09125-wfjcc feb cover

for the World Federation of

Societies of Intensive and

Critical Care Medicine

No. 1, Vol. 1

February 2004

World Federation

Journal of Critical CareJournal of Critical Care

www.world-critical-care.com

Inside this issue

• Non-invasive ventilation in the Intensive Care Unit

• Monitoring graphic displays of pressure,volume and flow: the usefulness of ventilator waveforms

• Practical aspects of haemofiltration

• Fulminant hepatic failure in paediatric patients:results of orthotopic liver transplantation

• Over humidification: an under recognised problem?

9th Congress of the World Federation of Societies of

Intensive and Critical Care Medicine27-31 August 2005

Buenos Aires, Argentina

It is our pleasure to report that Buenos Aires, the capital city ofArgentina, will be the seat for the 9th Congress of the WorldFederation of Societies of Intensive and Critical Care Medicine.

The Sociedad Argentina de Terapia Intensiva (SATI) wants toexpress its deepest appreciation for the support and assistancereceived. This will be the first time a World Congress in this fieldof medicine will be held in Latin America and it is therefore a greathonour for us. For this reason, we wish to state that while BuenosAires will be the host of the Congress, it will, in fact, be a Congresshosted by all of Latin America as Argentina holds strong cultural,social and scientific links with all Latin American countries.

The Organising Committee and SATI have decided to propose toall Latin American countries and the representatives of thedifferent Societies of the world to actively participate in theplanning of the scientific programme so as to be able to develop aprogramme for the Congress that will represent the interests for allWFSICCM members.

Apart from being able to benefit from the scientific activity, themain issue of the Congress, we invite you to enjoy Argentina’shospitality, its beautiful scenery and tourist centres, our culture,wines and food, the tango and our renowned Argentine steak. Ourneighbouring countries also offer wonderful landscapes and a vastrange of possibilities which would surely satisfy even the widest ofexpectations.

English is the official language for the Congress. Simultaneoustranslation into Spanish will be provided for Plenary Sessions andSymposia.

We look forward to your visit. Should your enquire anythingfurther, please do not hesitate to contact us.

Contact details

Congress OfficeAna Juan Congresos

Sarmiento 1562, 40F (C1042ABD)Buenos Aires, Argentina

Tel: (54) 11 4381 1777Fax: (54) 11 4382 6703

E-mail (registration): [email protected] (abstracts): [email protected] (scientific programme): [email protected] (exhibition): [email protected] (hotels): [email protected]

SATISarmiento 2046 108 C 1044AAFBuenos Aires, Argentina

E-mail: [email protected]: www.sati.org.ar

February 2004

World Federation Journal of Critical Care

Instructions for authors

World Federation Journal of Critical Care is theofficial journal of the World Federation of Societiesof Intensive and Critical Care Medicine. It isreceived as a benefit of membership of a Societyaffiliated to the World Federation by over 25000intensive and critical care physicians up to 90countries.

Articles

Articles in the following categories may besubmitted for publication.

Reviews: May address diagnosis and/or treatmentduring intensive care, equipment, monitoring,disposable items or discuss diseases commonlytreated in an intensive care unit. Reviews of newhealth technologies relevant to intensive andcritical care medicine are particularly welcomed.Authors are welcome to contact the Editor beforesubmission to inquire regarding the potentialsuitability of their review for the World FederationJournal of Critical Care. The Editor alsocommissions reviews on specific topics from authorswith specific knowledge, experience or expertise.(Up to 3000 words).

Original articles: Clinical studies relevant to thecare of critically ill patients are assessed forpublication. Experimental studies (i.e. using animalmodels or isolated organs and tissues), unlessdirectly relevant to critical illness, are usually notconsidered appropriate. (Maximum 2000 words).

Reports of clinical series: Particularly when localcircumstances provide unusual experience ofproblems seen less commonly elsewhere or therehas been innovation in the management of thecondition described. Well described series ofcritically ill patients managed with limitedresources are particularly welcomed. (Maximum2000 words).

Case reports: Consisting of brief, illustrative reportsof patients’ history and management duringintensive care should have a clear message forreaders in the form of a previously undescribedexperience, a potentially useful treatment deservingscientific evaluation or a potentially avoidablehazard. The discussion should highlight anyprevious similar reports, the importance of theissues identified and recommendations by theauthors. Case reports will usually be published asLessons from practice. (Maximum 1500 words).

Comment: Can address political, economic,educational and training issues or opinion relevantto intensive and critical care medicine. (Maximum2000 words).

Correspondence: Should address issues relevant toarticles recently published in the World FederationJournal of Critical Care. A copy of correspondenceis usually sent to the authors offering theopportunity to reply.

Manuscripts

Authors are encouraged to submit articles writtenin English. If this is not possible, articles in otherlanguages may be considered for publication butwill be translated into English. Assistance isavailable through the editing process for authorswhose first language is other than English.

Manuscripts should be prepared in accordance withthe Uniform Requirements for ManuscriptsSubmitted to Biomedical Journals developed by theInternational Committee of Medical JournalEditors 1. Authors are strongly encouraged to use aclear and simple writing style, remembering thatEnglish is not the first language of many of ourreaders. Critical comment from local colleaguesand review of the statistical methods used bysomeone experienced in clinical studies beforesubmission is likely to reduce the need for revisionof submitted manuscripts. The manuscript shouldbe typed on one side of single sheets of A4 or similarwhite paper with double spacing and margins of2.5cm (1 inch) at the top, bottom and both sides.

Format: Inspection of recent issues of the WorldFederation Journal of Critical Care provides a guide asto the preferred format and layout of articles. Thisis dependent on the type of article submitted.

• Title page: should contain the title, authors,their degrees and diplomas, the departmentaland institutional affiliation of each author, thename, address, telephone number, fax numberand e-mail address (if available) of the authorresponsible for correspondence.

• A summary (for reviews and original articles).

• The text of the article.

• Acknowledgments: including any potentialconflicts of interest, commercial affiliations ofrelevance and sources of financial or grantsupport.

• References: prepared in the style used in IndexMedicus including the abbreviations of journaltitles and first and last page numbers. Allauthors should be listed unless there are morethan six in which case the first three should begiven followed by et al. References should benumbered in the order in which they appear inthe text and be identified in the text by thisnumber.

• Tables, figure legends and figures.

The preferred form of submission is a single originalcopy and a copy on 3.5 inch computer disc. Theword processing program used for the copy oncomputer disc should be indicated in the coveringletter. Alternatively, two copies of the manuscriptmay be submitted.

Two copies of all figures must be included with themanuscript. Black and white figures should besubmitted as glossy prints or laser quality outputfrom a computer printer. Colour figures may also besubmitted but must be of equal print quality andclarity. If it is not obvious, the top of the figureshould be indicated by an arrow on the back.

Each table should be printed on a separate page.Tables or figures reproduced from other sourcesmust be accompanied by permission from theauthors and publishers of the original publication.

Covering letter: Manuscripts should be submittedwith a covering letter stating:

• The article has not been published in whole orpart elsewhere. (Publication in part or inabstract does not preclude publication in theWorld Federation Journal of Critical Care).

• The article has not be submitted elsewhere.

• If the manuscript should be returned to theauthors in the event that it is not accepted forpublication.

• That clinical studies had been approved by theappropriate local institutional ethicscommittee following principles described inthe Declaration of Helsinki and its revisions.

• That the authors accept that Copyright in themanuscript will pass to the World FederationJournal of Critical Care when the manuscriptis accepted for publication.

Editorial review

Authors of manuscripts that are clearly unsuitablefor publication in Intensive Care World will beadvised as soon as possible and such rejection doesnot necessarily indicate any adverse opinion on thecontent. It is usual for manuscripts to be reviewedby members of the Editorial Board or others chosenfor their knowledge of the subject of themanuscript. Following this process papers may berejected, returned to the authors with reviewerscomments on the understanding they will bereconsidered if the issues raised can be answeredsatisfactorily, or accepted for publication. Somebias is exerted towards articles received fromcountries with limited local medical publishingopportunities.

The manuscript, tables, figures and covering lettershould be sent to:

Dr Geoffrey J. DobbEditor, World Federation Journal of Critical Carec/o Intensive Care UnitRoyal Perth HospitalGPO Box X2213Perth WA 6847 AustraliaFax: (61) 8 9224 3196E-mail: [email protected]

The Editor and publishers reserve the right to editmanuscripts for length, format, style and spellingbefore publication, and to determine the timing andpriority of articles submitted for publication.Transfer of Copyright is a condition of publication.Statements and opinions expressed by authors arenot necessarily those of the Editor, Editorial Boardor publishers. The Editor, Editorial Board andpublishers disclaim any responsibility or liability inrelation to all published material and do notguarantee or endorse any product or treatment thatis named or described.

February 2004 page 1


Inside this issue

President’s report page 2

Editorial page 4

Non-invasive ventilation in the Intensive Care Unit page 5

Monitoring graphic displays of pressure,volume and flow: the usefulness of ventilator waveforms page 8

Practical aspects of haemofiltration page 13

Fulminant hepatic failure in paediatric patients:results of orthotopic liver transplantation page 17

Over humidification: an under recognised problem? page 23

World Federation news page 27

World Federation Journal ofCritical Care

ISSN 1447-9664

EditorGeoffrey J Dobb

Royal Perth Hospital, GPO Box X2212Perth, WA 6847 Australia

Editorial BoardEditor Europe – G Park (UK)

Editor America – P Lumb (USA)GA Barker (Canada)

D Crippen (USA)L Gattinoni (Italy)

K Hillman (Australia)PK Jain (India)

W Knaus (India)W Kox (Germany)

DR Miranda (The Netherlands)JL Vincent (Belgium)

Editorial AssociatesLars Berggren

Jose BessoSatish Bhagwanjee

Guillermo Dominguez-CheritAntonio GallesioAntonio Gullo

Francisco J De LatorreJean-Roger Le Gall

Rui MorenoFernando PalizasShirish PrayagJun Takezawa

Renato GG TerziGed Williams

World Federation Journal of Critical Carewill be distributed to approximately 25,000

intensivists from over 90 countries.

Published byCambridge Publishing –

a division of Cambridge Media17 Northwood Street

West Leederville, WA 6007 AustraliaWebsite: www.cambridgemedia.com.au

Copy Editor: Ceridwen Clocherty

Graphic Designer: Gordon McDade

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World FederationJournal of Critical CareFebruary 2004

February 2004


President’s report

Philip Lumb

The World Federation of Societies of Intensive and CriticalCare Medicine (WFSICCM) was established at a time whenthe professional intensive care world was small and composed ofinternational colleagues facing similar clinical challenges in theabsence of the advanced technology, global communicationsand organ specific knowledge we enjoy today. The goal of theWorld Federation was to provide easy access to new informationand to share knowledge that would transcend national bordersand improve the care of critically ill patients in all situationsworldwide.

Today, the WFSICCM coordinates the affiliation between 48national society members. Each country is represented at theWFSICCM’s General Assembly meetings held every four yearsin association with its international congress. Although theGeneral Assembly meeting supports an important and usefulfunction by creating a unique forum in which internationalconcerns, ideas and initiatives can be discussed, the WorldFederation has not fulfilled its objective to provide an ongoingand self-sustaining international resource that stimulates andcodifies research initiatives, educational programmes,professional communication and development of standardisedoutcomes. These unmet objectives stimulated the currentCouncil to refocus the organisation’s attention on its coremission and created the impetus to position the WFSICCM asthe representative international body and coordinating centreof excellence for all critical and intensive care societies. This isan arrogant yet democratically achievable goal and, ifsuccessful, likely to supplement rather than compete withnational society initiatives.

The recent SARS epidemic has demonstrated that theinternational medical community has a greater commonpurpose than its political counterpart, and it is likely that theWFSICCM can create a readily available data repository forfuture efforts requiring international collaboration in criticalcare. In the current Pulmonary Perspectives, Judith Mackaywrites that,

... living with SARS was akin to living an Agatha Christie novel.You are invited to an isolated country home for dinner and among theguests there is a killer. You don’t know who or where this person is;

you can’t see, hear, smell or touch the killer, but if the finger is putupon you, you might be dead. This it was, living at the front linewith SARS 1.

The World Federation is in a position to help the internationalcritical care community become less isolated and more personal.The extent of interpersonal relationships could extend fromready electronic access to the most recent treatment protocolsto contact information so that diagnostic questions andtherapeutic options can be discussed openly and in real time.These should be developed within our organisation andcommunity. It is unreasonable to anticipate that a newstructure must be established whenever new illnesses threatenthe international community; it is irresponsible not to respondto the challenge of creating the resource network likely to meetthe international critical care community.

This challenge is reflected in an editorial comment in the abovereferenced text. Deborah Shure says, “Hopefully, the rapidgalvanization of the international community in both the public healthand research arenas will prevent an epidemic worse than the one thathas already occurred”. The Word Federation, with the help of itsinternational members, intends to become the interpersonalclearing house and information central that will help cliniciansfeel less isolated and connected to a community of expertopinion and experience.

Our members responded individually, transnationally andeffectively to the SARS challenge. The CDC and otherinternational organisations were effective in disseminatinginformation about therapeutic and isolation requirements, andmany of our members were involved in personalcommunication with international colleagues. The WorldFederation Council believes the presence of a central site forinternational critical care specific information will provideclinicians an additional and valuable resource in the face offuture challenges. The ability to access information when itbecomes available and to study its use post hoc would providean invaluable research tool that would demonstrate the ways inwhich medical information modifies practice in response tounexpected challenges.

The WFSICCM intends to establish a critical carecommunication and database resource on behalf of our membersthat will enhance the ability not only to respond to futurenational and international medical challenges, but also, andperhaps more importantly, to provide our members with aresearch and quality improvement tool that will validatetherapeutic interventions and modifications in real time. The



WFSICCM is the unique critical care organisation thatrepresents national societies equally and provides the forum inwhich a critical analysis of global critical care performance canbe assessed.

In order to realise our expectations, the WFSICCM islaunching its website (http://www.world-critical-care.com) andintroducing the World Federation Journal of Critical Care on 1October 2003. Headquartered in Great Britain, theorganisation is ably supported by a new secretarial infrastructureand business development professionals.

Despite these improvements to administrative support, memberinvolvement will be the most important determinant andmeasure of success. Different from a national society in whichvolunteerism is recognised and rewarded by increased visibilityand responsibility within the national corporate network,contribution to the WFSICCM is more difficult to stimulateand reward. The Executive and Council are selected asrepresentatives to the WFSICCM by their national societiesand elected by the General Assembly; subsequently, the newlyelected Council selects its officers for four-year terms. Notsurprisingly, a corporate identity and institutional memory aredifficult to create in this environment, and therein lays futureopportunity and challenge.

A website and opportunity to contribute to an internationallydistributed, peer reviewed journal provide new opportunities forindividuals to contribute to the vision of an internationallyresponsive critical care community. Individual members ofrepresentative national societies may be unaware that they areparticipants in the World Federation; this benefit accruesthrough a $1 annual dues capitation fee paid by their homeorganisation.

Council is sponsoring the WFSICCM Academy that will permitphysician members to develop a personal learning profile onnew therapeutic agents. Tutorials leading to WFSICCMcertification will be developed by recognised clinical experts.Although these learning modules cannot substitute forindividual experience, nonetheless, before the introduction ofany new agent, it is helpful for practitioners to have a frankdiscussion of clinical subtleties that may improve early efficacy.The tutorial format will be a clinical expert discussion thatshould prove beneficial to clinicians who wish to supplementtheir knowledge prior to prescription. Following a post courseevaluation and examination, a certificate of completion will beissued to successful participants.

