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THEHONGKONG

MEDICALDIARYwww.fmshk.org VOL.14 NO.9 SEPTEMBER 2009

ISSN 1812 - 1691OFFICIAL PUBLICATION FOR THE FEDERATION OF MEDICAL SOCIETIES OF HONG KONG

Intensive Care

VOL.11 NO.5 MAY 2006 Editorial

1

VOL.14 NO.9 SEPTEMBER 2009

ContentsEditorial

� Editorial 2

Education Bulletin

� MCHK CME Programme Self-assessment Questions

Dr. Donald YC YUDr. Jane CK CHAN

Dr. Jane CK CHAN

� 5Adult Respiratory Distress Syndrome: Challenges and Triumphs

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37Medical Diary of September

Calendar of Events

39� Meetings39� Courses

� Sedation and Analgesia in the Intensive Care Unit Drug Review

31Dr. Judith SHEN

� Scuba Diving Life Style

35Dr. Gloria PEI

� Dermatological QuizDermatological Quiz

36Dr. Lai-yin CHONG

Society News

� 13Update of Renal Replacement Therapy in the ICUDr. Wing-wa YAN

� 19Molecular Adsorbents Recirculating System (MARS):Evidence and Management PitfallsProf. Sheung-tat FAN Dr. Alexander CHIU

� 23Mechanical Circulatory Support in the Intensive Care UnitDr. Elaine MC CHAUDr. Tak-fu TSE

� 29Infectious Disease Emergencies Dr. Samson SY WONGDr. Vincent CC CHENG

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Federation News 40

Published byThe Federation of Medical Societies of Hong Kong

EDITOR-IN-CHIEFDr. MOK Chun-on莫鎮安醫生

EDITORSDr. CHAN Chi-fung, Godfrey陳志峰醫生 (Paediatrics)Dr. CHAN Chun-hon, Edmond陳振漢醫生 (General Practice)Dr. KING Wing-keung, Walter金永強醫生 (Plastic Surgery)Dr. YU Kong-san俞江山醫生 (Orthopaedics & Traumatology)

EDITORIAL BOARDDr. CHAN Chi-wai, Angus陳志偉醫生 (General Surgery)Dr. CHAN, Norman陳諾醫生 (Diabetes, Endocrinology & Metabolism)Dr. CHIANG Chung-seung蔣忠想醫生 (Cardiology)Dr. CHIM Chor-sang,James詹楚生醫生 (Haematology)Dr. CHONG Lai-yin莊禮賢醫生 (Dermatology & Venereology)Dr. FAN Yiu-wah范耀華醫生 (Neurosurgery)Dr. FOO Wai-lum, William傅惠霖醫生 (Oncology)Dr. FONG Ka-yeung方嘉揚醫生 (Neurology)Prof. HO Pak-leung何　良醫生 (Microbiology)Dr. KWOK Po-yin, Samuel郭寶賢醫生 (General Surgery)Dr. LAI Kei-wai, Christopher賴奇偉醫生 (Respiratory Medicine)Dr. LAI Sik-to, Thomas黎錫滔醫生 (Gastroenterology & Hepatology)Dr. LAI Yuk-yau, Timothy賴旭佑醫生 (Ophthalmology)Dr. LAM Tat-chung, Paul林達聰醫生 (Psychiatry)Dr. LAM Wai-man, Wendy林慧文醫生 (Radiology)Dr. LEE Man-piu, Albert李文彪醫生 (Dentistry)Dr. LO, Richard羅光彥醫生 (Urology)Dr. LO See-kit, Raymond勞思傑醫生 (Geriatric Medicine)Dr. MAN Chi-wai文志偉醫生 (Urology)Dr. MOK, Mo-yin莫慕賢醫生 (Rheumatology)Dr. TSANG Wai-kay曾偉基醫生 (Nephrology)Dr. TSE Tak-fu謝德富醫生 (Cardiology)Prof. WEI I, William韋霖醫生 (Otorhinolaryngology)Dr. WONG Bun-lap, Bernard黃品立醫生 (Cardiology)

Design and Production

Editorial

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This September issue of the Hong Kong Medical Diaryon Intensive Care represents the very first time theMedical Diary has incorporated Intensive Care into thelist of medical topics to be shared with Diary readers.The breadth of mind of the Diary Editors forentertaining non-traditional medical subjects such asIntensive Care and the boldness in committing onewhole issue to this subject are much to be congratulatedon for making this issue possible. Much gratitude goesto the current and former Editors-in-Chief, Drs Chun-onMok and Walter King, for their kind encouragementand support. Much gratitude also goes to the esteemedauthors of this issue, who, based on their vastexperience in managing the critically ill in the intensivecare unit (ICU), have together produced this veryhandsome issue on Intensive Care.

Indeed the timing for the birth of this issue on IntensiveCare is just right. For a few decades after the initialdevelopment of negative pressure ventilators (or so-called iron lung) to support patients with respiratoryfailure during the polio epidemic, the ICU hadremained a rather humble shapeless place, usuallyserving as a post-operative recovery area, or as a poolednondescript repository for nursing ill patients requiringvarious vital organ monitoring and support. Over thepast two-plus decades, the explosion in our knowledgeand understanding of the pathophysiology of thecritically ill, along with the vast technological advancesand increasing practice of evidence-based medicine, hasenabled the modern-day ICU to provide much moremeticulous and well-contemplated ICU care targetingnot only at saving lives but also at minimisingiatrogenesis. In this issue, we are proud to presentupdates on acute renal support (by Dr. W. W. Yan), onacute liver support (by Dr. Alex Chiu and Prof S. T.Fan), on acute cardiac support (by Drs T. F. Tse andElaine Chau), on infectious disease emergenciescommonly seen in the ICU (by Drs. Vincent Cheng andSamson Wong), on optimising sedation and analgesia(by Dr. Judith Shen), and on respiratory support (by Dr.Donald Yu and myself). This issue thus provides abird's eye view of the fast expanding global literatureand experience in Intensive Care.

This issue inevitably suffers some important omissionsbecause of limited space. Sepsis, a common ICU entity,is not discussed here. For an evidence-based update onsepsis, our readers are encouraged to look up thewebsite www.survivingsepsis.org recently establishedjointly by the European Society of Intensive CareMedicine, the International Sepsis Forum and the U.S.-

based Society of Critical Care Medicine. The annualedition of The Yearbook of Intensive Care andEmergency Medicine edited by J.-L. Vincent, Professorand Head of a leading Intensive Care Department inEurope is another must-read source for those whowould like to sample the amazing progress made inIntensive Care over the years.

To match up to the artistic photography of the pastissues was a challenging task for me as an issue editoron Intensive Care, as the prototype image of IntensiveCare can be frightening and intimidating: a patientlying helplessly in bed with tubes and lines andmachines of various sizes and shapes hovering at thebedside. Fortunately, Professor Richard Yu has kindlygraced our cover with the beauty of a snowy winter.Many paradoxical emotions indeed come to mind whenone considers the ICU, such as hope/despair oraggressive intervention/end of life. Nonetheless, thebeauty of the ICU lies in the fact that this is the placewhere the sanctity of life is stretched to its farthestlimits, where timely appropriate therapeuticinterventions and organ support do matter, and wherelife tragedies and miracles can be seen together. That isthe challenge of Intensive Care, and that is whyIntensive Care can be a passion for someone like myselfsince my earlier days as the Director of the ICU atQueen Mary Hospital.

This issue probably breaks the Medical Diary's record intwo other ways. Firstly, mirroring the Intensive Caremulti-disciplinary practice, our authorship comprises ofexperts from many specialties. On board our authorshipteam are physicians, an anaesthetist and a surgeon;there are specialists in Cardiology, Critical CareMedicine/Intensive Care Medicine, HepatobiliarySurgery, Clinical Microbiology & Infection, andRespiratory Medicine. Mirroring the important bedsidecollaboration in the ICU, our multi-disciplinary team ofauthors have joined hands in the delivery of this issueto you. Secondly, the Life Style article contributed byDr Gloria Pei would likely be a first in depicting thepower of a mother's love for her little one, a truly heart-warming story.

Lastly, may I wish the Hong Kong Medical Diary everysuccess and our readers good health and happiness!

Editorial

Dr. Jane CK CHAN

Dr. Jane CK CHAN

Specialist in Respiratory Medicine

MD (U of Chicago), FRCPE, FHKCP, FHKAM (Medicine), PDipID (HK)Dip American Board of Internal Medicine (Pulmonary & Critical Care Medicine)

Editor

VOL.11 NO.5 MAY 2006 Editorial

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The Cover Shot

Prof. Richard YH YU

Early winter when the first snow fellafter X'mas in Erabandai inFukoshima, the image captured theserenity and tranquility of natureand its purity.

This photo impressionism is sharedwith Dr. Leo KK Wong who is mymentor and teacher.

MD(HK), PhD(Lond), FRCP,Hon FRACP, Hon FHKCP,Hon FPSHK

VOL.11 NO.5 MAY 2006 Medical Bulletin

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Case PresentationPatient 1. A young woman with rheumatoidarthritis and acute respiratory failure

BackgroundA 33 year-old obese Chinese female, nonsmoker, withlongstanding history of rheumatoid arthritis (RA) sincechildhood sequentially requiring systemic steroids,penicillamine, oral gold, plaquenil, and 4 years earlier,leflunomide (Arava ), was admitted directly to the ICUfor acute onset of high fever and oxygenation failure.There had been a prodrome of fever, nonproductivecough, shortness of breath, vomiting and diarrhoea fora few days prior to admission. Her chest examinationrevealed diffuse crepitations throughout both lungs.

InvestigationsHer chest x-ray on admission showed bilateral diffuseconsolidative changes (Figure 1A). Her white cell countwas 1.72 109/L with total neutrophil count of 1.31 109/Land lymphocyte of 0.25 109/L. The platelet count was 107109/L. Her CRP, procalcitonin and renal function testswere all normal. Her liver function tests were normalexcept for a SGOT of 109 U/l. The ESR was 35 mm/h. Asubsequent chest CT showed extensive ground glassconsolidation in both lungs sparing only the dorsal andapical regions consistent with acute pneumonitis (Figure1B). The working diagnosis was fulminant community-acquired pneumonia versus leflunomide-inducedinterstitial pneumonitis. Leflunomide was promptlydiscontinued. Cholestyramine was given to accelerate theclearance of leflunomide.

Workup for InfectionShe was pan-cultured on admission for high fever andwas promptly started on broad-spectrum antibioticsincluding a beta-lactam, a macrolide, and anti-PCP andanti-fungal therapy based on microbiology consultation.She developed an episode of hypotension on Day 3, forwhich stress dose steroids and intravenousimmunoglobulin were added for possible fulminantsepsis. One dose of G-CSF was given on Day 4 forpersistent leukopenia, followed by good sustainedrecovery of her white cell count in the ensuing days. Thelymphopenia persisted till Day 11. All microbiologicworkup turned out to be negative: sputum and bloodcultures, sputum for acid fast bacilli smear and PCR,urinary antigen for Legionella and Streptococcus,serologic titres for mycoplasma, nasopharyngealaspirate for influenza A and B, and serum CMV pp65.All her immune markers were also negative.

Stormy Course in Respiratory SupportThe patient required BIPAP support on Day 1immediately upon ICU admission because of pooroxygenation. A FIO2 of 50% on BIPAP could achieve anoxygen saturation (SpO2) of 80-85% only. Over thefollowing week, her oxygenation remained very

Dr. Donald YC YU

Adult Respiratory Distress Syndrome:Challenges and Triumphs

Dr. Donald YC YU

Dr. Jane CK CHAN

Dr. Jane CK CHAN




MD(HK), FRCP(LOND), FRCP(Edin), FHKCP

This article has been selected by the Editorial Board of the Hong Kong Medical Diary for participants in the CME programme of theMedical Council of Hong Kong (MCHK) to complete the following self-assessment questions in order to be awarded one CME creditunder the programme upon returning the completed answer sheet to the Federation Secretariat on or before 30 September 2009.

Figure 1A. Chest radiograph of Patient 1 on admission.

Figure 1B. Chest CT of Patient 1 on Day 8

Medical Bulletin

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marginal with SpO2 achievable above 90% at FIO2 of　70%. Mild exertion or coughing would precipitatemarked oxygen desaturation down to 70s%. On Day 11,as the patient's oxygenation deteriorated despite beingon BIPAP, with SpO2 barely above 90% on FIO2 80%,the patient was intubated and tracheostomy wasperformed. Ventilatory support showed a PEEP level of15 cm together with a FIO2 of about 60% to achieve aSpO2 of 90-91%. On Day 18, the patient wascommenced on bi-level ventilation for her fulminantARDS with severe oxygenation failure.

Empiric CorticosteroidsThe patient's fever peaked on Day 2 but gradually camedown (possibly from stress dose steroids) over the nextfew days and henceforth remained afebrile. On Day 9, inview of the totally negative microbiologic workup, multi-system presentation, leukopenia, lymphopenia, and thediffuse pneumonitis, the diagnosis of leflunomide-induced ARDS was felt to be likely. Pulse steroids in theform of daily methylprednisolone 500 mg for 2 days wasgiven for the worsening respiratory failure and fulminantARDS, followed by pharmacologic doses of steroids withgradual tapering over the next few weeks.

Inhaled Nitric OxideOn Day 22, a repeat CT scan of the chest showedworsening ground glass consolidation with reticularshadows consistent with evolving pneumonitis. On Day23, in view of the patient's worsening oxygenationfailure requiring FIO2 of 85%, inhaled nitric oxide (iNO)was initiated to enhance gas exchange and for fear ofoxygen toxicity. iNO at 5 parts per million (ppm) wasadministered via the InoVent. Within 12 hours of iNOadministration, the patient demonstrated pleasingresponse with improvement in the SpO2 thus enablingtapering down of FIO2. By Day 25, the patient's FIO2came down to as low as 50-55%. iNO was broughtdown gradually to 1 ppm and eventually off after atotal course of 6 days. FIO2 requirements remainedstable off iNO. On Day 34, the FIO2 requirements were35-40% only. On Day 38, a repeat CT chest showedpartial resolution of the alveolar process and lesseningof the interstitial reticular markings.

The Road to RecoveryHer clinical course was otherwise only complicated byKlebsiella-related ventilator-associated pneumoniawhich responded to prolonged course of antibiotics. OnDay 40, the patient was switched from IV steroids tooral prednisolone at 60 mg qd. By Day 45 she was ableto sustain spontaneous breathing most of the day. ByDay 55, the patient was completely off the ventilator,and was soon discharged from the ICU. The patientfinally went home after a hospital stay of 3 months.

Final DiagnosisLeflunomide-induced ARDS

Patient 2. An elderly woman with acuterespiratory failure following VATS lung biopsy

BackgroundA 78 year-old Chinese female, nonsmoker, with historyof hypertension and paroxysmal atrial fibrillation onwarfarin and amiodarone (Cordarone ) 100 mg bd, waselectively admitted to the hospital for wedge lung

biopsy under video-assisted thoracoscopy. There hadbeen a history of insidious onset of exertional dyspnoeaand recent chest x-ray and CT finding of bibasilarsubpleural infiltrates more on the left than right, withsome suggestion of honeycomb lung in the left base(Figure 2A and 2B). Pre-operative myocardial perfusionscan was normal, and so were her chest examinationand resting oximetry reading. VATS wedge biopsy ofthe left lower lobe was performed on Day 2. Intra-operatively, pleural fibrosis and lung nodularity werenoted on palpation. Histology of the resected lungshowed interstitial fibrosis with chronic inflammatoryinfiltrate consistent with usual interstitial pneumonitis.All stains for micro-organisms were negative.

Fulminant ARDS PostoperativelyOne day following wedge lung resection (Day 3), thepatient developed low grade fever, for which antibioticswere empirically started. On Day 4, she was noted tohave oxygen desaturation which rapidly progressed torequire BIPAP support at FIO2 of 65%. Auscultationrevealed a few bi-basilar crepitations. Chest x-rayshowed interval development of extensive airspaceconsolidation in both lungs, most prominent at both

Figure 2A: Chest radiographof Patient 2 nine days beforeadmission

Figure 2C. Chest radiographof Patient 2 two daysfollowing VATS lung biopsy

Figure 2B: Chest CT of Patient 2 five days before admssion


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ventilation and prolonged ICU stay. Mortality ratesremain high at 35-60%2. Management strategies forARDS have focused on combating the inciting insult,ventilatory optimisation and at times cautious use ofsteroids.

Drug-induced ARDSDrug-induced lung diseases can manifest in variousclinico-pathological entities as shown in Table 1, basedon the cellular mechanism of lung injury as well as thetempo of disease presentation, ranging from slowlyprogressive pneumonitis/fibrosis to acute respiratoryfailure arising from either diffuse alveolar damage(DAD), non-cardiogenic pulmonary oedema or alveolarhaemorrhage4,5. The aetiologic link to a certain drug canbe difficult, and is usually based on a history of drugexposure, histological evidence of lung damage, andexclusion of other causes of lung injury, especially theexclusion of active infection. In the milder cases,radiographic findings of subtle ground glass opacitiesand mild fibrosis can be elusive on conventional chest x-ray and may only be seen on CT scanning5.

Despite our clinical impression to the contrary,noncardiogenic pulmonary oedema, and to lesser extent,ARDS, are common clinical manifestations of drug-induced lung diseases6. The former can be mild and self-limited, with rapid recovery following the use of oxygenand diuretic therapy, and discontinuation of the culpritdrug. However, the more severe form, usuallypresenting as fulminant ARDS, as resulting from Ara-C,nitrofurantoin, or amiodarone, can be life-threateningand may require ventilatory support and administrationof steroids6. Drug-induced ARDS is by and large adiagnosis by exclusion; every effort has to be made toexclude other important causes of ARDS, includingsepsis, fulminant pneumonia and aspiration.

Leflunomide-induced ARDSLeflunomide (Arava ) is a disease-modifying anti-rheumatic drug for the treatment of rheumatoid arthritis(RA). The drug had been considered relatively safe forquite a few years since its launch in the U.S. and E.U. inthe late 1990s, with common adverse events beingnausea, diarrhoea, headache, deranged liver enzymes,rash, alopecia, respiratory infections and hypertension7.

However, within a few months after its release in Japanin September 2003, 48 cases of interstitial lung disease(ILD) were found among 4395 patients registered foruse in Japan, including 16 fatal cases, giving rise to anincidence of 1.1%, and a fatality of 30%8. A stormycourse of acute respiratory failure from leflunomideleading to fatality was described despite the use of highdose steroids9, 10. Pathological findings at autopsy werethat of DAD9. DAD manifested as widespread patchyground glass opacities0 and/or consolidation alsoappeared to be the predominant presenting findingradiographically11.

