for the World Federation of
Societies of Intensive and
Critical Care Medicine
No. 1, Vol. 1
February 2004
World
Federation...
9th Congress of the
World Federation of Societies of
Intensive and Critical Care Medicine
27-31 August 2005
Buenos Aires, ...
February 2004
World Federation Journal of Critical Care
Instructions for authors
World Federation Journal of Critical Care...
February 2004 page 1
World Federation Journal of Critical Care
Inside this issue
President’s report page 2
Editorial page ...
page 2 February 2004
World Federation Journal of Critical Care
President’s report
Philip Lumb
The World Federation of Soci...
February 2004 page 3
World Federation Journal of Critical Care
WFSICCM is the unique critical care organisation that
repre...
page 4 February 2004
World Federation Journal of Critical Care
Editorial
Welcome back!
Geoffrey J Dobb
The World Federatio...
February 2004 page 5
World Federation Journal of Critical Care
Non-invasive ventilation in the Intensive Care Unit
Introdu...
page 6 February 2004
World Federation Journal of Critical Care
improvement in the NIV group and a trend to reduced
mortali...
February 2004 page 7
World Federation Journal of Critical Care
‘Partial weaning’ from invasive to non-invasive ventilation...
page 8 February 2004
World Federation Journal of Critical Care
Introduction
Monitoring respiratory mechanics in the mechan...
February 2004 page 9
World Federation Journal of Critical Care
This can be identified by the inconsistent shape of the pre...
page 10 February 2004
World Federation Journal of Critical Care
Volume
The volume-time waveform takes its shape from the i...
February 2004 page 11
World Federation Journal of Critical Care
haemodynamic measurements and increase the risk of
barotra...
page 12 February 2004
World Federation Journal of Critical Care
Flow-volume loop
Flow volume loops are most often used to ...
February 2004 page 13
World Federation Journal of Critical Care
Abstract
Acute renal failure (ARF) is a common problem in ...
page 14 February 2004
World Federation Journal of Critical Care
The acceptance of CRRT in preference to intermittent dialy...
February 2004 page 15
World Federation Journal of Critical Care
Whether post-dilution haemofiltration (that is, the additi...
page 16 February 2004
World Federation Journal of Critical Care
balance can be achieved. Alarms for arterial and venous
pr...
February 2004 page 17
World Federation Journal of Critical Care
Abstract
Fulminant hepatic failure (FHF) caused by acute h...
page 18 February 2004
World Federation Journal of Critical Care
Five patients were considered unsuitable for transplantati...
February 2004 page 19
World Federation Journal of Critical Care
Results
Characteristics of patients receiving transplants
...
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
09125-WFJCC Feb Cover
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09125-WFJCC Feb Cover

  1. 1. 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?
  2. 2. 9th Congress of the World Federation of Societies of Intensive and Critical Care Medicine 27-31 August 2005 Buenos Aires, Argentina It is our pleasure to report that Buenos Aires, the capital city of Argentina, will be the seat for the 9th Congress of the World Federation of Societies of Intensive and Critical Care Medicine. The Sociedad Argentina de Terapia Intensiva (SATI) wants to express its deepest appreciation for the support and assistance received. This will be the first time a World Congress in this field of medicine will be held in Latin America and it is therefore a great honour for us. For this reason, we wish to state that while Buenos Aires will be the host of the Congress, it will, in fact, be a Congress hosted 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 to all Latin American countries and the representatives of the different Societies of the world to actively participate in the planning of the scientific programme so as to be able to develop a programme for the Congress that will represent the interests for all WFSICCM members. Apart from being able to benefit from the scientific activity, the main issue of the Congress, we invite you to enjoy Argentina’s hospitality, its beautiful scenery and tourist centres, our culture, wines and food, the tango and our renowned Argentine steak. Our neighbouring countries also offer wonderful landscapes and a vast range of possibilities which would surely satisfy even the widest of expectations. English is the official language for the Congress. Simultaneous translation into Spanish will be provided for Plenary Sessions and Symposia. We look forward to your visit. Should your enquire anything further, please do not hesitate to contact us. Contact details Congress Office Ana Juan Congresos Sarmiento 1562, 40 F (C1042ABD) Buenos Aires, Argentina Tel: (54) 11 4381 1777 Fax: (54) 11 4382 6703 E-mail (registration): iccm2005@anajuan.com E-mail (abstracts): registration@anajuan.com E-mail (scientific programme): scientific@anajuan.com E-mail (exhibition): congress@anajuan.com E-mail (hotels): turismo@anajuan.com SATI Sarmiento 2046 10 8 C 1044AAF Buenos Aires, Argentina E-mail: info@sati.org.ar Web: www.sati.org.ar
  3. 3. February 2004 World Federation Journal of Critical Care Instructions for authors World Federation Journal of Critical Care is the official journal of the World Federation of Societies of Intensive and Critical Care Medicine. It is received as a benefit of membership of a Society affiliated to the World Federation by over 25000 intensive and critical care physicians up to 90 countries. Articles Articles in the following categories may be submitted for publication. Reviews: May address diagnosis and/or treatment during intensive care, equipment, monitoring, disposable items or discuss diseases commonly treated in an intensive care unit. Reviews of new health technologies relevant to intensive and critical care medicine are particularly welcomed. Authors are welcome to contact the Editor before submission to inquire regarding the potential suitability of their review for the World Federation Journal of Critical Care. The Editor also commissions reviews on specific topics from authors with specific knowledge, experience or expertise. (Up to 3000 words). Original articles: Clinical studies relevant to the care of critically ill patients are assessed for publication. Experimental studies (i.e. using animal models or isolated organs and tissues), unless directly relevant to critical illness, are usually not considered appropriate. (Maximum 2000 words). Reports of clinical series: Particularly when local circumstances provide unusual experience of problems seen less commonly elsewhere or there has been innovation in the management of the condition described. Well described series of critically ill patients managed with limited resources are particularly welcomed. (Maximum 2000 words). Case reports: Consisting of brief, illustrative reports of patients’ history and management during intensive care should have a clear message for readers in the form of a previously undescribed experience, a potentially useful treatment deserving scientific evaluation or a potentially avoidable hazard. The discussion should highlight any previous similar reports, the importance of the issues identified and recommendations by the authors. Case reports will usually be published as Lessons from practice. (Maximum 1500 words). Comment: Can address political, economic, educational and training issues or opinion relevant to intensive and critical care medicine. (Maximum 2000 words). Correspondence: Should address issues relevant to articles recently published in the World Federation Journal of Critical Care. A copy of correspondence is usually sent to the authors offering the opportunity to reply. Manuscripts Authors are encouraged to submit articles written in English. If this is not possible, articles in other languages may be considered for publication but will be translated into English. Assistance is available through the editing process for authors whose first language is other than English. Manuscripts should be prepared in accordance with the Uniform Requirements for Manuscripts Submitted to Biomedical Journals developed by the International Committee of Medical Journal Editors1 . Authors are strongly encouraged to use a clear and simple writing style, remembering that English is not the first language of many of our readers. Critical comment from local colleagues and review of the statistical methods used by someone experienced in clinical studies before submission is likely to reduce the need for revision of submitted manuscripts. The manuscript should be typed on one side of single sheets of A4 or similar white paper with double spacing and margins of 2.5cm (1 inch) at the top, bottom and both sides. Format: Inspection of recent issues of the World Federation Journal of Critical Care provides a guide as to the preferred format and layout of articles. This is dependent on the type of article submitted. • Title page: should contain the title, authors, their degrees and diplomas, the departmental and institutional affiliation of each author, the name, address, telephone number, fax number and e-mail address (if available) of the author responsible for correspondence. • A summary (for reviews and original articles). • The text of the article. • Acknowledgments: including any potential conflicts of interest, commercial