On a lesser scale but equally informative is the recentlydistributed World Federation Calendar. In 2003, clinicalinformation about the use of a new pharmacologic agent ispresented in journal review format; in 2004, clinical ‘pearls’ ofinformation from internationally recognised intensivists will be

featured. The international scope and photographic excellenceof the Secretary-General, Dr. Gilbert Park, must be recognisedand applauded in this contribution.

Increased national and individual ownership for the WorldFederation’s goals will develop from greater familiarity with theorganisation and its administration. In addition to theeducational and communication facilities discussed previously,the website will also provide important information aboutorganisational structure, national membership, key contactinformation and critical links to information sources hosted bysociety members. A calendar of international conferences andspecial events will be updated regularly; additional informationwill be solicited from individual members.

A key component of the World Federation will be its utility toindividual members; feedback and critical reviews frommembers will be encouraged. Research initiatives areincreasingly costly with patient identity and privacy rulesfurther complicating transfer of information. A great deal canbe accomplished with appropriately designed questionnairesthat cross national and regional boundaries; the WFSICCM canprovide members the resources necessary to initiateappropriately powered and controlled studies. Further ideas willbe developed through member participation and feedback.

Several questions may remain: Is there a role for a world focusedintensive care organisation that will depend for its success uponsupport from national critical care societies, volunteerism fromindividual members, contributions from industry, consistency ofproduction and dissemination of new information in a timely,dependable and credible manner? Are there benefits to begained from a world organisation that cannot be provided bynational societies with international connections? Is the worldcommunity likely to respond favourably to information from anon-traditional source?

Despite these and other important concerns, the values of aworld focus and partnership among critical care professionalscannot be denied. There is intense competition amongnational societies to host the World Federation Congresses, andthe participation of internationally recognised critical carephysicians in local educational events is desired. Fiscalconstraints and travel restrictions often militate against greaterparticipation in many events, and the World Federation is theunique resource that can assemble the world’s leading cliniciansin an apolitical environment that fosters education, researchand the dissemination of new information. The mission is clear;the infrastructure is established; the vision is evolving; withinternational participation and support, the outcome is assured.

References1. Mackay J. Pulmonary Perspectives, September 2003; Volume 20, Issue 3.

February 2004


EditorialWelcome back!

Geoffrey J Dobb

The World Federation is delighted to be back with a publicationwhich is made available to all members of Societies of intensiveand critical care medicine affiliated to the Federation. There isnothing to be gained by recounting the events that resulted inus being unable to publish and distribute Intensive Care World asour publication was previously known. This will have beenfamiliar to most working in the worldwide community ofintensive and critical care medicine. To judge from the manyletters and messages received when it failed to arrive with theaccustomed regularity, it was missed by many.

The members of the Council of the World Federation areundoubtedly sadder and wiser as result of the challenges wehave faced over the last couple of years. However, we were ableto publish an issue of our newly named World Federation Journal

of Critical Care to coincide with the World Federation’sCongress in Sydney.

Returning now to regular publication has proved to be asignificant task. The joy of finally overcoming the legal,contractural and logistic issues associated with re-establishing aregular publication will be understood by all those who havebeen involved with their national Society’s publications. Wenow look forward to re-establishing relationships with ourreaders, authors and advertisers. Instructions to authors areincluded with this issue and we welcome appropriatecontributions.

The new publishers, Cambridge Media, have a strong trackrecord in publication and a portfolio that includesinternationally distributed medical and nursing journals. Theirsupport during the start-up phase has been invaluable. I am alsograteful to the members of the Editorial Board and the Councilof the World Federation for their support through a difficulttime.

Communication is the ‘glue’ that helps to maintain the identityof the World Federation. With the re-established website andthe journal, the World Federation is in better shape than it hasbeen for some time. We look forward to maintaining themomentum. With the next Congress to be held in Argentina

in 2005, the foundations of the Federation are looking betterthan ever. As critical care develops around the world, we lookforward to having even more societies join the WorldFederation family.

Stop pressAs the copy for this issue was finalised, the Council of theWorld Federation of Societies of Intensive and Critical CareMedicine recommended that the 2009 World FederationCongress be held in Italy. Several excellent bids to host the2009 Congress were received, making this a most difficultdecision. Final details have still to be agreed with the hostsocieties, but further information should be available for ournext issue.

Congress OfficeAna Juan Congresos

Sarmiento 1562, 40F (C1042ABD)Buenos Aires, Argentina

Tel: (54) 11 4381 1777Fax: (54) 11 4382 6703

E-mail (registration): [email protected] (abstracts): [email protected] (scientific programme): [email protected] (exhibition): [email protected] (hotels): [email protected]

SATISarmiento 2046 108 C 1044AAFBuenos Aires, Argentina

E-mail: [email protected]: www.sati.org.ar

9th Congress of the World Federation of Societies of

Intensive and Critical Care Medicine

27-31 August 2005

Buenos Aires, Argentina



Non-invasive ventilation in the Intensive Care Unit

IntroductionNon-invasive ventilation (NIV) is usually provided throughbilevel pressure supported ventilatory assistance deliveredwithout endotracheal intubation. Modern highly sophisticatedpurpose built bilevel positive airway pressure (BIPAP) devicesnow incorporate features such as titratable inspired oxygenfraction, leak compensation and adjustable positive end-expiratory pressure (PEEP) and pressure support (PS) withspontaneous-timed modes of ventilation (e.g. ‘Vision’ BiPAP).Continuous positive airway pressure (CPAP) is commonlydelivered using a similar non-invasive patient interface with amask. A BIPAP machine set to end-expiratory positive airwaypressure (EPAP) mode can be used as the pressure-generatingunit, though more simple devices are also available.

Kannan 1 recently reviewed the indications, mechanics andpracticalities of NIV in the Intensive Care Unit (ICU) forIntensive Care World. It is timely to highlight the evidenceunderlying some aspects of the use of NIV in the ICU and, inparticular:

• The use of CPAP for cardiogenic pulmonary oedema.

• The role of CPAP in avoiding re-intubation for severe non-hypercapnic hypoxaemia after surgery.

• BIPAP for acute respiratory failure in patients with chronicobstructive pulmonary disease (COPD) and other lungdisease.

• NIV support during diagnostic flexible bronchoscopy inpatients with severe hypoxaemia.

• BIPAP as a weaning strategy.

• BIPAP for home ventilation.

CPAP for cardiogenic pulmonary oedema The first description of CPAP was by Poulton 2 in 1936. He usedan ordinary vacuum cleaner in reverse-mode to blow air underpressure into the mouth of a patient with pulmonary oedema.Since then three randomised trials have investigated CPAP forcardiogenic pulmonary oedema 3-5. Bersten et al. 3 demonstratedthat respiratory rate, arterial pH, paCO2 and PaO2/FiO2 allimproved more rapidly in the patients receiving CPAP than thosereceiving usual medical care. The advantage was lost at 24 hoursbut the frequency of endotracheal intubation and duration ofhospital stay were less in the CPAP-treated group (zero vs 35%,p=0.005; mean difference 1.5 days respectively).

Ventilation and vital signs improved more rapidly using BIPAPwhen compared to CPAP in patients with cardiogenicpulmonary oedema in a small prospective randomisedcontrolled trial by Mehta et al. 6. The study stopped earlybecause the frequency of myocardial infarcts was significantlyhigher in the BIPAP group. This difference was probablyexplained by the lower frequency of chest pain in the CPAPgroup at recruitment.

CPAP is the cheaper and simpler mode of NIV and no clinicallyimportant advantages such as duration of hospital stay, need forendotracheal intubation or mortality have been demonstratedwith BIPAP. Therefore, CPAP is currently preferred tosupplement usual medical treatment in patients with acutecardiogenic pulmonary oedema.

The role of CPAP in avoiding re-intubation forsevere non-hypercapnic hypoxaemia after surgeryCPAP can reduce the need for reintubation in post-operativepatients with severe non-hypercapnic hypoxaemia. In 20consecutive patients who had undergone thoracic and/orabdominal surgery and met the hypoxaemia criterion(PaO2/FiO2<80) after extubation, 8-10cm H2O nasal CPAP (withFiO2 titration) overcame respiratory failure caused by atelectasisand/or left heart failure, so reintubation was avoided 7.

BIPAP for acute respiratory failure in patientswith COPD and other lung diseasesMeduri et al. 8 showed the effect on minute volume, tidal volumeand PaO2/FiO2 is similar whether mechanical ventilation isapplied using a face-mask or using endotracheal intubation. Theystudied 18 patients with type 2 acute respiratory failuremechanically ventilated for a mean of 25 hours and concludedface-mask mechanical ventilation is a viable alternative toendotracheal intubation for short-term (1-4 days) support.

Subsequently, eight randomised controlled trials 9-16 haveconfirmed the effectiveness of non-invasive positive pressureventilation for acute respiratory failure and only one clinical trialhas produced a negative result 17. The pooled results from thesestudies give an odds ratio of 0.22 (95% confidence interval 0.09-0.54) for a benefit of NIV compared to standard medicaltreatment in respect to the hospital mortality of COPD patientswith hypercapnic acute respiratory failure. That is, level 1evidence (Grade A recommendation) for its use 18.

The study by Bott et al. 10 included 60 COPD patients with acuterespiratory failure managed in a general ward. It is particularlyrelevant to patients with severe COPD not thought appropriatefor endotracheal intubation. The pH, pCO2 and dyspnoeascores were significantly better with a clinically relevant

Gregory McGrath MB BS FRACP FJFICMGeoffrey J Dobb BSc MB MRCP FRCA FANZCA FJFICMIntensive Care Unit, Royal Perth Hospital, Perth, WA, Australia

February 2004


improvement in the NIV group and a trend to reducedmortality (three vs nine deaths).

In another study in 31 patients, most with COPD, the need fortracheal intubation during the first 48 hours was significantlygreater in patients only receiving standard treatment comparedwith those also provided with NIV 13 (11 vs five patients,p<0.05). Duration of hospital stay and mortality were similarand there was no difference in the combined respiratory-therapist and nursing time spent per 8 hour shift by the bedsidebetween the patient groups (mean: NIV 200 minutes, standardtreatment 180 minutes).

Brochard’s group 12 also investigated the effect of NIV in COPDpatients in the ICU on the need for endotracheal intubation,randomising NIV with 20 cmH2O PS and zero PEEP againststandard treatment (Table 1). The NIV group had the betteroverall outcomes.

Wysocki et al. 14, in a study which excluded patients withCOPD, randomised 41 patients with acute respiratory failure toeither NIV (n=21) or standard treatment (n=20). A post-hocsubgroup analysis of the patients who were hypercapnic(pCO2>45mmHg) suggested the outcome was improved interms of the need for endotracheal intubation, duration ofhospital stay and mortality in the group receiving NIV whowere hypercapnic (absolute reduction 64%, 29% and 57%,respectively).

Martin et al. 16 also found the need for endotracheal intubationwas significantly less with NIV (6.4 intubations vs 21.3 per 100ICU bed-days; p=0.002) in patients with various aetiologies foracute respiratory failure, and the findings of Daskalopoulou et al.11 were similar (odds ratio for intubation in the NIV group 0.09;95% CI 0.00-4.38).

In a recently published comparison 19 of intermittent NIV withstandard treatment, which included supplemental oxygen butno ventilatory support in 52 immunocompromised patients withpulmonary infiltrates and fever, the results again favoured NIV.Fewer patients in the NIV group needed endotrachealintubation (12 vs 20, p=0.03), had serious complications (13 vs21, p=0.02) or died in hospital (13 vs 21, p=0.02).

When compared directly against conventional mechanicalventilation 15, NIV appears equally effective in improvingoxygenation but associated with fewer complications. In arandomised study of 64 patients, predominantly with type 1

acute respiratory failure (PaO2/FiO2<200mmHg), managementincluded either conventional mechanical ventilation or NIV(with a strategy to optimise PS to give tidal volumes 7-10 ml/kgand optimise PEEP to allow FiO2<0.6). Only 6% failed totolerate NIV, and in the NIV group 31% progressed to requiringendotracheal intubation.

The overall complication rate was 38% for the NIV group and66% for conventional ventilation (on intention to treat,p=0.02). The most frequent complications were sepsis frompneumonia and sinusitis.

The level 2 evidence available supports a grade Brecommendation for use of NIV in non-COPD causes of acuterespiratory failure.

NIV support for diagnostic flexiblebronchoscopy in severe hypoxaemiaHigh-risk patients who would otherwise need endotrachealintubation and mechanical ventilation to allow diagnosticflexible fibreoptic bronchoscopy and overcome concern aboutinducing hypoxaemia may be considered for awake-sedatedbronchoscopy through a BIPAP interface. Antonelli et al. 20

performed bronchoalveolar lavage (BAL) on eightimmunosuppressed patients with pneumonia and acuterespiratory failure (PaO2/FiO2<100mmHg) through a Bard facemask with t-seal adaptor connected to a ventilator in pressurecontrol mode ventilation (pressure 17cm H2O, PEEP 4cm H2O).No patient required endotracheal intubation, none developedhypercapnia or hypoxaemia and all had diagnostic BALsuccessfully performed.

A novel CPAP face-mask was used by Maitre et al. 21 in theirrandomised controlled trial in 30 hypoxaemic patients(PaO2/FiO2<300mmHg) who required diagnostic fibreopticbronchoscopy. In the group randomised to receive oxygen onlyseven out of 15 required mechanical ventilation afterbronchoscopy whereas only one of those performed duringCPAP developed ventilatory failure (intention to treat p<0.03)

BIPAP as a weaning strategyIntubated patients with COPD and type 2 acute respiratoryfailure can be difficult to wean from ventilatory support andmay need prolonged endotracheal intubation or tracheostomy.Nava and others, in a multicentre randomised trial 22, attemptedweaning at 48 hours in a group intubated on admission tohospital for severe hypercapnic respiratory failure.

Those who could not be extubated were randomised into twogroups. One group (n=25) was extubated to NIV and the other(n=25) continued with PS through the endotracheal tube.Over the next 60 days, 88% of the NIV group were weanedcompared to 68% of the group who remained intubated(p=0.02). The duration of hospital stay was less in the NIVgroup at 15.1+/-5.4 days compared with 24.0+/-13.7 days(p=0.005), and 60 day survival was significantly better (92% vs72% p=0.002).

NIV (n=43) Standard (n=42) p

Endotracheal intubation 26% 74% <0.001

Duration of stay 23 days 35 days =0.005

Mortality 9% 29% =0.02

Table 1. Outcome in 85 patients randomised to receive (NIV) or standard treatmentalone 12.



‘Partial weaning’ from invasive to non-invasive ventilation maybe sufficient to allow step-down of a patient to a lesser intensitycare facility or even to home ventilation. One third of patientswho failed conventional weaning from mechanical ventilationin a study by Scheinhorn 23 were successfully withdrawn fromventilator dependence using BIPAP (n=34). Home mechanicalventilation was established in 75/109 patients.