There does appear to be a difference in the susceptibilityto leflunomide-induced lung toxicity between differentethnic/geographic groups. Subsequent to the Japanesefindings, Canadian investigators conducted aretrospective population-based case controlepidemiologic study reviewing more than 60,000Canadian patients with RA on leflunomide between 1998and 2003 and found a much lower rate of leflunomide-

lower zones. (Figure 2C) In view of the rapidlydeteriorating condition and likely non-infectiouspneumonitis, the patient was given pulse steroids in theform of methylprednisolone 500 mg qd for 3 days fromDay 4 through Day 6 followed by prednisolone 50 mgqd beginning on Day 7. Diuretics were also given forpossible fluid overload. From Day 7 through Day 9, thepatient was put on spontaneous breathing with oxygenat 8 L+30%, achieving rather marginal O2 saturation of90-94%. On Day 10, the patient appeared ratherfatigued and tachypnoeic with a respiratory rate of 40,and required resumption of BIPAP. On Day 11, she wastransferred to the ICU for intubation and invasiveventilation using PEEP levels of 10 cm H2O and FIO2 of85%. However, her oxygenation failure remainedprofound requiring bi-level ventilation and FIO2 up to100%. A bronchoalveolar lavage did not reveal anyinfectious aetiology for her oxygenation failure. Serumimmune markers were normal. The working diagnosiswas fulminant ARDS secondary to acute and chroniclung injury from amiodarone. Amiodarone wasdiscontinued.

Empiric Treatment of Amiodarone-inducedARDSHigh dose steroids were continued. Oxygen radicalscavenger therapy was started using vitamin C, vitaminE, pentoxylline, and N-acetylcysteine. One dose of anti-tumour necrosis factor-alpha antibody was also givenfor possible cytokine storm associated with the acutelung injury. By Day 13, FIO2 requirement came down to75%-85% at a PEEP level of 10 maintaining a SpO2 of91%, by Day 15 FIO2 down to 55% with a SpO2 of 92%,and Day 16 FIO2 down to 45% with a SpO2 of 91-92%,consistent with encouraging clinical response.However, she continued to demonstrate heightenedrespiratory drive with persistent tachypnoea up to 40and marked use of accessory muscles despite fullventilatory support and generous doses of sedation.Her ICU course was further complicated by ratherdifficult-to-control atrial fibrillation, subcutaneousemphysema, right pneumothorax, steroid-induceddiabetes, and critical illness polyneuropathy. Thepatient was eventually off the ventilator on Day 30,discharged from ICU on Day 34, and discharged homeon Day 78.

Final DiagnosisAmiodarone-induced ARDS

DiscussionDefinition of ARDSThe acute respiratory distress syndrome (ARDS), firstdescribed in 19671, is characterised by diffuseinflammation of the lung's alveolar-capillary membranein response to various pulmonary and extra-pulmonaryinsults2 such as aspiration, pneumonia, sepsis, trauma,or pancreatitis. The 1994 American-Europeanconsensus3 on the definition of ARDS is acute onset of

Patients with ARDS invariably require mechanical

Hypoxaemia, with a PaO2/FIO2 ratio of 200 mmHg orless,Bilateral infiltrates on a frontal chest radiograph, andPulmonary artery wedge pressure < 18 mmHg or noclinical evidence of left atrial hypertension.

(1)

(2)(3)

Medical Bulletin

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inflammatory response similar to inhalation of organicdust15, and (2) direct drug-induced phospholipidosis17,arising from a direct toxic effect of the drug, andcharacterised by the histopathological findings of"foamy" changes in the alveolar macrophages15. Therole of free radicals in the pathogenesis of amiodaronetoxicity was further implicated in in vitro and in vivomodels of amiodarone lung15, 18.

However, beginning in the mid-to-late 1980s, it becameincreasingly apparent that the mechanism of lung injurymay differ between chronic amiodarone lung diseaseand acute amiodarone-mediated lung injury. In theformer, risk groups have been identified as those whoare elderly with pre-existing lung condition on doses of> 400 mg per day17. In the latter, which usually presentsas an acute and rapidly deteriorating, and at times fatal,illness, the risk factors revolve around concomitantinjury rendering the lung liable to amiodarone's acutetoxic damage. These injuries include angiography19,cardiothoracic surgery20, and lung surgery21,22 with themost common intraoperative denominator being highinspired oxygen concentrations23,24. Patients withpreexisting amiodarone lung were found to be at highrisk of developing ARDS after cardiothoracicoperations20. Patients without surgery but ventilated inthe ICU have also been found to be at risk ofdevelopment amiodarone-induced ARDS25.

Management of amiodarone-induced ARDS is largelysupportive. Steroids have been used empirically. In ourpatient, given the severe ARDS requiring highconcentrations of oxygen to support the patient'soxygenation, empiric use of anti-oxidant therapy wasgiven to minimise further oxygen toxicity. The empiricuse of anti-TNF alpha was to combat the likely cytokinestorm arising from activation of the alveolarmacrophages.

Pharmacotherapy for ARDSResearch efforts devoted to identifying the magicbullet for combating ARDS have largely beenunproductive. In the Cochrane review of 33randomised clinical trials involving over 3000 patients,no pharmacotherapy was found to show convincingimprovement in survival in patients with ARDS. Useof early high-dose steroids in ARDS was deemed notjustifiable26. The use of corticosteroids in late-phaseARDS remains controversial. An earlier, much quoted,small trial of 24 patients showed improved survivalwhen given moderate dose steroids at day 7 or moreafter the onset of ARDS, during the so-calledfibroproliferative phase of ARDS27. A recent multi-centre trial of 180 patients however showed highermortality when given corticosteroids at 14 days ormore after the onset of ARDS28. Two recent meta-analyses also arrived at conflicting conclusions: theAustralian researchers concluded that the use of low-dose corticosteroids was associated with improvedmortality and morbidity outcomes29, while the U.K.researchers concluded that despite a suggestion ofreduced mortality and increased ventilator-free dayswith steroids after the onset of ARDS, a definitive roleof corticosteroids in the treatment of ARDS in adultshas not been established30. Hence, effectivepharmacologic therapy for established ARDS remainscontroversial and extremely limited.

induced ILD, with the hospitalisation rate for ILD being8.1 per 10,000 per year (0.08%)12. This discrepancybetween Japan and the western countries in the incidenceof lung toxicity was also tacitly echoed in a consensusstatement written by a multi-disciplinary panel ofrheumatologists and general practitioners across the U.K.in late 2004. The consensus statement, published in early2005, amidst the publicity aroused by the Japaneseclinicians/investigators, did not include lung toxicity ontheir list of adverse events13.

A recent multivariate logistic regression risk analysis ofthe large Japanese registry revealed the following riskfactors for leflunomide-induced lung injury: preexistingILD, with odds ratio (OR) of 8.17, loading doseadministration (OR 3.97), smoking history (OR 3.12) andlow body weight (OR 2.91)14. Fatality was most observedin those with severe hypoxaemia requiring mechanicalventilation, high C-reactive protein level,hypoalbuminaemia, and persistent lymphopenia14.Nevertheless, de novo cases of lefulnomide-induced lunginjury in the absence of the above-mentioned risk factorsdo occur, as in our patient (Patient 1) and as reported inthe literature12.

Current Japanese recommendation places leflunomideas a second-line drug not to be used in smokers, orthose with low body weight or with preexisting ILD.Loading dose should not be given14. Careful monitoringfor drug toxicity is warranted, and when lung injurydevelops, accelerated drug elimination usingcholestyramine and early use of steroids constitute themainstay of treatment8.

Amiodarone-induced ARDSThe pulmonary toxicity associated with amiodaronetherapy is a major factor limiting the widespread use ofthis very effective anti-arrhythmic agent. Amiodarone-induced lung disease occurs in about 5-10% of patientsreceiving the drug15, manifesting itself in the form ofsubacute onset of dyspnoea and CT findings of diffuseinterstitial thickening (known as subacaute interstitialpneumonitis or fibrosis), or as nodular areas ofsubpleural consolidation with histological features ofbronchiolitis obliterans organising pneumonia, or asacute onset of dyspnoea and fever with CT findings ofdependent consolidation typical of ARDS16.

The pharmacokinetic properties of amiodaronepredispose the lung to amiodarone toxicity. Firstly,amiodarone is lipophilic with a large volume ofdistribution, hence the long elimination half-life at 45-60days and likely storage in organs with high lipid contentsuch as fat, lung and liver15. Secondly, amiodarone'sprincipal metabolite, desethylamiodarone, accumulatesin peripheral tissues providing a sustained reservoir, tothe extent that concentrations measured inunfractionated lung parenchyma significantly exceedthat of the heart, setting up the lungs up for toxic effectsof amiodarone17.

Mechanisms underlying lung toxicity have been poorlyunderstood, likely because of the heterogeneity ofamiodarone lung syndromes and correspondinghistopathological findings. Two prevalent hypotheseshave been (1) adaptative-immune-mediatedhypersensitivity reaction based on findings of an


9


Ventilatory Strategy for ARDSThe key advances in the management of ARDS in thepast decade lie largely in our better understanding ofthe mechanisms underlying ventilator-associated lunginjury (VALI), which could further exacerbate theongoing insult to the lung. One important contributorof VALI is regional alveolar overdistension(volutrauma)31. Lung-protective strategy using low-tidal volumes at 6 ml per kg of predicted body weighthave been proven in the ARDSNET study of over 800patients to improve ARDS mortality from 40% to 31%32.Hypercapnoea is deemed acceptable in this context.Another contributor of VALI is repetitive alveolarcollapse with shearing (atelectrauma)33. However,despite the interest in the use of high levels of PEEP foraddressing the problem of atelectrauma and for alveolarrecruitment, the clinical studies of high PEEP levelshave not been conclusive34,35. Current recommendationon the use of PEEP targets at PEEP levels which can beshown to improve rather than exacerbate the lungmechanics36.

Unconventional Support for ARDSTwo unconventional therapeutic modalities for ARDShave been hotly debated in the past decade: inhalednitric oxide (iNO) and prone positioning. Bothmodalities have been aimed to address the keypathophysiological derangement of ARDS: mismatchingof ventilation (V) and perfusion (Q) leading to gasexchange impairment. iNO serves as a selectivepulmonary vasodilator, offering the theoreticaladvantage of improving perfusion in areas of betterventilation, thereby enhancing V/Q matching. Over 10randomised trials on iNO have been conducted in thepast decade. Meta-analyses in 2003 and in 2007 bothshowed no significant effect of iNO on hospital mortality,duration of ventilation or ventilator-free days37. Therewas however improvement in the oxygenation indexwhich persisted till day 4 of therapy. Renal toxicity wasnoted. Routine use of iNO is not recommended. Someclinicians may still consider iNO as a temporarisingmeasure for life-threatening hypoxaemia.

While iNO may not be readily available in a medicalcentre, the application of prone positioning can beachieved at the bedside of any ICU. The concept ofprone positioning (PP) as a treatment for ARDS arisesfrom the finding of atelectatic lungs in the dependentdorsal regions in a supine patient with ARDS. Thereversal from supine to prone positioning allowsopening up of the atelectatic lungs, more favourablelung mechanics, better V/Q matching and less VALI38.Two recent meta-analyses seemed to have arrived atsimilar conclusions about the clinical efficacy of PP: PPdid not improve survival despite an improvement inoxygenation39,40. PP is therefore not recommended asroutine treatment for ARDS. However, a sustainedimprovement in oxygenation may support the use of PPin patients with severe hypoxaemia40.

ConclusionARDS represents a severe form of acute lung injuryrequiring intensive care support. The two cases offulminant drug-induced ARDS presented hererepresent triumph in combating a critical conditionusing conventional as well as unconventional wisdom.As drug-induced ARDS is largely a diagnosis byexclusion, thorough search for other possible aetiologiesis a must. Clinicians who regularly use these twodrugs, leflunomide and amiodarone, need to keepwatchful vigilance on the development of lung toxicityin those patients taking these drugs. Concommittantexposure to other possible pulmonary toxins, such ashigh-flow oxygen, needs to be avoided as much aspossible. Ventilatory support using low tidal volumeand optimal PEEP is considered the standard of care.Inhaled nitric oxide and prone positioning are notsupported by the literature but nevertheless may servea temporarising role for those with severe hypoxaemicfailure. Pharmacotherapy for ARDS remains verylimited.

Table 1. Clinicopathological entities associated with drug-induced lung disease 4, 5

*GGO = Ground glass opacities

Clinicopathologic entity

Hypersensitivity pneumonitis

Eosinophilic pneumonitis

Nonspecific interstitialpneumonia

Desquamative interstitialpneumonia

Diffuse alveolar damage

Non-cardiogenic pulmonaryedema

Alveolar hemorrhage

Bronchiolitis obliteransorganizing pneumonia

CT findings

Bilateral GGO* and poorlydefinedcentrilobular nodules

Peripheral alveolar infiltrates

Irregular linear opacities andGGO in subpleural distribution

Bilateral GGO

Diffuse air-space consolidation

Dependent air-spaceconsolidation

Diffuse air-space consolidation

Patchy GGO,consolidation and linearopacities

Examples of drugs

Methotrexate, gold therapy,cyclophosphamide, nitrofurantoin,antidepressants

Methotrexate, sulfasalazineminocycline, para-aminosalicylic acid,nitrofurantoin, NSAIDs

Amiodarone, chemotherapy

Methotrexate, interferons, etanercept

Bleomycin, busulphan, mitomycin

Cytosine arabinoside, beta2 agonists,blood products, narcotics

Oral anticoagulants, fibrinolytic agents,platelet glycoprotein inhibitors

Busulfan, cyclophosphamide,amiodarone, nitrofurantoin,methotrexate

Prognosis

Favourable withuse of steroids


Poor, fibrosis likely


Poor; death in50-60% patients

Favourable

Favourable


Respiratory failure

Yes but infrequently


Usually subacute


Yes typically

Yes typically

Yes typically

Usually subacute

Medical Bulletin

10


Ashbaugh DG, Bigelow DB, Petty TL et al. Acute respiratory distressin adults. Lancet 1967; 2:319-23.Ware LB & Matthay MA. The acute respiratory distress syndrome. NEngl J Med 2000; 342: 1334-49.Bernard GR, Artigas A, Brigham KL et al. Report of the American-European Consensus Conference on ARDS: Definitions, mechanisms,relevant outcomes and clinical trial coordination. Intensive CareMedicine 1994; 20:225-32.Khan AN, Irion KL & Nagarajaiah CP. Lung, drug-induced disease.Emedicine 2008; Section 1-10.Ellis SJ, Cleverley JR and Muller NL. Drug-induced lung disease: High-resolution CT findings. Am J Roentgen 2000; 175:1019-24.Lee-Chiong T, Jr & Matthay RA. Drug-induced pulmonary edema andacute respiratory distress syndrome. Clin Chest Med 2004; 25:95-104.Takeishi M, Akiyama Y, Akiba H et al. Leflunomide induced acuteinterstitial pneumonia. J Rheumatol 2005; 32:1160-3.Ito S & Sumida T. Interstitial lung disease associated withleflunomide. Internal Medicine 2004; 43:1103-4.Hirabayashi Y, Shimizu H, Kobayashi N et al. Leflunomide-inducedpneumonitis in a patient with rheumatoid arthritis. Internal Medicine2006; 45:689-91.Kamata Y, Nara H, Kamimura T et al. Rheumatoid arthritiscomplicated with acute interstitial pneumonia induced by leflunomideas an adverse reaction. Internal Medicine 2004; 43:1201-4.Sakai F, Noma S, Kurihara Y et al. Leflunomide-related lung injury inpatients with rheumatoid arthritis: Imaging features. Mod Rheumatol2005; 15:173-9.Suissa S, Hudson M & Ernst P. Leflunomide use and the risk ofinterstitial lung disease in rheumatoid arthritis. Arthritis &Rheumatism 2006; 54:1435-9.Maddison P, Kiely P, Kirkham B et al. Leflunomide in rheumatoidarthritis: Recommendations through a process of consensus.Rheumatology 2005; 44:280-6.Inokuma S, Sato T, Sagawa A et al. Proposals for leflunomide use toavoid lung injury in patients with rheumatoid arthritis. ModRheumatol 2008; 18:442-446.Martin WJ II. Mechanisms of amiodarone pulmonary toxicity. ClinChest Med 1990; 11:131-8.Pneumotox on line. Amiodarone. http://www.pneumotox.com/baseaccessed on 15 Sep 2008.Ashrafian H & Davey P. Is amiodarone an underrecognized cause ofacute respiratory failure in the ICU? Chest 2001; 120:275-82.Vereckei A, Blazovics A, Gyorgy I et al. The role of free radicals in thepathogenesis of amiodarone toxicity. J Cardiovasc Electrophysiol 1993;4:161-77.Wood DL, Osborn MJ, Rooke J et al. Amiodarone pulmonary toxicity:Report of two cases associated with rapidly progressive fatal adultrespiratory distress syndrome after pulmonary angiography. MayoClin Proc 1985; 60:601-603.Nalos PC, Kass RM, Gang ES et al. Life-threatening postoperativepulmonary complications in patients with previous amiodaronepulmonary toxicity undergoing cardiothoracic operations. J Thoracand Cardiovasc Surg 1987; 93:904-12.Mieghem WV, Coolen L, Malysse I et al. Amiodarone and thedevelopment of ARDS after lung surgery. Chest 1994; 105:1642-5.

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References Rose EP & Alves LE. Amiodarone and the development of ARDS afterlung surgery. Chest 1995; 107:885.Kay GN, Epstein AE, Kirklin JK et al. Fatal postoperative amiodaronepulmonary toxicity. Am J Cardiol 1988; 62:490-2.Saussine M, Colson P, Alauzen M et al. Postoperative acuterespiratory distress syndrome. Chest 1992; 102:3.Donaldson L, Grant IS, Naysmith MR et al. Acute amiodarone-induced lung toxicity. Intensive Care Med 1998; 24:626-30.Adhikari NKJ, Burns KEA & Meade MO. Pharmacologic therapies foradults with acute lung injury and acute respiratory distress syndrome(Review). The Cochrane Collaboration 2009; 1-57.Meduri G, Headley A, Golden E et al. Effect of prolongedmethylprednisolone therapy in unresolving acute respiratory distresssyndrome: A randomized controlled trial. JAMA 1998; 280:159-65.Steinberg K, Hudson L, Goodman R et al. Efficacy and safety ofcorticoesteroids for persistebt acute respiratory distress syndrome. NEngl J Med 2006; 354:1671-84.Tang BMP, Craig JC, Eslick GD et al. Use of corticosteroids in acutelung injury and acute respiratory distress syndrome: A systematicreview and meta-analysis. Crit Care Med 2009; 37:1594-603.Peter JV, John P, Graham PL et al. Corticosteroids in the preventionand treatment of acute respiratory distress syndrome (ARDS) in adults:Meta-analysis. BMJ 2008; 336:1006-9.Dreyfuss D, Soler P, Basset G et al. High inflation pressure pulmonaryedema: Respective effects of high airway pressure, high tidal volume,and positive end-expiratory pressure. Am Rev Respir Dis 1988;137:1159-64.The Acute Respiratory Distress Syndrome Network. Ventilation withlower tidal volumes as compared with tranditional tidal volumes foracute lung injury and the acute respiratory distress syndrome. N EnglJ Med 2000; 342:1301-8.Haitsma JJ, Lachmann B. Lung protective ventilation in ARDS: Theopen lung maneuver. Minerva Anesthesiol. 2006; 72:117-32.Mercat A, Richard JM, Vielle B et al. Positive end-expiratory pressuresetting in adults with acute lung injury and acute respiratory distresssyndrome: A randomized controlled trial. JAMA 2008; 299:646-55.Meade MO, Cook DJ, Guyatt GH et al. Ventilation strategy using lowtidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distresssyndrome. JAMA 2008; 299:637-645.Malhotra A. Low-tidal-volume ventilation in the acute respiratorydistress syndrome. N Engl J Med 2007; 357:1113-21.Adhikari NKJ, Burns KEA, Friedrich JO et al. Effect of nitric oxide onoxygenation and mortality in acute lung injury: systematic review andmeta-analysis. BMJ 2007; 334:779-87.Mancebo J, Fernandez R, Blanch L et al. A multicenter trial ofprolonged prone ventilation in severe acute respiratory distresssyndrome. Am J Respir Crit Care Med 2006; 173:1233-39.Alsaghir AH & Martin CM. Effect of prone positioning in patientswith acute respiratory distress syndrome: A meta-analysis. Crit CareMed 2008; 36:603-09.Sud S, Sud M, Friedrich JO et al. Effect of mechanical ventilation in theprone position on clinical outcomes in patients with acute hypoxemicrespiratory failure: A systematic review and meta-analysis. CMAJ2008; 178:1153-61.

