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Newsletter Apr 2005 Issue No.1Hong Kong Society of Palliative Medicine

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Dr. Doyle's Speech at Annual Convention of AAHPM

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Abstracts from 6th Asia Pacific Hospice Conference

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Report on the 6th Asia Pacific Hospice Conference, Seoul, Korea 2005

Dr. Lau Kam-shing, Chairman, Hong Kong Society of Palliative MedicineDr. Chan Kin-sang, HKSPM Representative to Asia Pacific Hospice Palliative Care Network (APHN)

The 6th Asia Pacific Hospice Conference was held in Seoul, Korea from 16th to 19th March 2005; hosted by the KoreanSociety for Hospice and Palliative Care in collaboration with Asia Pacific Hospice Palliative Care Network. The theme of theconference was "Changing Society and Human Life with Hospice Palliative Care". There were 1,200 participants from 28countries and 58 invited speakers made their presentations at 4 plenary sessions, 12 symposia, a controversy session, anda workshop. Two hundred and sixty-six free papers were presented at 12 oral and 2 poster sessions. The themes of theplenary sessions included: Changing Society and Human Life with Hospice Palliative Care, Cross-Cultural Differences inEthical Issues of End-of-Life, Update in Pain & Symptom Management and Service Development. A wide range of palliativecare topics and issues, including controversies, was covered, addressing different needs of the attendants.

The Hong Kong delegates had participated with enthusiasm both as speakers andaudience. Dr. KS Chan delivered two talks, one on the "Palliative Management ofDyspnoea" in the session of "Difficult Clinical Problems"; and the other on the HongKong palliative care development in the plenary session of service development. Otherspeakers from Hong Kong included Ms Amy Chow who gave an excellent talk on"Grief and Bereavement"; and Ms Cecilia Kwan who shared her experience on Post-graduate Hospice Nursing training in Hong Kong. Besides, there were 7 oralpresentations from HK; the presenters included Dr KK Yuen, Dr. PT Lam, Dr.Samantha Pang (2 papers), Dr. Cecilia Chan, Ms Clare Lai and Mr Wallace Chan.There were 6 poster presentations from Hong Kong.

As palliative care professionals from different countries gathered in this conference, other activities also took place with thisadvantage. The Second Global Summit of National Hospice and Palliative Care Associations was held immediately beforethe APHC 2005 in Seoul, Korea from 15 - 16 March 2005. The organising committee members were Dr Cynthia Goh(Singapore) -co-Chair; David Praill (UK) - co-Chair; Stephen Connor (USA); Sharon Baxter (Canada); Dr Daniela Mosiou(Romania); Dr Faith Mwangi Powell (Uganda); Dr Liz Gwyther (South Africa); Dr Roberto Wenk (Argentina), Professor DavidCurrow (Australia) and Dr Dinesh Goswami (India). The following themes were discussed within the summit, including:quality of care, advocacy (including drugs issues), governance, education and training, funding, world hospice and palliativecare day, children’s services, organisational development and information issues. They were planning to meet in Novemberto explore future plans for the network - including the 3rd global summit meeting. The summit was written up by theInternational Observatory on End of Life Care. Useful tools for national hospice and palliative care organisations would bepart of the report - including tools for advocacy and organisational development. The advocacy group also planned to submitfor the WHO World Health Assembly in May 2005. After the meeting, a Korea declaration on Hospice & Palliative CareMarch 2005 was drafted & signed by palliative workers from supporting countries. The declaration (and linked press release)from the summit is available at www.hpc-association.net.

Also, the 5th council of Asia Pacific Hospice Network (APHN) was elected on 17th March 2005 with Dr Enoch Lai (Taiwan)as Chairman, Dr Cynthia Goh (Singapore) as Honorary Secretary, Ms Yvonne Siu (Hong Kong) as Honorary Treasurer.Dr.KS Chan was co-opted as council member for another year.

Apart from these plentiful scientific and meaningful activities, wewere also overwhelmed by the hospitality of the organisors.Delegates from various countries gathered in the evening of"Cultural Night", and had the most relaxing time of enjoying theprograms presented by the delegates. The Hong Kong teamsang the songs of "The Lion Rock Mountain" and "Shalom", andof course, we earned a big applause from the audience. TheHong Kong delegates were united not only on the stage. Wesupported and shared with each other, including our meals. Wetook subway trips to downtown and humbly sat together on thefloor to enjoy the famous and popular Korean cuisine. In thepresence of our nursing colleagues, our nutrition was not aconcern! To no surprise, the famous ' ' was the hot topicover the table. Everyone would agree that the wonderful cultureand hospitality of the Korean people throughout the conferencemade for a most memorable meeting.