BIPAP for home ventilationPatients who need 24 hour ventilatory support at home usuallyhave a tracheostomy but, in selected cases, a non-invasiveinterface may be sufficient, especially if this is combined withsupplemental oxygen, glossopharyngeal breathing, apneumobelt, negative pressure ventilation devices ordiaphragmatic pacing to allow daytime freedom from the NIVinterface for meals, washing etc 24.

Such methods can be useful for selected patients withobstructive or interstitial lung disease as a bridge to lungtransplantation, allowing care away from the ICU. Quality oflife issues can detract from the merit of home BIPAP for patientswith end-stage lung disease who are not candidates for a lungtransplant. It may, however, still be worthwhile on a case bycase basis with appropriate community supports.

Other typical indications for home ventilation in which NIVmay have a role include neuromuscular and chest wall diseasesand central hypoventilation syndromes. After recovery from areversible exacerbation of their disease, such patients may bedischarged back home from the ICU 25.

ConclusionEvidence supports the role of non-invasive ventilation in theICU treatment of patients with acute respiratory failure causedby acute pulmonary oedema, post-operative hypoxaemia,hypercapnic exacerbations of COPD, non-COPD pulmonarycauses of acute respiratory failure, and also for assistingdiagnostic bronchoscopy in high risk patients. It may assist inweaning patients from ventilator dependence and make itpossible to discharge from the ICU patients dependent onchronic ventilatory support, ultimately to their home or as abridge to lung transplantation.

References1. Kannan S. Non-invasive ventilation. Intensive Care World 2000;

16(1):20-25.

2. Poulton PE. Left-sided heart failure with pulmonary oedema: its treatmentwith the “pulmonary plus pressure machine”. Lancet 1936; 2:981-983.

3. Bersten AD, Holt AW, Vedig AE, Skowronski GA & Baggoley CJ.Treatment of severe cardiogenic pulmonary oedema with continuouspositive airway pressure delivered by face mask. N Engl J Med 1991;325:1825-1830.

4. Lin M, Yang Y, Chiang H et al. Reappraisal of continuous positive airwaypressure therapy in acute cardiogenic pulmonary oedema: short term resultsand long term follow up. Chest 1995; 107:1379-1386.

5. Rasanen J, Heikklua J, Downs J et al. Continuous positive airway pressureby face mask in acute cardiogenic pulmonary oedema. Am J Cardiol 1985;55:296-300.

6. Mehta S, Jay GD, Woolard RH et al. Randomized prospective trial of bilevelverses continuous positive airway pressure in acute pulmonary edema. CritCare Med 1998; 25:620-628.

7. Kindgen-Milles D, Buhl R, Gabriel A et al. Nasal continuous positiveairway pressure: a method to avoid endotracheal reintubation inpostoperative high-risk patients with severe nonhypercapnic oxygenationfailure. Chest 2000; 117:1106-1111.

8. Meduri GU, Abou-Shala N, Fox RC et al. Noninvasive face maskmechanical ventilation in patients with acute hypercapnic respiratoryfailure. Chest 1991; 100:445-454.

9. Ahmed AH, Fenwick L, Angus RM et al. Nasal ventilation verses doxapramin the treatment of type II respiratory failure complicating chronic airflowobstruction. Thorax 1992; 47:A858.

10. Bott J, Carroll MP, Conway A et al. Randomised controlled trial of nasalventilation in acute ventilatory failure due to chronic obstructive airwaysdisease. Lancet 1993; 341:1555-1557.

11. Daskalopoulou E, Teara V, Fekete V et al. Treatment of acute respiratoryfailure in COPD patients with positive airway pressure via nasal mask(NPPV). Chest 1993; 103:S271.

12. Brochard L, Mancebo J, Wysocki M et al. Noninvasive ventilation for acuteexacerbations of chronic obstructive pulmonary disease. N Engl J Med1995; 333:817-822.

13. Kramer N, Meyer TJ, Meharg J et al. Randomized prospective trial ofnoninvasive positive pressure ventilation in acute respiratory failure. Am JRespir Crit Care Med 1995; 151:1799-1806.

14. Wysocki M, Tric L, Wolff MA et al. Noninvasive pressure supportventilation in patients with acute respiratory failure: a randomizedcomparison with conventional therapy. Chest 1995; 107:761-768.

15. Antonelli M, Conti G, Rocco M et al. A comparison of noninvasivepositive pressure ventilation and conventional mechanical ventilation inpatients with acute respiratory failure. N Engl J Med 1998; 339:429-435.

16. Martin TJ, Hovis JD, Costantino JP et al. A randomized prospectiveevaluation of noninvasive ventilation for acute respiratory failure. Am JRespir Crit Care Med 2000; 161:807-813.

17. Barbe F, Togores B, Rubi M et al. Noninvasive ventilatory support does notfacilitate recovery from acute respiratory failure in chronic obstructivepulmonary disease. Eur Respir J 1996; 9:1940-1945.

18. Keenan SP & Brake D. An evidence-based approach to noninvasiveventilation in acute respiratory failure. Crit Care Clin 1998; 14:359-372.

19. Hilberg, Gruson D, Vasgas F et al. Noninvasive ventilation inimmunosuppressed patients with pulmonary infiltrates, fever and acuterespiratory failure. N Engl J Med 2001; 344:481-487.

20. Antonelli M, Conti G, Riccioni L et al. Noninvasive positive-pressureventilation via face mask during bronchoscopy with BAL in high-riskhypoxemic patients. Chest 1996; 110:724-728.

21. Maitre B, Jaber S, Maggiore S et al. Continuous positive airway pressureduring fibreoptic bronchoscopy in hypoxemic patients: randomized double-blind study using a new device. Am J Respir Crit Care Med 2000; 162:1063-1067.

22. Nava S, Ambrosino N, Clini E et al. Noninvasive mechanical ventilationin the weaning of patients with respiratory failure due to chronic obstructivepulmonary disease. A randomized controlled trial. Ann Intern Med 1998;128:721-728.

23. Scheinhorn DJ, Artinian BM & Catlin JL. Weaning from prolongedmechanical ventilation. The experience at a regional weaning centre.Chest 1994; 105:534-539.

24. Simonds AK. From intensive care unit to home discharge in the 24 hventilator-dependent patient. Eur Respir Mon 1998; 8:364-379.

25. Hill NS & Goldberg AI. Mechanical ventilation beyond the intensive careunit. Chest 1998; 113(Suppl):289S-344S.

February 2004


IntroductionMonitoring respiratory mechanics in the mechanically

ventilated patient provides the clinician with insight into the

current state of lung function. Traditional monitoring of

respiratory mechanics includes the measurement of pressure,

volume and flow during both dynamic and passive inflation of

the lung. Adding inspiratory and expiratory pauses to lung

inflation allows the clinician to measure static and dynamic

lung compliance, inspiratory and expiratory resistance and

intrinsic positive end-expiratory pressure (PEEP). Placement of

an oesophageal balloon allows more sophisticated calculations

including the work of breathing and determination of chest wall

compliance 1-3.

In the last decade, mechanical ventilators have provided

clinicians with a new type of monitoring, commonly known as

ventilator graphics 4. Ventilator graphics include pressure-time,

flow-time and volume-time waveforms, and pressure-volume

(PV) and flow-volume loops. Ventilator graphics are less

concerned with calculation of physiologic parameters, but

rather provide the bedside practitioner with a real time display

of patient-ventilator interaction. This type of monitoring

requires pattern recognition, similar to reading

electrocardiogram rhythms.

The following is not a primer on monitoring respiratory

mechanics but provides examples of the usefulness of

monitoring ventilator graphics. It is important for clinicians to

understand respiratory mechanics, ventilator operation and

pathophysiology in order to realise the full value of ventilator

graphics. However, bedside clinicians can use ventilator

graphics to evaluate patient-ventilator interactions without

being a researcher or physiologist. Common waveforms that

depict clinical problems are presented.

Monitoring graphic displays of pressure, volume and flow:the usefulness of ventilator waveforms

Richard D Branson BA, RRTAssociate Professor of Surgery

Kenneth Davis Jr. MDAssociate Professor of Surgery and AnesthesiaAssistant Dean of Medical Education

Robert S Campbell RRTSenior Research Associate

University of Cincinnati, Department of SurgeryCincinnati, Ohio, USA

The scalars – pressure, volume and flow vs timeRepresentations of pressure, volume and flow vs time can be

useful in evaluating ventilator function as well as assessing

patient-ventilator interaction and lung mechanics. In many

instances, findings can be based on a single parameter.

However, with experience, the information derived from the

pressure and flow waveform viewed simultaneously aids in

identifying problems. The volume waveform is typically the

least useful parameter, except for leak detection.

Pressure

During volume control ventilation (VCV) the airway pressure

waveform results from the interaction of ventilator flow pattern

and flow rate together with lung impedance. Patient effort can

also alter the shape of the pressure waveform during both

inspiration and expiration. Observation of the pressure

waveform can be helpful in determining ventilator operation

and explaining changes seen during changes in ventilator

settings or mode.

The use of a decelerating flow pattern during ventilatory support

of patients with acute respiratory distress syndrome (ARDS) has

been shown to improve oxygenation in several investigations 5-7.

This improvement in oxygenation can be attributed to the

increase in mean airway pressure resulting from the effects of

flow pattern on the airway pressure pattern 8. Interestingly,

mechanical ventilators use two techniques during a change in

flow pattern from constant flow to decelerating flow.

The first method maintains peak flow constant, therefore

requiring an increase in inspiratory time to maintain the same

tidal volume (Figure 1a). The Puritan-Bennett 7200 uses this

technique. The second method maintains inspiratory time

constant while increasing peak flow by 150% (Figure 1b).

Further complicating matters, various ventilators utilise a 50%

decelerating flow, which simply means flow at end inspiration is

50% of the peak flow. These various flow patterns result in

significantly different airway pressure patterns, mean and peak

airway pressures, helping to explain the variable results of

research regarding flow patterns.

During assist/control ventilation in the VCV mode, the shape

of the airway pressure waveform can alert the clinician to flow

dysynchrony. During volume ventilation, if patient demand

exceeds set flow, the work of breathing is markedly increased 9, 10.



This can be identified by the inconsistent shape of the pressure

waveform. Commonly, the pressure waveform appears

‘scalloped’, as patient demand exceeds ventilator output.

Delivery of a passive breath (by activating a manual breath) and

comparison of the passive breath to patient triggered breaths is

particularly helpful in evaluating this common clinical problem

(Figure 2).

Pressure support ventilation (PSV) is a mode of mechanical

ventilation heralded by proponents as providing optimal patient

comfort and reducing patient ventilator dysynchrony 11, 12. The

rapid initial flow during PSV helps alleviate the flow

dysynchrony seen in Figure 3.

However, PSV can result in cycle dysynchrony. Cycle

dysynchrony occurs when the patient inspiratory timing and the

ventilator’s PSV algorithm clash 13. This phenomenon is seen

when the patient actively exhales to end the breath. All

ventilators use flow as the cycle variable for PSV. However,

every ventilator uses a different level of flow (a percentage of

peak flow or a preset terminal flow) and also incorporates

secondary cycle criteria consisting of pressure and time 14.

Typically the longest inspiratory time allowed during PSV is 3

seconds and the maximum pressure allowed is controlled by the

high pressure alarm setting or is pre-set.

Figure 2. Pressure and flow waveforms demonstrating flow dysynchrony duringvolume controlled ventilation. The first breath is an unassisted breath. Allother breaths demonstrate the effects of patient demand on the airwaypressure waveform. Comparison of the unassisted breath to the assistedbreaths improves detection of flow dysynchrony.

Figure 4. Typical volume waveform seen in the presence of an airleak. Note thatvolume does not return to baseline during exhalation (arrow).

Figure 3. PSV using the Puritan-Bennett 7200. Normal flow cycling criteria is5L/min. In this example the breath is cycled at a flow of 35L/min. Activeexhalation by the patient causes the breaths to be pressure cycled.

Figure 1. A: Change from constant (square) flow to decelerating flow waveformusing a ventilator which maintains the peak flow constant resulting in anincrease in inspiratory time. B: Change from constant (square) flow to fulldecelerating flow waveform (peak flow to 0L/min) and a 50% deceleratingflow waveform (peak flow to 50% of peak flow) using a ventilator whichmaintains inspiratory time constant resulting in an increase in peakinspiratory flow.

In our experience, ventilators using later flow cycle criteria

(Puritan Bennett 7200 – 5L/min and Siemens 300 – 5% of peak

flow) provide an inspiratory time longer than the patient’s

neural timing. The result is shown in Figure 4, where

inspiration should end at 5L/min (PB 7200), but is pressure

cycled instead. Newer ventilators with adjustable flow cycle

variables may help alleviate this problem.

February 2004


Volume

The volume-time waveform takes its shape from the inspiratory

flow pattern and, aside from verifying inspired and expired tidal

volumes, is not particularly helpful. One instance where the

volume-time waveform does provide assistance, is in the face of

a leak. Leaks in the circuit or within the patient (incompetent

endotracheal tube cuff, bronchopleural cutaneous fistula) may

all cause alterations in the volume waveform.

In these cases, the expired limb of the volume waveform fails to

return to zero. Most ventilator graphic packages will reset the

volume waveform to zero before delivery of the next breath.

With the volume scale at an appropriate resolution, the volume

of gas ‘lost’ to the leak can be determined. This allows the

clinician to alter ventilator settings to reduce the leak, if

desired. Figure 4 shows the effects of a leak on the volume and

flow waveforms. By inspecting the flow waveform, the leak (in

litres per minute) can be determined as well. This information

can be used to set the continuous flow in flow triggering systems

to assist in compensating for the leak.

Flow

The inspiratory and expiratory flow waveforms aid the clinician

in evaluating lung compliance and in detecting the presence of

PEEP 1, 2, 15, 16. During volume control, the flow waveform is set

by the operator. However, during pressure control ventilation,

the decelerating inspiratory flow pattern is effected by the

impedance of the respiratory system. As impedance increases,

the slope of the deceleration is steeper (Figure 5).

When lung impedance is decreased, inspiratory flow may

remain >0L/min at end inspiration. This is commonly seen

during use of pressure control ventilation for the patient with

chronic obstructive pulmonary (COPD) disease. This

interaction between inspiratory flow and impedance can guide

the clinician in setting the inspiratory time during pressure

control ventilation for ARDS. If inspiratory flow remains

>0L/min, inspiratory time can be lengthened until flow=0L/min

or a short inspiratory pause is identified (Figure 6). This

increase in inspiratory time allows an increase in tidal volume

and the possibility of reducing peak inspiratory pressure.

The expiratory flow-time waveform alerts the caregiver to the

presence of PEEP 2, 15, 16. When expiratory flow fails to return to

0L/min, before delivery of the succeeding breath, air trapping

and PEEP result (Figure 7). This is a common finding during

assist-control ventilation of the patient with COPD or may

result during the use of pressure control inverse ratio

ventilation. In the former case, the effects of PEEP reduce the

patient’s ability to trigger the ventilator, complicate

Figure 5. Changes in the flow waveform during pressure control ventilation as lungcompliance is reduced. Note that the angle of deceleration increases and aninspiratory pause is produced as compliance diminishes.

Figure 8. PEEP created during pressure control inverse ratio ventilation. Theexpiratory pause and increase in pressure (arrow) depicts the total PEEP.

Figure 6. The effects of lengthening inspiratory time during pressure controlventilation. The first breath demonstrates flow >0L/min at end inspiration(arrow). In the second breath, inspiratory time is lengthened until endinspiratory flow =0L/min (double arrow). This resulted in an increase intidal volume from 520mL to 590mL.

