaTSS<8(OR22.9,95%CI8.2–65.4,p<0.001)
4 Discussion
Inthisstudyasemi-recumbent(30◦)orsupine nurs-ingpositionforpatientswithseveretetanushadnoeffect
onthefrequencyandrateofHCAP.Thisresultcontrasts with two previous studies in general ICU patients A
Trang 6Table 3
Outcome in 229 study patients
Supine Semi-recumbent Odds ratio (95% CI) p-value (n = 112) (n = 117)
Mechanical ventilation 39 (34.8%) 53 (45.2%) 0.65 (0.37–1.14) 0.106 Gastrointestinal bleed 30 (26.8%) 34 (29.1%) 0.89 (0.48–1.66) 0.701
Mean (range) dose of benzodiazepine used (mg/kg/day) 0.98 (0.50–1.46) 0.89 (0.44–1.47) 0.482 Mean (range) dose of pipecuronium used (mg/kg/day) 0.41 (0.04–1.08) 0.59 (0.20–0.97) 0.818 Stress ulcer prophylaxis given 26 (23.2%) 28 (23.9%) 0.96 (0.50–1.85) 0.898
Mean (range) duration in hospital (days) 27 (3–121) 29 (3–108) 0.468
Data are number (%) unless otherwise indicated.
ICU: intensive care unit.
ventilatedpatientsonageneralICUwererandomisedto
nursinginasemi-recumbent(45◦)versusasupineposition
reducedthefrequencyofHCAPfrom34%to8%(p=0.003)
andmicrobiologicallyconfirmedpneumoniafrom23%to
5%(p=0.018).15Thisstudy,whichwasstoppedbeforethe
plannedsamplesizehadbeenreached,showedthatsupine
bodyposition,enteralnutrition,mechanicalventilationfor
7daysor moreand aGlasgowComaScoreof lessthan
9wereindependentriskfactorsforHCAP.Asubsequent
randomised trial comparingnursing ventilated patients
ata45◦semi-recumbentpositionversus10◦ inthe
con-trolgroupfailedtopreventthedevelopmentofVAP.16In
thatstudy, inwhich bed elevationwasmonitoredby a
transducerwithpendulum,itwasobservedthatitproved
impossibletomaintainthetargetedbackrestelevationof
45◦forsemi-recumbentpositioningandthemeanachieved
treatmentpositionwas28◦
Theoropharynxofpatientswhohaveatracheostomyor
whoaremechanicallyventilated,rapidlybecomecolonised
with an abnormal bacterial flora, particularly
Gram-negativebacteria.Refluxofcolonisedgastriccontentsinto
theoropharynxprobablycontributestothisprocess
Sub-sequentaspirationoftheseorganismsintotherespiratory
tractis suggested to be partof the pathogenicprocess
leadingtoHCAP.Studieswithradioactivelylabelledgastric
contentsindicatethatpositioningventilatedpatientsina
semi-recumbentpositionreducesrefluxintothe
orophar-ynxandsubsequentaspirationintothelung.17,18 Thisis
therationalefornursingpatientsinthesemi-recumbent
position.Itispossiblethatthepathogenesisof
pneumo-niain tetanuspatientsmaydiffer fromotherventilated
patients.Ofnoteallpatientsinthisstudywhodeveloped
HCAPhadatracheostomy,whereas intheotherstudies
thepatientswereintubatedviatheoralroute.14–16Reflux
of gastriccontents intotheoropharynx andsubsequent aspiration intothe lung may bea less important route
by which pneumonia develops on patients with a tra-cheostomyandexogenousinfectionviathetracheostomy maybemoreimportantthanendogenousinfectionfrom theoropharynx.19Ofnote,patientsinthissettinghad a surgicaltracheostomyratherthanthepercutaneous(PERC) tracheostomiesmorecommonlyusedinICUsindeveloped countries
The30◦anglemaybeinsufficienttopreventthereflux
of gastriccontents intotheoropharynx andsubsequent aspirationintothelung.InthestudyofDrakulovic15the patientsweresemi-recumbentat45◦whereasinthestudy
ofvanNieuwenhoven16itprovedimpossibletomaintain theplannedangle45◦,anaveragetreatmentpositionof28◦
wastheresultonday1andwasdownto23◦byday7.15,16
Inthecurrentstudyweaimedfora30◦angleandthiswas checkedtwicedaily.Itwasnotedthatpatientstendedto slipdownthebedandthatitwasdifficulttomaintainthe
30◦elevation.Alimitationofthisstudyisthatwedidnot formallydocumenttheadherencetotheintendeddegree
ofelevation.Ithasalsobeensuggestedthatmaintaining
asupinepositioninthecontrolgroupasinthestudyof Drakulovic15ledtoahigherthannormalrateofHCAPthan
isthecaseifasmaller10◦angleismaintainedasinthe studyofvanNieuwenhoven.16