Dr. Chan Kin Sang at presentation

Hong Kong delegates at the conference reception

Conference Report_________________________________________HKSPM Newsletter 2005 April Issue 1 p 2

Front & back photos: Winter in Montreal by Dr. Doris Tse

Editorial____________________________________________________HKSPM Newsletter 2005 April Issue 1 p 3

Editorial : The Last StopDr. Doris Tse, Editor-in-Chief

We all agree bereavement work should commencebefore death of the patient. However, to health careworkers in certain settings, they would feel absurd andinappropriate to talk about loss of patient especiallywhen the focus of care has not transited from cure topalliation. Talking about loss is embarrassing, and maybe misinterpreted as abandonment by families.

To doctors, the care for the patient might end asdeath is certifed. To nurses, the care for the patientmight end as the corpse is transported safely to themortuary. Few doctors realise that the dying scene,which includes their act of declaring death, would bepart of the vivid memory as the family recalls. Dr.Lerman1 shared his reflections on the inadequacy ofhimself and medical training in this aspect as hewitnessed the death of his father; and how the juniordoctor handled the process. On the other hand, aqualitative study in Bradbury Hospice2 has reported thatinvolvement of the family in the last office of thedeceased, together with the humanistic approach andsupportive attitude of nurses were highly appreciated bythe bereaved. The bereaved experienced a sense ofcompleteness, a continuation of relationship, fulfillmentof responsibility, conveyed messages of gratitude andrespect, and enhancement of the acknowledgment ofthe reality of death.

Most health care workers know little about theexperience of the bereaved after the families have leftthe ward with the corpses. Some relatives may beidentified as having needs for bereavement support andbeing referred. However, the needs of the bereavedwhile in the mortuary may be overlooked and neglected.Hospital mortuary is a place seldom visited by mosthospital staff. It is often situated in a remote corner ofthe hospital compound, away from the main entrance.Nonetheless, this is the exit of some of our patients whocome in through the main door. Though this is the laststop in the hospital for the deceased, this is just thebeginning for the bereaved, and may have a significantimpact on the subsequent grieving process.

It seems that media has little interest in reporting"good and positive" news about mortuary; and hencethe scarcity of reports related as I search for them.However, the down side will always draw attention, nomatter how unpopular the topic used to be. In 2001, theUK media reported a striking scene of seven corpsesstored in a hospital chapel, draped in sheets. The legsand the face of one corpse were visible. Blames andaccountability were focus of discussion. However, theincident had also drawn attention to some of the"neglected" long standing problems, including outdatedfacilities and design due to under-funding.3

In Hong Kong, as in other countries, palliative careworkers do have the sensitivity of addressing theconcerns of the bereaved during the dying process andbeyond. In this issue of Newsletter, Ms Amy Ip and Dr.Antony Leung reported the renovation project of themortuary in Haven of Hope Hospital. The design of themortuary has been thoughtfully planned, incorporatingthemes and symbols to support and aid the bereaved inthe process, and possibly facilitates the transformationprocesses in grief.4

It is still a long way to extend this concept to allhospitals, especially the acute hospitals. In CaritasMedical Centre, an acute regional hospital with aPalliative Care Unit, a "Care for the Bereaved" Projectis launched to foster the support to the bereaved inacute ward settings.5 Results from questionnaire surveyon 199 doctors and nurses, and semi-structuredinterview with five bereaved family members gave me(as the Coordinator of the Project) information about theattitude of staff and the relatives, and the gaps in theservice. Staff awareness, practical guidelines andinformation leaflet, education and training, andappropriate physical setting are regarded by staff to beimportant in promotion of care. Although only fivebereaved family members were interviewed, there wasa strong voice that respectful handling of the dead bodywas of paramount importance to them; and that themortuary condition should be improved to alleviate theirdistress and grief. What they appreciated most was thechance to give feedback, which they would nototherwise do. Improvement work has been performed,with recommendations from the team, though it is farfrom full scale renovation. What sheds light is that withthe re-development of the hospital, the recommendationby the team of the "Care for the Bereaved Project" isaccepted, so as to facilitate the function of the mortuaryas a place for expression and containment of emotions.