affiliations of relevance and sources of financial or grant support. • References: prepared in the style used in Index Medicus including the abbreviations of journal titles and first and last page numbers. All authors should be listed unless there are more than six in which case the first three should be given followed by et al. References should be numbered in the order in which they appear in the text and be identified in the text by this number. • Tables, figure legends and figures. The preferred form of submission is a single original copy and a copy on 3.5 inch computer disc. The word processing program used for the copy on computer disc should be indicated in the covering letter. Alternatively, two copies of the manuscript may be submitted. Two copies of all figures must be included with the manuscript. Black and white figures should be submitted as glossy prints or laser quality output from a computer printer. Colour figures may also be submitted but must be of equal print quality and clarity. If it is not obvious, the top of the figure should be indicated by an arrow on the back. Each table should be printed on a separate page. Tables or figures reproduced from other sources must be accompanied by permission from the authors and publishers of the original publication. Covering letter: Manuscripts should be submitted with a covering letter stating: • The article has not been published in whole or part elsewhere. (Publication in part or in abstract does not preclude publication in the World Federation Journal of Critical Care). • The article has not be submitted elsewhere. • If the manuscript should be returned to the authors in the event that it is not accepted for publication. • That clinical studies had been approved by the appropriate local institutional ethics committee following principles described in the Declaration of Helsinki and its revisions. • That the authors accept that Copyright in the manuscript will pass to the World Federation Journal of Critical Care when the manuscript is accepted for publication. Editorial review Authors of manuscripts that are clearly unsuitable for publication in Intensive Care World will be advised as soon as possible and such rejection does not necessarily indicate any adverse opinion on the content. It is usual for manuscripts to be reviewed by members of the Editorial Board or others chosen for their knowledge of the subject of the manuscript. Following this process papers may be rejected, returned to the authors with reviewers comments on the understanding they will be reconsidered if the issues raised can be answered satisfactorily, or accepted for publication. Some bias is exerted towards articles received from countries with limited local medical publishing opportunities. The manuscript, tables, figures and covering letter should be sent to: Dr Geoffrey J. Dobb Editor, World Federation Journal of Critical Care c/o Intensive Care Unit Royal Perth Hospital GPO Box X2213 Perth WA 6847 Australia Fax: (61) 8 9224 3196 E-mail: geoffrey.dobb@health.wa.gov.au The Editor and publishers reserve the right to edit manuscripts for length, format, style and spelling before publication, and to determine the timing and priority of articles submitted for publication. Transfer of Copyright is a condition of publication. Statements and opinions expressed by authors are not necessarily those of the Editor, Editorial Board or publishers. The Editor, Editorial Board and publishers disclaim any responsibility or liability in relation to all published material and do not guarantee or endorse any product or treatment that is named or described.
  4. 4. February 2004 page 1 World Federation Journal of Critical Care 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 of Critical Care ISSN 1447-9664 Editor Geoffrey J Dobb Royal Perth Hospital, GPO Box X2212 Perth, WA 6847 Australia Editorial Board Editor 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 Associates Lars Berggren Jose Besso Satish Bhagwanjee Guillermo Dominguez-Cherit Antonio Gallesio Antonio Gullo Francisco J De Latorre Jean-Roger Le Gall Rui Moreno Fernando Palizas Shirish Prayag Jun Takezawa Renato GG Terzi Ged Williams World Federation Journal of Critical Care will be distributed to approximately 25,000 intensivists from over 90 countries. Published by Cambridge Publishing – a division of Cambridge Media 17 Northwood Street West Leederville, WA 6007 Australia Website: www.cambridgemedia.com.au Copy Editor: Ceridwen Clocherty Graphic Designer: Gordon McDade Advertising enquiries to: Stewart Taylor Pathfinder ICS Ltd Grand Union Office Park Packet Boat Lane, Cowley Uxbridge, UB8 2GH, United Kingdom Tel: (44) 1895 460046 Fax: (44) 1895 859859 E-mail: stewart@pathfinderics.com World Federation Journal of Critical Care February 2004
  5. 5. page 2 February 2004 World Federation Journal of Critical Care President’s report Philip Lumb The World Federation of Societies of Intensive and Critical Care Medicine (WFSICCM) was established at a time when the professional intensive care world was small and composed of international colleagues facing similar clinical challenges in the absence of the advanced technology, global communications and organ specific knowledge we enjoy today. The goal of the World Federation was to provide easy access to new information and to share knowledge that would transcend national borders and improve the care of critically ill patients in all situations worldwide. Today, the WFSICCM coordinates the affiliation between 48 national society members. Each country is represented at the WFSICCM’s General Assembly meetings held every four years in association with its international congress. Although the General Assembly meeting supports an important and useful function by creating a unique forum in which international concerns, ideas and initiatives can be discussed, the World Federation has not fulfilled its objective to provide an ongoing and self-sustaining international resource that stimulates and codifies research initiatives, educational programmes, professional communication and development of standardised outcomes. These unmet objectives stimulated the current Council to refocus the organisation’s attention on its core mission and created the impetus to position the WFSICCM as the representative international body and coordinating centre of excellence for all critical and intensive care societies. This is an arrogant yet democratically achievable goal and, if successful, likely to supplement rather than compete with national society initiatives. The recent SARS epidemic has demonstrated that the international medical community has a greater common purpose than its political counterpart, and it is likely that the WFSICCM can create a readily available data repository for future efforts requiring international collaboration in critical care. In the current Pulmonary Perspectives, Judith Mackay writes that, ... living with SARS was akin to living an Agatha Christie novel. You are invited to an isolated country home for dinner and among the guests 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 put upon you, you might be dead. This it was, living at the front line with SARS1 . The World Federation is in a position to help the international critical care community become less isolated and more personal. The extent of interpersonal relationships could extend from ready electronic access to the most recent treatment protocols to contact information so that diagnostic questions and therapeutic options can be discussed openly and in real time. These should be developed within our organisation and community. It is unreasonable to anticipate that a new structure must be established whenever new illnesses threaten the international community; it is irresponsible not to respond to the challenge of creating the resource network likely to meet the international critical care community. This challenge is reflected in an editorial comment in the above referenced text. Deborah Shure says, “Hopefully, the rapid galvanization of the international community in both the public health and research arenas will prevent an epidemic worse than the one that has already occurred”. The Word Federation, with the help of its international members, intends to become the interpersonal clearing house and information central that will help clinicians feel less isolated and connected to a community of expert opinion and experience. Our members responded individually, transnationally and effectively to the SARS challenge. The CDC and other international organisations were effective in disseminating information about therapeutic and isolation requirements, and many of our members were involved in personal communication with international colleagues. The World Federation Council believes the presence of a central site for international critical care specific information will provide clinicians an additional and valuable resource in the face of future challenges. The ability to access information when it becomes available and to study its use post hoc would provide an invaluable research tool that would demonstrate the ways in which medical information modifies practice in response to unexpected challenges. The WFSICCM intends to establish a critical care communication and database resource on behalf of our members that will enhance the ability not only to respond to future national and international medical challenges, but also, and perhaps more importantly, to provide our members with a research and quality improvement tool that will validate therapeutic interventions and modifications in real time. The