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MCHK CME Programme Self-assessment QuestionsPlease read the article entitled "Adult Respiratory Distress Syndrome: Challenges and Triumphs" by Dr. Jane CKCHAN and Dr. Donald YC YU and complete the following self-assessment questions. Participants in the MCHKCME Programme will be awarded 1 CME credit under the Programme for returning completed answer sheets via fax(2865 0345) or by mail to the Federation Secretariat on or before 30 September 2009. Answers to questions will beprovided in the next issue of The Hong Kong Medical Diary.

Amiodarone lung disease can be predicted based on the dosage used and the total duration of therapy.

Leflunomide-induced lung disease is almost unheard of in the U.K. experience.

Amiodarone lung toxicity is exacerbated by its prolonged half life and its lipophilic properties.

The clearance of leflunomide can be accelerated by the use of n-acetyl-cysteine.

Prior use of methotrexate has been shown to increase the chance of leflunomide-induced lung disease.

There have been no significant advances in the management of ARDS in the past 10-20 years.

The use of corticosteroids in ARDS is considered standard practice.

The use of inhaled nitric oxide has not been proven to improve survival in patients with ARDS.

Drug-induced ARDS remains a diagnosis of exclusion, with all efforts required to rule out active infection.

Low tidal volume ventilation has been shown to cause ventilator-associated lung injury.

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Questions 1-10: Please answer T (true) or F (false)


11


Please return the completed answer sheet to the Federation Secretariat on or before 30 September 2009 fordocumentation. 1 CME point will be awarded for answering the MCHK CME programme (for non-specialists)self-assessment questions.

Name (block letters):____________________________________ HKMA No.:

HKDU No.:

CDSHK No.:

___ ___ - ___ ___ ___ ___ X X (x)HKID No.:

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ANSWER SHEET FOR SEPTEMBER 2009

Answers to August 2009 Issue

Human Swine Influenza

1 2 3 4 5 6 7 8 9 10

1 . T 2 . T 3 . F 4 . F 5 . F 6 . F 7 . T 8 . T 9 . F 10 . F

Adult Respiratory Distress Syndrome: Challenges and Triumphs

Dr. Donald YC YU

Dr. Jane CK CHAN




MD(HK), FRCP(LOND), FRCP(Edin), FHKCP

Upcoming Certificate Courses of the Federation of Medical Societies of Hong Kong

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13


IntroductionIn 2004, the term Acute Kidney Injury (AKI) wasproposed to represent the entire spectrum of acute renalfailure (ARF) with clinical manifestations ranging froma minimal elevation in serum creatinine to anuric renalfailure.1 The reported prevalence of AKI in critically illpatients could be as high as 25% in some developedcountries, and only about 4% of this group receivedrenal replacement therapy (RRT), with an ensuinghospital mortality up to 60%. Controversies exist inmany aspects of RRT for AKI despite decades ofdevelopment. However, definitive findings on the doseof RRT were available last year. It is hoped that, withthe continued international collaboration, a clearerpicture would emerge in other areas of RRT.

Classification of Acute Kidney InjuryThe RIFLE Classification2

In evaluating the clinical efficacy in AKI studies,meaningful conclusions can only be drawn when thereis a common standard of reference. An expert panelfrom the Acute Dialysis Quality Initiative (ADQI)established a consensus definition called RIFLE in 2002(www.ADQI.net). In summary, the acronym RIFLErefers to three severity grades (in ascending order ofRisk, Injury and Failure) and two clinical outcomes(Loss and End-stage renal failure). The severity gradingis based on the change from baseline of either serumcreatinine or urine output, whichever is greater. In thesubsequent years, RIFLE criteria have been validated bydifferent groups worldwide. With these new criteria,the prevalence of acute kidney injury is 2-to-10 foldgreater than previously reported, ranging from 15.4 to78.3%.3 RIFLE was also valuable in outcome predictionand correlated well with mortality.3

The AKIN Classification [Table 1]However, according to the data that have emergedusing RIFLE staging criteria, smaller changes in serumcreatinine than those considered in the RIFLE criteriamight also be associated with adverse outcomes. TheADQI group, and representatives from threenephrology societies (American Society of Nephrology,International Society of Nephrology and NationalKidney Foundation) and the European Society ofIntensive Care Medicine met and decided to modify theRIFLE criteria. A new classification system, the Acute

Kidney Injury Network (AKIN) Classification, wasdeveloped. It retained the emphasis on changes in bothurine output and serum creatinine [Table 1]

Fluid overload unresponsive to diuretic treatmentHyperkalaemia (>6.5 mmol/L or rapidly rising level)Azotaemia (urea >36 mmol/L)Severe acidaemia (pH <7.1)Oliguria (urine output <200ml in 12 hours) or anuria(urine output < 50ml in 12 hours)Uraemia complications like bleeding, pericarditis orencephalopathy

1.2.3.4.5.

6.

Drug overdose with dialysable or filtratable toxinsPatients requiring a large amount of fluid, parenteralnutrient, or blood product but at risk of developingpulmonary oedema or acute respiratory distresssyndromeCardiac failureHyperthermia or hypothermia (core temperature >39.5oC or <30oC)Severe dysnatraemia ([Na] >160 mmol/L or < 115mmol/L)

1.2.

3.4.

5.

Indications & Timing for RRTThe usual indications for initiating RRT are:

However, in the past decade, the indications for RRThave been extended widely to include many other non-renal indications including: 4

Modified from RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease)criteria. The staging system proposed is a highly sensitive interim staging systemand is based on recent data indicating that a small change in serum creatinineinfluences outcome. Only one criterion (creatinine or urine output) has to befulfiled to qualify for a stage.Given wide variations in indications and timing of initiation of renal replacementtherapy (RRT), individuals who receive RRT are considered to have met thecriteria for stage 3 irrespective of the stage they are in at the time of RRT.

a

b

Update of Renal ReplacementTherapy in the ICU

Dr. Wing-wa YAN

Dr. Wing-wa YAN

Director, Department of Intensive Care, Pamela Youde Nethersole Eastern HospitalMBBS(HK), MSc(CUHK), MRCP(UK), FRCP(Lond, Edin), FHKCP, FHKAM(Medicine)

Tabel 1. Acute Kidney Injury Network Classification/Staging Systema

Stage

1

2

3b

Serum creatinine cr iter ia

Increase in serum creatinine of more than orequal to 26.4 mol/l or increase to more than orequal to 150% to 200% (1.5- to 2-fold) frombaseline

Increase in serum creatinine to more than 200%to 300% (> 2- to 3-fold) from baseline

Increase in serum creatinine to more than 300%(> 3-fold) from baseline (or serum creatinine ofmore than or equal to 354 mol/l with an acuteincrease of at least 44 mol/l

Urine output cr iter ia

Less than 0.5 ml/kgper hour for more than6 hours

Less than 0.5 ml/kgper hour for more than12 hours

Less than 0.3 ml/kgper hour for 24 hoursor anuria for 12 hours

Medical Bulletin

14


The concept of 'prophylactic haemodialysis' was firstintroduced in 1960. Patients with ARF receiving earlydialysis tended to have better wound healing, fewerhaemorrhages, improved nutritional support and bettersurvival. Since then, blood urea has been regarded asone of the markers for the timing of intervention; thethreshold having decreased from 54 mmol/L in the1960s to 33 mmol/L in 1970s.5 In the Conger's study ofpost-traumatic ARF, five out of eight patients survivedafter receiving early dialysis at a mean blood urea of 18mmol/L; while only two out of 10 survived whendialysis was initiated at a mean urea of 43 mmol/L.6

Survival benefit was also demonstrated in patientssuffering from ARF after cardiac surgery. One recentstudy addressed early versus late intensive initiation ofcontinuous veno-venous haemodiafiltration (CVVHDF)in patients with less than 100 mL urine in the 8consecutive hours after operation.7 Early versus lateinitiation (average lapse 0.88 vs 2.56 days) wasassociated with reduced ICU stay (8 vs 12 days),reduced ICU mortality (18 vs 48%), and reducedhospital mortality (24 vs 56%).

Nevertheless, this observed benefit could not berepeated in the Bouman's study.8 One-hundred and sixcritically ill patients were prospectively evaluated toassess the combined effect of early against late-initiationas well as low-volume (LVHF) against high-volumehaemofiltration (HVHF). Patients were randomised intoone of the three groups: early HVHF (72-96 L/day),early LVHF (24-36 L/day), and late LVHF (24-36 L/day).On average, the early group started haemofiltration 7hours after inclusion with the mean starting urea of 17.1mmol/L; while the late group starting 42 hours afterinclusion with a mean urea of 37.4 mmol/L. There wasno difference in 28-day mortality nor renal recoveryamong the three groups.

Thus, the best evidence on the optimal timing forinitiating RRT is still lacking and more studies areneeded to address these issues. Based on the currentlyavailable data and the author's experience, earlyinitiation of RRT is preferable.

Dose of Renal Replacement TherapyDose Required

While in end-stage renal failure, the delivered spKt/V of1.2 per dialysis (or urea reduction ratio of 65%) are theaccepted minimal standards in reducingmorbidity/mortality. The minimum dose for patientswith ARF has once been a great controversy in the fieldof Intensive Care. Thanks to the recent release of twolarge randomised control trials9,10 on the dose of RRTfor patients with ARF, it has been concluded that thereis no evidence to support the use of continuous renalreplacement therapy (CRRT) at a dose greater than25mL/kg/hour. A summary of studies on dosing andoutcome in CRRT is listed in [Table 2].8-13

The ATN trial (Acute renal failure Trial Network)published in 2008 in the United States did not showany survival benefit with intensive dialysis therapy.9This study recruited 1164 critically ill patients withARF to compare any mortality difference between the

conventional dose group with the more intense dosegroup. The rate of death was similar; 53.6% in theintensive therapy and 51.5% in the less-intense therapygroups. There was no difference in the duration of RRTor recovery of renal function.

Similarly, the RENAL trial (Randomised Evaluation ofNormal against Augmented Level of renalreplacement therapy in the ICU)10 conducted by theAustralian and New Zealand group showed no 90-daymortality difference between the conventional dosegroup and the intensive therapy group (44.68% vs44.66%, p=0.993). This study recruited 1,465 patientswith severe ARF in ICUs, who were randomised toreceive post-dilutional CVVHDF at 25 mL/kg/h in theconventional group against 40 mL/kg/h in theintensive therapy group. The primary outcome of 90-day mortality showed no difference between the twodosages, and besides, all secondary outcome indicatorsincluding ICU mortality, hospital mortality,mechanical ventilation day, ICU length of stay,hospital length of stay, RRT day, RRT dependence atday 28 and day 90 also showed no difference.

High-volume Haemofil trat ion(HVHF) in Sepsis PatientsFor patients with severe sepsis or septic shock, there is anoverwhelming systemic overflow of pro-inflammatoryand anti-inflammatory mediators, leading to generalisedendothelial damage, multiple organ dysfunction andaltered cellular immunological responsiveness. Theremoval of sepsis pro-inflammatory and anti-inflammatory mediators may help in the treatment ofsevere sepsis. Cytokines levels in sepsis were found to belowered only with HVHF (~45ml/kg/h) but notconventional continuous veno-venous haemofiltration(CVVH) (17ml/kg/h).14 Early animal studies and smallscale human trials provided good data on improving thehaemodynamic status and survival with HVHF. In theRonco study published in the Lancet in 2000, althoughthere was no overall survival difference between the twogroups with 35 and 45 ml/kg/h doses, a significantsurvival difference was detected between these groups ina subgroup analysis for patients with sepsis.11

A large randomised trial is going on to confirm thisunsettled dosing issue in RRT for patients with sepsis.The IVOIRE study (hIgh VOlume in Intensive care)15 inEurope will study the use of standard volume (35mL/kg/h) against HVHF (70 mL/kg/h) in ARF patientswith septic shock. It aims to enroll 460 patients to detect a15% absolute risk reduction in 30-day mortality

Circuit Patency in CRRTIn an international survey of 345 centres,16 the majorconcerns of health care workers about CRRT was the useof anticoagulant, frequent clotting of extracorporealcircuit and the subsequent increased nursing workload.CRRT downtime ranged from 8 to 28% of the totaltreatment time.17 Clotting of circuit was the major reason(74%) for the treatment loss. Therefore, it is essential tomaintain circuit patency in order to minimise thediscrepancy between prescribed and delivered doses.


15


1. unfractionated heparin2. low-molecular-weight heparin (LMWH)3. citrate4. prostacyclin / prostaglandin E15. nafamostat mesilate6. direct thrombin inhibitor, e.g. r-hirudin

Commonly used anticoagulants in CRRT are:

However, if the use of systemic anticoagulation iscontraindicated, one of the alternatives is to flush thesystem with saline and administer the replacementsolution pre-dilutionally. Even with these measures,significant clotting is still encountered in up to 15 to40% of patients. According to the recently publishedBEST Kidney multi-national observational study,18

around one third of the patients received CRRT withoutany anticoagulation. Among the various anticoagulants,use of un-fractionated heparin ranked the highest(42.9%), followed by regional citrate anticoagulation(9.9%) and then nafamostat mesilate (6.1%)

Unfractionated heparin remains the standard systemicanticoagulant with the benefit of wide clinicalexperience, low cost, ease of use, ability to monitor thelevel of anticoagulation and availability of antidotes likeprotamine if needed. Heparin acts by binding to andactivating anti-thrombin III, which in turn inhibits

factors IXa, Xa, and thrombin. The anticoagulant effectcan be achieved by giving an initial bolus of 10 to 20U/kg heparin; followed by continuous infusion of 3 to20 U/kg/h to achieve 1.5 to 2 times of the normalactivated clotting time or activated partialthromboplastin time. For patients at risk of bleeding, alower dose or a 'tight' heparin regimen with a bolus of 5to 10 U/kg; followed by infusions of 5 to 10 U/kg/h canbe used.19

Low-molecular-weight heparin consists of only shortpolysaccharide chains with average molecular weight inthe range of 3000 to 7000 daltons and its biologicalactivity is quantified by the extent of factor Xainhibition. Hence, dosing differs between differentbrands of LMWH and the haemofilter used. Withrespect to unfractionated heparin, LMWH has theadvantage of longer half-life, greater bioavailability,dose-independent clearance, less heparin inducedthrombocytopenia and less bleeding because of lessimpact on platelet function. In addition, the half-life ofLMWH is prolonged in renal failure and a singleinjection at start of CRRT usually suffices for up to 5hours.19 For example, enoxaparin 40 mg (4000-5000 anti-factor Xa units or 60-70 anti-factor Xa units/kg) can begiven as a loading dose, followed by 10 to 40 mg every6 hours if needed.19

TABLE 2. Summary of Studies on Continuous Renal Replacement Treatment (CRRT) Dosing and Outcomes

Study

Roncoet al, 112000

Boumanet al, 82002

Saudanet al, 122006

ATN trial, 92008

Tolwaniet al, 132008

RENALstudy,By ANZgroup 102009

No.

425

106

206

1124

200

1465

Randomisations

3 Arms comparing3 different doses(n=146 vs 139 vs 140)

3 Arms comparingEHV vs ELV vs LLV(n=35 vs 35 vs 30)

2 Arms comparing2 different doses(n=102 vs 104)

2 Arms comparingintense vs less-intensetherapy(n=563 vs 561)

2 Arms comparing2 different doses(n=100 vs 100)

2 Arms comparing 2different doses(n=743vs 722)

Prescr ibeddose(mL/kg/h)

20 vs 35 vs 45

48.2 vs 20.1vs 19.7

25 vs 44

36.2 vs 21.5(forIHD/SLED,6x/wk vs3x/wk withKt/V of 1.2-1.4 persession)

20 vs 35

25 vs 40

Delivered dose

>85% prescribeddose

Not mentioned

Achieved 87 %vs 83% of thedelivered dose

35.8 vs 22.0

17 vs 29

22.0 vs 33.4

Pr imaryoutcome

Survival at 15days

Survival at 28days; renalrecovery

28 dayssurvival;90 dayssurvival

60 daysmortality

Survival toICU dischargeor 30 days

90 daymortality

Results

41% vs 57%vs 58%

74.3 % vs68.8% vs 75%(all except 1 inELV)

39% vs 59%

34% vs 59%

51.2% vs48.0%

56% vs 49%

44.68 vs44.66%

CRRT mode

Post-dilution CVVH:QB 120-240 mL/min

Post-dilution CVVH:EHV-QB 200 mL/min, QR 72 L/dayELV-QB 100-150 mL/min, QR 24-36L/dayLLV-QB 150 mL/min, QR 24-36L/day

Pre-dilution:CVVH (low dose)-QB 100-125mL/min, QR 1-2.5 L/hCVVHDF (high dose)-QB 100-125mL/min, QR 1-2.5 L/h, QD 1-1.5 L/h

CVVHDF:Intensive-QB 150 mL/min, QD 1410mL/h, QR 1390 L/hLess intensive-QB140 mL/min, QD 820mL/h, QR 83 mL/h

For both arms:Haemodynamically unstable-CVVHF/SLEDHaemodynamically stable-IHD

Pre-dilution CVVHDF:Standard dose-QB 100-150 mL/min,QD 1005 mL/h, QR 793 mL/hHigh dose-QB 100-150 mL/min, QD1831 mL/h, QR 1406 mL/h

Post-dilution CVVHDFQb >150 ml/min

CVVH denotes continuous veno-venous haemofiltration; CVVHDF continuous veno-venous haemodiafiltration; EHV early high volume; ELV early lowvolume; ICU intensive care unit; IHD intermittent haemodialysis; LLV late low volume; QB blood flow; QD dialysate flow; QR replacement rate; SLEDsustained low-efficiency dialysisStatistically significant

*

Medical Bulletin

16


Regional Citrate Anticoagulation (RCA)Citrate chelates the calcium in the extracorporeal circuitto mediate its anticoagulant effect.20-24 This citrate-calcium complex is biologically inert and is partlyremoved through the haemofilter. The remainingcalcium citrate enters the body and mixes with thecentral venous blood. As the central venous blood flowis much greater than the circuit blood flow rate, the lowionised calcium concentration in the circuit is raised tosuch a level that any systemic anticoagulant effect isminimal. Therefore, citrate anticoagulation only existsregionally within the circuit. The citrate-calciumcomplex re-entered the body is dissociated back to freeionised calcium and citrate. All the residual effects ofcitrate are terminated by the liver, where it ismetabolised through the tricarboxylic acid cycle intobicarbonate in a 1:3 ratio. To prevent filter clotting, apre-filter citrate concentration of 3.5 to 4 mmol/L isneeded to keep the ionised calcium concentration in thecircuit to below 0.25 mmol/L.19,21 Because of the net lossof calcium in the form of citrate-calcium complex in theultrafiltrate, a small amount of calcium supplement isneeded. It is usually given intravenously via a separatecentral venous line and its rate is titrated to give anormal ionised calcium concentration.