Figure 7. Classic appearance of the expiratory flow waveform (arrows) duringPEEP. The failure of expiratory flow to return to 0L/min prior to deliveryof the next breath detects PEEP, but cannot determine it quantitatively.



haemodynamic measurements and increase the risk of

barotrauma 17, 18. When PEEP is intentionally created during

inverse ratio ventilation, monitoring can be facilitated by

graphic display of the expiratory hold manoeuvre (Figure 8) 19, 20.

PV loop

The PV curve has received considerable attention recently as a

method of determining the appropriate PEEP setting during

ARDS 21-24. However, the dynamic PV curve obtained from the

ventilators graphic display cannot provide this information

under normal conditions. This is particularly true when a

pressure-limited breath is used. In order for the PV curve to be

used for determination of the lower inflection point, the

following conditions must be met 23:

• No patient respiratory activity (typically requires sedation

and short term paralysis).

• The patient/ventilator system must be leak free (typically

the endotracheal tube cuff must be inflated higher than

required for normal ventilation).

• Ventilator settings should include: constant flow, volume

ventilation; flow <15L/min; 0cm H2O PEEP. A high

pressure alarm setting should also be adjusted to prevent

lung overdistension.

• Before measurement, the lung volume should be allowed to

reach functional residual capacity (this usually requires a

period of 5-10 seconds at 0 PEEP).

When the patient is inactive and ventilator set appropriately,

determination of both the lower and upper inflection points of

the respiratory system is possible. The role of the PV curve in

preventing ventilator induced lung injury, setting PEEP, and

preventing alveolar overdistension is a topic of intense scrutiny25-27. Once the PV curve has been created and inflection points

determined, clinicians must decide the appropriate application

of this information.

Figure 9 depicts the measurement of the PV curve using the

slow flow technique, with inflection points identified. It

should be remembered that in some instances (late ARDS,

chest wall restriction) that inflection points may not be

identifiable.

During VCV, overdistension can commonly be identified by

evaluating the PV curve. When overdistension is present, the

PV curve shifts to the right towards end inspiration, creating a

‘beak’ (large pressure change with small volume change). This

is shown in Figure 10. Observation of this type of pattern

during VCV warrants a reduction in set tidal volume or change

to pressure control ventilation.

Figure 9. Slow flow technique for measuring the PV curve in ARDS. This PV curvedemonstrates a lower inflection point (arrow), but not an upper inflectionpoint.

Figure 10. Characteristic shape of the PV curve during volume ventilationdemonstrating overdistension (arrow). This is indicative of the upperinflection point and is associated with alveolar overdistension.

Figure 11. Flow volume curves, before (A) and after (B) bronchodilator therapy in amechanically ventilated patient with chronic obstructive pulmonary disease.Note the increase in peak expiratory flow and the reduction in flowlimitation towards end exhalation.

February 2004


Flow-volume loop

Flow volume loops are most often used to evaluate expiratory

airflow obstruction, particularly when viewed before and after

bronchodilator administration. Figure 11 demonstrates the

flow-volume curve before bronchodilator administration and a

second curve determined 30 minutes after four puffs of albuterol

from a metered dose inhaler in the ventilator circuit. It is not

necessary to measure expiratory resistance to evaluate the

success of bronchodilator administration in this instance 28-30.

Simple visual observation of the flow-volume loop is sufficient.

These examples represent some of the common uses of

ventilator graphics. An understanding of physiology,

pathophysiology and ventilator operation is necessary to use

graphics to the fullest extent. In our opinion, ventilator

graphics are invaluable for monitoring patient-ventilator

interaction.

References1. Truwit JD & Marini JJ. Evaluation of thoracic mechanics in the ventilated

patient. Part I: Primary measurements. J Crit Care 1988; 3:133-150.

2. Ranieri VM, Grasso S, Fiore T et al. Auto-positive end-expiratory pressureand dynamic hyperinflation. Clin Chest Med 1996; 17:379-394.

3. Truwit JD & Marini JJ. Evaluation of thoracic mechanics in the ventilatedpatient. Part II: applied mechanics. J Crit Care 1988; 3:199-213.

4. Branson RD & Hess DR. Bedside monitoring of respiratory mechanics. In:Branson RD, Hess DR & Chatburn RL. Respiratory Care Equipment (2nded). Lippincott, Williams & Wilkins. Philadelphia PA 1999 p.303-324.

5. Davis Jr K, Branson RD, Campbell RS & Porembka DT. Comparison ofvolume control and pressure control ventilation: Is flow waveform thedifference? J Trauma 1996; 41:808-814.

6. Al-Saady N & Bennett ED. Decelerating inspiratory flow waveformimproves lung mechanics and gas exchange in patients on intermittentpositive pressure ventilation. Intensive Care Med 1987; 11:68.

7. Rappaport SH, Shpiner R, Yoshihara G et al. Randomized, prospective trialof pressure-limited versus volume-controlled ventilation in severerespiratory failure. Crit Care Med 1994; 22:2.

8. Marini JJ & Ravenscraft SA. Mean airway pressure: physiologicdeterminants and measurements. Crit Care Med 1992; 20:1461-1472.

9. Hubmayr RD. Setting the ventilator. In: Tobin MJ (Ed). Principles andPractice of Mechanical Ventilation. New York: McGraw Hill, 1994.

10. Marini JJ, Rodriquez RM & Lamb V. Bedside estimation of work ofbreathing during mechanical ventilation. Chest 1986; 89:56-63.

11. MacIntyre NR. Respiratory function during pressure support ventilation.Chest 1986; 89:677-683.

12. Brochard l, Pluskwa F & LeMaire F. Improved efficacy of spontaneousbreathing during inspiratory pressure support. Am Rev Respir Dis 1987;136:411-415.

13. Branson RD & Campbell RS. Pressure support ventilation, patient-ventilator synchrony and ventilator algorithms. Respiratory Care 1998;43:1045-1047.

14. Campbell RS & Branson RD. Ventilatory support for the 90s: Pressure

support ventilation. Respir Care 1993; 38:526-537.

15. Gottfried SB, Reissman H & Ranieri VM. A simple method for the

measurement of intrinsic positive end-expiratory pressure during controlled

and assisted modes of mechanical ventilation. Crit Care Med 1992; 20:621-

629.

16. Rossi A, Gottfried SB, Zocchi L et al. Measurement of static compliance of

the total respiratory system in patients with acute respiratory failure during

mechanical ventilation. The effect of intrinsic positive end-expiratory

pressure. Am Rev Respir Dis 1985; 131:672-677.

17. Jubran A, Van de Graaff WB & Tobin MJ. Variability of patient-ventilator

interaction with pressure support ventilation in patients with chronic

obstructive pulmonary disease. Am J Respir Crit Care Med 1995; 152:129-

136.

18. Smith TC & Marini JS. Impact of PEEP on lung mechanics and work of

breathing in severe airflow obstruction. J Appl Physiol 1988; 65:1488-1499.

19. Gurevitch MJ, VanDyke J, Young ES et al. Improved oxygenation and lower

peak airway pressure in severe adult respiratory distress syndrome: Treatment

with inverse ratio ventilation. Chest 1986; 89:211.

20. Tharatt RS, Allen RP & Albertson TE. Pressure controlled inverse ratio

ventilation in severe adult respiratory failure. Chest 1988; 94:755.

21. Brochard L. Respiratory pressure-volume curves. In: Tobin MJ (Ed).

Principles and Practice of Intensive Care Monitoring. New York: McGraw-

Hill, 1998.

22. Lu Q, Vieira SRR, Richecoeur J et al. A simple automated method for

measuring pressure-volume curves during mechanical ventilation. Am J

Respir Crit Care Med 1999; 159:275-282.

23. Servillo G, Svantesson C, Beydon L et al. Pressure-volume curves in acute

respiratory failure: automated low flow inflation versus occlusion. Am J


24. Ranieri VM, Brienza N, Santostasi S et al. Impairments of lung and chest

wall mechanics in patients with acute respiratory distress syndrome. Am J


25. Amato MBP, Barbas CSV, Medeiros DM et al. Effect of a protective-

ventilation strategy on mortality in the acute respiratory distress syndrome.

N Engl J Med 1998; 338:347-354.

26. Stewart TE, Mead MO, Cook DJ et al. Evaluation of a ventilation strategy

to prevent barotrauma in patients at high risk for acute respiratory distress

syndrome. N Engl J Med 1998; 338:355-361.

27. Brower RG, Shanholtz CB, Fessler HE et al. Prospective, randomized,

controlled clinical trial comparing traditional versus reduced tidal volume

ventilation in acute respiratory distress syndrome patients. Crit Care Med

1999; 27:1492-1498.

28. Hess D & Tabor T. Comparison of six methods to calculate airway

resistance during mechanical ventilation. J Clin Monit 1993; 9:275-282.

29. Gay PC, Patel HG, Nelson SB et al. Metered dose inhalers for

bronchodilator delivery in intubated, mechanically ventilated patients.

Chest 1991; 99:66-71.

30. Dhand R, Jubran A & Tobin MJ. Bronchodilator delivery by metered-dose

inhaler in ventilator-supported patients. Am J Respir Crit Care Med 1995;

151:1827-1833.



AbstractAcute renal failure (ARF) is a common problem in theintensive care unit (ICU), often as a component of multipleorgan failure. Intermittent haemodialysis was the standardtreatment for ARF but in many units continuous renalreplacement therapy (CRRT) is now the treatment of choice.Several manufacturers have developed machines specificallydesigned for continuous venovenous haemofiltration (CVVH)in the ICU.

This article reviews some of the practical aspects of renalreplacement therapy including the choice of method, vascularaccess, pre-compared with post-filter infusion of substitution orreplacement fluid, choice of filter, choice of substitution fluid,the apparatus and staff training. The controversial issue ofinflammatory mediator clearance by haemofiltration is discussed.

IntroductionARF is a common problem in ICUs. In contrast to chronicrenal failure, ARF is usually not caused by primary renaldiseases, but develops in the context of multisystem organfailure (MSOF). The standard treatment for patients withchronic renal failure is haemodialysis and it is usually welltolerated by these patients. In contrast, intermittenthaemodialysis in patients with MSOF is associated withnegative effects on haemodynamic function and gas exchange.

Moreover, MSOF patients are often in such a catabolic statethat daily haemodialysis is needed to restore metabolichomeostasis. These factors together make intermittenthaemodialysis an unattractive option for MSOF patients and ithas been replaced in many units by some form of CRRT.

Continuous arteriovenous haemofiltration (CAVH) wasinitially the method of choice to treat ARF patients with someform of continuous therapy 1-2. As systemic blood pressuresupplies the perfusion pressure of the filter, ultrafiltrate volume

was limited to 12 litres per 24 hours. This low ultrafiltratevolume and the low inherent clearance of CAVH make itdifficult to maintain adequate metabolic control in patientsneeding intensive care.

Solutions to this problem are the addition of a dialysiscomponent to the system, creating continuous arteriovenoushaemofiltration (CAVH) 3-4 or the insertion of a roller pumpinto the arterial limb of the filter, creating pumped CAVH.Later, the latter technique was replaced by CVVH, abolishingthe need of arterial cannulation.

Now, CVVH is so well accepted in ICUs that multiplemanufacturers have developed machines specifically designedfor CVVH to deliver renal replacement therapy in the ICU.This article is describes the practical aspects of acute renalreplacement therapy in the ICU including:

• The choice of renal replacement therapy.

• Potential additional value of high volume haemofiltration.

• Vascular access and pre- versus post-dilution.

• Filter choice.

• Substitution fluid.

• Apparatus.

• Training aspects.

Choice of renal replacement therapyNumerous studies have shown that continuous techniques areassociated with better metabolic control than intermittenttechniques. An important advantage of continuous techniquesis that the large amounts of infusion fluids that are needed forantibiotics, enteral feeding and inotropic drug infusions can beadministered to the patient without disturbing the fluid balance 5.

Several studies that used historical control groups indicate thatCRRT is associated with an improved survival and a shorter stayin the ICU 6. In the Netherlands, another consideration in thechoice is that many more hospitals have ICUs than hospitalswith a haemodialysis department. Although even 12 years ago,some groups suggested that it was almost unethical to deliverCRRT to patients in the ICU if no back up from ahaemodialysis department was present, this view is notsupported nor defended any longer. One of the reasons it isimpossible to defend this point of view is that ARF seldom leadsto chronic renal failure. Also, the few hospitals withhaemodialysis departments could never treat all the patientswith ARF.

Practical aspects of haemofiltration

AF Grootendorst MD PhDDepartment of Intensive Care

I. van Stijn MDR. Peters MDDepartment of Internal Medicine

St. Clara Hospital, Rotterdam, The Netherlands

February 2004


The acceptance of CRRT in preference to intermittent dialysisin ICUs is apparent because more than 90% of the ICUs in theNetherlands treat renal failure with some form of continuoustherapy 7. This leaves us with the question – which form ofcontinuous therapy should be preferred. CAVH is now seldomused because it is simply incapable of maintaining adequatemetabolic control in most of the intensive care patients.Venovenous forms of renal replacement therapy have theinherent disadvantage of needing more complex apparatus thanneeded for CAVH, but this apparatus has become so widelyaccepted in the ICU that it is no longer a significantdisadvantage. In practice, CVVH is the therapy of choice inmost ICUs with CAVHD the second choice.

Additional value of high volume CVVH overother forms of renal replacement therapySince 1984, several studies have investigated whether someform of haemofiltration would have additional value in thetreatment of patients with MSOF by removing the mediators ofsepsis that are responsible for MSOF and hypotension. Itappears that any form of haemofiltration, either low or highvolume, is capable of removing mediators of sepsis. Thiscapability was demonstrated by the presence of these mediatorsin the ultrafiltrate 8-11. This led to several other studies thataimed to show that CVVH using high volume ultrafiltrate issuperior to low ultrafiltrate volume techniques.

Unfortunately, while the animal experimental studies were welldesigned, most of the clinical studies were not. In summary, theanimal studies conclude that high volume filtration in animalmodels of septic shock leads to improved haemodynamics andimproved gas exchange, and that the magnitude of thesebeneficial effects is related to the ultrafiltrate volume 12. Inpatients, no randomised prospective trial has been performed toanswer this question. Studies using historical control groupsindicate that CVVH is associated with a marked reduction inmortality, length of stay in the ICU, improved haemodynamicsand improved gas exchange 11, 13. In addition, it appears that lowvolume haemofiltration using CAVH improves haemodynamicparameters after cardiopulmonary bypass surgery 14.

After these initial clinical studies, several more recentinvestigations have examined whether the presence ofmediators of sepsis in the ultrafiltrate reduced their serumconcentrations. All these studies show that haemofiltrationdoes remove mediators of sepsis, but does not lead to theexpected reduction in the serum concentrations 9, 11. Severalexplanations may explain this phenomenon:

• The study period was too short to show the reduction inserum concentrations of mediators of sepsis.

• The blood-membrane contact stimulates mediatorproduction, counteracting the effects of elimination.

• The serum compartment is filled with mediators of sepsisfrom the tissue compartment. In this case, the absence ofreduction of serum levels of mediators of sepsis would notimply that the therapy is useless. This hypothesis issupported by in vitro experiments using human blood towhich a standard amount of sepsis mediators are added thatshow a reduction in the serum concentrations of mediatorswith filtrations.