  6. 6. February 2004 page 3 World Federation Journal of Critical Care WFSICCM is the unique critical care organisation that represents national societies equally and provides the forum in which a critical analysis of global critical care performance can be assessed. In order to realise our expectations, the WFSICCM is launching its website (http://www.world-critical-care.com) and introducing the World Federation Journal of Critical Care on 1 October 2003. Headquartered in Great Britain, the organisation is ably supported by a new secretarial infrastructure and business development professionals. Despite these improvements to administrative support, member involvement will be the most important determinant and measure of success. Different from a national society in which volunteerism is recognised and rewarded by increased visibility and responsibility within the national corporate network, contribution to the WFSICCM is more difficult to stimulate and reward. The Executive and Council are selected as representatives to the WFSICCM by their national societies and elected by the General Assembly; subsequently, the newly elected Council selects its officers for four-year terms. Not surprisingly, a corporate identity and institutional memory are difficult to create in this environment, and therein lays future opportunity and challenge. A website and opportunity to contribute to an internationally distributed, peer reviewed journal provide new opportunities for individuals to contribute to the vision of an internationally responsive critical care community. Individual members of representative national societies may be unaware that they are participants in the World Federation; this benefit accrues through a $1 annual dues capitation fee paid by their home organisation. Council is sponsoring the WFSICCM Academy that will permit physician members to develop a personal learning profile on new therapeutic agents. Tutorials leading to WFSICCM certification will be developed by recognised clinical experts. Although these learning modules cannot substitute for individual experience, nonetheless, before the introduction of any new agent, it is helpful for practitioners to have a frank discussion of clinical subtleties that may improve early efficacy. The tutorial format will be a clinical expert discussion that should prove beneficial to clinicians who wish to supplement their knowledge prior to prescription. Following a post course evaluation and examination, a certificate of completion will be issued to successful participants. On a lesser scale but equally informative is the recently distributed World Federation Calendar. In 2003, clinical information about the use of a new pharmacologic agent is presented in journal review format; in 2004, clinical ‘pearls’ of information from internationally recognised intensivists will be featured. The international scope and photographic excellence of the Secretary-General, Dr. Gilbert Park, must be recognised and applauded in this contribution. Increased national and individual ownership for the World Federation’s goals will develop from greater familiarity with the organisation and its administration. In addition to the educational and communication facilities discussed previously, the website will also provide important information about organisational structure, national membership, key contact information and critical links to information sources hosted by society members. A calendar of international conferences and special events will be updated regularly; additional information will be solicited from individual members. A key component of the World Federation will be its utility to individual members; feedback and critical reviews from members will be encouraged. Research initiatives are increasingly costly with patient identity and privacy rules further complicating transfer of information. A great deal can be accomplished with appropriately designed questionnaires that cross national and regional boundaries; the WFSICCM can provide members the resources necessary to initiate appropriately powered and controlled studies. Further ideas will be developed through member participation and feedback. Several questions may remain: Is there a role for a world focused intensive care organisation that will depend for its success upon support from national critical care societies, volunteerism from individual members, contributions from industry, consistency of production and dissemination of new information in a timely, dependable and credible manner? Are there benefits to be gained from a world organisation that cannot be provided by national societies with international connections? Is the world community likely to respond favourably to information from a non-traditional source? Despite these and other important concerns, the values of a world focus and partnership among critical care professionals cannot be denied. There is intense competition among national societies to host the World Federation Congresses, and the participation of internationally recognised critical care physicians in local educational events is desired. Fiscal constraints and travel restrictions often militate against greater participation in many events, and the World Federation is the unique resource that can assemble the world’s leading clinicians in an apolitical environment that fosters education, research and the dissemination of new information. The mission is clear; the infrastructure is established; the vision is evolving; with international participation and support, the outcome is assured. References 1. Mackay J. Pulmonary Perspectives, September 2003; Volume 20, Issue 3.
  7. 7. page 4 February 2004 World Federation Journal of Critical Care Editorial Welcome back! Geoffrey J Dobb The World Federation is delighted to be back with a publication which is made available to all members of Societies of intensive and critical care medicine affiliated to the Federation. There is nothing to be gained by recounting the events that resulted in us being unable to publish and distribute Intensive Care World as our publication was previously known. This will have been familiar to most working in the worldwide community of intensive and critical care medicine. To judge from the many letters and messages received when it failed to arrive with the accustomed regularity, it was missed by many. The members of the Council of the World Federation are undoubtedly sadder and wiser as result of the challenges we have faced over the last couple of years. However, we were able to publish an issue of our newly named World Federation Journal of Critical Care to coincide with the World Federation’s Congress in Sydney. Returning now to regular publication has proved to be a significant task. The joy of finally overcoming the legal, contractural and logistic issues associated with re-establishing a regular publication will be understood by all those who have been involved with their national Society’s publications. We now look forward to re-establishing relationships with our readers, authors and advertisers. Instructions to authors are included with this issue and we welcome appropriate contributions. The new publishers, Cambridge Media, have a strong track record in publication and a portfolio that includes internationally distributed medical and nursing journals. Their support during the start-up phase has been invaluable. I am also grateful to the members of the Editorial Board and the Council of the World Federation for their support through a difficult time. Communication is the ‘glue’ that helps to maintain the identity of the World Federation. With the re-established website and the journal, the World Federation is in better shape than it has been for some time. We look forward to maintaining the momentum. With the next Congress to be held in Argentina in 2005, the foundations of the Federation are looking better than ever. As critical care develops around the world, we look forward to having even more societies join the World Federation family. Stop press As the copy for this issue was finalised, the Council of the World Federation of Societies of Intensive and Critical Care Medicine recommended that the 2009 World Federation Congress be held in Italy. Several excellent bids to host the 2009 Congress were received, making this a most difficult decision. Final details have still to be agreed with the host societies, but further information should be available for our next issue. Congress Office Ana Juan Congresos Sarmiento 1562, 40 F (C1042ABD) Buenos Aires, Argentina Tel: (54) 11 4381 1777 Fax: (54) 11 4382 6703 E-mail (registration): iccm2005@anajuan.com E-mail (abstracts): registration@anajuan.com E-mail (scientific programme): scientific@anajuan.com E-mail (exhibition): congress@anajuan.com E-mail (hotels): turismo@anajuan.com SATI Sarmiento 2046 10 8 C 1044AAF Buenos Aires, Argentina E-mail: info@sati.org.ar Web: 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