Citrate is commonly formulated in 4% tri-sodium citrateor anticoagulant-citrate-dextrose A (ACDA) or asproprietary products like Gambro Prismocitrate 10/2and Fresenius multiFiltrate Ci-Ca system (4% tri-sodium citrate).

Although RCA is superior in keeping circuit patency,the metabolic problems associated with it make itunpopular. These include: hypernatraemia, metabolicalkalosis and the potential for hypocalcaemia(secondary to accumulation of citrate). Thecontraindications for RCA are severe liver dysfunctionand massive blood transfusion. Its underlying rationaleis the increased risk of citrate accumulation causingtoxicity. Citrate toxicity should be suspected wheneverionised calcium is persistently low or the total toionised calcium ratio is higher than 2.5.22 Symptoms ofhypocalcaemia include paraesthesia, nausea, cramps,tetany, hypotension, decrease in cardiac output, or aprolonged QT interval.19

In order to reduce the metabolic side effects related toRCA, the concentrations of sodium and bicarbonate inthe replacement solution, during RCA setup, should becarefully adjusted. Close monitoring of electrolytesincluding sodium, potassium, arterial blood gases,ionised and total calcium, during CRRT, is essential.

RCA has been adopted as the default mode for CRRT inour department since 1995. Our experience with RCA ispromising. It is safe and well accepted by our doctorsand nurses. Overt metabolic complications have neveroccurred.

ConclusionAKI is common among the critically-ill and RRT isfrequently used to support these patients. Emerginginternational consensus classification is available tobetter stratify AKI patients so that future studies aremeaningful for comparison. Although the adequacy ofRRT dosing has been determined in recent good qualitytrials, there still exist areas of uncertainties about RRT.Further studies are needed to address the indications,optimal timing of initiation and the types ofanticoagulants.

longer circuit / filter lifesafe for use even in patients with bleedingtendency or who had recent surgeryless microthrombi formation within filter tubulesless platelet activationless blood transfusion required

1.2.

3.4.5.

The advantages of using RCA are: 25-28

Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: reportof an initiative to improve outcomes in acute kidney injury. Critical Care2007;11(2):R31.Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute DialysisQuality Initiative workgroup. Acute renal failure-definition, outcomemeasures, animal models, fluid therapy and information technology needs:the Second International Consensus Conference of the Acute DialysisQuality Initiative (ADQI) Group. Crit Care 2004;8:R204-212.Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidneyinjury are associated with hospital mortality in critically ill patients: a cohortanalysis. Crit Care 2006;10:R73.Bellomo R, Ronco C. Continuous renal replacement therapy in the intensivecare unit. Intensive Care Med 1999;25:781-789Palevsky PM. Dialysis modality and dosing strategy in acute renal failure.Semin Dial 2006;19:165-170.Conger JD. A controlled evaluation of prophylactic dialysis in post-traumaticacute renal failure. J Trauma 1975;15:1056-1063.Demirkilic U, Kuralay E, Yenicesu M, et al. Timing of replacement therapyfor acute renal failure after cardiac surgery. J Card Surg 2004;19:17-20.Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, Zandstra DF,Kesecioglu J. Effects of early high-volume continuous venovenoushemofiltration on survival and recovery of renal function in intensive carepatients with acute renal failure: a prospective, randomized trial. Crit CareMed 2002;30:2205-2211.VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH,O'Connor TZ, et al. Intensity of renal support in critically ill patients withacute kidney injury. N Engl J Med 2008;359:7-20Bellomo R. RCT of normal vs. augmented level of renal replacement therapyin ICU-RENAL. The George Institute for International Health website:http://www.thegeorgeinstitute.org/research/renal/studies/rct-of-normal-vs.-augmented-level-of-renal-replacement-therapy-in-icu---renal.cfm. Accessed23 Aug 2007.Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuousveno-venous haemofiltration on outcomes of acute renal failure: aprospective randomized trial. Lancet 2000;356:26-30.Saudan P, Niederberger M, De Seigneux S, et al. Adding a dialysis dose tocontinuous hemofiltration increases survival in patients with acute renalfailure. Kidney Int 2006;70:1312-1317.Tolwani AJ, Campbell RC, Stofan BS, Lai KR, Oster RA, Wille KM. Standardversus high-dose CVVHDF for ICU-related acute renal failure. J Am SocNephrol 2008;19:1233-1238.Bellomo R. Blood purification in sepsis: reasonable scientific hypothesis orpipe dream? Crit Care Med 2001;3:202-205Honore P. Haemofiltration study: IVORE (hIgh VOlume in Intensive Care).ClinicalTrials.gov website: http://clinicaltrials.gov/ct/show/NCT00241228.Accessed 23 Aug 2007.Ronco C, Zanella M, Brendolan A, et al. Management of severe acute renalfailure in critically ill patients: an international survey in 345 centers.Nephrol Dial Transplant 2001; 16:230-237.Monti G, Herrera M, Kindgen-Milles D, et al. The DOse REsponseMulticentre International Collaborative Initiative (DO-RE-MI). ContribNephrol 2007;156:434-443.Uchino S, Bellomo R, Morimatsu H, et al. Continuous renal replacementtherapy: a worldwide practice survey: The beginning and ending supportivetherapy for the kidney (B.E.S.T. kidney) investigators. Intensive Care Med2007;33:1563-1570.Ward DM. The approach to anticoagulation in patients treated withextracorporeal therapy in the intensive care unit. Adv Ren Replace Ther1997;4:160-173.Mehta RL, McDonald BR, Aguilar MM, Ward DM. Regional citrateanticoagulation for continuous arteriovenous hemodialysis in critically illpatients. Kidney Int 1990;38:976-981.Flanigan MJ, Pillsbury L, Sadewasser G, Lim VS. Regional hemodialysisanticoagulation: hypertonic tri-sodium citrate or anticoagulant citratedextrose-A. Am J Kidney Dis 1996;27:519-524.Meier-Kriesche HU, Gitomer J, Finkel K, DuBose T. Increased total to ionizedcalcium ratio during continuous venovenous hemodialysis with regionalcitrate anticoagulation. Crit Care Med 2001;29:748-752.Tolwani AJ, Campbell RC, Schenk MB, Allon M, Warnock DG. Simplifiedcitrate anticoagulation for continuous renal replacement therapy. Kidney Int2001;60:370-374.Palsson R, Laliberte KA, Niles JL. Choice of replacement solution andanticoagulant in continuous venovenous hemofiltration. Clin Nephrol2006;65:34-42.Bagshaw SM, Laupland KB, Boiteau PJ, Godinez-Luna T. Is regional citratesuperior to systemic heparin anticoagulation for continuous renalreplacement therapy? A prospective observational study in an adult regionalcritical care system. J Crit Care 2005;20:155-161.Monchi M, Berghmans D, Ledoux D, Canivet JL, Dubois B, Damas P. Citratevs. heparin for anticoagulation in continuous venovenous hemofiltration: aprospective randomized study. Intensive Care Med 2004;30:260-265.Kutsogiannis DJ, Gibney RT, Stollery D, Gao J. Regional citrate versussystemic heparin anticoagulation for continuous renal replacement incritically ill patients. Kidney Int 2005;67:2361-2367.Joannidis M, Oudemans-van Straaten HM. Clinical review: Patency of thecircuit in continuous renal replacement therapy. Crit Care 2007;11:218.

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References


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Liver failure, regardless of aetiology, is a disease ofexcessive mortality, and the only effective treatment sofar is liver transplantation. Because of organ shortage,patient instability and various other reasons, livertransplantation may not be performed in time in manyoccasions. Throughout time, different artificial liversupport systems have been developed with the hope offilling this time gap by temporarily supporting the liverand stabilising the patient so that one can be bridged totransplantation.

Molecular Adsorbents Recirculating System (MARS) isa non-biological artificial liver support systemdeveloped according to the prototype designed byStange and Mitzner at the University of Rostock,Germany, in 19931. MARS is a form of bloodpurification system that utilises albumin as dialysate toremove protein-bounded toxins in patients of liverfailure2. The system consists of three interconnectedcircuits. The patient's blood cycling in an extracorporealcircuit is dialysed against an albumin circuit through aspecific dialyser running in countercurrent. Themembrane of the dialyser is impermeable to albuminmolecules, essential proteins or hormones, but it allowsthe transport of bilirubin and other toxins across it bymeans of a non-energy-dependent process known asligandification and deligandification into the albumindialysate circuit. The dialysate is then regeneratedonline after passing through a charcoal adsorptioncolumn and an anion exchange resin column. Hydro-soluble toxins, urea, excessive electrolytes and fluid areregulated through a third circuit, which can be astandard haemodialysis machine or a continuous renalreplacement therapy (Figure 1).

EvidenceEvidence relating to the efficacy of MARS can becategorised into three levels: biochemical efficacy,physiological improvement, and clinical benefits. Thebiochemical efficacy of MARS has been well proven.Toxins as removable by MARS documented in theliterature include bilirubin, ammonia, aromatic aminoacids, tryptophans, short-chain fatty acids, bile acids,GABA-like substances, nitric oxides and cytokines3.Most of the toxins removable by MARS are implicatedin the development of hepatic encephalopathy, portalhypertension or other inflammatory changes in liverfailure. Amongst all, reduction of bilirubin, either totalor direct, is the most consistent as demonstrated by allstudies. It should be noted that bilirubin, at least inadult patients, is not a deadly toxin as such. Its use ismainly regarded as a surrogate marker for otherhepatotoxins that are not routinely measured in dailyclinical practice.

The physiological benefits demonstrated by the MARSsystem include lowering of intracranial pressure (ICP),reduction of portal pressure, and improvement ofblood pressure and systemic vascular resistance.Reduction of ICP in liver failure by MARS was firstreported in animal studies4 and subsequently also in acase report5. Elevated ICP implies cerebral oedemawhich is one of the most common causes of death inpatients with acute liver failure. Reduction of ICPimplies that cerebral oedema is under control and thepatient may be able to gain more time to bridge totransplantation.

In patients with liver failure, particularly those withcirrhosis, portal hypertension is a significant factorcontributing to ascites formation, variceal bleedingand hepatorenal syndrome. MARS has been shown tobe able to reduce the hepatic venous pressure gradient,an indirect measurement of portal pressure. This effectis not only observed during treatment, but sustainedfor up to 24 hours after MARS6. The mechanism ofreduction of portal pressure is unknown, but isbelieved to be mediated through removal of vasoactivesubstances like nitric oxide in the splanchniccirculation by MARS.

The haemodynamic benefits brought about by MARS inpatients having liver failure include raised mean arterialpressure, increased systemic vascular resistance, andreduced cardiac output. Haemodynamic effect isparticularly prominent in patients with cirrhosis duringtreatment7,8. In patients with acute liver failure,

Prof. Sheung-tat FAN

Molecular Adsorbents Recirculating System(MARS): Evidence and Management Pitfalls

Prof. Sheung-tat FAN

Dr. Alexander CHIU

Department of Surgery, The University of Hong Kong, Hong KongMS, MD, PhD, DSc, FRCS (Glasg & Edin), FACS, FHKAM (Surg), FCSHK

Dr. Alexander CHIU

Adult Intensive Care Unit, Queen Mary Hosptial, Hong KongMBChB, MRCP (UK), FHKCP, FHKAM (Med), FRCP (Edin)

Figure 1 :The MARS circuit (with permission fromGambro, Inc)

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increased vascular tone could also be observed, but theresult is not as sustained9. These findings illustrate thatMARS is haemodynamically well tolerated and wouldnot cause hypotension as such. From our experience,however, we find transitory hypotension rathercommon at the beginning of treatment, and small dosesof vasopressor are frequently needed to sustain bloodpressure. We attribute this to release of cytokinessecondary to platelet activation and change in rheologyof blood10 circulating through the extracorporealsystem.

The effects of MARS on two most commoncomplications of liver failure have been studied.Mitzner et al. reported a significantly lower mortalityrate in patients with type 1 hepatorenal syndrometreated with MARS compared with those havingstandard medical therapy11. The major shortcoming ofthis study was that there were only 13 patients involvedand in fact only one patient in the treatment survivedbeyond 30 days. Earlier studies of MARS on hepaticencephalopathy were mainly non-randomised studiesand reported lower mortality in treatment groups12.Hassanein et al. reported the use of MARS in patientswith severe hepatic encephalopathy in a large-scalerandomised controlled trial and concluded that thetreatment was associated with earlier and morefrequent improvement in encephalopathy grading13. Itshould be noted, however, that the trial was notdesigned to address the impact of MARS on survival.

MARS is not without complications. The most commoncomplication of MARS is platelet reduction. In ourexperience, the drop in platelet per treatment is around5 to 10%, but it may be up to 20% in some cases.Though it might not seem significant in most patientswith platelet count more than 100x10^9/L, it does raiseconcern in cirrhotic patients with splenomegaly inwhich they commonly have thrombocytopenia to startwith and when repeated treatments are needed. Weempirically give platelet transfusion before MARS topatients with platelet count less than 30x10^9/L. In ourexperience, four major bleeding episodes might havebeen related to MARS (2 intracranial bleeding, 1variceal bleeding and 1 intra-abdominal bleeding afterliver transplantation). However, given the inclination ofdeveloping these complications in such critical patients,it may be unjustifiable to attribute occurrences of theseepisodes to MARS. Worldwide, the opinion is thatMARS treatment is safe and does not cause additionalbleeding risk.

Other documented complications of MARS includehypoglycaemia during treatment14, electrolytedisturbances15, and non-cardiogenic pulmonaryoedema16. As MARS is one form of extracorporealcircuit, it shares the potential complications thatextracorporeal circuits usually have, including catheter-related infection, haematoma and circuit thrombosis.

Anticoagulation in treatment by MARS is a difficulttopic. In our unit, we have moved from noanticoagulation to the use of low molecular weightheparin, and then to heparin priming in which thesystem is flushed with heparin saline before use. Giventhe nature of the disease of patients treated, we havenot used systemic anticoagulation, albeit it is claimed to

be safe according to other centres' experience. Thecoagulation profile of patients with liver failure variessignificantly and represents the interplay betweenthrombocytopenia, platelet dysfunction and alsoreduced synthesis of clotting factors and antithrombinfrom liver. In order to develop a tailor-madeanticoagulation strategy, some researchers haveadvocated the use of thromboelastography (TEG) tomonitor these patients during treatment17,18. We havealso tried to apply this monitor in our practice, butbecause TEG interpretation is in itself open to a lot ofdebate, we feel that it is still a research tool rather thanfor routine clinical use. Circuit thrombosis is notnecessarily due to inadequate anticoagulation. Circuitblood flow and turbulences, as well as position andproperties of the dialysis catheter, could be contributingfactors to inadequate anticoagulation.

Management PitfallsMARS is by no means a salvage treatment for liverfailure. The most serious management pitfall isimplementing MARS as a last resort hoping that thetreatment can reverse the detrimental effects of liverfailure at a time when the patient is already moribund.In our practice, we employ MARS as an earlyintervention to prevent deterioration, preferably whenthe patient is not too ill. We render MARS treatment tothose showing rapid velocity but not high absolutevalue in biochemical deterioration, those with grade 2hepatic encephalopathy, and those with hepatorenalsyndrome with urine output still more than0.5ml/kg/hr. We believe it is at these time points thatMARS can alleviate organ damage and retardprogression of the disease through hepatotoxinremoval. On the contrary, if MARS treatment isrendered late in the course of liver failure, the benefit ofhepatotoxin removal will become minimal amidst theoverwhelming cascade of physiological damagesbrought about by multi-organ failure19.

Another management pitfall is indiscriminate use ofMARS for all patients with liver failure. In fact, MARSis not applicable to all patients; only a selected few canbenefit from it. The selection criteria for MARScandidates in our unit are listed in Table 1. Based onthese criteria, less than 25% of the patients admittedwith liver failure to our intensive care unit are eligiblefor the treatment. Certain subgroups of patients, such asthose with acute decompensated Wilson disease, haveappeared to respond particularly well to MARS20.Selection of suitable candidates and initiation of MARSat appropriate timing are the two most importantfactors to improve the success rate of MARS treatment.

The third management pitfall is utilising MARS as ameans to reverse liver failure. Although native liverrecovery with MARS has been reported in the literatureand also occasionally encountered in our experience, itis unpredictable as to which patients will respondfavourably. It is therefore inappropriate to commendthe treatment as one which can promote liver recovery.In our centre, the sole objective of performing MARS isto stabilise patients' conditions and to bridge them totransplantation. It should be clearly explained topatients who are undergoing MARS but not aiming forliver transplantation that the treatment would only


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bring about short-term improvement to theirconditions. Hopefully, recognition and appropriatefuture consideration of these management pitfalls willoffer possibilities for further refinement of the use ofMARS in patients with liver failure.

ConclusionSince MARS was first launched into clinical applicationin year 2000, research materials published on this topichave exceeded 500, mostly descriptive studies with onlya handful of randomised trials amongst them. Given thelack of concrete evidence to demonstrate the survivalbenefit of MARS, it is understandable that clinicians areskeptical to commit to such treatment which isexpensive to run, has a complex operative procedure,and, most importantly, not without risk. It should benoted, however, that liver failure is a disease associatedwith high mortality and limited treatment options. Anysuggestion or evidence, despite being observational oruncontrolled, should therefore not be overlooked andneglected casually. Moreover, the lack of conclusiveresult from randomised controlled trials could also bedue to fallacies and limitations of study methodology.Heterogeneity of the disease, existence of confoundingfactors, e.g. availability of liver transplantation, and lackof reliable tools to prognosticate patients and to monitortreatment efficacy are all factors that need to beconsidered in the design of studies on MARS.

In summary, utilisation of MARS treatment requires acomprehensive understanding of its benefits andlimitations if optimal outcome is to be achieved. Furtherstudies to delineate and refine the clinical indications,timing of initiation and operative details are needed togive clinicians a better idea of how to implement suchservice in practice.

Competing Interests:Nothing to declare.