• The filters that were used in the studies were not the rightfilters to remove the targeted mediators of sepsis. Severalstudies indicate, for instance, that polysulphone hardlyremoves IL-6, in contrast to other filters 15.

High volume haemofiltration remains a primary focus ofattention among the potential treatments for MSOF. There areno prospective randomised trials as yet to demonstrate efficacy,though at least two studies are underway. The choice of filtermay be a critical factor in determining the results of thesestudies if one assumes that one or a couple of mediators of sepsisplay a pivotal role in the genesis of MSOF. However, no suchmediator has been identified, so it is questionable if focusing onthe removal of one mediator is the right direction for futureresearch. Another approach to studying the effects ofhaemofiltration is to assess the capability of serum to activatemacrophages and leukocytes, comparing serum beforehaemofiltration to serum after haemofiltration or to study thechanges in phagocytosis by macrophages 16.

Choice of vascular access, pre- versus post-dilutionThe standard access for any form of CVVH therapy is a doublelumen catheter. A disadvantage of these catheters isrecirculation. One study indicates that changing the arterialand venous limb of the catheter may drastically increase theamount of recirculation. In this study, a filter flow of 200ml/minwas associated with a recirculation of 6.5%; reversing thearterial and venous limb increased this percentage to 19.7% 17.This may not seem a lot, but on treatment with an ultrafiltrateproduction of 100L per day, nearly 20L are needed just toabolish the effect of recirculation.

The choice of the venous site is dictated by the normalconsiderations that are used to choose the introduction site,especially with regards to the risk of infection. The risk is leastin the subclavian position, the internal jugular is next and thefemoral position carries the greatest risk of catheter infection.All vascular access catheters available in the Netherlands allowa flow of at least 300ml/min.



Whether post-dilution haemofiltration (that is, the addition of

replacement fluid for the amount lost as ultrafiltrate after the

filter, taking into account the overall fluid balance) is superior

to pre-dilution haemofiltration is unclear. Pre-dilution

haemofiltration is usually preferred because the decrease in

haematocrit during the passage through the filter can lead to

clotting problems. This problem is most marked when low filter

flows are combined with high ultrafiltrate flows. The

disadvantage of pre-dilution haemofiltration is decreased

efficacy, as the concentration of molecules that have to be

removed decreases by the admixture of substitution

(replacement) fluids. This decreased efficacy can be overcome

by increasing the ultrafiltrate flow, with the consequent effect

on substitution fluid flow as shown in Table 1.

The choice between pre- and post-dilution haemofiltration

depends on the limiting factor in the therapy. If substitution

fluid cost is the limiting factor, post-dilution haemofiltration

has the advantage. If filter flow is limited and substitution fluid

cost is not a limiting factor, pre-dilution haemofiltration can be

very effective.

Filter choice

The first haemofilters that became available were made of

Cuprophane. The biocompatibility of Cuprophane is low so

blood-membrane contact causes adverse haemodynamic effects,

a sharp drop in blood leucocyte and platelet counts and an

increase in serum concentrations of adhesion molecules.

Synthetic filters made using polyamide, polyacrylonitryl and

polysulphone induce lower levels of adhesion molecules, which

is reflected by smaller drops in leucocyte and platelet counts 18.

The clinical relevance of these findings is unclear. Filters vary

widely in their ability to adsorb mediators of sepsis or remove

these mediators by convective elimination.

The target volume of ultrafiltrate determines the surface area of

the filter used. For low volume haemofiltration a filter of 0.5-

0.6m2 is adequate. The ultrafiltrate volume produced using

filters with a surface area of 1.8m2 is much greater than needed.

It is logical to choose the smallest membrane surface area

consistent with producing the desired ultrafiltrate volume to

minimise the negative effects of blood-membrane contact. In

experimental settings, we achieved an ultrafiltrate flow of

6L/hour with filters of 0.6m2. When haemofiltration is used

only as renal replacement therapy and not with the purpose of

removing mediators of sepsis, there is insufficient information to

prefer one filter over another.

Substitution fluids

Substitution fluids use either lactate or bicarbonate as buffer.

The lactate versus bicarbonate issue has been subject to many

discussions and publications. Strong opinions seem to dictate

the choice. In reality, the liver transforms lactate very rapidly

into bicarbonate. A recent clinical study did not show any

advantage of bicarbonate substitution over lactate substitution

fluid 19. However, patients with liver failure were excluded from

this study.

At this moment it seems safe to conclude that no hard data are

available to demonstrate that bicarbonate has an advantage

over lactate buffer solutions and that, if there is an advantage, it

is particularly in patients with liver failure. Of course, liver

failure is relatively frequent in patients needing intensive care,

so many units still choose bicarbonate substitution fluid.

CVVH apparatus

Apparatus specifically designed to deliver CVVH in the ICU

usually has three pumps, one for perfusion of the filter, another

for ultrafiltrate flow and a third pump for the substitution fluid

flow. By electronic coupling of these pumps, almost any desired

Assuming a molecule with a sieving coefficient of 1, theclearance with pre-dilution and post-dilution are Quf andQuf* Qb/(Qb+Qsub), respectively (Quf: ultrafiltrate flow, Qb:blood flow, Qsub: substitution fluid flow).

Assuming similar blood flows during either pre- or post-dilution haemofiltration, urea clearance is increased duringpre-dilution when the substitution fluid flow is increased, asillustrated in the following example:

Post-dilution Pre-dilution

Blood flow (ml/min) 250 250

Haematocrit 0.36 0.36

Substitution flow (ml/min) 80 240

Ultrafiltrate flow (ml/min) 80 240

Maximum haematocrit 0.48 0.36

Urea clearance (ml/min) 80 120

Table 1. An example comparing the effect of pre-dilution versus post-dilution (i.e.adding the substitution or ‘replacement’ fluid before or after the haemofilter)on the clearance rate.

February 2004


balance can be achieved. Alarms for arterial and venous

pressures are present.

Most of these systems use some form of balance system to

measure the amount of ultrafiltrate and substitution fluid.

Imbalances can occur by inadvertent placement of other

apparatus on the balance. This can severely disturb the fluid

balance in these patients. For these reasons other systems have

been developed, using a burette system in which a burette is

filled to 20ml and then emptied. This system has the advantage

of being independent of balances. The disadvantage is the

potential lack of accuracy that might be expected in a system

that requires 5000 burette changes each day if the ultrafiltrate

volume is 100Ls. However, recent clinical tests have shown

that this apparatus is very accurate 20.

Another advantage of this apparatus is that it is very user-

friendly. In hospitals with dialysis departments, the

responsibility for supervising renal replacement therapies in the

ICU can be controversial. Often, a solution is chosen in which

dialysis nurses are responsible for initiating of therapy and the

intensive care nurses for its maintenance. When this solution

is chosen, the problem arises that many dialysis nurses work

part-time and that the pool of nurses is very large. This

decreases the chance that any specific dialysis nurse has enough

recent experience with the apparatus used in the ICU.

The solution used in the Netherlands is to treat a number of

chronic dialysis patients with this apparatus, maintaining the

experience of dialysis nurses with the apparatus. For the units

in the Netherlands’ hospitals without dialysis departments, the

machines’ suppliers usually offer training programmes for the

whole pool of intensive care nurses.

Conclusions

More than 90% of renal replacement therapy in the ICUs of the

Netherlands is delivered by some form of CVVH therapy.

Several user-friendly devices are now available and training of

the ICU nurses is part of the product. The role of high volume

haemofiltration in multiple organ failure is as yet unclear but is

the subject of several ongoing clinical studies.

Based on personal experience, CVVH can be recommended in

high risk patients with therapy resistant septic shock. Those

units that accept this indication have observed rapid

improvements in haemodynamics and a rapid reduction in the

amount of inotropic drugs required to maintain an adequate

circulation. The role of CVVH in the treatment of MSOF is

less clear.

References1. Kramer P, Wigger W, Rieger J, Matthaei D & Scheler F. Arteriovenous

hemofiltration: a new and simple method for treatment of over-hydratedpatients resistant to diuretics. Klin Wochensch 1977; 55:1121-1122.

2. Lauer A, Saccaggi A, Ronco C, Belledonne M, Glabman S & Bosch JP.Continuous arteriovenous hemofiltration in the critically ill patient; clinicaluse and operational characteristics. Ann Intern Med 1983; 99:455-460.

3. Geronemus R & Schneider N. Continuous arteriovenous hemodialysis: anew modality for treatment of acute renal failure. Trans Am Soc ArtifIntern Organs 1984; 30:610-613.

4. van Geelen JA, Vincent HH & Schalekamp MADH. Continuousarteriovenous haemofiltration and hemodiafiltration in acute renal failure.Nephrol Dial Transplant 1988; 3:181-186.

5. Forni LG & Hilton PJ. Continuous hemofiltration in the treatment of acuterenal failure. N Engl J Med 1997; 336:1303-1309.

6. Kruczynski K, Irvine-Bird K, Toffelmire EB & Morton AR. A comparison ofcontinuous arteriovenous hemofiltration and intermittent hemodialysis inacute renal failure in the intensive care unit. ASAIO J 1993; 39:M778-781.

7. Bommel EFH van & Poussen HH. Continuous or intermittent treatmentfor acute renal failure: where do we stand? Am J Kidney Dis 1997; 30(S4):S72-79.

8. Bellomo R, Tipping P & Boyce N. Interleukine-6 and Interleukine-8extraction during continuous venovenous hemodiafiltration in septic acuterenal failure. Renal failure 1995; 17:457-466.

9. Sander A, Armbruster W, Sander B, Daul AE, Lange R & Peters J.Hemofiltration increases IL-6 clearance in early systemic inflammatoryresponse syndrome but does not alter IL-6 and TNF-a plasma concentration.Intensive Care Med 1997; 23:878-884.

10. Van Bommel EFH, Hesse CJ, Jutte NHPM, Zietse R, Bruining HA &Weimar W. Cytokine kinetics (TNF-a, IL-1b, IL-6) during continuoushemofiltration: a laboratory and clinical study. Contrib Nephrol 1995; 116:62-75.

11. Heering P, Morgera S, Schmitz FJ et al. Cytokine removal andcardiovascular hemodynamics in septic patients with CVVH. IntensiveCare Med 1997; 23:288-296.

12. Grootendorst AF, Bommel van EFH, Hoven van der B, Leengoed LAMG &Osta van GALM. High volume hemofiltration improves hemodynamics ofendotoxin-induced shock in the pig. Crit Care 1992; 7:67-75.

13. Krüger I, Jacobi C & Landwehr P. Effects of continuous venovenoushemofiltration on pulmonary function and hemodynamics in postoperativeseptic multiorgan failure. Contrib Nephrol 1995; 116:108-111.

14. Coraim F, Pauser G, Stellwag F, Werner T & Ziegler W. Positivemodification of hemodynamics in post cardiac surgery patients byhemofiltration. Improved method for the demonstration of myocardialdepressant factor in hemofiltrate. Anaesthetist 1985; 34: 236-240.

15. Bouman CS, van Olden RW & Stoutenbeek CP. Cytokine filtration andadsorption during pre- and postdilution hemofiltration in four differentmembranes. Blood Purif 1998; 16: 261-268.

16. DiScipio AW & Burchard KW. Continuous arteriovenous hemofiltrationattenuates polymorphonuclear phagocytosis in porcine intra-abdominalsepsis. Am J Surg 1997; 173:174-180.

17. Carreras Poster 1995 San Diego.

18. Grooteman MPC, Nubé MJ, Limbeek J van, Houte AJ van, Daha MR &Geelen JA van. Biocompatibility and performance of a modified cellulosicand a synthetic high-flux dialyser: a randomised crossover comparisonbetween cellulose triacetate and polysulfon. ASAIO J 1995; 41:215-220.

19. Thomas AN, Guy JM, Kishen R, Geraghty IF, Bowles BJM & Vadgama P.Comparison of lactate and bicarbonate buffered haemofiltration fluids: usein critically ill patients. Nephrol Dial Transplant 1997; 12:1212-1217.

20. Peters R, Grootendorst AF. In press.



AbstractFulminant hepatic failure (FHF) caused by acute hepatitis (AH)

is a very severe illness. With supportive medical treatment the

mortality is 70-95%. Orthotopic liver transplantation (OLT)

has become an accepted procedure for the management of end

stage liver disease and improves prognosis. This study reviews

the results of liver transplantation in 35 children with FHF who

met transplantation criteria.

Sixty two children with FHF, meeting liver transplantation

criteria, were admitted to a paediatric intensive care unit

(PICU) in a 63 month period; 72.5% hepatitis A (HAV) and

27.5% non-ABC. Thirty nine transplants were performed in 35

children. Five patients were considered unsuitable for

transplantation and 21 patients died before a suitable donor

could be found. One patient recovered with supportive

treatment. The prognostic value of different variables was

assessed to define a mortality model for the group as a whole and

for transplanted children. The time variable analysed was

duration of follow up expressed in days.

The children receiving transplants mean age was 56.7 months

(+40.0), mean weight was 19.2kg (+8.6) and mean follow up

period was 458.5 days (+541.8). The patients’ mean

encephalopathy stage was 1.80 (+1.0) and mean score on the

Glasgow Coma Scale was 11.9 (+2.9). Twenty four children

had HAV (68.5%) and 11 non-ABC (31.5%).

The mortality in patients undergoing transplantation was 37%(13/35); all but one died in the immediate postoperative period.Survival was 63% (22/35) at a mean follow up of 458 days (4-1676). Overall mortality in non-transplanted children was 96%(26/27). Multivariate analysis showed a higher risk of death inthe immediate postoperative period in patients with more thanfive days on mechanical ventilation (MV); p<0.008.

HAV is the most frequent cause of FHF in Argentina. OLTreduces mortality in patients with FHF admitted to PICU, andhas become an effective alternative treatment for FHF.

IntroductionAH is one of the major causes of liver disease worldwide 1.Clinical presentation, regardless of aetiology, ranges fromasymptomatic illness to FHF. This syndrome is caused by severefunctional liver impairment with hepatocyte necrosis, leadingto rapid development of hepatic encephalopathy in patientswho do not have pre-existing liver disease 2. New syndromeshave been described recently according to the time intervalbetween jaundice and the onset of encephalopathy 3, 4.

Mortality ranges from 70-95% 5-7 and cerebral oedema is themain cause of death 8, 9. Supportive care alone has beenunsuccessful in the management of FHF, and OLT has become awidely accepted treatment with a 56-80% survival rate 10-13.

In November 1992, a liver transplantation programme was setup at the Children’s Hospital Dr JP Garrahan 14, 15. Favourableoutcomes in the first elective cases motivated the use of thisprocedure in patients with FHF. This study reports ourexperience with OLT in 62 patients with FHF admitted to thePICU.

Patients and methodsBetween January 1993 and May 1998, 62 patients with FHFadmitted to our PICU met the King’s College criteria 16 for livertransplantation; 35 boys and 27 girls. The cause of hepaticfailure was HAV in 45 children (72.5%) and non-A, non-B,non-C hepatitis (non-ABC) in 17 (27.5%). None of thepatients had a history of pre-existing liver disease. Signs of liverfailure, defined as an increase in prothrombin time (PT) andplasma level of clotting factor V (FV) below 50% of normal,were present. All children had jaundice and marked increasesin serum aminotransferases. FHF was diagnosed in patientsdeveloping encephalopathy within 8 weeks from the onset ofjaundice.