  8. 8. February 2004 page 5 World Federation Journal of Critical Care Non-invasive ventilation in the Intensive Care Unit Introduction Non-invasive ventilation (NIV) is usually provided through bilevel pressure supported ventilatory assistance delivered without endotracheal intubation. Modern highly sophisticated purpose built bilevel positive airway pressure (BIPAP) devices now incorporate features such as titratable inspired oxygen fraction, leak compensation and adjustable positive end- expiratory pressure (PEEP) and pressure support (PS) with spontaneous-timed modes of ventilation (e.g. ‘Vision’ BiPAP). Continuous positive airway pressure (CPAP) is commonly delivered using a similar non-invasive patient interface with a mask. A BIPAP machine set to end-expiratory positive airway pressure (EPAP) mode can be used as the pressure-generating unit, though more simple devices are also available. Kannan 1 recently reviewed the indications, mechanics and practicalities of NIV in the Intensive Care Unit (ICU) for Intensive Care World. It is timely to highlight the evidence underlying some aspects of the use of NIV in the ICU and, in particular: • 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 chronic obstructive pulmonary disease (COPD) and other lung disease. • NIV support during diagnostic flexible bronchoscopy in patients with severe hypoxaemia. • BIPAP as a weaning strategy. • BIPAP for home ventilation. CPAP for cardiogenic pulmonary oedema The first description of CPAP was by Poulton2 in 1936. He used an ordinary vacuum cleaner in reverse-mode to blow air under pressure into the mouth of a patient with pulmonary oedema. Since then three randomised trials have investigated CPAP for cardiogenic pulmonary oedema 3-5 . Bersten et al. 3 demonstrated that respiratory rate, arterial pH, paCO2 and PaO2/FiO2 all improved more rapidly in the patients receiving CPAP than those receiving usual medical care. The advantage was lost at 24 hours but the frequency of endotracheal intubation and duration of hospital 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 BIPAP when compared to CPAP in patients with cardiogenic pulmonary oedema in a small prospective randomised controlled trial by Mehta et al. 6 . The study stopped early because the frequency of myocardial infarcts was significantly higher in the BIPAP group. This difference was probably explained by the lower frequency of chest pain in the CPAP group at recruitment. CPAP is the cheaper and simpler mode of NIV and no clinically important advantages such as duration of hospital stay, need for endotracheal intubation or mortality have been demonstrated with BIPAP. Therefore, CPAP is currently preferred to supplement usual medical treatment in patients with acute cardiogenic pulmonary oedema. The role of CPAP in avoiding re-intubation for severe non-hypercapnic hypoxaemia after surgery CPAP can reduce the need for reintubation in post-operative patients with severe non-hypercapnic hypoxaemia. In 20 consecutive patients who had undergone thoracic and/or abdominal surgery and met the hypoxaemia criterion (PaO2/FiO2<80) after extubation, 8-10cm H2O nasal CPAP (with FiO2 titration) overcame respiratory failure caused by atelectasis and/or left heart failure, so reintubation was avoided7 . BIPAP for acute respiratory failure in patients with COPD and other lung diseases Meduri et al.8 showed the effect on minute volume, tidal volume and PaO2/FiO2 is similar whether mechanical ventilation is applied using a face-mask or using endotracheal intubation. They studied 18 patients with type 2 acute respiratory failure mechanically ventilated for a mean of 25 hours and concluded face-mask mechanical ventilation is a viable alternative to endotracheal intubation for short-term (1-4 days) support. Subsequently, eight randomised controlled trials 9-16 have confirmed the effectiveness of non-invasive positive pressure ventilation for acute respiratory failure and only one clinical trial has produced a negative result17 . The pooled results from these studies give an odds ratio of 0.22 (95% confidence interval 0.09- 0.54) for a benefit of NIV compared to standard medical treatment in respect to the hospital mortality of COPD patients with hypercapnic acute respiratory failure. That is, level 1 evidence (Grade A recommendation) for its use18 . The study by Bott et al.10 included 60 COPD patients with acute respiratory failure managed in a general ward. It is particularly relevant to patients with severe COPD not thought appropriate for endotracheal intubation. The pH, pCO2 and dyspnoea scores were significantly better with a clinically relevant Gregory McGrath MB BS FRACP FJFICM Geoffrey J Dobb BSc MB MRCP FRCA FANZCA FJFICM Intensive Care Unit, Royal Perth Hospital, Perth, WA, Australia
  9. 9. page 6 February 2004 World Federation Journal of Critical Care improvement in the NIV group and a trend to reduced mortality (three vs nine deaths). In another study in 31 patients, most with COPD, the need for tracheal intubation during the first 48 hours was significantly greater in patients only receiving standard treatment compared with those also provided with NIV 13 (11 vs five patients, p<0.05). Duration of hospital stay and mortality were similar and there was no difference in the combined respiratory- therapist and nursing time spent per 8 hour shift by the bedside between the patient groups (mean: NIV 200 minutes, standard treatment 180 minutes). Brochard’s group12 also investigated the effect of NIV in COPD patients in the ICU on the need for endotracheal intubation, randomising NIV with 20 cmH2O PS and zero PEEP against standard treatment (Table 1). The NIV group had the better overall outcomes. Wysocki et al. 14 , in a study which excluded patients with COPD, randomised 41 patients with acute respiratory failure to either NIV (n=21) or standard treatment (n=20). A post-hoc subgroup analysis of the patients who were hypercapnic (pCO2>45mmHg) suggested the outcome was improved in terms of the need for endotracheal intubation, duration of hospital stay and mortality in the group receiving NIV who were hypercapnic (absolute reduction 64%, 29% and 57%, respectively). Martin et al.16 also found the need for endotracheal intubation was significantly less with NIV (6.4 intubations vs 21.3 per 100 ICU bed-days; p=0.002) in patients with various aetiologies for acute 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 comparison19 of intermittent NIV with standard treatment, which included supplemental oxygen but no ventilatory support in 52 immunocompromised patients with pulmonary infiltrates and fever, the results again favoured NIV. Fewer patients in the NIV group needed endotracheal intubation (12 vs 20, p=0.03), had serious complications (13 vs 21, p=0.02) or died in hospital (13 vs 21, p=0.02). When compared directly against conventional mechanical ventilation 15 , NIV appears equally effective in improving oxygenation but associated with fewer complications. In a randomised study of 64 patients, predominantly with type 1 acute respiratory failure (PaO2/FiO2<200mmHg), management included either conventional mechanical ventilation or NIV (with a strategy to optimise PS to give tidal volumes 7-10 ml/kg and optimise PEEP to allow FiO2<0.6). Only 6% failed to tolerate NIV, and in the NIV group 31% progressed to requiring endotracheal intubation. The overall complication rate was 38% for the NIV group and 66% for conventional ventilation (on intention to treat, p=0.02). The most frequent complications were sepsis from pneumonia and sinusitis. The level 2 evidence available supports a grade B recommendation for use of NIV in non-COPD causes of acute respiratory failure. NIV support for diagnostic flexible bronchoscopy in severe hypoxaemia High-risk patients who would otherwise need endotracheal intubation and mechanical ventilation to allow diagnostic flexible fibreoptic bronchoscopy and overcome concern about inducing hypoxaemia may be considered for awake-sedated bronchoscopy through a BIPAP interface. Antonelli et al. 20 performed bronchoalveolar lavage (BAL) on eight immunosuppressed patients with pneumonia and acute respiratory failure (PaO2/FiO2<100mmHg) through a Bard face mask with t-seal adaptor connected to a ventilator in pressure control mode ventilation (pressure 17cm H2O, PEEP 4cm H2O). No patient required endotracheal intubation, none developed hypercapnia or hypoxaemia and all had diagnostic BAL successfully performed. A novel CPAP face-mask was used by Maitre et al. 21 in their randomised controlled trial in 30 hypoxaemic patients (PaO2/FiO2<300mmHg) who required diagnostic fibreoptic bronchoscopy. In the group randomised to receive oxygen only seven out of 15 required mechanical ventilation after bronchoscopy whereas only one of those performed during CPAP developed ventilatory failure (intention to treat p<0.03) BIPAP as a weaning strategy Intubated patients with COPD and type 2 acute respiratory failure can be difficult to wean from ventilatory support and may need prolonged endotracheal intubation or tracheostomy. Nava and others, in a multicentre randomised trial22 , attempted weaning at 48 hours in a group intubated on admission to hospital for severe hypercapnic respiratory failure. Those who could not be extubated were randomised into two groups. 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 weaned compared to 68% of the group who remained intubated (p=0.02). The duration of hospital stay was less in the NIV group at 15.1+/-5.4 days compared with 24.0+/-13.7 days (p=0.005), and 60 day survival was significantly better (92% vs 72% 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 treatment alone12 .