Stange J, Ramlow W, Mitzner S, Schmidt R, Klinkmann H.Dialysis against a recycled albumin solution enables the removalof albumin-bound toxins. Artif Organs. 1993 Sep; 17 (9): 809-813.Stange J, Mitzner SR, Risler T, Erley CM, Lauchart W, Goehl H, etal. Molecular adsorbent recycling system (MARS): clinical resultsof a new membrane-based blood purification system forbioartificial liver support. Artif Organs. 1999 Apr; 23 (4): 319-330.Chiu A, Fan ST. MARS in the treatment of liver failure:controversies and evidence. Int J Artif Organs. 2006 Jul; 29 (7):660-667.Sen S, Rose C, Ytrebo LM, Davies NA, Nedredal GI, Drevland SS,et al. Effect of albumin dialysis on intracranial pressure increasein pigs with acute liver failure: a randomized study. Crit CareMed. 2006 Jan; 34 (1): 158-164.Pugliese F, Ruberto F, Perrella SM, Cappannoli A, Bruno K,Martelli S, et al. Modifications of intracranial pressure aftermolecular adsorbent recirculating system treatment in patientswith acute liver failure: case reports. Transplant Proc. 2007 Jul-Aug; 39 (6): 2042-2044.Sen S, Mookerjee RP, Cheshire LM, Davies NA, Williams R, JalanR. Albumin dialysis reduces portal pressure acutely in patientswith severe alcoholic hepatitis. J Hepatol. 2005 Jul; 43 (1): 142-148.

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Catalina MV, Barrio J, Anaya F, Salcedo M, Rincon D, ClementeG, et al. Hepatic and systemic haemodynamic changes afterMARS in patients with acute on chronic liver failure. Liver Int.2003; 23 Suppl 3: 39-43.Donati G, Piscaglia F, Coli L, Silvagni E, Righini R, Pini P, et al.Acute systemic, splanchnic and renal haemodynamic changesinduced by molecular adsorbent recirculating system (MARS)treatment in patients with end-stage cirrhosis. Aliment PharmacolTher. 2007 Sep; 26 (5): 717-726.Lai WK, Haydon G, Mutimer D, Murphy N. The effect ofmolecular adsorbent recirculating system on pathophysiologicalparameters in patients with acute liver failure. Intensive CareMed. 2005 Nov; 31 (11): 1544-1549.Replogle RL, Meiselman HJ, Merrill EW. Clinical implications ofblood rheology studies. Circulation. 1967 Jul; 36 (1): 148-160.Mitzner SR, Stange J, Klammt S, Risler T, Erley CM, Bader BD, etal. Improvement of hepatorenal syndrome with extracorporealalbumin dialysis MARS: results of a prospective, randomized,controlled clinical trial. Liver Transpl. 2000 May; 6 (3): 277-286.Heemann U, Treichel U, Loock J, Philipp T, Gerken G, Malago M,et al. Albumin dialysis in cirrhosis with superimposed acute liverinjury: a prospective, controlled study. Hepatology. 2002 Oct; 36(4 Pt 1): 949-958.Hassanein TI, Tofteng F, Brown RS, Jr., McGuire B, Lynch P,Mehta R, et al. Randomized controlled study of extracorporealalbumin dialysis for hepatic encephalopathy in advancedcirrhosis. Hepatology. 2007 Dec; 46 (6): 1853-1862.Khoo AL, Tham LS, Lim GK, Lee KH. Hypoglycemia innondiabetic patients undergoing albumin dialysis by molecularadsorbent recirculating system. Liver Transpl. 2003 Sep; 9 (9): 949-953.Doria C, Doyle HR, Mandala L, Marino IR, Caruana G,Gruttadauria S, et al. Changes in serum electrolytes duringtreatment of patients in liver failure with molecular adsorbentrecirculating system. Int J Artif Organs. 2003 Oct; 26 (10): 918-923.Doria C, Mandal AL, Scott VL, Marino IR, Gruttadauria S,Miraglia R, et al. Noncardiogenic pulmonary edema induced by amolecular adsorbent recirculating system: case report. J ArtifOrgans. 2003; 6 (4): 282-285.Faybik P, Bacher A, Kozek-Langenecker SA, Steltzer H, KrennCG, Unger S, et al. Molecular adsorbent recirculating system andhemostasis in patients at high risk of bleeding: an observationalstudy. Crit Care. 2006 Feb; 10 (1): R24.Doria C, Mandala L, Smith JD, Caruana G, Scott VL, GruttadauriaS, et al. Thromboelastography used to assess coagulation duringtreatment with molecular adsorbent recirculating system. ClinTransplant. 2004 Aug; 18 (4): 365-371.Chiu A, Chan LM, Fan ST. Molecular adsorbent recirculatingsystem treatment for patients with liver failure: the Hong Kongexperience. Liver Int. 2006 Aug; 26 (6): 695-702.Chiu A, Tsoi NS, Fan ST. Use of the molecular adsorbentsrecirculating system as a treatment for acute decompensatedWilson disease. Liver Transpl. 2008 Oct; 14 (10): 1512-1516.

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Acute circulatory failure resulting in cardiogenic shock isa common problem encountered in the intensive careunit. Cardiogenic shock is defined by the presence of thefollowing haemodynamic parameters: sustainedhypotension (systolic blood pressure <90mmHg or meanarterial pressure of 30mmHg below basal level),adequate or elevated left ventricular (LV) filling pressure(e.g. left ventricular end-diastolic pressure >18mmHg orright ventricular end-diastolic pressure or pulmonaryartery wedge pressure > 15mmHg) and reduced cardiacoutput (cardiac index <1.8L/min/m2 without support or<2.0-2.2 L/min/m2 with support). Clinical manifestationsof cardiogenic shock include signs of poor tissueperfusion such as cold extremities, oliguria and/orclouded sensorium, in the setting of myocardialdysfunction. Causes of cardiogenic shock include acutemyocardial infarction with or without mechanicalcomplications (e.g. ventricular septal rupture, papillarymuscle rupture with acute mitral regurgitation,contained free wall rupture), acute myocarditis, tako-tsubo (or stress-induced) cardiomyopathy, acute valvularregurgitation, or any other cause of acute severe leftventricular (LV) or right ventricular (RV) dysfunction.

The mainstay of treatment for cardiogenic shock ispharmacological support using inotropic agents, suchas dobutamine, dopamine and norepinephrine, andphosphodiesterase inhibitors, such as milrinone. Theseagents improve short-term haemodynamics at theexpense of increased oxygen demand by increasingmyocardial ATP consumption, which may bedeleterious over long-term. Calcium-sensitising agentswith inodilatory properties such as levosimendan,which does not increase oxygen demand and is less pro-arrhythmogenic, have been shown to have a statisticallynon-significant but consistently lower mortality thandobutamine at six months in the treatment of acutedecompensated heart failure1. Another agent whichmay be used to treat acute decompensated heart failureis a recombinant B-type natriuretic peptide callednesiritide. However, pooled analysis of randomisedcontrolled trials showed increased risk of death at 1month2 and worsening renal function with nesiritidecompared to usual therapy3.

Mechanical Circulatory SupportIn circumstances where a potentially reversible cause ofacute heart failure has been identified or where cardiacsurgery or transplantation is considered an option forrefractory heart failure, mechanical circulatory supportsystems are available which can maintain the patientuntildefinitivetreatment is instituted. Mechanicalcirculatory

support can be life-saving in acute cardiogenic shock andparticularly useful as a bridge to recovery in cases offulminant myocarditis. There is evidence that patientswith fulminant myocarditis, i.e. those with severehaemodynamic compromise, rapid onset of symptomsand fever, have a better long-term prognosis than thosewith acute nonfulminant myocarditis if they survive theinitial period of cardiogenic shock4. Therefore, in thesepatients, an aggressive approach including mechanicalcirculatory support is warranted. Time from onset ofillness to recovery of ventricular function in fulminantmyocarditis usually takes 2 to 3 weeks5. Mechanicalcirculatory support includes placement of intra-aorticcounterpulsation balloon pumps (IABP), extracorporealmembrane oxygenation systems (ECMO), andventricular assist devices (VAD).

Intra-aortic Balloon Pump (IABP) orCounterpulsationIntra-aortic balloon pump (IABP) is the most commonlyused mechanical support for cardiogenic shock. The IABPis commonly inserted percutaneously through the femoralartery (Figure 1) but, in patients with peripheral vasculardisease, it may be inserted through the brachial artery6. Bysynchronising inflation and deflation to the patient'scardiac cycle, the IABP improves coronary and peripheralperfusion during diastolic balloon inflation and augmentsleft ventricular performance during systolic balloondeflation by reducing the afterload (Figure 2).

Mechanical Circulatory Supportin the Intensive Care UnitDr. Elaine MC CHAU

Dr. Tak-fu TSEDr. Elaine MC CHAU

Cardiology Centre, HK Sanatorium & Hospital, Hong KongMB,BS(Lond), MRCP(UK), FHKCP, FHKAM, FRCP (Edin), FRCP (Lond)

Dr. Tak-fu TSE

Specialist in CardiologyMB,BS(HK), FRCP (Lond), FRCP (Edin), FRCP (Glas), FHKCP, FHKAM

Figure 1. The IABP is inserted percutaneouly via the femoralartery and positioned in the thoracic aorta distal to the leftsubclavian artery and proximal to the renal arteries

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Apart from left ventricular failure and cardiogenicshock, indications for IABP include support of high riskpatients for percutaneous coronary intervention, cardiacsurgery for post-myocardial infarction ventricularseptal defect or acute mitral regurgitation, stabilisationof heart failure patients undergoing general anaesthesiaand bridge to heart transplant. Its use is contraindicatedin severe aortic valvular insufficiency which mayworsen during diastolic regurgitation, aortic dissection,peripheral vascular disease and tachyarrhythmias.

Vascular complications associated with the use of IABPinclude limb ischaemia, aortic or arterial injury such asperforation and dissection, femoral artery thrombosis,peripheral embolisation, and visceral ischaemia. Othercomplications may be balloon related (such as incorrectpositioning, gas embolisation) or related to infection orentrapment. In patients with peripheral vasculardisease and diabetes, sheathless method rather thansheathed technique should be used7.

E x t r a - c o r p o r e a l M e m b r a n eOxygenation (ECMO)ECMO is a form of extracorporeal life support wherebyan external pump system carries the venous blood fromthe large central veins of the patient to an oxygenator (agas exchange device) where the blood becomesenriched with oxygen and has carbon dioxide removed.The oxygenated blood then re-enters the patient'scirculation, either through the aorta or arterial system(so-called veno-arterial ECMO) (Figure 3) or throughthe venous system (veno-venous ECMO). Veno-arterial ECMO provides support for severe cardiacfailure with or without respiratory failure and can beset up by using peripheral cannulation of the femoralartery and vein (Figure 4), so-called percutaneouscardiopulmonary support system (PCPS). Veno-arterialECMO may be applied for the short-term managementof cardio-respiratory failure or cardiac failure refractoryto inotropic and IABP support. Common indicationsinclude acute fulminant myocarditis8, severe acuterespiratory distress syndrome (ARDS)9, acutedecompensated dilated cardiomyopathy, ischaemiccardiogenic shock, drug overdose or sepsis withprofound cardiac depression and as a bridge to longer-term ventricular assist device10. Veno-venous ECMO

involves return of oxygenated blood to the venoussystem of the patient, usually the right atrium via theinternal jugular vein, and is the preferred mode ofsupport for isolated respiratory failure, such as ARDS11.In ARDS, ECMO provides life support without relianceon high-pressure high-oxygen mechanical ventilationfor gas exchange, thereby reducing the release ofinflammatory mediators from the damaged native lung,and buys time necessary for the lung to heal.

The major components of ECMO involve the bloodpump ('the heart') and the oxygenator ('the lung').Previously roller pumps were standard for ECMOtherapy but the mechanical stress results in rupture andembolism of tube particles. These complications areavoided with the use of centrifugal pumps. The

Figure 2. Inflation and deflation of the IABP are synchronizedto the patient's cardiac cycle - A. With balloon inflation duringdiastole, there is increased coronary artery blood and systemicperfusion; B. With balloon deflation during systole, oxygendemand is reduced, resulting in increased stroke volume andreduced afterload.

Figure 3. Different components of an ECMO system - the mainconsole controls the flow rate of the centrifugal blood pump,which drives the venous blood from the patient through theoxygenator prior to returning the blood to the arterial side ofthe patient's circulation.

Figure 4. Blood is accessed from the large central veins such asthe inferior vena cava and returned to the arterial system in theaorta after passing through the oxygenator of the ECMOsystem.


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duration of ECMO support depends on the type ofoxygenator used. With silicone-membrane ormicroporous hollow-fibre oxygenators, plasma leakagetypically occurs after a few days, necessitating circuitchangeover. However, with diffusion membraneoxygenators such as the QuadroxD (JostraMedizintechnik AG, Hirrlingen, Germany), the hollow-fibre technology utilises a true non-microporousmembrane and avoids plasma leak problem. Thesystem is ideal for prolonged perfusion up to 14 dayswith the longest duration reported to be 46 days12.

Like the IABP, the PCPS is also contraindicated in aorticdissection and severe aortic valve regurgitation.Potential complications associated with the use ofECMO include vascular complications, haemolysis,mechanical problems with clots or air in the system,oxygenator thrombosis and bleeding tendency with useof heparin.

In case of IABP failing to support the patient, PCPS orV-A ECMO can immediately provide adequateperfusion to all organs irrespective of the lungcondition. However, PCPS cannot augment coronaryblood flow and may increase left ventricular afterload.Combination of IABP and PCPS is clinically feasible andhas been shown in animal models to have importantadvantages over PCPS alone, especially in ischaemiccardiomyopathy13,14. Combined use of IABP andECMO reduces left ventricular wall stress and oxygenconsumption while increasing the end-systolicelastance13 and reduces tissue acidosis and myocardialnecrosis14.

Ventricular Assist Devices (VAD)Patients with advanced heart failure in New York HeartAssociation class III and IV may be classified into sevenclinical profiles in the Interagency Registry ofMechanically Assisted Circulatory Support(INTERMACS) to allow optimal selection formechanical circulatory support, especially ventricularassist devices (VAD). 80% of such devices are beingused in the two profiles with the highest levels ofclinical compromise, namely those "crash and burn"patients (INTERMACS profile 1) and "sliding oninotropes" patients (INTERMACS profile 2)15. There aremany types of VAD, with the first-generation VADbeing pulsatile devices, the second-generation VADbeing the axial flow pumps and the third-generationVAD being centrifugal pumps which are bearinglessand designed for long-term support. In the past, use ofthe extracorporeal or implantable VAD requiressurgical implantation in the operating theatre.Recently, VAD which may be inserted percutaneouslyhave been developed for clinical use. For example, theTandemHeart Percutaneous Ventricular Assist Device(pVAD) is an extracorporeal continuous-flowcentrifugal pump. A cannula is inserted through thefemoral vein, across the interatrial septum and into theleft atrium. The TandemHeart pump withdrawsoxygenated blood from the left atrium and returns it toone or both femoral arteries via arterial cannulas(Figure 5). Compared with IABP, the pVAD canprovide better haemodynamic improvement, in termsof increased cardiac output, reduced pulmonary wedge

pressure and higher meanarterial pressure16,17, andlower serum lactate level17.Potential complications withthis device include limbischaemia, disseminatedintravascular coagulation(DIC) , bleeding fromcannulat ion s i te andinfection. Another devicecalled the Impella RecoverLP 2.5 is a minimallyinvasive catheter-basedventricular assist device,which is inserted using theSeldinger technique throughthe femoral artery. The tipof the catheter contains a"pigtail" which rests in theleft ventricle18.

Evolving Role of MechanicalCirculatory SupportNowadays, VAD is not only used as a bridge to hearttransplantation in severe heart failure but increasinglyused as a bridge to myocardial recovery or asdestination therapy (i.e. for permanent use in patientswho are not candidates for heart transplantation).There is evidence that, in some severe heart failurepatients, prolonged complete unloading of the leftventricle (LV) with VAD may lead to structural reverseremodelling and functional improvement of the LV.This is true not only in myocarditis patients19 but also innon-ischaemic dilated cardiomyopathy patients20. Thetime frame for myocardial recovery can vary fromweeks to months. Currently the use of implantablelong-term VAD is associated with major complicationssuch as embolic stroke, mechanical device failure,infection and need for sternotomy. Development ofbearingless centrifugal pumps, smaller devices andpartial cardiac support system which can be implantedwith a minimally invasive procedure21 will hopefullyminimise some of the problems.

ConclusionAt present, IABP, ECMO and VAD are available asmechanical circulatory support for cardiogenic shock.The IABP is convenient to be applied but can onlyprovide limited additional cardiac output, which maynot be adequate for critical situations. ECMO canprovide total circulatory support but suffers thedrawback of extracorporeal circulation such asactivation of cellular elements and the need of anoxygenator. The duration of use is limited to 2 to 6weeks. Implantable VAD has the potential to provide

Figure 5. Diagramaticr ep r esentat ion o f apercutaneous ventricularassist device (pVAD) whichwithdraws oxygenatedblood from the left atriumand returns it to the femoralartery via arterial cannula

Medical Bulletin

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Kopp R, Dembinski R, Kuhlen R. Role of extracorporeal lungassist in the treatment of acute respiratory failure. MinervaAnestesiol 2006; 72: 587-595Horton S, Thuys C, Bennett M et al. Experience with the JostraRotaflow and QuadroxD oxygenator for ECMO. Perfusion 2004;19: 17-23Bavaria JE, Furukawa S, Kreiner G et al. Effect of circulatoryassist devices on stunned myocardium. Ann Thorac Surg 1990;49: 123-128Lazar HL, Treanor P, Yang XM et al. Enhanced recovery ofischemic myocardium by combining percutaneous bypass withintraaortic balloon pump support. Ann Thorac Surg 1994; 57:663-668Stevenson LW, Pagani FD, Young JB et al. INTERMACS profilesof advanced heart failure: the current picture. J Heart LungTransplant 2009; 28:535-541Burkhoff D, Cohen H, Brunckhorst C et al. A randomizedmulticenter clinical study to evaluate the safety and efficacy of theTandemHeart percutaneous ventricular assist device versusconventional therapy with intraaortic balloon pumping fortreatment of cardiogenic shock. Am Heart J 2006; 152(3): 469 e1-e8Thiele H, Sick P, Boudriot E et al. Randomised comparison ofintra-aortic balloon support with a percutaneous left ventricularassist device in patients with revascularized acute myocardialinfarction complicated by cardiogenic shock. European Heart J2005; 26(13): 1276-1283Henriques J, Remmelink M, Baan J et al. Safety and feasibility ofelective high-risk percutaneous coronary intervention procedureswith left ventricular support of the Impella Recover LP 2.5. Am JCardiol 2006; 97:990-992Ferrar DJ, Holman WR, McBride LR et al. Long-term follow-up ofThoratec ventricular assist device bridge-to-recovery patientssuccessfully removed from support after recovery of ventricularfunction. J Heart Lung Transplant 2002; 21:516-521Birks EJ, Tansley PD, Hardy J et al. Left ventricular assist deviceand drug therapy for the reversal of heart failure. New Engl JMed 2006; 355: 1873-1884Meyns B, Klotz S, Simon A et al. Proof of concept: hemodynamicresponse to long-term partial ventricular support with theSynergy Pocket Micro-pump. J Am Coll Cardiol 2009; 54: 79-86

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weeks. Implantable VAD has the potential to providelonger-term support but the device is expensive andimplantation requires surgical expertise. PercutaneousVAD and partial mechanical cardiac support, currentlyunder investigation, are attractive alternatives becauseof ease of insertion but are not yet widely available.