In the past, and in some of the places in Chinanowadays, the dead body of the beloved is kept athome for rituals and mourning to take place. This is avehicle for facilitating grief. In contemporary society,procedures related to handling of dead body andrelated rituals may hardly fulfill any meaningful andtherapeutic functions. Should we not do somethingbefore the dead rise up and protest?

References1. Romanoff BD, Terenzio M. Rituals and the grieving process. Death

Studies 1998:22(8);697-714.2. Kwan C. Families’ experiences of the last office of the deceased

family members in the hospice setting. Int J Palliative Nursing2002:8(6);266-275.

3. Kamran A. Death underfunded: The mortuary service needsresources not resignations. BMJ 2001:322(7280);186-188.

4. Last office service in palliative care: Experience sharing from themortuary renovation project in Haven of Hope Hospital. Ip A,Leung A. HKSPM Newsletter 2005 Issue 1:p13-15.

5. Fostering support to the bereaved in acute ward settings: Care forthe Bereaved Project. Suen M, Tse D, Wu Kitty, Yung G, Ko F.Poster presentation, 6th Asia Pacific Hospice Conference, Korea,2005.

The Hong Kong Society of Palliative Medicinehas the greatest pleasure to share with you theinspiring speech delivered by Dr. Derek Doyle,our Honorary Advisor, with the courtesy ofDr. Derek Doyle and International Association forHospice and Palliative Care. Congratulations toDr. Derek Doyle, and our most sincere gratitudeto a giant who has made a difference in PalliativeCare world wide.

Hello to you all. Good morning. Pleaseaccept my sincere apologies that I cannot be withyou in person. Nothing would have pleased memore than joining you all in New Orleans but Iwould not dare disobey my cardiologist.

Getting this prestigious award surprised andthrilled me more than I can begin to describe. Myimmediate reaction was that you had mistakenme for someone else, or that you thought I haddone more in life than is actually the case! Iremain puzzled why you chose me butnevertheless am delighted. Just working inpalliative care is itself such an honour and sorewarding that anything extra is a huge bonus.

Jim Cleary tells me that my leading theeditorial team of the Oxford Textbook of PalliativeMedicine was one reason for honouring me. Inthat case I am getting an award for having had alot of fun, for working with some of the bestpeople in the world, and for getting a chance tolearn new things every single day. Editing such abook meant surviving countless computerproblems and also working with a great team ofcopy editors, printers and publishers in SouthIndia where the book was produced.

Jim also suggested I say a few words,perhaps distilling just a few of my thoughts after35 years in palliative medicine. I am delighted todo so. If I bore you don’t hesitate to fall asleep – Iwon’t be able to see you. I have a few anxietiesabout the direction in which we are going andabout some of the things that are happening.

Dr Derek Doyle’s response on receiving in absentia the 2005 Lifetime Achievement Awardof the American Academy of Hospice and Palliative Medicine (AAHPM).This was presented on DVD to the Annual Convention of the AAHPM inNew Orleans 20 January 2005 where Liliana De Lima received the award on Dr Doyle’s behalf.

Let me share them with you.The first is that we are fast becoming

experts in the clinical pharmacology of pain andsymptom management more than in relationshipsand ‘total caring’. May I remind you that the first"modern" hospices were formed in the late 1960slargely because of published consumer opinions– the expressed disappointments anddisillusionments of patients and relatives aboutwhat today we call " end-of-life care" There is nodenying that one recurring theme was poorsymptom control. The other was the medicalprofession’s apparent lack of interest in howpatients and carers felt, what they feared andneeded to know, how lonely, unwanted andneglected they felt and how insensitive wedoctors often were. What the patients craved forwas companionship, evidence that even in theirdying they were still valued, appreciated, wantedand even ‘useful’ in our materialistic andsecularised society. Today I wonder if we are indanger of over-emphasising physical comfort atthe expense of the "softer" side of palliative care,the one-to-one relationship with the dying. Isuggest to you that palliative medicine should bean exercise in befriending and sharing as muchas an exercise in therapeutics or clinicalpharmacology.