  10. 10. February 2004 page 7 World Federation Journal of Critical Care ‘Partial weaning’ from invasive to non-invasive ventilation may be sufficient to allow step-down of a patient to a lesser intensity care facility or even to home ventilation. One third of patients who failed conventional weaning from mechanical ventilation in a study by Scheinhorn 23 were successfully withdrawn from ventilator dependence using BIPAP (n=34). Home mechanical ventilation was established in 75/109 patients. BIPAP for home ventilation Patients who need 24 hour ventilatory support at home usually have a tracheostomy but, in selected cases, a non-invasive interface may be sufficient, especially if this is combined with supplemental oxygen, glossopharyngeal breathing, a pneumobelt, negative pressure ventilation devices or diaphragmatic pacing to allow daytime freedom from the NIV interface for meals, washing etc24 . Such methods can be useful for selected patients with obstructive or interstitial lung disease as a bridge to lung transplantation, allowing care away from the ICU. Quality of life issues can detract from the merit of home BIPAP for patients with end-stage lung disease who are not candidates for a lung transplant. It may, however, still be worthwhile on a case by case basis with appropriate community supports. Other typical indications for home ventilation in which NIV may have a role include neuromuscular and chest wall diseases and central hypoventilation syndromes. After recovery from a reversible exacerbation of their disease, such patients may be discharged back home from the ICU25 . Conclusion Evidence supports the role of non-invasive ventilation in the ICU treatment of patients with acute respiratory failure caused by acute pulmonary oedema, post-operative hypoxaemia, hypercapnic exacerbations of COPD, non-COPD pulmonary causes of acute respiratory failure, and also for assisting diagnostic bronchoscopy in high risk patients. It may assist in weaning patients from ventilator dependence and make it possible to discharge from the ICU patients dependent on chronic ventilatory support, ultimately to their home or as a bridge to lung transplantation. References 1. Kannan S. Non-invasive ventilation. Intensive Care World 2000; 16(1):20-25. 2. Poulton PE. Left-sided heart failure with pulmonary oedema: its treatment with 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 continuous positive 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 airway pressure therapy in acute cardiogenic pulmonary oedema: short term results and long term follow up. Chest 1995; 107:1379-1386. 5. Rasanen J, Heikklua J, Downs J et al. Continuous positive airway pressure by 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 bilevel verses continuous positive airway pressure in acute pulmonary edema. Crit Care Med 1998; 25:620-628. 7. Kindgen-Milles D, Buhl R, Gabriel A et al. Nasal continuous positive airway pressure: a method to avoid endotracheal reintubation in postoperative high-risk patients with severe nonhypercapnic oxygenation failure. Chest 2000; 117:1106-1111. 8. Meduri GU, Abou-Shala N, Fox RC et al. Noninvasive face mask mechanical ventilation in patients with acute hypercapnic respiratory failure. Chest 1991; 100:445-454. 9. Ahmed AH, Fenwick L, Angus RM et al. Nasal ventilation verses doxapram in the treatment of type II respiratory failure complicating chronic airflow obstruction. Thorax 1992; 47:A858. 10. Bott J, Carroll MP, Conway A et al. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet 1993; 341:1555-1557. 11. Daskalopoulou E, Teara V, Fekete V et al. Treatment of acute respiratory failure 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 acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995; 333:817-822. 13. Kramer N, Meyer TJ, Meharg J et al. Randomized prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 1995; 151:1799-1806. 14. Wysocki M, Tric L, Wolff MA et al. Noninvasive pressure support ventilation in patients with acute respiratory failure: a randomized comparison with conventional therapy. Chest 1995; 107:761-768. 15. Antonelli M, Conti G, Rocco M et al. A comparison of noninvasive positive pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998; 339:429-435. 16. Martin TJ, Hovis JD, Costantino JP et al. A randomized prospective evaluation of noninvasive ventilation for acute respiratory failure. Am J Respir Crit Care Med 2000; 161:807-813. 17. Barbe F, Togores B, Rubi M et al. Noninvasive ventilatory support does not facilitate recovery from acute respiratory failure in chronic obstructive pulmonary disease. Eur Respir J 1996; 9:1940-1945. 18. Keenan SP & Brake D. An evidence-based approach to noninvasive ventilation in acute respiratory failure. Crit Care Clin 1998; 14:359-372. 19. Hilberg, Gruson D, Vasgas F et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever and acute respiratory failure. N Engl J Med 2001; 344:481-487. 20. Antonelli M, Conti G, Riccioni L et al. Noninvasive positive-pressure ventilation via face mask during bronchoscopy with BAL in high-risk hypoxemic patients. Chest 1996; 110:724-728. 21. Maitre B, Jaber S, Maggiore S et al. Continuous positive airway pressure during 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 ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease. A randomized controlled trial. Ann Intern Med 1998; 128:721-728. 23. Scheinhorn DJ, Artinian BM & Catlin JL. Weaning from prolonged mechanical 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 h ventilator-dependent patient. Eur Respir Mon 1998; 8:364-379. 25. Hill NS & Goldberg AI. Mechanical ventilation beyond the intensive care unit. Chest 1998; 113(Suppl):289S-344S.
  11. 11. page 8 February 2004 World Federation Journal of Critical Care Introduction Monitoring 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 compliance1-3 . In the last decade, mechanical ventilators have provided clinicians with a new type of monitoring, commonly known as ventilator graphics4. 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, RRT Associate Professor of Surgery Kenneth Davis Jr. MD Associate Professor of Surgery and Anesthesia Assistant Dean of Medical Education Robert S Campbell RRT Senior Research Associate University of Cincinnati, Department of Surgery Cincinnati, Ohio, USA The scalars – pressure, volume and flow vs time Representations 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 investigations5-7 . 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 increased9, 10 .