Mebazaa A, Nieminen MS, Parker M et al. Levosimendan vsdobutamine for patients with acute decompensated heart failure:the SURVIVE randomized trial. JAMA 2007; 297:1883-1991Sackner-Bernstein JD, Kowlski M, Fox M et al. Short-term risk ofdeath after treatment with nesiritide for decompensated heartfailure: a pooled analysis of randomized controlled trials. JAMA2005; 293(15): 1900-1905Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk ofworsening renal function with nesiritide in patients with acutelydecompensated heart failure. Circulation 2005; 111:1487-1491McCarthy RE, Boehmer JP, Hruban RH et al. Long-term outcomeof fulminant myocarditis as compared with acute (nonfulminant)myocarditis. N Engl J Med 2000; 342:690-695)Chau EMC, Chow WH, Chiu CSW et al. Treatment and outcomeof biopsy-proven fulminant myocarditis in adults. International JCardiology 2006; 110:405-406Noel BM, Gleeton O, Barbeau GR. Transbrachial insertion of anintraaortic balloon pump for complex coronary angioplasty.Catheter Cardiovasc Interv 2003; 60: 36-39Erdogan HB, Goksedef D, Erentug V et al. In which patientsshould sheathless IABP be used? An analysis of vascularcomplications in 1211 cases. J Cardiac Surgery 2006; 21(4): 342-346Oshima K, Kunimoto F, Hinohara H. Fulminant myocarditistreated with percutaneous cardiopulmonary support system(PCPS). Ann Thorac Cardiovasc Surg 2008; 14(2): 75-80Hemmila MR, Rowe SA, Tamer NB et al. Extracorporeal lifesupport for severe acute respiratory distress syndrome. Ann Surg2004; 240: 595-607Pagani FD, Aaronson KD, Swaniker F et al. The use ofextracorporeal life support in adult patients with primary cardiacfailure as a bridge to implantable left ventricular assist device.Ann Thorac Surg 2001; 71: S77-81

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Infectious disease emergencies (IDEs) are not uncommon.However, even in a classical infectious diseases textbook,only intracranial infection, bacteraemia, and fulminantpneumonia are included in the relevant chapter. Inpractice the spectrum of IDEs manifesting in an inpatientsetting is much wider1,2. We define or will define as anyclinically and microbiologically documented infectionthat by itself or as a complication of its treatment isliable to result in (i) irreversible local tissue or organdamage, permanent functional loss, or (ii) imminentdeath without urgent medical or surgical interventionor progressive system inflammatory responsesyndrome, to the extent that advanced life support orintensive care would soon be required.

Strategies in the Diagnosis of IDEConstant vigilance, a systematic approach to any clinicalproblem, and timely consultation will enable earlydetection of conditions requiring urgent treatment, sothat optimal management may be implemented early toprevent irreversible complications or death. All infectionsmay initially be minor and appear innocuous, such ascellulitis developing from an inapparent skin wound.However, if the initial infective process is uncontrolledby the host defence mechanisms or appropriate therapy,it may result in potentially life-threatening diseases, suchas group A streptococcal necrotising fasciitis orStreptococcus suis meningitis. It is essential that thediagnosis be made when the area of necrosis or extent ofmeningeal involvement is still limited. At this early stage,even though the pathology has been established andbacteria could be isolated from tissues or CSF, the clinicalsigns may not be typical. Nevertheless, the benefit ofcorrect treatment at this stage is the greatest. Similarly,antibiotic-induced morbilliform rash is not an IDE, buterythema multiforme involving the mucosa heralds one.It may be too late if an IDE is declared only when frankskin exfoliation or gastrointestinal bleeding occurs. Theclinical examples of IDEs encountered in our clinicalconsultation service are listed in Table 1.

Causes for Failure to Make an EarlyDiagnosisFailure to recognise an emergency was related toseveral factors, the commonest being a presentation thatdoes not conform to classic descriptions of the disease,such as deafness rather than neck rigidity in acutepyogenic meningitis. Furthermore, typical features maypresent in an atypical clinical setting. For example, CMVretinitis is a well-known complication in HIV-infected

patients, requiring urgent anti-viral treatment, butsuspicion of this entity may not be raised in non-AIDScases. This illustrates the need to account for each acuteclinical manifestation despite apparent incongruence.

Sometimes, diseases usually not directly related to theclinical specialty of the referring clinicians may also bemissed. In this era of specialisation, clinicians often relyon their colleagues to deal with problems that do not fallstrictly within their specialty. Thus, a considerablenumber of adverse reactions to antimicrobial agents werenot recognised early.

Clinicians may also face difficulties with uncommonorganisms and their associated pathology such asBartonella henselae, rickettsiae, Leptospira, Haemophilusaphrophilus, and Vibrio vulnificus. Similarly, rarecomplications of common infections may not beappreciated such as Clostridium difficile-related toxicmegacolon. A better liaison between the infectious diseasespecialist and the clinician can enable mutual exchange ofknowledge and experience and ultimately result inimproved care of patients in the early stages of an IDE.

Infectious Disease Emergencies

Dr. Samson SY WONG

Dr. Samson SY WONGDr. Vincent CC CHENG

Assistant Professor, Department of Microbiology, The University of Hong Kong, Queen Mary HospitalMBBS (HK), DTM&H (UK), FRCPath (UK), FHKAM (Clinical Microbiology and Infection)

Dr. Vincent CC CHENG

Specialist in Clinical Microbiology & Infection, Department of Microbiology, The University of Hong KongMBBS (HK), MRCP (UK), PDipID (UK), FRCPath, FHKCPath, FHKAM (Pathology)

Table 1. Examples of infectious disease emergencies encountered inthe clinical consultation service at the Department ofMicrobiology, Queen Mary Hospital.Organ systemCentral nervous systemand eye

Cardiovascular system

Upper respiratory tract

Lower respiratory tractand thorax

Alimentary system andperitoneum

Skin and soft tissue

Bone and jointSystemic

Antibiotic-induced

ExamplesAcute meningitisCerebral and epidural abscessCytomegalovirus retinitisSubdural empyema, endophthalmitis, cavernoussinus thrombosis, VZV anterior uveitis and keratitis,rhinocerebral mucormycosisInfective endocarditisInfected aortic aneurysm or graftPyopericardium, cardiac tamponadeImminent upper airway obstruction, e.g. mucositis,abscessFungal sinusitis, rhinocerebral mycosisFulminant pneumoniaMiliary tuberculosisCavitary pneumonia with pneumothoraxMassive haemoptysis (aspergillosis in oldtuberculous cavity)Procedure-related mediastinitisTertiary peritonitisToxic megacolon (amoebic, typhoid)Neutropenic ileocaecitisEmphysematous cholecystitisNecrotising fasciitis and Fournier's gangreneGas gangreneOrbital cellulitisPyogenic arthritisSepsis in immunocompromised patients includingpost-splenectomy sepsis and neutropenic sepsisSevere sepsis and others*Hepatitis, renal failureXanthopsia, hearing lossAllergic reactionsConvulsion

Including gas gangrene, tetanus, severe falciparum malaria, hantavirus haemorrhagic feverwith renal syndrome, chickenpox in an oncology patient, dengue haemorrhagic fever,bleeding due to severe thrombocytopenia as a result of rubella and infectious mononucleosis,toxic shock syndrome, perinephric abscess, emphysematous pyelonephritis, pyonephrosis.

*

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Luk WK, Wong SSY, Yuen KY, Ho PL, Woo PCY, Lee RA, Chau PY. In-patient emergencies encountered by an infectious disease consultation service. Clin Infect Dis 1998;26:695-701.Nicolasora N, Kaul DR. Infectious disease emergencies. Med Clin North Am 2008;92:427-441.Norrby SR. Infectious disease emergencies: role of the infectious disease specialist. Clin Microbiol Infect 2005;11 Suppl 1:9-11.

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ReferencesManagement of IDERegarding the care of patients with IDEs, the commonest contribution of the infectious disease specialist is to advise on the choice of appropriate antimicrobials. The proficiency of infectious disease specialists in antimicrobial chemotherapeutics also enables them to initiate modification of the dosage or route of administration as appropriate. Another contribution of the infectious disease team is the delineation, after thorough evaluation of patients and further investigations, of problems that were not apparent to the referring clinician. For example, necrotising fasciitis due to V. vulnificus is known to be rapidly progressive, and an early diagnosis can make a significant difference in the eventual outcome. Our experience is that needle aspiration is pivotal in establishing an aetiological diagnosis and indicating the choice of antimicrobials. Early extensive debridement, as guided by the Gram smear of the resection margin, is crucial for a favourable outcome. In the long run, the infectious disease team will help to raise the awareness of this IDE, alerting clinicians to future occurrences of similar conditions, and recognising the early outbreak of deadly disease like SARS3.

Clues to Early Recognition of IDEPatients with a systemic inflammatory response should be carefully evaluated for any underlying focus of infection that may not be apparent initially. Occupational history, local signs, or subtle radiological findings can also be useful pointers to the diagnosis and its emergency nature. Any condition involving vital organs such as the central nervous system (brain, spinal cord, and eye), the cardiovascular system (especially heart valves), and the upper airway should alert clinicians to the potential for irreversible damage due to an infection. Emergencies can arise as a result of serious toxicity from treatment; they are usually due to drugs, including hypersensitivity reactions, potentially irreversible organ toxicity, or other side effects.

Society News

News from Member SocietiesManagement Society for Healthcare ProfessionalsUpdated office-bearers for the year 2009-2010 are as follows: President: Dr. Kong-san YU; Honorary Secretary: Ms. Virginia Wai-chun CHEUNG; Honorary Treasurer: Dr. Raymond Wai-kit CHAN

The FMSHK would like to send its congratulations to the new office-bearers and look forward to working together with the society.

VOL.11 NO.5 MAY 2006 Drug Review

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IntroductionCritically ill patients in the intensive care unit (ICU)requiring mechanical ventilation frequently experiencepain, anxiety, sleep deprivation and distress. Sedationand analgesics are commonly used to provide comfortand relieve pain. Commonly used agents includebenzodiazepines, propofol, opioids and the neweragents, remifentanil and dexmedetomidine.

There is now an increasing awareness that importantcomplications from sedative agents and the way theyare used, can occur.1 Oversedation can prolong weaningfrom ventilation and ICU duration of stay.2

Undersedation may contribute to increased sympatheticactivity, myocardial ischaemia, poor ventilatorsynchrony, hypercatabolism, immunosuppression andaccidental dislodgements of lines and tubes. Finally,sedation and analgesia may increase delirium, whichcan occur in up to 80% of ICU patients, withoutachieving increased comfort.

Current practice varies widely.1,3 New trends andresearch are therefore focused not only on which is thebest pharmacological agent, but also on monitoring thedepth and adequacy of sedation and protocolssedation use.

Indications for SedationAppropriate evaluation and management of causes ofdistress are essential to optimal management of sedation.Preexisting medical conditions such as alcohol orsubstance abuse, chronic sedative use, psychiatric illness,alzheimers, gout, chronic pain may contribute to theexperience of distress and influence choice of agent.4Identifying new causes of pain related to the acute illnessis also crucial. Management of root causes such asbedsores, wound infections and changing medicalconditions should not be masked by use of sedatives.Simple measures such as frequent turning, removingrestraints if possible, or minimizing light and noise toallow night time sleep patterns may also improve patientcomfort. Communication and explanation to the patientduring interventions can significantly allay anxiety.

Pharmacological intervention should be consideredonly after treatable predisposing and precipitatingfactors have been managed, prior psychiatric and painmedications have been resumed, and the ICUenvironment has been optimized for patient comfort.

Monitoring of Sedation and AnalgesiaPain evaluation in the ICU is generally poorly done.Patient self reporting with a visual analogue scale (VAS)is most preferred, although often difficult in the ICUsetting. Table 1 shows the Critical Care PainObservation Tool.5

Sedation scales such as the Ramsay Sedation Scale, TheRichmond Agitation Sedation Scale (RASS), SedationAgitation Score, and Motor Activity Assessment Scaleare shown in Table 2 and have all been validated for usein the ICU.6 Whilst such sedation scales allow betterdocumentation, reduced sedation and analgesic use,and shorter duration of ventilation, widespread use hasnot yet been adopted.6,7

Objective measures of depth of sedation include the useof electroencephalograms (EEG), bispectral index (BIS)and the Narkotrend index.6 None of these arecommonly employed.

Sedative and Analgesic AgentsDrugs used for analgesia and sedation in the ICU arecompared in Table 3. Choices of sedative agents aredetermined by the underlying cause of discomfort, thesensitivity of patients to the agents and the likely lengthof sedation required. Optimal strategies match thepatients needs with a particular drugs' pharmacokineticand pharmacodynamic profile. The context sensitivehalf times indicate the change in half time clearance of adrug, when the preexisting duration of infusion isconsidered. During prolonged infusions, drugs areredistributed to saturate body compartments, and whenstopped, clearance is prolonged.

IV Induction AgentsPropofol had been extensively used as an ICU sedativeinfusion. With a high clearance, propofol sedativeinfusions allowed shorter times between termination ofinfusion and extubation. A recent meta-analysis8

concluded using propofol infusion reduced duration ofmechanical ventilation and length of ICU stay onlywhen compared with long acting benzodiazepines, butnot when compared with midazolam.

Side effects include myocardial depression, reducedsystemic vascular resistance, hypertriglyceraemia,elevated amylase levels and green urine.

Sedation and Analgesia in theIntensive Care Unit

Dr. Judith SHEN

Dr. Judith SHEN

MBBS, FJFICM, HKCA(IC), FANZCA, FHKCA(Anaes), FHKAM, PDipID

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Its' use has been curtailed by the increasing awareness ofpropofol infusion syndrome. This results in severemetabolic acidosis and muscle necrosis, likely due toimpairment of fatty acid chain oxidation and inhibitionof oxidative phosphorylation in mitochondria.

Thiopentone infusions are mainly used in refractorystatus epilepticus or refractory intracranial hypertension.Hepatic enzyme saturability means zero order kineticswith prolonged infusions resulting in prolongedwakening times, as well as myocardial depression andimmunosuppression.

Ketamine infusions are used in resistant statusasthmaticus. A phencyclidine derivative, it produces adissociative anaesthesia, analgesia and amnesia. Sideeffects include sympathetic stimulation with increasedcardiac work, and delirium.

BenzodiazepinesBenzodiazepines bind to the GABAA ligand gated Cl-channel to produce sedation and hypnosis. Midazolamhas the highest clearance, and minimal haemodynamiceffects and is the most commonly used sedativeinfusion.3,6 Concerns include increased delirium,dependence and withdrawal agitation.

OpioidsOpioids produce analgesia, narcosis and anxiolysis. Sideeffect concerns include respiratory depression, histaminerelease, bradycardia, hypotension, nausea and vomitingand poor gastric motility. Withdrawal agitation is also aconcern.

There are differences in specific agents. Morphine'shistamine release contribute to increased pruritis andpotential bronchospasm, compared with fentanyl.Accumulation after continuous drug infusion can lead toprolonged drug effects.

Remifentanil is an ultrashort acting ester opioidcommonly used in anaesthesia. It's metabolism is nonorgan dependant and is by nonspecific blood and tissueesterases to an inactive metabolite. This means it has astable context sensitive half time (3-10 mins). Offset istherefore independent of length of preceding infusion.Studies have shown shorter weaning from mechanicalventilation and duration of ICU stay compared with otheropioids.9 Increased relative costs is a concern. Concernsare similar to those of other opioids and includebradycardia, hypotension and acute onset withdrawal. Inaddition because of rapid offset of effects, alternativeanalgesia may be required when infusions are stopped.

Loading dose is 1 g/kg over 1 minute. Infusionconcentrations are commonly 20, 25 or 50 g/ml. Infusionrates of 0.1-0.15 g/kg/min can be continued andincreased by 0.025 g/kg/min at 5 min intervals to amaximum rate of 0.2 g/kg/min.

2 AgonistsDexmedetomidine is a new potent 2 agonist acting in the

locus ceruleus, causing inhibiting sympatheticstimulation, analgesia, sedation, without causingrespiratory depression. Studies have shown improvedweaning in patients with agitation from opioid orbenzodiazepine withdrawal.10 Dexmedetomidine wascompared with midazolam in 375 mechanicallyventilated ICU patientsfor up to 30 days of continuousinfusion.RASS scores were kept between -1 to +1.11

Riker et al . found less delirium, (54% indemedetomidine group vs 76.6% in midazolam group,p<0.01) in less tachycardia and hypertension, and lesstime on ventilators (3.7days in dexmedetomidinegroup vs 5.6days in midazolam group p<0.05).Delirium has been independently associated withcognitive impairment and 6 month mortality.Concerns include hypotension, bradycardia, andabsence of approval for infusions longer than 24 hours.There is a study underway by the US NIH clinicaltrials group comparing dexmedetomidine andpropofol for sedation of ICU patients.

Infusion concentrations are commonly 4 g/ml with aloading dose of 1 g/kg recommended over 10 minutes.Infusion rates of 0.2-0.7 g/kg/hr can be continued for 24hours. In the study, infusions were continued up to 30days.

Antipsychotic AgentsHaloperidol is effective in the management of deliriumand has been recommended by the SCCM guidelines.1Boluses of 1-5mg are useful in conjunction with othersedative anxiolytics. Side effects can include QTprolongation, hypotension and extrapyramidalmovement tics.

Neuromuscular Blocking AgentsNeuromuscular blocking agents are used sparingly intoday's ICU. Concerns include critical illness myopathy,and awareness from inadequate sedation. Currentindications are reserved for patients with difficultventilation from high airway pressures, prevention ofshivering in patients undergoing hypothermia, andmalignant intracranial hypertension. Cisatracurium androcuronium are the commonly used non depolarizingmuscle relaxants, because of their relativecardiostability. Cisatracurium undergoes hoffmansdegradation and similar to remifentanil is metabolizedby tissue and plasma esterases.

Sedations UseAlthough new drugs continue to become available, it isincreasingly recognized that it is how sedatives are usedthat requires a new approach.