Fulminant hepatic failure in paediatric patients:results of orthotopic liver transplantation

Jorge S. Sasbón MDPaediatric Intensive Care Unit

Mónica Centeno MDPaediatric Intensive Care Unit

Mirta Ciocca MDGastroenterology Department

Gustavo Bianco MDLiver Transplant Unit

Miriam Cuarterolo MDGastroenterology Department

Oscar Imventarza MDLiver Transplant Unit

Hospital de Pediatría Dr. JP GarrahanCombate de los Pozos, Buenos Aires, Argentina

February 2004


Five patients were considered unsuitable for transplantation:two because of genetic syndromes, one patient with sepsis andtwo children with multiple organ failure (MOF). Twenty onepatients died before a suitable donor could be found, all patientsbecause of severe liver insufficiency and MOF. One patientrecovered with supportive treatment alone. Thirty five patientsunderwent liver transplantation.

Laboratory investigations to identify the cause of AH includedanalyses for IgM antibodies to HAV, hepatitis B surface antigen(HBs Ag), IgM and IgG antibodies to the hepatitis B coreantigen, antibodies to the hepatitis C virus (anti.HCV) andHCV RNA. Other hepatotropic viruses (Epstein Barr virus,Cytomegalovirus, Herpes virus types 1 and 2), auto-immunehepatitis and Wilson’s disease were excluded.

Encephalopathy was classified into four stages 17. Cerebraloedema was suggested by the presence of one or more of thefollowing clinical signs – arterial hypertension, hyperventilation,opisthotonus, decerebrate posture, cardiac arrhythmias, seizures,poorly reactive pupils or asymmetric pupils. The GlasgowComa Scale (GCS) was used for neurological assessment andprognosis, evaluating eye, verbal and motor responses 18. Thisscale was chosen because it is routinely used in the PICU for theclinical management of patients.

Treatment

Preoperative management

All patients were given similar standard supportive care:intravenous glucose infusion, lactulose, neomycin and selectivebowel decontamination 19, 20. Fresh frozen plasma was given topatients with active bleeding or before invasive procedures.Routine blood tests were performed daily. Computedtomography scans and electroencephalograms were performed asindicated by the neurological status. Endotracheal intubationand MV were instituted in patients with encephalopathy stagesIII-IV. Patients with clinical or tomographic signs of cerebraloedema were hyperventilated, positioned 30° head up andreceived 20% mannitol.

Surgical procedure

Thirty nine transplants were performed in 35 patients. Themean donor weight was 75kg. Thirty two grafts were ABOidentical and seven non-identical: three ABO-incompatible(O/A) and four ABO-compatible (A/O+B/O). The meandonor/recipient weight ratio was 5:1.

Eight full size grafts (21%) were used and the remaining 31(79%) were reduced in size using previously describedtechniques 21, 22. Segments II-III-IV were used in four; segmentsII-III in 22, two being split livers; and segments I-II-III-IV infive patients.

Liver removal from the donor was performed rapidly and

reductions were done on the back table. Reduced size grafts

were implanted with using the piggy-back technique 23.

Postoperative management

After surgery, patients were admitted to a separate isolation

unit, with two beds and independent nursing staff. Patients

were given a triple drug immunosuppressive regimen consisting

of corticosteroids, cyclosporine and azathioprine. Acute

rejection episodes were treated with methylprednisolone

boluses and steroid recycling. When this treatment was

unsuccessful, OKT3 was administered, and recently we used

FK506. Ductopenic rejection was also treated with FK506.

Patients who developed postoperative renal failure underwent

early haemofiltration through a double lumen venous catheter

using a haemofilter (Dialfilter 20 and Minifilter polusTM

Gambro) and the immunosuppression was changed to a 14 day

OKT3 course (2.5-5mg/day, intravenously). Three patients

with ABO incompatible grafts were treated with OKT3 and one

of them underwent plasmapheresis.

Statistical analyses

The independent variables entered in the multivariate analysis

were the following: age (months); weight (kg); aetiology; time

to admission; stay in PICU; time to register on waiting list; time

on waiting list; postoperative stay in PICU; duration of MV

before transplantation; duration of MV after transplantation;

time between jaundice and onset of encephalopathy.

Death was a dependent variable. The time variable analysed

was the total follow up period in days defined as:

time to admission + time to register on waiting list +

time on waiting list + post-transplant period in PICU

These comprised the time between the onset of illness and the

final outcome – discharge from PICU or death. Time intervals

are expressed as number of days. Multivariate analysis using the

Cox model were performed to test the prognosis significance of

the entered variables expressed as Relative Risk (RR).

Univariate analysis was performed using the Chi square test for

dichotomic variables, and the Mann-Whitney U test for

continuous variables. The ROC curve was used to determine

the cut off point for duration of MV in PICU after

transplantation.

Two-tailed p values were calculated and all values below 0.05

were considered statistically significant. Data was processed

using CSS/ Statistica version 5.1 software (StatSoft Corp, Tulsa,

USA) and graphics were performed on Delta Graph

Professional version 4 MacIntosh Ilci computer.



Results

Characteristics of patients receiving transplants

Thirty nine liver transplants were performed in 35 children; 14girls and 21 boys. The cause of hepatitis was HAV in 24patients (68%) and non-ABC hepatitis in 11 patients (32%).Three children required re-transplantation because of primarygraft failure in the immediate post-operative period and anotherpatient 1108 days after transplantation because of chronicrejection. At the time of transplantation, 15 patients had stageI encephalopathy, 10 had stage II, 9 had stage III and one hadstage IV (mean encephalopathy stage: 1.8+1.0). The GlasgowComa Scale was <6 in one; 6-8 in seven; 10-12 in nine; and 13-15 in 18 patients (Tables 1 & 2).

Cranial CT scans were performed in 13 patients. Findings werenormal in eight and cerebral oedema was demonstrated in fivepatients (four with grade III encephalopathy and one with gradeIV). Endotracheal intubation and MV were indicated in 10children before transplantation (mean 0.9 days, range 0-7 days).

Results of transplantation

For the total group of 62 patients there was no statisticallysignificant effect of age, sex, weight, or aetiology on the finaloutcome. Patients who received a transplant had similarclinical characteristics to those who did not receive a transplantat the time of listing. However, liver transplantation had asignificant effect on survival compared to than supportivetreatment alone (p<0.0001) (Table 3). The survival in patientsundergoing transplantation for FHF caused by HAV hepatitiswas 75% compared with 45% in patients with non-ABChepatitis (not significant). Twenty patients with FHF caused byHAV who did not receive a transplant died (95%) and only onesurvived. All six patients with non-ABC hepatitis nottransplanted died.

Of the 35 patients who underwent liver transplantation, 23(65%) had an immediate successful outcome. Complicationsoccurring during the stay in PICU included: nine episodes ofinfection (eight bacterial and one fungal); seven acute rejectionepisodes in seven patients, who recovered with treatment; eightpatients developed renal failure, two required haemofiltrationand one child needed further surgery for abdominal bleeding.One patient died 95 days after transplantation fromhaemophagocitic syndrome and fungal sepsis. The 22 otherpatients were alive and leading a normal life, 4 months to 4years after transplantation.

Twelve patients (35%) died in the early post-operative period inthe PICU after a mean of 12+8, range 7-18 days. The cause ofdeath was MOF in 10 patients, brain death in one and refractoryhypoxaemia in another. Three children had primary non-function, three had fungal sepsis – two Candida parapsilosis, oneCandida albicans – and five had bacterial sepsis, two of them also

Variables Mean ± SD Min-Max

Age (months) 56.7 ±40.0 14-171

Weight (kg) 19.2 ±8.64 9-41

Aetiology: non-ABC hepatitis 11 (32%)Hepatitis A 24 (68%)

Pre admission illness (days) 27.4 ±16.9 7-90

Stay in PICU (days) 2.63 ±2.51 0-8

Time to register on waiting list (days) 2.59 ±4.75 0.75-27

Time on waiting list (days) 4.55 ±4.33 4-30

Post-transplant stay in PICU (days) 10.4 ±6.35 4-30

Days ventilated pre-transplant 0.91 ±1.71 0-7

Days ventilated post-transplant 5.81 ±6.04 0.75-30

Jaundice to encephalopathy (days) 16.4 ±13.5 0-50

Mean ± SD Min-Max

Activated partial thromboplastin time (Sec.) 110.3 ±47.9 5-240

PT (%) 12.4 ±5.15 3-24

FV (%) 15.7 ±7.84 4-35

SGOT (UI) 640.9 ±629.5 39-2543

SGPT (UI) 708.1 ±596.7 30-2100

Bilirubin (mg/dl) 27.3 ±7.69 9.1-46

Table 1. Characteristics of the 36 patients who underwent transplantation.

Table 2. Laboratory results in the 35 patients who underwent transplantation.

Survived Died Chi squaren: 24 n: 38 p

AetiologyHAV (45) 19 42.3% 26 57.7%Non-ABC (17) 5 29.4% 12 70.6% 0.329

TreatmentTransplant (35) 23 46.9% 12 34.3%Supportive (27) 1 3.7% 26 96.2% <0.0001

Table 3. Effect of aetiology of hepatitis and transplantation on survival in all 62patients.

February 2004


showing acute rejection. Renal failure occurred in six patients,

four requiring haemofiltration and two haemodialysis. Six

children had severe haemorrhage, three needing re-operation in

the presence of disseminated intravascular coagulopathy. Three

patients developed acute respiratory distress syndrome.

In univariate analysis the duration of MV during the ICU stay

after surgery (p=0.008) was associated with high mortality

(Table 4) and this remained significant (p=0.036) in

multivariate analysis, with five days of MV having the

maximum area under the ROC curve (Area 0.78, p<0.001;sensitivity 75%, specificity 70%). The risk of death increasedby 23% for each day greater than five on MV.

Causes for prolonged MV were lung infection (35%),neurological complications (22%), interstitial pulmonaryoedema (14%) and dialysis for acute renal failure (9%).

DiscussionThe aetiology of FHF varies in different countries. In developedcountries the most frequent cause is non-A non-B hepatitis, as inthe King’s College series where this was the cause in 26 of 31patients with FHF, followed in frequency by drug toxicity 24-27. Inthe United States of America, Whitington’s series of 30 childrenwith FHF had 18 with non-A non-B hepatitis 28. However, morerecently, Debray has reported on 24 children with HAV whoshowed evidence of liver failure, 11 of these either dying orreceiving a liver transplant 29. In another report, Willnerconcluded that HAV caused serious illness and death during anepidemic in Memphis and Shelby County, Tennessee 30.

In Argentina the most frequent cause of FHF is HAV. Inchildren under 15 years, 85% of the cases of hepatitis are causedby HAV, 20% non-ABC hepatitis and 16% hepatitis B virus 31, 32.In our series of 62 patients with FHF, 45 (73%) were caused byHAV and 17 non-ABC (27%). No other causes of FHF werefound, a remarkable difference when compared to other regionsin the world 33. Most children in this study were less than fiveyears old, and only a few were adolescents. This finding isconsistent with an Argentine study in 1000 adults of which95% had antibodies to HAV 34.

Medical treatment of FHF alone is associated with a highmortality. Liver transplantation is currently accepted as analternative treatment for adults 35. In recent years, severalcentres have reported similar results in children. In the seriesreported by Tan and colleagues, 12 children aged 1 month to 14years underwent transplantation for FHF. Eight patientssurvived (66%) in the 18 month follow up period 36. Devictor etal. 37 reported the results of liver transplantation in 19 childrenwith FHF aged 3 months to 15 years. Thirteen patients (68.4%)survived without sequelae 6 months to 4 years aftertransplantation.

Our results are similar, with 65% surviving the immediate postoperative period in the PICU and just one late death during thefollow up period ranging from 4 months to 4 years aftertransplantation. Most patients who did not receive a transplantdied (96%). We believe this is a consequence of two majorfactors:

• Late referral to the hospital with severe neurologicaldeterioration. The mean stay in the PICU was 2.6 days andrapid clinical deterioration occurred once encephalopathydeveloped.

Survived Died p valuen: 23 n: 12

Age (months) 57.6 ±37.2 54.7 ±46.5 0.60

Weight (kg) 19.5 ±1.8 8 ±9.8 0.51

Pre admission illness(days) 28.1 ±18.3 26.2 ±14.6 0.93

Stay in PICU (days) 2.4 ±2.2 3.0 ±3.0 0.67

Time to register on list(days) 2.22 ±2.53 3.3 ±7.5 0.62

Time on waiting list(days) 4.25 ±3.38 5.1 ±5.9 0.97

Post-transplant PICUstay (days) 9.35 ±5.35 12.3 ±7.8 0.19

Ventilated pre-transplant 0.78 ±1.33 1.2 ±2.3 0.69(days)

Ventilated post-transplant 3.9 ±3.8 9.4 ±7.9 <0.008(days)

Time interval jaundiceto Enceph. (days) 17.9 ±12.3 13.6 ±15.8 0.23

Encephalopathy (grades) 1.8 ±1.0 1.75 ±1.14 0.94

Glasgow CS (points) 12.1 ±2.8 1.5 ±3.20 0.61

APTT (sec) 102.8 ±43.4 124.8 +-54.6 0.29

Prothrombin time (%) 11.9 ±54.8 13.2 ±4.5 0.52

FV (%) 15.9 ±7.8 15.4 ±8.2 0.59

SGOT UI 770 ±664 566.4 ±578.3 0.68

SGPT UI 702 ±591 718.9 ±634.1 0.81

Bilirubin(mg/dl) 27.7 ±7.8 26.3 ±7.8 0.61

Aetiology:HAV 18 (75%) 6 (25%)Non-ABC 5 (45.5%) 6 (54.5%) 0.13

Table 4. Characteristics of the 35 patients undergoing transplantation in relation tosurvival (mean + standard deviation).



• A prolonged waiting period for a suitable donor with a meandelay of 4.5 days, increasing the frequency of pre-operativecomplications.

The dilemma for clinicians is to determine which patients havea reasonable chance of spontaneous recovery and which requireliver transplantation. A decision for transplantation istherefore based on the presence of factors that are predictive ofpoor outcome. In our centre, we apply the Kings CollegeHospital criteria to identify these patients. However, it isimpossible to accurately predict death or liver regeneration inan individual child and in rare instances patients haverecovered while waiting for a donor. More recently, liver biopsyhas been proposed to assess the percentage of hepatic necrosisand therefore the potential for recovery withouttransplantation. In transplantation, timing is crucial to patientoutcome because many are in a poor clinical condition andrapidly worsen while on the waiting list 38-41. The availability ofsuitable donor organs is limited and any delay increases the riskof infections, permanent brain damage and death.

Hepatic encephalopathy is rapidly progressive in children, andis predictive of a poor prognosis. Patients develop cerebraloedema and rapid measures must be taken to control intra-cranial pressure. Whether patients in a coma or with severeencephalopathy should undergo transplantation is controversialgiven the high morbidity and mortality during and after theprocedure. However, complete recovery can occur even inchildren with severe neurological impairment. In the presentseries, patients with encephalopathy stage II or more and aGlasgow Coma Scale <8 had a poor prognosis (58% died). Thisemphasises the need for referral to a specialised transplantcentre before neurological symptoms develop.