  12. 12. February 2004 page 9 World Federation Journal of Critical Care 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 during volume controlled ventilation. The first breath is an unassisted breath. All other breaths demonstrate the effects of patient demand on the airway pressure waveform. Comparison of the unassisted breath to the assisted breaths improves detection of flow dysynchrony. Figure 4. Typical volume waveform seen in the presence of an airleak. Note that volume does not return to baseline during exhalation (arrow). Figure 3. PSV using the Puritan-Bennett 7200. Normal flow cycling criteria is 5L/min. In this example the breath is cycled at a flow of 35L/min. Active exhalation by the patient causes the breaths to be pressure cycled. Figure 1. A: Change from constant (square) flow to decelerating flow waveform using a ventilator which maintains the peak flow constant resulting in an increase in inspiratory time. B: Change from constant (square) flow to full decelerating flow waveform (peak flow to 0L/min) and a 50% decelerating flow waveform (peak flow to 50% of peak flow) using a ventilator which maintains inspiratory time constant resulting in an increase in peak inspiratory 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.
  13. 13. page 10 February 2004 World Federation Journal of Critical Care 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 PEEP2, 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 lung compliance is reduced. Note that the angle of deceleration increases and an inspiratory pause is produced as compliance diminishes. Figure 8. PEEP created during pressure control inverse ratio ventilation. The expiratory pause and increase in pressure (arrow) depicts the total PEEP. Figure 6. The effects of lengthening inspiratory time during pressure control ventilation. The first breath demonstrates flow >0L/min at end inspiration (arrow). In the second breath, inspiratory time is lengthened until end inspiratory flow =0L/min (double arrow). This resulted in an increase in tidal volume from 520mL to 590mL. Figure 7. Classic appearance of the expiratory flow waveform (arrows) during PEEP. The failure of expiratory flow to return to 0L/min prior to delivery of the next breath detects PEEP, but cannot determine it quantitatively.
  14. 14. February 2004 page 11 World Federation Journal of Critical Care 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 ARDS21-24 . 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 met23 : • 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 scrutiny 25-27 . 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 curve demonstrates a lower inflection point (arrow), but not an upper inflection point. Figure 10. Characteristic shape of the PV curve during volume ventilation demonstrating overdistension (arrow). This is indicative of the upper inflection point and is associated with alveolar overdistension. Figure 11. Flow volume curves, before (A) and after (B) bronchodilator therapy in a mechanically ventilated patient with chronic obstructive pulmonary disease. Note the increase in peak expiratory flow and the reduction in flow limitation towards end exhalation.
  15. 15. page 12 February 2004 World Federation Journal of Critical Care 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. References 1. 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 pressure and dynamic hyperinflation. Clin Chest Med 1996; 17:379-394. 3. Truwit JD & Marini JJ. Evaluation of thoracic mechanics in the ventilated patient. 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 (2nd ed). Lippincott, Williams & Wilkins. Philadelphia PA 1999 p.303-324. 5. Davis Jr K, Branson RD, Campbell RS & Porembka DT. Comparison of volume control and pressure control ventilation: Is flow waveform the difference? J Trauma 1996; 41:808-814. 6. Al-Saady N & Bennett ED. Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive pressure ventilation. Intensive Care Med 1987; 11:68. 7. Rappaport SH, Shpiner R, Yoshihara G et al. Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure. Crit Care Med 1994; 22:2. 8. Marini JJ & Ravenscraft SA. Mean airway pressure: physiologic determinants and measurements. Crit Care Med 1992; 20:1461-1472. 9. Hubmayr RD. Setting the ventilator. In: Tobin MJ (Ed). Principles and Practice of Mechanical Ventilation. New York: McGraw Hill, 1994. 10. Marini JJ, Rodriquez RM & Lamb V. Bedside estimation of work of breathing 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 spontaneous breathing 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 Respir Crit Care Med 1997; 155:1629-1636. 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 Respir Crit Care Med 1997; 156:1082-1091. 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.
  16. 16. February 2004 page 13 World Federation Journal of Critical Care Abstract Acute renal failure (ARF) is a common problem in the intensive care unit (ICU), often as a component of multiple organ failure. Intermittent haemodialysis was the standard treatment for ARF but in many units continuous renal replacement therapy (CRRT) is now the treatment of choice. Several manufacturers have developed machines specifically designed for continuous venovenous haemofiltration (CVVH) in the ICU. This article reviews some of the practical aspects of renal replacement therapy including the choice of method, vascular access, pre-compared with post-filter infusion of substitution or replacement fluid, choice of filter, choice of substitution fluid, the apparatus and staff training. The controversial issue of inflammatory mediator clearance by haemofiltration is discussed. Introduction ARF is a common problem in ICUs. In contrast to chronic renal failure, ARF is usually not caused by primary renal diseases, but develops in the context of multisystem organ failure (MSOF). The standard treatment for patients with chronic renal failure is haemodialysis and it is usually well tolerated by these patients. In contrast, intermittent haemodialysis in patients with MSOF is associated with negative effects on haemodynamic function and gas exchange. Moreover, MSOF patients are often in such a catabolic state that daily haemodialysis is needed to restore metabolic homeostasis. These factors together make intermittent haemodialysis an unattractive option for MSOF patients and it has been replaced in many units by some form of CRRT. Continuous arteriovenous haemofiltration (CAVH) was initially the method of choice to treat ARF patients with some form of continuous therapy 1-2 . As systemic blood pressure supplies the perfusion pressure of the filter, ultrafiltrate volume was limited to 12 litres per 24 hours. This low ultrafiltrate volume and the low inherent clearance of CAVH make it difficult to maintain adequate metabolic control in patients needing intensive care. Solutions to this problem are the addition of a dialysis component to the system, creating continuous arteriovenous haemofiltration (CAVH) 3-4 or the insertion of a roller pump into the arterial limb of the filter, creating pumped CAVH. Later, the latter technique was replaced by CVVH, abolishing the need of arterial cannulation. Now, CVVH is so well accepted in ICUs that multiple manufacturers have developed machines specifically designed for CVVH to deliver renal replacement therapy in the ICU. This article is describes the practical aspects of acute renal replacement 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 therapy Numerous studies have shown that continuous techniques are associated with better metabolic control than intermittent techniques. An important advantage of continuous techniques is that the large amounts of infusion fluids that are needed for antibiotics, enteral feeding and inotropic drug infusions can be administered to the patient without disturbing the fluid balance5 . Several studies that used historical control groups indicate that CRRT is associated with an improved survival and a shorter stay in the ICU6 . In the Netherlands, another consideration in the choice is that many more hospitals have ICUs than hospitals with a haemodialysis department. Although even 12 years ago, some groups suggested that it was almost unethical to deliver CRRT to patients in the ICU if no back up from a haemodialysis department was present, this view is not supported nor defended any longer. One of the reasons it is impossible to defend this point of view is that ARF seldom leads to chronic renal failure. Also, the few hospitals with haemodialysis departments could never treat all the patients with ARF. Practical aspects of haemofiltration AF Grootendorst MD PhD Department of Intensive Care I. van Stijn MD R. Peters MD Department of Internal Medicine St. Clara Hospital, Rotterdam, The Netherlands