Choices in Useage Include:

1. Continuous infusion2. Bolus3. Daily stop sedation trials4. Sleep aids5. Sedation protocols6. Monitoring of sedation

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A number of studies have shown the benefit of dailystop of sedation trials over continuous infusions. Kresset al. demonstrated a reduction in duration ofmechanical ventilation, length of ICU stay and fewerinvestigations to look for cause of unexplained changesof mental status.12,13

Most recently, the ABC trial randomized 335 ventilatedpatients to a protocol that paired spontaneousawakening trials (SATs)-ie, daily interruption ofsedatives-with spontaneous breathing trials (SBTs)versus SBTs alone.14 Patients in the intervention groupspent more days breathing without assistance than thecontrol group (14.7 days vs 11.6 days; mean difference3.1 days, 95% CI 0.7 to 5.6; p=0.02) and were dischargedfrom intensive care (median time 9.1 days vs 12.9 days;p=0.01) and the hospital earlier (median time.9 days vs19.2 days; p=0.04). More patients in the interventiongroup self-extubated. (16 patients vs six patients; 6.0%difference, 95% CI 0.6% to 11.8%; p=0.03), but thereintubation rates were similar. Patients in theintervention group were less likely to die than werepatients in the control group (HR 0.68, 95% CI 0.50 to0.92; p=0.01). For every seven patients treated with theintervention, one life was saved. (NNT 7.4, 95% CI 4.2 to35.5) They concluded daily wake and breath trialsimprove outcomes and should be employeduniversally.

Nurse driven protocols have been validated andinvolve nurse assessment of:5,6

ConclusionsCritically ill ventilated patients benefit from theoptimization of their sedation and analgesiamanagement. Sedation strategies must incorporate arecognition and management of causes and precipitantsfor pain and anxiety in ICU patients. Using sedationscales can improve sedation titration and minimize overand undersedation. Newer agents for sedation infusion

such as dexmedetomidine and remifentanil add to thearmament of the intensive care physician. The use ofdaily sedation interruption together with dailyspontaneous wean protocols has been shown todecrease mortality in the critically ill.

1. Sedation/Agitation Scale2. Haemodynamic stability3. Titration of sedation agent selected4. Daily stop of Sedation

Jacobi J, Fraser GL et al. "Clinical practice guidelines for thesustained use of sedatives and analgesics in the critically illadult".Task Force of the American College of Critical CareMedicine (ACCM) of the Society of Critical Care Medicine(SCCM), American Society of Health-System Pharmacists (ASHP),American College of Chest Physicians. CCM. 2002;30(1):119-41.Arroliga AC, Thompson BT et al. "Use of sedatives, opioids andneuromuscular blocking agents in patients with acute lung injuryand acute respiratory distress syndrome." CCM 2008;36(4):1083-8)Arroliga AC Frutos-Vivar F et al. "Use of sedatives andneuromuscular blockers in a cohort of patients receivingmechanical ventilation." Chest 2005;128; 496-506Broyles LM, Colbert "Clinicians evaluation and management ofmental health, substance abuse and chronic pain conditions in theintensive care unit" CCM 2008;36(1):87-93)Sessler et al. "Evaluating and monitoring analgesia and sedationin the intensive care unit." Critical Care 2008;12(Suppl 3):S2Sessler C, Varney K "Patient focused sedation and analgesia in theICU" CHEST 2008;133(2):552-565Botha JA, Mudholker P. The effect of a sedation scale onventilation hours, sedative, analgesic and inotropic use in theintensive care unit. Crit Care Resusc 2004; 6:253-7)HoKM, NgJY "The use of propofol for medium and long termsedation in critically ill adult patients: a meta-analysis." ICM2008;34(11):1969-79Muellejans B, Lopez A, et al "Remifentanil versus fentanyl foranalgesia based sedation to provide patient comfort in theintensive care unit: a randomized, double-blind controlled trial"[ISRCTN43755713].Crit Care. 2004 Feb;8(1):R1-R11. Epub 2003Nov 20.Arpino PA Kalafas K. "Feasibility of dexmedetomidine infacilitating extubation in the intensive care unit" J Clin PharmTher 2008;33(1):25-30.Riker R, Shehabi Y et al. "Dexmedtomidine vs Midazolam forsedation of Critically Ill Patients." JAMA 2009;301(5): 489-500Kress JP, Pohlman et al. Daily interruption of sedation infusionsin critically ill patients undergoing mechanical ventilation. NEJM2000; 342:1471-7Kollef, MH, Levy, NT, Ahrens, TS, et al The use of continuous IVsedation is associated with prolongation of mechanicalventilation. Chest 1998;114,541-548,Girard TD, Kress JP "Efficacy and safety of a paired sedation andventilator weaning protocol for mechanically ventilated patients inintensive care (Awakening and Breathing Controlled trial): arandomised controlled trial." Lancet. 2008 Jan 12;371(9607):126-34.)

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References

Table 1 Critical Care Pain Observational Tool

Indicator

Facial expression

Body movements

Muscle tension

Compliance with theventilator

OR Vocalisation(extubated patients)

Scores for each of the four domains are summed, with a total score of 0 to 8 [34].Sessler et al. Critical Care 2008 12(Suppl 3):S2

Score

Relaxed, neutral: 0Tense: 1Grimacing: 2Absence of movements: 0Protection: 1

Restlessness: 2

Relaxed: 0Tense, rigid: 1Very tense or rigid: 2Tolerating ventilator or movement: 0Coughing but tolerating: 1Fighting ventilator: 2Talking in normal tone or no sound: 0Sighing, moaning: 1Crying out, sobbing: 2

Descr iption

No muscular tension observedPresence of frowning, brow lowering, orbit tightening, and levator contractionAll of the above facial movements plus eyelid tightly closedDoes not move at all (does not necessarily mean absence of pain)Slow, cautious movements, touching or rubbing the pain site, seeking attention throughmovementsPulling tube, attempting to sit up, moving limbs/thrashing, not following commands,striking at staff, trying to climb out of bedNo resistance to passive movementsResistance to passive movementsStrong resistance to passive movements, inability to complete themAlarms not activated, easy ventilationAlarms stop spontaneouslyAsynchrony: blocking ventilation, alarms frequently activatedTalking in normal tone or no soundSighing, moaningCrying out, sobbing

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Table 2 Four Subjective Sedation Assessment Scales: A Comparison of Their Scoring

Agitated

Calm

Sedated

Source

Richmond Agitation SedationScale (RASS)+4 Combative+3 Very agitated+2 Agitated+1 Restless0 Alert and calm

-1 Drowsy-2 Light sedation-3 Moderate-4 Deep sedation-5 UnarousableSessler CN et al. AJRCCM 2002;166(10) :1338-44

Ramsay Scale

1 Anxious, agitated, both

2 Cooperative, orientated & tranquil3 Patient responds to command only4 Brisk response to light glabella tap5 sluggish response to light glabella tap6 No response

Ramsay MA et al. BMJ 1974;2(5920):656-9

Motor Activity Assessment Scale

6 Dangerously agitated,uncooperative5 Agitated4 Restless but cooperative3 Calm and cooperative

2 Responsive to touch, name,both1 Responsive only to noxiousstimuli0 UnresponsiveDevlin JW et al. CCM 1999;27(7) :1271-5

Sedation Agitation Scale

7 Dangerously agitated6 Very agitated5 Agitated

4 Calm and cooperative

3 Sedated2 Very Sedated1 Unarousable

Riker R et al. CCM 1994 ;22(3):433-40

Table 3 A Comparison of Commonly Used ICU Sedative and Analgesic AgentsDrugMidazolam-Benzodiazepine

Propofol

Morphine-Opioid

Remifentanil-Opioid

Dexmedetomidine

EliminationCyt P450Active metabolite

Conjugation

ConjugationActive metabolite

Tissue Esterases

Cyt P450Gluc?uronidation

Duration1-4hlonger if elderlyliver/renal failure3-10 mins

2-4hrif long infusionliver/renal failure10-20 mins

6minsin liver failure

Dosing IVLD 2-5mgMD 1-10mg/hr

MD 5-150g/kg/min

LD 2-4mgMD 1-20mg/hr

LD 1 g/kg- 1minMD 0.6-1.5g/kg/hrLD 1 g/kg-10mnMD 0.2-0.7g/kg/hr for 24hr

Concentration1mg/ml

10mg/mlUndiluted

1mg/ml

20, 25, 50 g/ml

2 g/ml

AdvantagesShort actingCardiac stable

Short ActingRapid offsetICPwean timeAnxiolyticHR, RRCheapNo accumulation rapidoffsetwean timeRapid offsetNo respiratory depressionWithdrawal Mxwean timedelirium

DisadvantagesDeliriumDependanceWithdrawalPropofol infusionsyndromeBP, lipid,amylaseResp depression,BP, withdrawal,GI absorbtionHR, BP, ICPacute withdrawal

HR, BP,Not > 24hrsexpensive

Relative Cost$$$

$$$$

$

$$$

$$$$$

Members' BenefitsThe Federation of Medical Societies of Hong Kong

The Federation, in cooperation with Kingsway Concept Limited, offers adiscount on petrol and diesel purchases of HK$0.9/litre from Caltex, Shell,Esso and Sinopec to members and their families of all Ordinary andAssociate member societies under the Federation. Please contact ourSecretariat on 2527 8898 and [email protected] or Kingsway Concept Limitedon 2541 1828 and [email protected] for further details and termsfor this offer.

VOL.11 NO.5 MAY 2006 Lifeff Stytt le

35


When I was five years old and living in California, Inearly drowned in a neighbour's swimming pool. I stillremember the frantic struggle to keep my head abovewater, my heart pounding so hard that I thought mychest would burst and the overwhelming fear and panicuntil I was pulled to safety. Perhaps because of thispersonal history, I made sure my two daughters learnedto be good swimmers and to love the water. We enjoyedmany beach holidays while they were growing up, butas they became more competent and adventurousswimmers, I was more likely to be found close to theshore (wearing a life vest for security) or covered withsunblock and reading at the poolside.

On one such holiday, my elder daughter took a resortscuba diving course with her father. My youngerdaughter was too young to participate so she and Isnorkelled. From the surface we could see the two ofthem amongst all the beautiful fish and coral. The sunwarmed our backs as we floated mesmerised by theview. It was like looking down into a giant aquarium.My elder daughter was so enthused by her first scubaexperience that when we returned to Hong Kong sheand her father immediately enrolled in a course tobecome PADI certified divers. When my youngerdaughter reached eligible age, it was clear that shewould have to take the course alone unless I agreed totake it with her. Truthfully, given my childhoodtrauma, I was not at all keen and was in fact more thana little scared. However, my love and empathy for mylittle daughter was greater than the sum of all my fears.Besides, I did not want to be left completely behind, sothe two of us signed up.

Despite my determination, the prospect of diving wasstressful. I dealt with this in the same manner that mostdoctors face difficult circumstances: hope for the best,but prepare for the worst. My 11 year-old and I studiedthe course material together in the evenings after shefinished her regular schoolwork and on weekends.Actually, it was fun reviewing and explaining basic gaslaws, concepts of balance and buoyancy, andrudimentary lung and exercise physiology. I insistedthat we also study water safety rules, underwaterdangers (such as currents, venomous plants andanimals, sharks, etc.) and common water-relatedinjuries and illnesses. We both passed the writtenexaminations without difficulty and moved onto thepractical skills. Completely comfortable around water,my daughter had no trouble passing the closed waterexam which was conducted in a swimming pool. Forme, though, just putting on the wetsuit, which fit rathertoo snugly on my not-so-buffed middle-aged body, was

a huge struggle, and I found that the mask (I don'tknow how people can sleep with a CPAP mask) seemedto heighten the sense of tension and anxiety.Furthermore, descending underwater to scuba requiresthe diver to wear weights, to actively deflate a flotationdevice and not to kick one's finned legs to propelupward. These steps to "let go" of the surface arecounter-intuitive for someone who had nearly drowned- even more so than might be expected for a person whoby nature is rather cautious and has been accused byher children as being somewhat obsessive andcontrolling. While I really wanted to be able to divewith my little daughter and though intellectually Iknew that I was prepared and perfectly "safe," I felt allmy childhood fears and anxiety about drowningresurface during the closed water dive. It was reallyterrible.

Our teacher was incredibly patient and kind. His day-job was as an investment banker, yet he seemed tounderstand my difficulties. He knew that I was farbeyond my comfort zone. He suggested that I just thinkthings through and take my time. Convinced thatdiving was something that I really wanted to do andwould enjoy, he volunteered to spend extra sessionswith me to practise all the skills and help me feel moreconfident. I am forever grateful for his gentleencouragement and forbearance. Without his generosityand support, I might have given up at this stage. By thetime we were scheduled to take the open water test inAustralia, I felt I was ready.

We had been to the resort where we scheduled the openwater examination before and I knew that the safetystandards were very high. A dive boat took us out nearCod Hole in the Great Barrier Reef. It was a glorious,cloudless day. As we waited for our divemaster'sinstruction to descend, we bobbed at the ocean surface,suspended at the interface between infinite skies andthe seemingly endless deep below. We were just threelittle specks in a vast blue universe.

The divemaster signalled us to descend. The gentlerocking of the surface waves was soon echoed by thesounds of our own breathing. The rhythm and pace ofour respiration were somehow reassuring, anaffirmation that we were fine. Below the surface, thewaters were teeming with life. The colourful, somealmost highlighter-fluorescent-hued, tropical fish werelike confetti in the sunlight streaming from above. Theplant life was similarly vibrant. The coral gardens werespectacular. It was all so beautiful and now mydaughter and I were not just looking at, but were part

Scuba Diving

Dr. Gloria PEI

Dr. Gloria PEI

Consultant in Internal Medicine, Hong Kong Adventist HospitalMD(UCLA, USA), DABIM, HKCP, FHKAM

Life Style

36


of, this fantastic aquarium. When we resurfaced at theend of our dive, my little daughter read my mind whenshe exclaimed, "Wow, that was great!"

My daughter and I successfully completed the examand were PADI certified on her twelfth birthday.Luckily for us, there are many wonderful divedestinations in the region, and we try to take a dive tripevery year. Our experiences have been amazing. Oneyear, we woke up before 5 am so that we could see thehumphead wrasses feed. As dawn broke, they came,maybe 50 of them, like a majestic herd of bison or aregiment of soldiers all marching in one direction.Then, suddenly, in a flash, they all turned and swamaway in the direction from which they came. (This sightwas so impressive, that my daughters insisted that wedo it again the next morning! It was just as startling thesecond time.) On one occasion, my daughters and Ihovered in the vortex of circling jack fish, the silverbodies swirling and enclosing us in a little pisceantornado. One of my favourite photographs of myyounger daughter is of her swimming alongside aNapolean fish as big as she was. The fish was big andfriendly, like the family dog, leaning into us andallowing us to pet its body. It swam beside her until it

was time for us to return to the dive boat and thencontinued alongside the boat for a while. On anothertrip, we came across a group of 15 sea turtles restingnear some barrel sponges. It was like a scene out of"Finding Nemo." As we passed near them, they beganto swim. I found myself looking eye to eye with onelarge turtle, which perhaps had been swimming in thewaters as long as I had been alive. Its eyes were clearand shiny. We have seen many sharks over the years.The sight of their natural grace and beauty do not fillone fear, but rather deep awe.

These are just some of the memories I will cherishforever and which draw me back to the waters. Idecided to learn to scuba dive for the sake of mydaughters, but I have benefitted far more than theyhave from the experience. Becoming a PADI-certifieddiver has been a transforming, instructive andrewarding process, and scuba diving is an activity that Inow truly enjoy. In addition to being able to continuean activity with my now grown daughters, throughdiving, I have learned to appreciate that we are nevertoo old to face a challenge, to overcome fears, or to learnnew skills with which we can continue to explore ourbeautiful world.

Dermatological Quiz

Dermatological Quiz

Dr. Lai-yin CHONG

Dr. Lai-yin CHONG

(See P. 41 for answers)

A 50-year-old man developed these asymptomatic patches at hisabdominal walls for six months. The lesions gradually increased in size.There were no systemic symptoms. He was otherwise well in health. Onpalpation, these lesions were indurated and confined to the abdominalwall. Skin scraping for fungi was negative.

1. What is your provisional diagnosis and differential diagnoses?2. What investigations will you perform?3. What are the treatment options available?4. What is the prognosis of this disease?

Multiple circumscribed scleroticpatches with active border at theabdomen

Questions:

Yaumatei Dermatology Clinic, Social Hygiene ServiceMBBS(HK), FRCP(Lond, Edin, Glasg), FHKCP, FHKAM(Med)

VOL.11 NO.5 MAY 2006 Medical Diaryrr of September

37


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Medical Diaryrr of September

38


Ms. Paulina TANGTel: 2527 8898 Fax: 2865 0345

8:00 pm - 10:00 pm17 THUFMSHK Executive Committee MeetingOrganised by: The Federation of Medical Societies of Hong Kong, Venue: CouncilChambers, 4/F., Duke of Windsor Social Service Building, 15 Hennessy Road, Wanchai,Hong Kong

Miss Viviane LAMTel: 2527 84523 CME Points

2:00 pm

12:30 pm

2:00 pm

13 SUNHKMA Certificate Course on Family Medicine 2009Organised by: The Hong Kong Medical Association, Speakers: Dr. TANG Kuen YanAlfred & Dr. HO Chung Ping, Venue: Queen Elizabeth Hospital

Ms. Christine WONGTel: 2527 8285

8:00 pm3 THUHKMA Council MeetingOrganised by: The Hong Kong Medical Association, Dr. H.H. TSE, Venue: HKMAHead Office, 5/F., Duke of Windsor Social Service Building, 15 Hennessy Road,Wanchai, Hong Kong

Ms. Dora HOTel: 2527 8285

3:00 pm5 SATHKMA Trailwalker Training Session 4Organised by: The Hong Kong Medical Association, Venue: MacLehose Stage 6-8

Dr. Y.C. POTel: 2990 3788 Fax: 2990 37892 CME Points (College of Surgeonsof Hong Kong)

7:30 am9 WEDHK Neurosurgical Society Monthly Academic Meeting - CavernomaOrganised by: HK Neurosurgical Society, Chairman: Dr. WONG Wai Kei, Speaker: Dr.WONG Ping Hong Derek, Venue: Seminar Room, G/F, Block A, Queen ElizabethHospital, Kowloon

Ms. Erica HUNGTel: 2527 8898 Fax: 2865 0345Website: http://www.fmshk.org6 CNE Points /CME/CPD Accreditation inApplication

2:15 pm - 4:30 pm12 SATCertificate Course on Clinical Ethics in PracticeOrganised by: The Federation of Medical Societies of Hong Kong & Hong KongBioethics Association, Speakers: Various, Venue: Lecture Hall, 4/F, Duke of WindsorSocial Service Building, 15 Hennessy Road, Wanchai, Hong Kong

Ms. Dora HOTel: 2527 828516 WED

HKMA Golf TournamentOrganised by: The Hong Kong Medical Association, Venue: Hong Kong Golf Club

2:00 pm Miss Alice TANG /Mr. Kevin CHANTel: 2527 8285 / 2595 694114 MON

Management of Drug Abusers on Public-Private Interface - Session OneOrganised by: HKMA -Tin Shui Wai, Tuen Mun and Yuen Long Community Networksand New Territories West Cluster Anti-Drug Abuse Committee of Tuen Mun Hospital,Chairman: Dr. LEE Fook Kay Aaron, Speakers: Various, Venue: Lecture Theatre, 2/F,Ambulatory Care Center, Tuen Mun Hospital, 23 Tsing Chung Koon Road, NewTerritories