My second anxiety may sound like acontradiction of what I have just said. There is avery real danger that in a few years’ timepalliative care and palliative medicine will be theleast "evidence-based" subject in medicineunless vastly more research is done. If thathappens we will lose the respect of colleagues inother specialties and the quality of our care willinevitably suffer. We simply have to do moreresearch of the highest possible quality. Doing sowill not be a denial of our holistic approach.Science and compassion are not mutuallyantagonistic, as some seem to think. Objectivityand subjectivity can and do co-exist. In fact in ourwork they can be synergistic.

Dr. Doyle receives Lifetime Achievement Award fromAmerican Academy of Hospice and Palliative Medicine

_____________________________________________________HKSPM Newsletter 2005 April Issue 1 p 4

I remain anxious that, unthinkingly, we makeclaims that are not always true. For example, isour approach always interdisciplinary or is itsometimes more an exercise in which palliativemedicine doctors delegate tasks andresponsibilities to others? Every day we hear ofnurses and therapists doing things that weretraditionally done by doctors but how often do wehear of doctors taking on some of the rolestraditionally done by others? Is all this to enabledoctors to do their work better and provide bettercare, or is it to reduce their workload? We claimthat palliative care is always holistic but do mostof us have as much training and skill in spiritualityas we have in pharmacology? Do we see thataspect of our work as intuitive, something thatflows naturally from our own faith andphilosophy? If we do, I suggest to you we aredeceiving ourselves. How many of us have beentrained in the humanities? How many of us feelcompetent and confident in caring for peoplefrom different cultures and creeds? If we look atwhat is happening in the world around us todaythe answer must be that none of us has a right tofeel either competent or confident with regard tocultures and creeds different from our own.

Lastly – some of you can waken up now – Iremain concerned that millions, (yes, millions, notthousands) millions of people have no accesswhatsoever to palliative care services or even todoctors and nurses who have learnt anythingabout palliative care. Some of these deprivedpeople are in our own countries in the Westbecause we have done so little to get palliativemedicine into the curricula of all our medicalschools. (Fewer than 10 countries in the west canclaim that palliative care is taught in all theirmedical schools.) Most of the deprived are in theless affluent, less sophisticated countries – thosethat we patronisingly call "developing countries."Why are we not doing more for them? Do wewant palliative care to be regarded as one of theluxuries we in the West take for granted –something that you get when you have alreadyhad the best that modern medicine, surgery andoncology can offer?

Could it be that most of us don’t even knowhow desperate is their need – not only can theyseldom hope to cure - they often have littlemodern equipment, few modern drugs and little ofthe means and the knowledge to alleviateappalling suffering? Why are we not twinning our

units with some abroad? Why are we not offeringto visit them and share what little we know? Arewe frightened that they will see our approach tothem as further evidence of interference orliberation by the West?

Believe me, if we do it more prepared tolearn than to teach, more ready to share than topatronise, and do so without paternalism– ourcolleagues abroad will welcome our friendshipand the spirit in which we share ourselves withthem. It is for that reason I see the InternationalAssociation for Hospice and Palliative Care as soimportant. Unless we act now we shall go downin history as yet another example of the West’sself-centered indulgence when, as you and Iknow so well, access to palliative care is a basichuman right, not a luxury.

Let me urge you to keep palliative caresimple rather than increasingly sophisticated,never to forget why it started, and, in this age ofapathy and cynicism, to remain as excited aboutit in the days to come as you and I were when wefirst came into this work.

I often feel we live in a world endangered byfour things -apathy, cynicism, materialism andfundamentalism; fundamentalism that might beeconomic, political or religious. Fundamentalismsees everything in black and white and knows noshades of grey, nothing between right and wrong,them and us. Out of fundamentalism , whateverits basis, spring arrogance, insensitivity, self-righteousness, and inhumanity to our fellow menand women Palliative care is one answer, oneresponse to those dangers facing our society. Itfocuses on the individual and proclaims to eachman and woman in our secularised, materialisticworld: "You matter - not because you are dying,not because you are a clinical challenge to us,not because you are a shareholder - but becauseyou are you!" We owe it to the world to share allwe know and all we love about palliative care. Ifwe in palliative care and palliative medicine fail tolook beyond our shores we shall deservedly die.

Again – thank for your kindness and thisgreat honour you have bestowed on me.