  17. 17. page 14 February 2004 World Federation Journal of Critical Care The acceptance of CRRT in preference to intermittent dialysis in ICUs is apparent because more than 90% of the ICUs in the Netherlands treat renal failure with some form of continuous therapy 7 . This leaves us with the question – which form of continuous therapy should be preferred. CAVH is now seldom used because it is simply incapable of maintaining adequate metabolic control in most of the intensive care patients. Venovenous forms of renal replacement therapy have the inherent disadvantage of needing more complex apparatus than needed for CAVH, but this apparatus has become so widely accepted in the ICU that it is no longer a significant disadvantage. In practice, CVVH is the therapy of choice in most ICUs with CAVHD the second choice. Additional value of high volume CVVH over other forms of renal replacement therapy Since 1984, several studies have investigated whether some form of haemofiltration would have additional value in the treatment of patients with MSOF by removing the mediators of sepsis that are responsible for MSOF and hypotension. It appears that any form of haemofiltration, either low or high volume, is capable of removing mediators of sepsis. This capability was demonstrated by the presence of these mediators in the ultrafiltrate 8-11 . This led to several other studies that aimed to show that CVVH using high volume ultrafiltrate is superior to low ultrafiltrate volume techniques. Unfortunately, while the animal experimental studies were well designed, most of the clinical studies were not. In summary, the animal studies conclude that high volume filtration in animal models of septic shock leads to improved haemodynamics and improved gas exchange, and that the magnitude of these beneficial effects is related to the ultrafiltrate volume 12 . In patients, no randomised prospective trial has been performed to answer this question. Studies using historical control groups indicate that CVVH is associated with a marked reduction in mortality, length of stay in the ICU, improved haemodynamics and improved gas exchange11, 13 . In addition, it appears that low volume haemofiltration using CAVH improves haemodynamic parameters after cardiopulmonary bypass surgery14 . After these initial clinical studies, several more recent investigations have examined whether the presence of mediators of sepsis in the ultrafiltrate reduced their serum concentrations. All these studies show that haemofiltration does remove mediators of sepsis, but does not lead to the expected reduction in the serum concentrations 9, 11 . Several explanations may explain this phenomenon: • The study period was too short to show the reduction in serum concentrations of mediators of sepsis. • The blood-membrane contact stimulates mediator production, counteracting the effects of elimination. • The serum compartment is filled with mediators of sepsis from the tissue compartment. In this case, the absence of reduction of serum levels of mediators of sepsis would not imply that the therapy is useless. This hypothesis is supported by in vitro experiments using human blood to which a standard amount of sepsis mediators are added that show a reduction in the serum concentrations of mediators with filtrations. • The filters that were used in the studies were not the right filters to remove the targeted mediators of sepsis. Several studies indicate, for instance, that polysulphone hardly removes IL-6, in contrast to other filters15 . High volume haemofiltration remains a primary focus of attention among the potential treatments for MSOF. There are no prospective randomised trials as yet to demonstrate efficacy, though at least two studies are underway. The choice of filter may be a critical factor in determining the results of these studies if one assumes that one or a couple of mediators of sepsis play a pivotal role in the genesis of MSOF. However, no such mediator has been identified, so it is questionable if focusing on the removal of one mediator is the right direction for future research. Another approach to studying the effects of haemofiltration is to assess the capability of serum to activate macrophages and leukocytes, comparing serum before haemofiltration to serum after haemofiltration or to study the changes in phagocytosis by macrophages16 . Choice of vascular access, pre- versus post- dilution The standard access for any form of CVVH therapy is a double lumen catheter. A disadvantage of these catheters is recirculation. One study indicates that changing the arterial and venous limb of the catheter may drastically increase the amount of recirculation. In this study, a filter flow of 200ml/min was associated with a recirculation of 6.5%; reversing the arterial and venous limb increased this percentage to 19.7% 17 . This may not seem a lot, but on treatment with an ultrafiltrate production of 100L per day, nearly 20L are needed just to abolish the effect of recirculation. The choice of the venous site is dictated by the normal considerations that are used to choose the introduction site, especially with regards to the risk of infection. The risk is least in the subclavian position, the internal jugular is next and the femoral position carries the greatest risk of catheter infection. All vascular access catheters available in the Netherlands allow a flow of at least 300ml/min.
  18. 18. February 2004 page 15 World Federation Journal of Critical Care 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 fluid19 . 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, the clearance with pre-dilution and post-dilution are Quf and Quf* 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 during pre-dilution when the substitution fluid flow is increased, as illustrated 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.
  19. 19. page 16 February 2004 World Federation Journal of Critical Care 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 accurate20 . 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. References 1. Kramer P, Wigger W, Rieger J, Matthaei D & Scheler F. Arteriovenous hemofiltration: a new and simple method for treatment of over-hydrated patients 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; clinical use and operational characteristics. Ann Intern Med 1983; 99:455-460. 3. Geronemus R & Schneider N. Continuous arteriovenous hemodialysis: a new modality for treatment of acute renal failure. Trans Am Soc Artif Intern Organs 1984; 30:610-613. 4. van Geelen JA, Vincent HH & Schalekamp MADH. Continuous arteriovenous 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 acute renal failure. N Engl J Med 1997; 336:1303-1309. 6. Kruczynski K, Irvine-Bird K, Toffelmire EB & Morton AR. A comparison of continuous arteriovenous hemofiltration and intermittent hemodialysis in acute renal failure in the intensive care unit. ASAIO J 1993; 39:M778-781. 7. Bommel EFH van & Poussen HH. Continuous or intermittent treatment for 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-8 extraction during continuous venovenous hemodiafiltration in septic acute renal 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 inflammatory response 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 continuous hemofiltration: a laboratory and clinical study. Contrib Nephrol 1995; 116: 62-75. 11. Heering P, Morgera S, Schmitz FJ et al. Cytokine removal and cardiovascular hemodynamics in septic patients with CVVH. Intensive Care 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 of endotoxin-induced shock in the pig. Crit Care 1992; 7:67-75. 13. Krüger I, Jacobi C & Landwehr P. Effects of continuous venovenous hemofiltration on pulmonary function and hemodynamics in postoperative septic multiorgan failure. Contrib Nephrol 1995; 116:108-111. 14. Coraim F, Pauser G, Stellwag F, Werner T & Ziegler W. Positive modification of hemodynamics in post cardiac surgery patients by hemofiltration. Improved method for the demonstration of myocardial depressant factor in hemofiltrate. Anaesthetist 1985; 34: 236-240. 15. Bouman CS, van Olden RW & Stoutenbeek CP. Cytokine filtration and adsorption during pre- and postdilution hemofiltration in four different membranes. Blood Purif 1998; 16: 261-268. 16. DiScipio AW & Burchard KW. Continuous arteriovenous hemofiltration attenuates polymorphonuclear phagocytosis in porcine intra-abdominal sepsis. 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 cellulosic and a synthetic high-flux dialyser: a randomised crossover comparison between 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: use in critically ill patients. Nephrol Dial Transplant 1997; 12:1212-1217. 20. Peters R, Grootendorst AF. In press.