An epidemiological study in the United States found 169,666cases of viral hepatitis between 1983 and 1989 with a mortalityof 0.9%. The mortality was lowest for HAV (0.4%),intermediate for hepatitis B (1.2%) and highest for non-A non-B hepatitis (2.5%). Patients >50 years and <5 years of age hada higher mortality for all types of hepatitis 42. We found nodifferences related to age or aetiology for the total group.However, in the transplanted patients there was a trend formore patients with HAV to survive (75%) compared with non-ABC hepatitis (45%).

The mean stay in PICU was 10.4 days and 92% of the patientsdied during this period. The highest mortality was in those whowere on MV for more than 5 days.

Graft availability remains limited and this problem is worsenedby the rapid deterioration of children with FHF. Under thesecircumstances, we are forced to use reduced and hyper-reducedsize grafts and ABO incompatible livers which worsens theintraoperative and immediate postoperative outcomes 43. Eightpatients in this series received a full size liver graft, 79% received

a reduced size graft and 70% a hyper-reduced size graft 44. Thirtytwo donors were ABO-identical and seven were non-identical 45.

Patients with FHF can present several defects in immunologicalfunction 46. These defects, together with the use of antibioticsand immunosuppressive drugs, increase the risk of developingbacterial and fungal infections. In this series, infectionsoccurred more frequently and were more severe in patients whodied. Prolonged hospital stay, including stay in PICU beforetransplantation, increases the risk of general postoperativecomplications, particularly infections. If sepsis is suspected,aggressive use of antibiotics and antifungal agents must bestarted.

In this study, the patients who did not survive transplantationcorresponded to those with longer hospital stays in PICU,delayed entry and longer time on waiting list than those whosurvived 47.

Renal failure occurs in 50-80% of patients with FHF 48. Fluidoverload increases intracranial pressure in patients with cerebraloedema and produces pulmonary oedema, favouring thedevelopment of lung complications. Hourly diuresis should bestrictly monitored and management with diuretics (loop orosmotic) is usually successful. However, some children mayrequire haemofiltration. Eight patients who survived in thecurrent series suffered acute renal failure (35%), two requiringhaemofiltration. Among patients who did not survivetransplantation, six suffered acute renal failure (50%), threeneeding haemofiltration and another two haemodialysis. Renalimpairment was more frequent and severe in patients with afatal outcome.

ConclusionHAV is a frequent cause of FHF in Argentina. Medicalmanagement alone has a high mortality rate. OLT has greatlyimproved the prognosis for patients with fulminant hepatitisachieving survival rates of 65%. Prompt referral to a specialisedcentre before the development of encephalopathy isrecommended. OLT is now an effective treatment for childrenwith FHF in our country.

References1. Boletin Epidemiologico. Organización Panamericana de la Salud 1985;

6:5:1-6.

2. Trey C & Davidson CS. The management of fulminant hepatic failure. InPopper H & Schaffner F (Eds). Progress in Liver Disease (vol 3). New York:Grune & Stratton 1970, p282-298.

3. O’Grady JG, Schalm S & Williams R. Acute liver failure: redefining thesyndromes. Lancet 1993; 342:273-275.

4. Gimson AE, O’Grady JG, Ede RJ, Portman B & Williams R. Late onsethepatic failure: clinical, serological and histological features. Hepatology1986; 6:288-294.

5. Jones EA & Schafer DF. Fulminant hepatic failure. In: Zakim D & BoyerTD (Eds). Hepatology. A Textbook of Liver Diseases (2nd ed).Philadelphia: Saunders, 1990, p460-492.

February 2004


6. Russell G, Fitzgerald JF & Clark JH. Fulminant hepatic failure. Medicalprogress. J Pediatr 1987; 111:313-319.

7. Bernau J, Rueff B & Benhamou JP. Fulminant and subfulminant liverfailure: definitions and causes. Semin Liver Dis 1986; 6:97-106.

8. Ware AJ, D’Agostinho A & Combes B. Cerebral edema: a major complicationof massive hepatic necrosis. Gastroenterology 1971; 61:877-884.

9. Gimson AES, White YS & Eddleston WF. Clinical and prognostic differencesin fulminant hepatitis A, B and Non -A Non-B. Gut 1983; 24:1194-1198.

10. Cattral MS & Levy G. Artificial liver support-Pipe dream or reality. N EnglJ Med 1994; 4:268-269.

11. Bismuth H, Didier S, Denis C & Rene A. Orthotopic liver transplantationin fulminant and subfulminant hepatitis. The Paul Brousse experience.Ann Surg 1995; 2:109-119.

12. Ascher NL, Lake JR, Emond JC & Roberts JP. Liver transplantation forfulminant hepatic failure. Arch Surg 1993; 128:77-681.

13. Devictor D, Thairi C, Rousset A et al. Management of fulminant hepaticfailure in children. An analysis of 56 cases. Critical Care Medicine 1993;21(9):5:348-349.

14. Ciocca M, Sasbón J, Bianco G, Cuarterolo M, Cervio G, Rojas L,Imventarza O et al. Transplante hepático. Nuestros primeros 50 casos.Medicina Infantil 1995; II(4):228-233.

15. Invertaza O, Bianco G, Ciocca M, Sasbón J, Centeno M et al. Livertransplant program in Argentina: Development and preliminary results.Transplantation Proceedings 1994; 1:1-3.

16. O’Grady JG, Alexander GJM, Hayllar KM & Williams R. Early indicatorsprognosis in fulminant hepatic failure. Gastroenterology 1989; 97:439-445.

17. Gitlin N. Hepatic encephalopaty. In: Zakim D & Boryer TD (Eds).Hepatology: a textbook of liver disease (3rd ed). Philadelphia: WBSaunders, 1996; Vol I:605-617.

18. Teasdale G & Jennett B. Assessment of coma and impaired consciousness:a practical scale. Lancet 1974; 2:81-84.

19. Rolando N, Gimson AE, Wade J, Philipatt-Howard J, Cosewell M & WilliamsR. Prospective controlled trial of selective parenteral and enteralantimicrobial regimen in fulminant liver failure. Hepatology 1993; 17:196-201.

20. Riordan SM & Williams R. Current concepts: treatment of hepaticencefalopathy. N E J of M 1997; 337:473-479.

21. Starzl TE, Iwatsuki S & Esquivel CO. Refinements in the surgical techniqueof liver transplantation. Semin Liver Dis 1985; 5:349-356.

22. Starzl TE, Koep LJ & Schroter GP. Liver replacement for pediatric patients.Pediatrics 1979; 63:825- 829.

23. Tzakis A, Todo S & Starzl TE. Piggy back orthotopic liver transplantationwith preservation of the inferior vena cava. Ann Surg 1989; 210:649-552.

24. Bernau J. Fulminant and subfulminant viral hepatitis. Rev Pract 1990;40:1652-1655.

25. Wright TL. Etiology of fulminant hepatic failure: is another virus involved?Gastroenterology 1993; 104:648-653.

26. Hoofangle JH, Carithers RL, Schapiro C & Ascher N. Fulminant hepaticfailure: summary of a workshop. Hepatology 1995; 21:240-252.

27. Psacharopoulos HT, Mowat AP & Davies M. Fulminant hepatic failure inchildhood: an analysis of 31 cases. Arch. Dis Child 1980; 55:252-25.

28. Whitington P. Liver disease in children. In: Suchy FJ. Fulminant HepaticFailure in Children. Mosby 1994 Year Book Inc, p180-205.

29. Debray D, Cullufi P, Devictor D, Fabre M & Bernard O. Liver failure inchildren with Hepatitis A. Hepatology 1997; 26:1018-1022.

30. Willner IR, Uhl MD, Howard SC, Williams EQ, Rieley CA & Waters B.Serious hepatitis A: an analysis of patients hospitalized during an urbanepidemic in the United States. Ann. Int. Med. 1998; 128:111-114.

31. Ciocca M, Sasbón J, Cuarterolo M, Esperanza A, Bianco G & Imventarza O.Falla hepatica fulminante por hepatits viral en niños. Medicina Infantil1996; 4:293-294.

32. Ramonet M, Ciocca M, Nuñez MH, Afazani A, Arusa O & Planes N.Etiologia de la hepatitis viral aguda en una población pediatrica. Medicina1985; 45:273-278.

33. Feray C, Gigou M, Samuel D, Reyes G, Bernau J, Reynes M & Bismuth H.Hepatis C virus RNA and hepatitis B virus DNA in serum and liver ofpatients with fulminant hepatitis. Gastroenterology 1993; 104:549-555.

34. Nath N, Mazzur S & Frang C. Prevalencia de los anticuerpos contra el virusa de la hepatitis (VHA) en donantes de sangre en 13 paises y territorios delhemisferio occidental. Boletin Oficina Sanitaria Panamericana 1981;90(5):425-429.

35. Chapman RW, Forman D, Peto R & Smallwood R. Liver transplantation foracute hepatic failure? Lancet 1990; 335:32-35.

36. Tan KC, Mondragon RS, Vougas V, Mieli-Vergani G, Heaton ND, MowatAP, Baker A, Koukoulis, Portman B & Williams R. Liver transplantation forfulminant hepatic failure and late onset hepatic failure in children. Br J Surg1992; 79:1192-1194.

37. Devictor D, Desplanques L, Debray D, Ozier Y, Dubousset AM, Valayer J,Houssin D, Bernard O & Huault G. Emergency liver transplantation forfulminant liver failure in infants and children. Hepatology 1992; 5:1156-1162.

38. Van Thiel DV. When should a decision to proceed with transplantationactually be made in cases of fulminant or subfulminant hepatic failure: atadmission to hospital or when a donor organ is made available. J Hepatol1993; 17:1-2.

39. Williams R & Wendon J. Indications for orthotopic liver transplantation infulminant liver failure. Hepatology 1994; 1:5S-10S.3

40. Starzl TE & Fung J. Between Scylla and Charbydis. Ann Surgery 1995;2:107-108.

41. Pauwels A, Mostefa-Kara, Florent C & Levy VG. Emergency livertransplantation for acute liver failure. Evaluation of London and Clichycriteria. J Hepatol 1993; 17:124-127.

42. Centers for Disease Control. Summary of notifiable diseases. United States,1991; MMWR 1992; 40-53.

43. Bismuth H & Houssin D. Reduced size orthotopic liver grafts in hepatictransplantation in children. Surgery 1984; 95:367-370.

44. Otte JB, de Ville de Goyet J, Sokal E, Alberti D, Moulin D, de Hemptine B& Veyckemans F. Size reduction of the donor liver is a safe way to alleviatethe shortage of size matched organs in pediatric liver transplantation. AnnSurg 1990; 211:146-157.

45. Gugenheim J, Samuel D, Reynes M & Bismuth H. Liver transplantationacross ABO blood group barriers. Lancet 1990; 336:519-523.

46. Wyke RJ, Rajkovic IA, EDdleston ALWF & Williams R. Defectiveopsonization and complement deficiency in serum from patients withfulminant hepatic failure. Gut 1980; 24:746-750.

47. Rolando N, Harvey F & Brahm J. Fungal infection: a common unrecognizedcomplication of acute liver failure. J Hepatol 1991; 12:1-9.

48. Pappas SC. Fulminant hepatic failure. In: Gitwick G, LaBrecque DR &Moody FG (Eds). Disease of the Liver and Biliary Tract. St. Louis: Mosby-Year Book Inc, 1992: 615-629.



Abstract

Humidification is recognised as an essential procedure in the

successful management of ventilated patients. In the absence of

internationally accepted means of monitoring the efficiency of

humidification, over humidification is a potential problem.

Over-humidification is largely unrecognised and can lead to

delayed weaning of ventilated patients. This article reviews the

complications of over humidification and the ways to prevent it.

Introduction

Mechanical ventilation with tracheal intubation or

tracheostomy bypasses the upper airway and the normal heat

and moisture exchanging process of inspired gases. When the

upper airway is bypassed, humidification is necessary to prevent

hypothermia, inspissation of airway secretions, destruction of

airway epithelium and atelectasis.

This may be accomplished using either a heated humidifier or a

heat and moisture exchanger (HME). Heated humidifiers

operate actively to increase the heat and water vapour content

of inspired gas. HMEs operate passively by storing heat and

moisture from patient’s exhaled gas and releasing it to the

inhaled gas 1. Recently, a new device has come on the market

called the active heat and moisture exchange filters (aHMEF)

which combines the benefits of HME humidifier and a hot water

bath. It consists of a small heated humidifier on the patient side

of the HME. This is separated from the airway by a Goretex

membrane. The membrane regulates the amount of water

vapour added to the inspired gas. The drier the inspired gases,

the more water vapour that passes through the membrane. The

major advantage of the aHMEF is its auto-regulation 2.

Emphasis has always been on under humidification when thissubject is discussed and while the importance of deliveringwarm, humidified gas to patients ventilated through a trachealtube is widely accepted, over humidification is an underrecognised problem 3. This paper concentrates on overhumidification, because there is very little informationavailable about the possible effects of excess humidification incritically ill patients. Our interest came about because of anobservation during a clinical trial when we noted overhumidification while using a hot water bath device. Othershave also experienced the problem of over humidification 4.

Normal physiologyNinety percent of air humidification occurs before the airreaches the lungs during inspiration. Approximately 1 litre perday of water is used in the humidification process 5. The netbalance for human respiration is water loss of approximately250-500ml/day. Inhaled air is humidified to 100% and contains43.9mgH2O/L as it reaches the alveoli.

The point at which gases reach alveolar conditions (370C and100% relative humidity) is known as the isothermic saturationboundary (ISB). Under normal conditions ISB (i.e. the pointat which inspired air reaches 370C and 100% saturation) is justbelow the carina. The position of the ISB is fairly constant,even at the extremes of environmental conditions.

Lung disease and fluid status can also affect the ISB. Above theISB, the respiratory tract performs the function of acountercurrent HME. Below the ISB, temperature and watercontent remain relatively constant (Table 1).

What is optimal humidity?The optimal humidity of the inspired gas of ventilated patientshas not been established yet, and the minimal acceptable levelis still a matter of controversy.

Some data suggest that 23-33mgH2O/L is desirable with atracheal temperature of 320C. However, others have suggestedthat higher temperatures 35-370C are adequate, leading toabsolute humidity up to 44mgH2O/L. However, publishedvalues in the literature range from 17-44mgH2O/L. In man,during ‘nose’ breathing of room air, temperature in thesubglottic space is 320C, relative humidity is 98%, and the watercontent is 32.8mg/L.

Dery et al. found a temperature of 330C and water content of25mg/L in the larynx during ‘nose’ breathing and a temperatureof 350C and water content of 35mg/L at a point 9cm below thevocal cords.

Over humidification: an under recognised problem?

Senthil Thiyagarajan DA FRCASpecialist Registrar In AnaestheticsJVF Intensive Care UnitAddenbrooke’s HospitalCambridge, UK

Gilbert R Park MD FRCADirector of Intensive Care ResearchJVF Intensive Care UnitAddenbrooke’s HospitalCambridge, UK

February 2004


By simultaneous recordings of air stream temperature at six

points in the bronchial tree, Mc Fadden et al. found that during

quiet breathing of room air, the temperature was 320C in the

upper trachea and 35.50C in the sub-segmental bronchi.

Thus, under normal circumstances, it can be assumed that the

upper tracheal temperature ranges between 30-330C, and the

relative humidity is 95%, providing a water content of 30mg/L.