Derek Doyle(Scotland)

_____________________________________________________HKSPM Newsletter 2005 April Issue 1 p 5

[email protected]

Original article______________________________________________HKSPM Newsletter 2005 April Issue 1 p 6

1. Levinson W, Gorawara-Bhat R, Lamb J. A study of patient cluesand physician responses in primary care and surgical settings.JAMA 2000; 284: 1021-7.

2. Banmen J. Satir’s Systemic Brief Therapy Training Program.Counselling Praticum Workbook for Professionals. Translatedversion in Chinese; translated by Lam M. Taiwan: Shiuh-Li LiuhMemorial Foundation, 2003: pp 8-12.

3. Carver CS, Scheier MF, Weintraub JK. Assessing copingstrategies: a theoretically based approach. Journal of Personalityand Social Psychology 1989; 56: 267-83.

4. Fawzy FI. Psychosocial interventions for patients with cancer:what works and what doesn’t. Eur J Cancer 1999; 35: 1559-64.

5. De Ridder D, Schreurs K. Developing interventions forchronically ill patients: is coping a helpful concept? ClinicalPsychology Review 2001; 21: 205-40.

6. Beckham JC, Burker EJ, Lytle BL, et al. Self-efficacy andadjustment in cancer patients: a preliminary report. Behav Med1997; 23: 138-42.

7. 11:17.8. 25:35-369. 10:1610.11. Op. cit 2. pp 13-4.12.13.14. Op. cit 2. p 115.16.17. Op. cit 2. p 32


Surgery, radiotherapy and chemotherapy are thethree main modalities to treat cancers. Even withvarious developments in these treatment tactics inpast decades, many cancers are still incurable. Inaddition, these treatment strategies are associatedwith their own limitations. The success of surgery isdependent on the tumour site and its anatomicalrelationship with adjacent neovascular structures. Theradiotherapy exploits the presence of differentialradiosensitivity between the tumour and normal tissue.Furthermore, both surgery and radiotherapy cannottreat metastatic diseases. The treatment targets ofchemotherapy are the rapidly dividing cells, includingboth normal and tumour cells. The anti-cancer effect isbased on the assumption that cancer cells grow fasterthan normal cells. The non-differentiating effect ofchemotherapy on rapidly dividing cells thus producethe commonly seen mucositis, hair loss, marrowsuppression from its effects on cells of mucosa, hairfollicles, haemopoietic tissue with high proliferatingrate. As tumour is composed of heterogenouspopulation of cells, including those with slowproliferating activity, these cell portions may becomechemoresistent.

Normal cell growth and division are largely underthe control of a network of chemical and molecularsignals that give instructions to cells. Geneticalterations can disrupt the signaling process so thatcells no longer grow and divide normally, or no longerdie when they should. Advancement in biomedicalresearch yielded an enormous amount of informationabout the molecular events that take place during thedevelopment of cancer. New drugs are discoveredthat work by targeting the biological pathwaysimportant in cancer, interfering with the cancer cellgrowth, division, and spread in different ways and atvarious points. It was thought that by targetingspecific alterations in cancer cells, these agents mightbe more effective in killing tumour cells and sparingthe normal cells from harmful effects. Hence, theymay also have a major impact on survival and qualityof life of the cancer patient. Targeted cancer therapiesinclude several types of drugs which basically can bedivided into the following:

1) "Small-molecule" drugs block specific enzymes andgrowth factor receptors involved in cancer cell growth.These drugs are also called signal-transductioninhibitors e.g. Gleevec® (STI–571 or imatinibmesylate), Iressa® (ZD1839 or gefitinib).

Dr. Inda S. SoongDepartment of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital

2) "Apoptosis-inducing" drugs cause cancer cells toundergo apoptosis (programmed cell death) byinterfering with proteins involved in the process e.g.Velcade® (bortezomib).3) Monoclonal antibodies e.g. Herceptin® (Trastu-zumab), angiogenesis inhibitors e.g. Thalidomide,Avastin® (Bevacizumab), cancer vaccines, and genetherapy.The following paragraphs will discuss in brief some ofthe agents that are or will be more commonly in usefor solid tumours nowadays.

Signal-transduction inhibitorsSignal-transduction inhibitors are small mole-

cules that block or inhibit a particular intra-cellularprocess from functioning. The targets are usually thecellular receptors, enzymes or genes involving insignal transduction pathway in cell growth. Some ofthe U.S. Food and Drug Association (FDA) approvedagents are Gleevec® (STI–571 or imatinib mesylate),Iressa® (ZD1839 or gefitinib), Tarceva® (erlotinib).