  20. 20. February 2004 page 17 World Federation Journal of Critical Care Abstract Fulminant 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 in the immediate postoperative period in patients with more than five days on mechanical ventilation (MV); p<0.008. HAV is the most frequent cause of FHF in Argentina. OLT reduces mortality in patients with FHF admitted to PICU, and has become an effective alternative treatment for FHF. Introduction AH is one of the major causes of liver disease worldwide 1 . Clinical presentation, regardless of aetiology, ranges from asymptomatic illness to FHF. This syndrome is caused by severe functional liver impairment with hepatocyte necrosis, leading to rapid development of hepatic encephalopathy in patients who do not have pre-existing liver disease 2 . New syndromes have been described recently according to the time interval between jaundice and the onset of encephalopathy3, 4 . Mortality ranges from 70-95% 5-7 and cerebral oedema is the main cause of death 8, 9 . Supportive care alone has been unsuccessful in the management of FHF, and OLT has become a widely accepted treatment with a 56-80% survival rate10-13 . In November 1992, a liver transplantation programme was set up at the Children’s Hospital Dr JP Garrahan 14, 15 . Favourable outcomes in the first elective cases motivated the use of this procedure in patients with FHF. This study reports our experience with OLT in 62 patients with FHF admitted to the PICU. Patients and methods Between January 1993 and May 1998, 62 patients with FHF admitted to our PICU met the King’s College criteria16 for liver transplantation; 35 boys and 27 girls. The cause of hepatic failure was HAV in 45 children (72.5%) and non-A, non-B, non-C hepatitis (non-ABC) in 17 (27.5%). None of the patients had a history of pre-existing liver disease. Signs of liver failure, defined as an increase in prothrombin time (PT) and plasma level of clotting factor V (FV) below 50% of normal, were present. All children had jaundice and marked increases in serum aminotransferases. FHF was diagnosed in patients developing encephalopathy within 8 weeks from the onset of jaundice. Fulminant hepatic failure in paediatric patients: results of orthotopic liver transplantation Jorge S. Sasbón MD Paediatric Intensive Care Unit Mónica Centeno MD Paediatric Intensive Care Unit Mirta Ciocca MD Gastroenterology Department Gustavo Bianco MD Liver Transplant Unit Miriam Cuarterolo MD Gastroenterology Department Oscar Imventarza MD Liver Transplant Unit Hospital de Pediatría Dr. JP Garrahan Combate de los Pozos, Buenos Aires, Argentina
  21. 21. page 18 February 2004 World Federation Journal of Critical Care Five patients were considered unsuitable for transplantation: two because of genetic syndromes, one patient with sepsis and two children with multiple organ failure (MOF). Twenty one patients died before a suitable donor could be found, all patients because of severe liver insufficiency and MOF. One patient recovered with supportive treatment alone. Thirty five patients underwent liver transplantation. Laboratory investigations to identify the cause of AH included analyses for IgM antibodies to HAV, hepatitis B surface antigen (HBs Ag), IgM and IgG antibodies to the hepatitis B core antigen, antibodies to the hepatitis C virus (anti.HCV) and HCV RNA. Other hepatotropic viruses (Epstein Barr virus, Cytomegalovirus, Herpes virus types 1 and 2), auto-immune hepatitis and Wilson’s disease were excluded. Encephalopathy was classified into four stages 17 . Cerebral oedema was suggested by the presence of one or more of the following clinical signs – arterial hypertension, hyperventilation, opisthotonus, decerebrate posture, cardiac arrhythmias, seizures, poorly reactive pupils or asymmetric pupils. The Glasgow Coma Scale (GCS) was used for neurological assessment and prognosis, evaluating eye, verbal and motor responses 18 . This scale was chosen because it is routinely used in the PICU for the clinical management of patients. Treatment Preoperative management All patients were given similar standard supportive care: intravenous glucose infusion, lactulose, neomycin and selective bowel decontamination 19, 20 . Fresh frozen plasma was given to patients with active bleeding or before invasive procedures. Routine blood tests were performed daily. Computed tomography scans and electroencephalograms were performed as indicated by the neurological status. Endotracheal intubation and MV were instituted in patients with encephalopathy stages III-IV. Patients with clinical or tomographic signs of cerebral oedema were hyperventilated, positioned 30° head up and received 20% mannitol. Surgical procedure Thirty nine transplants were performed in 35 patients. The mean donor weight was 75kg. Thirty two grafts were ABO identical and seven non-identical: three ABO-incompatible (O/A) and four ABO-compatible (A/O+B/O). The mean donor/recipient weight ratio was 5:1. Eight full size grafts (21%) were used and the remaining 31 (79%) were reduced in size using previously described techniques21, 22 . Segments II-III-IV were used in four; segments II-III in 22, two being split livers; and segments I-II-III-IV in five 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 technique23 . 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.
  22. 22. February 2004 page 19 World Federation Journal of Critical Care Results Characteristics of patients receiving transplants Thirty nine liver transplants were performed in 35 children; 14 girls and 21 boys. The cause of hepatitis was HAV in 24 patients (68%) and non-ABC hepatitis in 11 patients (32%). Three children required re-transplantation because of primary graft failure in the immediate post-operative period and another patient 1108 days after transplantation because of chronic rejection. At the time of transplantation, 15 patients had stage I encephalopathy, 10 had stage II, 9 had stage III and one had stage IV (mean encephalopathy stage: 1.8+1.0). The Glasgow Coma 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 were normal in eight and cerebral oedema was demonstrated in five patients (four with grade III encephalopathy and one with grade IV). Endotracheal intubation and MV were indicated in 10 children before transplantation (mean 0.9 days, range 0-7 days). Results of transplantation For the total group of 62 patients there was no statistically significant effect of age, sex, weight, or aetiology on the final outcome. Patients who received a transplant had similar clinical characteristics to those who did not receive a transplant at the time of listing. However, liver transplantation had a significant effect on survival compared to than supportive treatment alone (p<0.0001) (Table 3). The survival in patients undergoing transplantation for FHF caused by HAV hepatitis was 75% compared with 45% in patients with non-ABC hepatitis (not significant). Twenty patients with FHF caused by HAV who did not receive a transplant died (95%) and only one survived. All six patients with non-ABC hepatitis not transplanted died. Of the 35 patients who underwent liver transplantation, 23 (65%) had an immediate successful outcome. Complications occurring during the stay in PICU included: nine episodes of infection (eight bacterial and one fungal); seven acute rejection episodes in seven patients, who recovered with treatment; eight patients developed renal failure, two required haemofiltration and one child needed further surgery for abdominal bleeding. One patient died 95 days after transplantation from haemophagocitic syndrome and fungal sepsis. The 22 other patients were alive and leading a normal life, 4 months to 4 years after transplantation. Twelve patients (35%) died in the early post-operative period in the PICU after a mean of 12+8, range 7-18 days. The cause of death was MOF in 10 patients, brain death in one and refractory hypoxaemia in another. Three children had primary non- function, three had fungal sepsis – two Candida parapsilosis, one Candida 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 square n: 24 n: 38 p Aetiology HAV (45) 19 42.3% 26 57.7% Non-ABC (17) 5 29.4% 12 70.6% 0.329 Treatment Transplant (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 62 patients.

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