Miss Viviane LAMTel: 2527 84521 CME Point

HKMA CME - Glitazone for Type 2 DM Management - Insights from Recent Outcome TrialsOrganised by: The Hong Kong Medical Association, Speaker: Dr. CHAN Wing Bun,Venue: Mongkok

Miss Alice TANGTel: 2527 8285

Rhinitis, Sinusitis and Nasal Polyposis - Practical Suggestions for General PractitionersOrganised by: HKMA - Central, Western & Southern Community Network, Chairman:Dr. CHAN Hau Ngai Kingsley, Speaker: Dr. Paul LAM, Venue: The HKMA Dr. Li ShuPui Professional Education Centre, 2/F, Chinese Club Building, 21-22 Connaught RoadCentral, Hong Kong

Miss Viviane LAMTel: 2527 84522 CME Points

HKMA/MPS Risk Management WorkshopOrganised by: The Hong Kong Medical Association, Speaker: Dr. Anne KOLBE & Dr. JoBURNAND, Venue: The HKMA Dr. Li Shu Pui Professional Education Centre, 2/F,Chinese Club Building, 21-22 Connaught Road Central, Hong Kong

Department of Surgery, HongKong Sanatorium & HospitalTel: 2835 8698 Fax: 2892 75111 CME Point (Active)

8:00 am - 9:00 am4 FRIJoint Surgical Symposium - Latest Achievements and DevelopmentsOrganised by: Department of Surgery, The University of Hong Kong & Hong KongSanatorium & Hospital, Chairman: Prof. William WEI, Speakers: Dr. CHAN Yu-Wai &Dr. Vivian MOK, Venue: Hong Kong Sanatorium & Hospital


2:00 pm6 SUNHKMA Badminton TournamentOrganised by: The Hong Kong Medical Association, Venue: MacLehose MedicalRehabilitation Centre


7:00 pm - 8:30 pm Certificate Course on Dental Nursing in Oral SurgeryOrganised by: The Federation of Medical Societies of Hong Kong & The Hong KongAssociation of Oral and Maxillofacial Surgeons Limited, Speakers: Various, Venue:Lecture Hall, 4/F, Duke of Windsor Social Service Building, 15 Hennessy Road,Wanchai, Hong Kong


7:00 - 8:30 pm2WED

Certificate Course on Clinical OphthalmologyOrganised by: The Federation of Medical Societies of Hong Kong & The Hong KongOphthalmological Society, Speakers: Various, Venue: Lecture Hall, 4/F, Duke ofWindsor Social Service Building, 15 Hennessy Road, Wanchai, Hong Kong

Miss Alice TANGTel: 2527 82851.5 CME Points

1:00 pm

8:00 pm - 10:00pm

1 TUEHKMA - Tai Po Community Network CME Lecture: Management of Skin AllergiesOrganised by: HKMA - Tai Po Community Network, Speaker: Dr. HO Hok KungMarco, Venue: Tai Po

Ms. Paulina TANGTel: 2527 8898 Fax: 2865 0345

FMSHK Officers' MeetingOrganised by: The Federation of Medical Societies of Hong Kong, Venue: Gallop, 2/F.,Hong Kong Jockey Club Club House, Shan Kwong Road, Happy Valley, Hong Kong

Date / Time Function Enquiry / Remarks

(20)

(19,26)

(21)

Mr. Sean WONG / Mr. P.C. YUTel: 2771 6622

12:00 pm - 3:00 pm10 THUThe Cosmetic Academic Exchange Workshop for BTXA (Botulinum Toxin Type A)Organised by: Hugh Source (International) Ltd, Venue: The Mira Hong Kong Hotel(TST), Registration: Limited seat, please book in advance (Free admission)

Miss Viviane LAMTel: 2527 84521 CME Point

2:00 pm HKMA Structured CME Programme with Hong Kong Sanatorium & Hospital Year2009 - New Trends in Management of Vitreo-Retinal-Macular Diseases - FromDiagnosis to TreatmentOrganised by: The Hong Kong Medical Association, Speaker: Dr. CHAN Wai Man,Venue: The HKMA Dr. Li Shu Pui Professional Education Centre, 2/F, Chinese ClubBuilding, 21-22 Connaught Road Central, Hong Kong

(6,7,8,9,10,11,12,15,16,17,19,20,21,22)

(11,18,25)

(9,16,23,30)

VOL.11 NO.5 MAY 2006 Calendar of Events

39



7:00 pm - 8:30 pm22 TUECertificate Course on Respiratory Medicine 2009Organised by: The Federation of Medical Societies of Hong Kong; Hong Kong ThoracicSociety & American College of Chest Physicians (HK & Macau Chapter), Speakers:Various, Venue: Lecture Hall, 4/F, Duke of Windsor Social Service Building, 15Hennessy Road, Wanchai, Hong Kong


7:30 pm19 SATHKMA Trailwalker Training Session 5Organised by: The Hong Kong Medical Association, Venue: MacLehose Stage 4-6

MeetingsAnnual Scientific Meeting in Anaesthesiology 2009Organised by: The Hong Kong College of Anaesthesiologists & The Society of Anaesthetists of Hong Kong, Chairman: Dr. S.T.TAN, Venue: The Hong Kong Academy of Medicine Building, Enquiry: ASM 2009 Secretariat, Tel: 2559 9973, Fax: 2547 9528,Email: [email protected], Website: http://www.anaesthesiology.hk

3rd Joint Scientific Meeting of The Royal College of Radiologists and Hong Kong College of Radiologists and 17th AnnualScientific Meeting of Hong Kong College of RadiologistsOrganised by: The Royal College of Radiologists & Hong Kong College of Radiologists, Venue: Hong Kong Academy ofMedicine, Jockey Club Building, 99 Wong Chuk Hang Road, Aberdeen, Hong Kong, Enquiry: Secretariat, Tel: 2871 8788, Fax:2554 0739, Email: [email protected], Website: http://www.hkcr.org

OSHK A-Z Symposia Series "B" - Symposium: "B" Isphosphonate-Related Osteonecrosis of the Jaw and the New OSHKGuidelines on Osteoporosis ManagementOrganised by: The Osteoporosis Society of Hong Kong, Venue: Shanghai Room, Level 8, Langham Place Hotel, Mongkok,Kowloon, Enquiry: Secretariat, Tel: 2881 4295, Fax: 2159 7242

International Symposium on Hepatology 2009 / 22nd Annual Scientific MeetingOrganised by: The Hong Kong Association for the Study of Liver Diseases, Venue: Hong Kong Convention and ExhibitionCentre, Enquiry: Ms. Melissa LEUNG, CMPMedica Pacific Limited, Tel: 2116 4348, E-mail: [email protected]

Hong Kong Surgical Forum - Winter 2010Organised by: Department of Surgery, the University of Hong Kong, Queen Mary Hospital & Hong Kong Chapter of AmericanCollege of Surgeons, Venue: Undeground Lecture Theatre, New Clinical Building, Queen Mary Hospital, Pokfulam, HongKong, Enquiry: Forum Secretariat, Tel: 2855 4855 / 2855 4886, Fax: 2819 3416, Email: [email protected], Website:http://www3.hku.hk/surgery/forum/php

23-25/10/2009

31/10/2009 -1/11/2009

1/11/2009

8/11/2009

9/1/2010

CoursesAdvanced Trauma Life Support (ATLS) Student CourseOrganised by: Department of Surgery, Queen Mary Hospital & Hong Kong Chapter of the American College of Surgeons,Venue: The Jockey Club Skills Development Centre, C3, Main Block, Queen Mary Hospital, Pokfulam, Hong Kong, Enquiry:Course Administrator, Tel: 2855 4885 / 2855 4886, Fax: 2819 3416, Email: [email protected], Web site:http://www.hku.hk/surgery

Advanced Trauma Care for Nurses (ATCN) Provider CourseOrganised by: Department of Surgery, Queen Mary Hospital & Hong Kong Chapter of the American College of Surgeons # TheJockey Club Skills Development Centre, C3, Main Block, Queen Mary Hospital, Pokfulam, Hong Kong Enquiry: CourseAdministrator Tel: 2855 4885 / 2855 4886 Fax: 2819 3416 Email: [email protected] Web site: http://www.hku.hk/surgery

PALS Paediatric Advanced Life Support Course 2009Organised by: Hong Kong College of Paediatricians, the Heart Institute for Children, Hope Children's Hospital, Illinois, USA& Hong Kong Paediatric Nurses Association, Speakers: Various, Venue: A & E Training Centre, Tang Shiu Kin Hospital,CME Accreditation: 12 Points for Provider Course, Enquiry: Ms. Vanessa WONG, Tel: 2871 8773, Fax: 2785 1850, Email:[email protected], Website: http://www.paediatrician.org.hk/entcnews.htm (Application starting now untilAugust 09)

Advanced Medical Life Support (AMLS) Provider CourseOrganised by: Department of Surgery, Queen Mary Hospital & Hong Kong Chapter of the American College of Surgeons,Venue: The Jockey Club Skills Development Centre, C3, Main Block, Queen Mary Hospital, Pokfulam, Hong Kong, Enquiry:Course Administrator,Tel: 2855 4885 / 2855 4886, Fax: 2819 3416, Email: [email protected] Web site: http://www.hku.hk/surgery

20-22/11/2009

20-21/11/2009

3-7/10/2009

12-13/12/2009

Dr. James C.M. HO / Dr. JohnnyW.M. CHANTel: 2855 4999 Fax: 2872 58281 CME Point

6:30 pm - 8:00 pm24 THU(1) Bubbles, Bubbles, Bubbles (2) TB or not TBOrganised by: Hong Kong Thoracic Society / ACCP(HK & Macau Chapter),Chairpersons: Dr. YU Wai Cho & Dr. WONG Mo Lin Maureen, Speakers: Dr. JonesKWOK, Dr. YEUNG Yiu Cheong & Dr. YAU Pak Yuen, Venue: LG1, Lecture Room,Ruttonjee Hospital, Hong Kong

Ms. Cathy HUNG / Mr. Ringo NGTel: 2549 5123

4:00 pm - 6:00 pm26 SATRecounting the Experience and Impact of Hong Kong Students Who Studied Medicinein War-time ChinaOrganised by: Hong Kong Museum of Medical Sciences Society, Chairman: Dr. LEEKin Hung, Speakers: Dr. Joseph PAN, Dr. CHUA Sin Giap & Dr. Ramon RUIZ, Venue:Auditorium, 4/F, Li Shu Pui Block, Hong Kong Sanatorium & Hospital, Hong Kong

Miss Viviane LAMTel: 2527 8452CME Points

2:00 pm

7:30 pm

27 SUNHKMA Structured CME Programme with PMH Year 2009 (8) - i) Use of Drugs in OldAge ii) Hypertension on Old AgeOrganised by: The Hong Kong Medical Association, Speakers: Dr. KONG Tak Kwan &Dr. AU Kai Man, Venue: G8 Hall, Princess Margaret Hospital


HKMA Tennis TournamentOrganised by: The Hong Kong Medical Association, Venue: Kowloon Tong Club

Miss Alice TANGTel: 2527 82851.5 CME Points

2:00 pm23 WEDHKMA-Shatin Doctors Network - Certificate Course on OsteroporosisOrganised by: HKMA-Shatin Doctors Network, Chairman: Dr. Ben FONG, Speakers:Ms. Jamie LAU & Ms. Barbara CHAN, Venue: Shatin

Date / Time Function Enquiry / Remarks

Federation News

40


The Federation President Cup Soccer Five Tournament 2009 was held in Macau on the 12 July 2009. Prior to the tournament, Dr. Kingsley Chan delivered a session sharing on the "Update Treatment on Acne" on 11 July 2009 evening, which was sponsored by Stiefel Laboratories. 45 participants attended the dinner, with 17 practising doctors in Macau.

The Soccer Five Tournament was held on Sunday, 12 July 2009. There were eight participating teams, six from Hong Kong and two from Macau. They were:

The tournament started as early as 8.30am. After rounds of 16 matches, it finished at 5.40pm. Congratulations to the winning teams:

The two Top Scorers go to Mr. Nicholas Chan of the Pfizer Corporation (HK) Ltd team and Mr. Alex Lam of the Federation Inviting Team.

The event ended with a cocktail party and award presentation ceremony.

Alcon (Hong Kong) Limited (HK)AstraZeneca Hong Kong Limited (HK)Centro Hospitalar Conde de Sao Januario, CHCSJ (Macau)Federation Inviting Team (HK)Hong Kong Ophthalmological Society (HK)Hong Kong Medical Association (HK)Kiang Wu Hospital (Macau)Pfizer Corporation (HK) Ltd (HK)

Champion - Pfizer Corporation (HK) Ltd 1st Runner up - Federation Inviting Team 2nd Runner up - AstraZeneca Hong Kong Limited

The Federation President Cup Soccer Five Tournament 2009

Invited guests officiating at the opening ceremonyFrom left to right: Dr. Jimmy Lai (Committee), Ms. Tina Yap (Committee), Dr. Susanna Lo (2nd Vice President), Dr. Raymond Lo (1st Vice President), Dr. Dawson Fong (President), Dr. Lee Pui I (President of Macau Physician Association of Public Hospital), Dr. Tse Hung-hing (President of HKMA), Dr. Liu Wing-hong (Co-chairmen), Mr. Nelson Lam (Co-chairmen), Dr. Kingsley Chan (Co-chairmen) 1st Runner up - Federation Inviting Team

2nd Runner up - AstraZeneca Hong Kong Limited

Top Scorers From left to right: Mr. Nicholas Chan (Pfizer Corporation (HK) Ltd), Dr. Liu Wing-hong (Co-chairmen), Mr. Alex Lam (Federation Inviting Team)

The Champion - Pfizer Corporation (HK) Ltd

VOL.11 NO.5 MAY 2006 Medical Diaryrr of September

41


Dr. Lai-yin CHONG

Yaumatei Dermatology Clinic, Social Hygiene ServiceMBBS(HK), FRCP(Lond, Edin, Glasg), FHKCP, FHKAM(Med)

PatronThe HonourableDonald TSANG, GBM 曾蔭權先生

PresidentDr. FONG To-sang, Dawson 方道生醫生

1st Vice-PresidentDr. LO See-kit, Raymond 勞思傑醫生

2nd Vice-PresidentDr. LO Sze-ching, Susanna 盧時楨醫生

Hon. TreasurerMr. LAM Lop-chi, Nelson 林立志先生

Deputy Hon. TreasurerMr. LEE Cheung-mei, Benjamin 李祥美先生

Hon. SecretaryDr. CHAN Sai-kwing 陳世炯醫生

Executive Committee MembersDr. CHAN Chi-fung, Godfrey 陳志峰醫生Dr. CHAN Chi-kuen 陳志權醫生Dr. CHAN Hau-ngai, Kingsley 陳厚毅醫生Dr. CHIM Chor-sang, James 詹楚生醫生Dr. CHOI Kin 蔡堅醫生Ms. KU Wai-yin, Ellen 顧慧賢女士Dr. LEE Kin-man, Philip 李健民醫生Dr. MAN Chi-wai 文志衛醫生Dr. MOK Chun-on 莫鎮安醫生Dr. MUI, Winnie 梅麥惠華醫生Dr. NG Yin-kwok 吳賢國醫生Dr. YU Chau-leung, Edwin 余秋良醫生Dr. YU Kong-san 俞江山醫生

The Federation of Medical Societies of Hong Kong4/F Duke of Windsor Social Service Building,15 Hennessy Road, Wanchai, Hong KongTel: 2527 8898 Fax: 2865 0345

PresidentDr. TSE Hung-hing 謝鴻興醫生

Vice- PresidentsDr. CHAN Yee-shing, Alvin 陳以誠醫生Dr. CHOW Pak-chin 周伯展醫生

Hon. SecretaryDr. LO Chi-fung, Ernie 羅智峰醫生

Hon. TreasurerDr. LEUNG Chi-chiu 梁子超醫生

Council RepresentativesDr. CHAN Yee-shing 陳以誠醫生Dr. CHOI Kin 蔡堅醫生

Chief ExecutiveMrs. LEUNG, Yvonne 梁周月美女士Tel: 2527 8285 (General Office)

2527 8324 / 2536 9388 (Club House in Wanchai / Central)Fax: 2865 0943 (Wanchai), 2536 9398 (Central)Email: [email protected]: http://www.hkma.org

PresidentDr. WU, Adrian 鄔揚源醫生

Vice-PresidentDr. LO See-kit, Raymond 勞思傑醫生

Hon. SecretaryDr. LI, Anthony 李志毅醫生

Hon. TreasurerDr. LEUNG, Clarence 梁顯信醫生

Council RepresentativesDr. LO See-kit, Raymond 勞思傑醫生Dr. CHEUNG Tse-ming 張子明醫生Tel: 2527 8898 Fax: 2865 0345

Board of DirectorsPresident

Dr. FONG To-sang, Dawson 方道生醫生1st Vice-President

Dr. LO See-kit, Raymond 勞思傑醫生2nd Vice-President

Dr. LO Sze-ching, Susanna 盧時楨醫生Hon. Treasurer

Mr. LAM Lop-chi, Nelson 林立志先生Hon. Secretary

Dr. CHAN Sai-kwing 陳世炯醫生Directors

Dr. CHAN Chi-kuen 陳志權醫生Mr. CHAN Yan-chi, Samuel 陳恩賜先生Dr. CHIM Chor-sang, James 詹楚生醫生Mr. LEE Cheung-mei, Benjamin 李祥美先生Dr. WONG Mo-lin, Maureen 黃慕蓮醫生

Founder Members

Answer to Dermatological Quiz

1. Morphoea (localized scleroderma)The differential diagnoses in this patient included mycosisfungoides, tinea corporis and erythema annularecentrifugum. Morphoea is an inflammatory diseaseprimarily affects dermis and subcutaneous fat of skin,resulting in sclerosis and deformity. It is a distinct entitywith a clinical course completely different from systemicscleroderma, though histologically the two conditions areidentical in the skin lesions. Morphoea occasionally can begeneralized and simulate diffuse scleroderma, but systemicinvolvements are absent. Raymond's phenomenon is alsoabsent in morphoea but present in 90% of systemicscleroderma.

Skin biopsy for histopathology should be done to confirmthe diagnosis.

Various topical medications have been used but the resultsare unsatisfactory in general. These include topical orintralesional corticosteroids, topical calcineurin inhibitors,topical vitamin A and vitamin D analogues. Forgeneralized morphoea, UVA1 or bath PUVA phototherapyseems promising. For rapidly progressive disablingdisease, weekly methotrexate combined with pulsedtherapy of corticosteroids has recently been advocated bysome workers.

With the absence of systemic involvement, morphoea is notfatal as in its systemic counterpart. However, it does causesignificant morbidity with the resulted disfigurement, orfunctional disabilities due to contractures. In severe lesions,the underlying muscle and bone may be involved. Thedisease often progresses for several years before finallyregresses and burns out.

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Documents

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