In patients who receive mechanical ventilation, 95-100%

relative humidity should be adequate for inspired gases with an

absolute humidity of 25-30mgH2O/L.

Tsuda and others 6 reported that the optimal range of humidity

was determined to be 100% water saturation between 25-300C.

They observed structural changes in the tertiary bronchi of dogs

inhaling 100% water-saturated air at 350C. No changes was

observed after 24 hours in dogs which had inhaled 100% water-

saturated air at 250C under anaesthesia or at 300C without

anaesthesia.

Types of humidifiers 9-13

An ideal humidifier is said to provide heat and moisture, offer

bacterial filtration and safety, have low resistance to flow, be

disposable or easily sterilised, be low cost and without technical

service requirements (Table 2) 7.

Absolute humidity

Absolute humidity (AH) is the amount of water vapour contained inair (mg·H2O·L-1). AH at saturation (AHs) is the maximum amount ofwater vapour that air can contain at a given temperature.

Relative humidity

Relative humidity is the ratio of actual water vapour in the aircompared to how much water vapour the air is capable of holding(its capacity). Relative humidity’s unit of measure is %.

Dew point

The temperature level where a fully saturated gas begins tocondense. This is often referred to as rain out in a patient circuit.

Temperature

The air temperature plays a key role when discussinghumidification. At any given temperature air can hold a specificamount of water vapour. Basically the higher the temperature, themore capacity the air has to hold water vapour.

Active humidifiers

For example, hot water bath. They operate actively to increase theheat and water vapour content of inspired gas.

Advantages:

• Very efficient – ‘gold standard’

Disadvantages:

• Water condensation can act as a source of infection

• High maintenance cost

• Increased workload for nursing staff

• Potential for electrical shock with heated humidifiers

• Hyperthermia

• Thermal injury to airway from heated humidifier – burns tothe patient and meltdown of tubing if heated-wire circuits arecovered or if the circuits and humidifiers are incompatible

• Inadvertent overfilling of hot water baths can result inunintentional tracheal lavage

Passive humidifiers

For example HME. They operate passively by storing heat andmoisture from the patient’s exhaled gas and releasing it to theinhaled gas.

Advantages:

• Preservation of the patient’s heat and water level (recover70% of expired heat and humidity)

• Reduction of the workload of nursing staff

• Ventilator circuits keep clean

• Reduction of the cost of mechanical ventilation

• Safe use for long-term ventilation (controversial)

• Few connections

• Reduction in pneumonia rate

Disadvantages:

• Tracheal tube occlusion (the most significant complication)

• Small increase in airway resistance (3.1+/- 2.5mbar/l.s) 8

Combined humidifiers

For example active heat and moisture exchanging filter (aHMEF).They act as both active and passive humidifiers.

Advantages:

• Low capital cost

• Low running cost

• Adequate humidification for majority of the patients

Table 1. Definitions related to humidification.

Table 2. Types of humidifiers.



Complications of over humidificationHumidified gas is a carrier of both water and energy. Thevolume of water in the gas stream depends on whether the wateris in a molecular form (vapour), particulate form (aerosol), orbulk form (liquid). The energy content of gas stream is the sumof the sensible heat (temperature) of the air and any waterdroplets in it and the heat of vaporisation (latent energy) of anywater vapour present. Latent heat energy is much larger thansensible heat energy, so saturated air contains much moreenergy than dry air. Thus every breath contains a water volumeand energy (thermal) challenge to the airway mucosa.

When the challenge exceeds the homeostatic mechanisms,airway dysfunction starts first at the cellular and secretion leveland then progresses to whole airway function. A largechallenge will result in quick progression of dysfunction. Earlydysfunction is generally reversible so large challenges with shortexposure times may not cause irreversible injury 4.

Water load

The mechanisms of airway injury caused by excess water are notwell studied. Over humidification is complicated by excesswater load. This can further lead to alveolar collapse andatelectasis. The lung atelectasis is caused by obstruction ofsmall bronchi with the condensed and retained water, andinhibition of surfactant release and/or production.Degeneration of bronchial cilia has also been shown in cases ofover hydration. As a consequence, alteration in functionalresidual capacity or lung compliance has been reported with theuse of over humidified gas inhalation. Thus, it is reasonable tokeep the inspiratory gas temperatures below 350C when usingthe heated humidifier system.

Mucociliary function

Excess humidification can lead to impaired function ofmucociliary elevator. It may result from an increased volume ofmucus requiring clearance so that the capacity of themucociliary elevator may be exceeded.

Hypothermia

If inspired gases are not heated but large amounts of water areadministered to the respiratory tract, this may lead to a fall inbody temperature due to loss of latent heat of evaporation.

Thermal injury

The mechanisms of thermal injury in epidermal cells have beenwell studied, although specific observations of injurymechanisms in the airway are sparse. The findings of theepidermal studies can readily be applied to airway mucosal cells,however. This work demonstrates that it is prudent to avoid

raising the average tracheal mucosal temperature above

approximately 43-450C. Thus respiratory gases that arrive at

the tracheal end of the endotracheal tube should average less

than 43-450C and 100% RH.

It should be noted that to deliver temperatures of this

magnitude in the trachea would require higher gas temperatures

at the circuit piece. These temperatures are much greater than

the upper temperature limits imposed on humidifiers by

international standards. Additionally, the reports of pulmonary

thermal injury associated with humidifiers have been solely as

the result of equipment malfunction or misuse – a situation that

is increasingly less likely to occur with the control and

monitoring features of modern devices.

Recognition

Patients whose humidification is excessive will often have

excessive watery secretions. This in turn leads to episodes of

uncontrollable coughing and would also need frequent

suctioning.

Regular sputum scoring is also helpful in recognising over

humidification. The score we use in our unit is the

Addenbrooke’s Secretion Score. It has got 4 grades based on

the characteristic of the tracheal secretion (Table 3). Over

humidification is defined as the occurrence of grade 2 secretions

requiring four or more suctioning episodes each hour for two

consecutive hours. Under humidification is defined as the

occurrence of grade 4 secretions for two consecutive hours.

Grade 1

Absent secretions

Grade 2

Watery secretions – sputum sucked cleanly up suction catheter

Grade 3

Normal secretions – some sputum remains on inside of catheter,but can be cleared by aspiration of water

Grade 4

Thick secretions – some sputum remains on the inside of thecatheter and is not cleared by aspirating water

Table3. Addenbrooke’s Secretion Score.

February 2004


PreventionIt is very important to tailor the humidification system to the

individual patient and not just accept ‘one size fits all’. The

figure below shows an algorithm for the use of humidification in

the critically ill patients needing mechanical ventilation

(Figure 1).

References1. AARC Clinical Practice Guideline. Humidification during mechanical

ventilation. Respir Care 1992; 37:887-890.

2. Kapadia F, Shelly MP, Anthony JM & Park GR. An active heat andmoisture exchanger. Br J Anaesth 1992; 69:640-2.

3. Hirsch A, Tokayer JL, Robinson MJ & Sackner MA. Effects of dry air andsubsequent humidification on tracheal mucous velocity in dogs.

4. Williams RB. The effect of excessive humidity. Respir Care Clin North Am1998; 4:215-228.

5. Proetz AW. Physiology of the nose from the standpoint of the plastic

surgeon. Arch Otolaryngology 1944; 39: 514.

6. Tsuda T, Noguchi H, Takumi Y & Aochi O. Optimum humidification of

air administered to a tracheostomy in dogs. Scanning electron

microscopy and surfactant studies. Brit J Anaesthesia 49(10):965-977.

7. Boots RJ, Howe S, George N, Harris FM & Faoagali J. Clinical utility of

hygroscopic heat and moisture exchangers in intensive care patients.

Crit Care Med 1997; 25(10):1707-1712.

8. Anaesthetist 1996 Jun; 45(6):518-25.

9. Chamney AR. Humidification requirements and techniques.

Anaesthesia 1969; 24:602.

10. Chatburn RL. Physiologic and methodological issues regarding humidity

therapy. J Pediatr 1989; 114:416-420.

11. Department of Health and Social Security. Evaluation of heated

humidifiers. Health Equipment Information 1987; 177.

12. Emergency Care Research Institute. Heated humidifiers. Health Devices

1987; 16(7):223.

13. Klein EF Jr & Graves SA. ‘Hot pot’ tracheitis. Chest 1974; 65:225226.

INTUBATED PATIENT

How long will be patient be intubated?

<12 hours 12-24 hours >24 hours

History of chronic pulmonary diseaseHMEF with increased sputum production aHMEF

Under humidificationTracheal tube obstructs with sputum.

Sputum unable to be aspirated

Over humidificationProfuse secretions

>1 catheter of mucoid secretions/h)

Hot water humidifier

Figure 1



World Federation news

Council meeting

The Council of the World Federation met in Cancun, Mexicoin June 2003. The Federation is grateful to the OrganisingCommittee of the Pan-American Iberic Association of CriticalCare Medicine and Ricardo Martinez Zubieta for facilitating themeeting by inviting members of Council to speak at theCongress. A heavy schedule of lectures and Council meetingsdid, however, make it hard to enjoy the delights of Cancun.Even so, the warmth of the welcome and generosity of our hostswill be remembered by all the Council members who were ableto attend.

The agenda for the Council meeting included:

• The finalising of a process for selection of the site for the2009 Congress of the World Federation.

• An update on arrangements for the 2005 Congress of theWorld Federation to be held in Buenos Aires. The meetingis now to be based at the Sheraton’s facilities and thescientific program is supported by an International AdvisoryCommittee and collaborative links with the other SouthAmerican Societies of Intensive and Critical CareMedicine. A world ‘who’s who’ of well known contributorsto our speciality have already confirmed their participation.Further information on the World Federation’s 2005Congress is available at www.iccm.2005.com.ar

• Contract arrangements between hosts and the WorldFederation for the holding of the Congress. It is hoped sucharrangements will provide certainty for all the organisationsinvolved in such a complex event, with a budget exceeding$1m.

• The handing of abstracts for the World Federation Congress.

• The founding and future links with the World Federation ofCritical Care Nurses.

• Financial statements.

• Establishment of a secretariat to provide a permanent basefor the Federation and a place where all business, financialand other transactions can be centralised. Several proposalswere received, principles established on which to base aselection, and the proposals were reviewed by Council. Thecost for services was remarkably similar for all the proposalsreceived but, on the balance of services to be provided andother links, Council resolved that the Secretariat be hostedby ‘Pathfinder’.

• A contract and financial arrangements for the publicationof the World Federation’s journal.

• The finalisation of the re-establishment of the WorldFederation’s website. A huge amount of work had beendone on this by the Secretary General, Dr Gilber Park, andfurther discussions centred on maintaining the website as aliving, growing entity that will be of value to physiciansworldwide working in intensive or critical care medicine.

• Potential projects to increase income for the WorldFederation and assist it in fulfilling its goals and vision.

• Strategic planning for the future role of the Federation, withextensive discussions on this topic and establishment ofprinciples that will guide Council for at least the next 2years.

• Place and time for the next meeting of Council. This willbe in Trieste, Italy with thanks to the support and generosityof Professor Antonino Gullo and APICE.

Executive meetings

The executive, Philip Lumb, Gilbert Park and Geoff Dobb,have met by a series of teleconferences in order to progress theFederation’s business between face to face meetings. Organisingthese across the time zones of California, Western Australia andthe United Kingdom has been challenging, with a time spanfrom mid-afternoon to 6am the next day! Nevertheless, this hasproved a very effective way of making the necessary decisionsand ensuring tasks are completed.

The Secretariat

The Secretariat has been established at Pathfinder. Ms LizTaylor is now working on behalf of the Federation and willprovide a constant point of first contact to facilitatecommunication between member Societies, their officers andindividual members and the Federation. Contact details are:

Liz Taylor, Council AdministratorWorld Federation of Societies of Intensive & Critical CareMedicineTel: (44)1189 701 204 Fax: (44)1189 701 204

The website goes live

After a huge amount of work over many months, the websiteagain became ‘live’ in October 2003. Please visit the site atwww.world-critical-care.org

February 2004


Pravin Amin (Organising Chairman)Shruti Nagarkar (Organising Secretary)

Web: www.criticare2004.orgConference e-mail: [email protected]

This 10th Anniversary Conference of the ISCCM willfeature 3 days of main conference from 6-8 February2004 where topics of current interest will be discussedand debated such as sepsis, ARDS, renal failure,nutrition, endocrine dysfunction in ICU, etc. Postersand papers will be presented and assessed daily.

The Preconference programme 4-5 February 2004

• 2 day courses in trauma, CPR and the FCCS.

• Half day workshops on CPR, haemodynamics, renalreplacement therapy, ventilation, nutrition, ABGand electrolyte and procedures in ICU will be taughtto small groups.

• An 8 hour postgraduate CME for practitioners ofboth adult and paediatric critical care medicine,separately.

• An 8 hour course on understanding evidence basedmedicine.

10th Annual Conference ofThe Indian Society of Critical Care Medicine

CRITICARE-20044-8 February 2004

Mumbai, India

The site already has more content than our previous site and itis planned to develop it further. We gratefully acknowledge thegenerosity of the publishers of the former World Federationjournal Intensive Care World in agreeing that back issues ofIntensive Care World can be available (and shortly alsosearchable) on the website. It is hoped this will provide a usefulresource and archive.

A new name for our journal

Unfortunately, we have had to break a link with the past inchanging the name of the World Federation’s official journal.It is hoped that the World Federation Journal of Critical Carewill rapidly become known throughout the world intensiveand critical care community. With its broad distribution andthe largest medical intensive and critical care readership,there is a huge opportunity to put the problems of the recentpast behind us.

10th Annual Conference of the Indian Societyof Critical Care Medicine

This will be held from 4-8 February 2004 in Mumbai, withPravin Amin as Chairman and Shruti Nagarkar as OrganisingSecretary. Further information is available fromwww.criticare2004.org or by sending an e-mail message [email protected]. An innovation highlighted in theconference brochure is that mobile telephones ringing duringconference sessions will be confiscated – perhaps this should betaken up by all intensive and critical care conferences.

11th International Symposium on Shock and Critical Care

With an exceptional international Faculty, this meeting,organised by the Indonesian Foundation of Critical CareMedicine, will be held from 13-15 August 2004 at the BaliInternational Convention Centre, Nusa Dua, Bali, Indonesia –surely one of the world’s most delightful settings for aconference. Further information is available [email protected] marked for the attention of Ms Alwida.

13th Congress of the Western PacificAssociation of Critical Care Medicine

Preparations for the 13th Congress of the Western PacificAssociation of Critical Care Medicine, which will be heldduring 10-13 June 2004, in Seoul, Korea, are proceedingsmoothly. The deadline for Abstract submissions is 29 February2004, with notification of acceptance by 22 March 2004.

Your participation in the 13th Congress of WPACCM isencouraged. The sessions will be available in English. If youneed any additional information on the congress, please visitour website at http://www.wpaccm2004.org or e-mail or fax us atthe secretariat.

Secretariat of the 13th Congress of the WPACCMINTERCOM Convention Services, Inc.10th FL. Samick Lavied’or Bldg.,720-2 Yeoksam 2-dong, Gangnam-guSeoul 135-920, KoreaTel: (82) 2 564 4367Fax: (82) 2 565 2434E-mail: [email protected]

World Federation of Societies of Intensive and Critical Care Medicine

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