TherateofHCAPinthis studywas38–39/1000 ven-tilateddays Thisrateis highcompared withdeveloped countrysettingsbutwithintherangereportedin mechan-ically ventilatedpatientsindevelopingcountries.20–22 It waslowerthanwehadexpectedbasedonpreviousward experience In the period leading up to the study sev-eralchanges weremadein thewardinfrastructure and nursingcaretoimproveinfectioncontrol.Thismayhave contributedtothelowerpneumoniafrequencyduringthe courseofthestudy.Thestudysizeasaresult,lacked ade-quate powerto show the50% reduction in pneumonia
Trang 7analysis,therewasnosuggestionofalowerpneumonia
frequencyinthesemi-recumbentpatients
The development of pneumonia was independently
associated with an older age and a longer duration of
mechanical ventilation consistent withother studies of
pneumoniainpatientsreceivingmechanicalventilation.14
We used a blindnon-directedbronchial lavagemethod
with quantitative cultures to determine the organism
causing pneumonia.12 This method was appropriate
for the local situation and gave a range of
organ-isms consistent withstudies of VAP from othersimilar
locations.21–23
Mortalityinthis studywasindependently associated
witholderage,currentorpreviousinjectingdrugmisuse
andthepresenceofautonomicinstability.Olderageisa
wellrecognizedriskfactorformortalityintheseriouslyill
andthepresenceofautonomicinstabilityariskfactorfor
mortalityinpatientswithseveretetanus.2,4,5,24The
asso-ciationwithinjectingdrugusersislikelytoberelatedto
theincreasedmortalityintetanusassociatedwith
intra-muscular injections.25In this groupofpatients, theTTS
providedagoodpredictorofmortality.Themortalityrate
wasslightly higher in thepatientsmanaged ina
semi-recumbentpositionbutthiswasnotanindependentrisk
factorformortalityinmultivariateanalysisalthoughthe
studywasnotpoweredtolookatthisoutcome.The
over-all complicationrate,and the needfor a tracheostomy,
wassignificantlygreaterinthesemi-recumbentpatients
comparedwiththoseinthesupinepositiondespitesimilar
admissioncharacteristics.Theneedformechanical
ventila-tion,hypotensionandautonomicinstabilityalsooccurred
morefrequentlyinthesemi-recumbentgroupbutthe
dif-ferenceswerenotsignificant
5 Conclusion
Insummary,thisstudysuggeststhatnursingpatients
withseveretetanusina semi-recumbentpositionatan
elevation of 30◦ does not prevent the development of
HCAP Thisresultis likely tobegeneralisable tosevere
tetanuspatientsmanagedinother similarlocationsbut
not necessarilytotetanuspatientsmanagedina
devel-opedcountryICUortogeneralICUpatients.Alternative
strategies areneeded topreventpneumonia inpatients
withseveretetanus
Authors’contributions: HTL,JP,NTNN,LMY,JJFandCMP
conceived thestudyandwrotetheprotocol;allauthors
participatedintheconductofthestudy;NTNN,LMY,NTB,
TTDT,NMD,JIC,LTandCMPcontributedtodata
interpre-tationandanalysis;CMPwrotethefirstdraftofthepaper
Allauthorsreadandrevisedthemanuscriptandapproved
thefinalversion.CMPandJJFareguarantorsofthepaper
Acknowledgements: Wethankthehospitalleadersatthe
HospitalforTropicalDiseases(HoChiMinhCity,Vietnam)
fortheirsupportofthisworkandthestaffofthetetanus
wardandthemicrobiologylaboratoryfortheirhelpwith
theconductofthisstudy
Funding: ThestudywasfundedbytheWellcomeTrustof GreatBritain(grantreference089276/Z/09/Z).Thestudy sponsorshad noroleinthestudydesign,thecollection, analysis,orinterpretationofthedata,thewritingofthe report,orthedecisiontosubmitthepaperforpublication Competinginterests: Nonedeclared
Ethicalclearance: TheScientificand EthicalCommittee
oftheHospitalfor TropicalDiseases(HoChiMinh City, Vietnam) approved the study Informed verbal consent wasobtainedbeforeentryintothestudyfromthepatient
or their relatives if the patient couldnot provide con-sent.ThestudywasconductedincompliancewiththeICH andDeclarationofHelsinkiGuidelinesandwasregistered
onaclinicaltrialsdatabase(ClinicalTrials.govIdentifier: NCT01331252)
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