Imatinib (Gleevec®) is a small molecule inhibitoron the by-product of the Philadephia (Ph)chromosome, Bcr-Abl tyrosine kinase, which isresponsible for blocking the signal for stopping thewhite blood cell production. Imatinib also inhibits theactivity of Kit (CD117), one of the tyrosine kinases thatdrives the growth and division of gastro-intestinalstromal tumours (GISTs). Imatinib is approved in theEU, U.S. and other countries for treating patients withKit (CD117) positive GISTs, which is inoperable and/ormetastasized. The usual dosage is 400mg – 600mgper oral per day. From the available evidence, Imatinibresulted in a reduction in more than 50% in tumoursize in over half of patients with advanced inoperableor metastatic GISTs.1 Prior to Imatinib, treatmentoptions other than surgery were limited and offeredlittle efficacy. Side effects during treatment in GIST areusually mild and moderate, which include: headache,nausea, vomiting, diarrhoea, dyspepsia, myalgia,muscle spasm and cramps, joint swelling, dermatitis,eczema, rash, edema, fluid retention.

Gefitinib (Iressa®) is a signal transductioninhibitor blocking the epidermal growth factorreceptors (EGFRs) on the surface of cancer cells. Thereceptors allow epidermal growth factor (EGF) toattach to them. The binding of EGF activates anenzyme called tyrosine kinase, which in turn cantrigger chemical processes inside the cell to make itgrow and divide. Gefitinib is FDA approved as

Molecular Targeted Therapy in Solid TumoursPalliative Medicine Doctors' Meeting_____________________________HKSPM Newsletter 2005 April Issue 1 p 8

Correspondence: [email protected]

monotherapy for the treatment of patients with locallyadvanced or metastatic non-small cell lung cancer(NSCLC) after failure of both platinum-based anddocetaxel chemotherapies. The recommended dosageis 250mg per oral daily. It induces responses in 9.6%to 19% of NSCLC patients treated previously withplatinum and taxane chemotherapy.2,3 It improvesdisease-related symptoms and induces radiographictumour regressions.2 Response rates are higher innon-smokers, females, and patients with adeno-carcinoma and bronchioloalveolar carcinoma. In tworandomized trials comparing the addition of Gefitinibwith standard platinum combination chemotherapy,however, no improvement in response rates,progression-free survival, or overall survival wasshown.4,5 Side effects of Gefitinib are usually mild ormoderate with common ones including diarrhoea,acne-like rash, nausea, vomiting. A rare adverseeffect, interstitial lung disease (ILD), have beenobserved in patients receiving Iressa® at an overallincidence of about 1%. Approximately 1/3 of the caseshave been fatal. The reported incidence of ILD wasabout 2% in the Japanese post-marketing experience,about 0.3% in approximately 23,000 patients treatedwith Gefitinib in a US expanded access program andabout 1% in the studies of first-line use in NSCLC (butwith similar rates in both treatment and placebogroups). Patients often present with acute onset ofdyspneoa, sometimes associated with cough or low-grade fever, often becoming severe within a short timeand requiring hospitalization. ILD has occurred inpatients who have received prior radiation therapy(31% of reported cases), prior chemotherapy (57% ofreported patients), and no previous therapy (12% ofreported cases).

Monoclonal AntibodiesMonoclonal antibodies work by recognizing a

protein expressed on the surface of the specificcancer cell and then binding onto it. They destroy thecancer by either triggering the body’s immune systemto attack the cancer cell resulting in killing the cell itself(apoptosis) or attaching a cancer drug or a radioactivesubstance to the antibody, which delivers them directlyto the cancer cell. Examples of FDA approved agentsare Mabthera® (rituximab), Herceptin® (trastuzumab),Erbitux® (cetuximab).

Rituximab is a chimeric murine/human mono-clonal antibody directed against the CD20 antigen onthe surface of B-lymphocytes. The CD20 antigen isexpressed on more than 90% of B-cell lymphomas.Once the Fab domain of rituximab binds to the CD20antigen on B lymphoid cells, the Fc domain will induceimmune cytolytic mechanism such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

Rituximab is approved by FDA for relapsed orchemoresistent indolent B-cell Non Hodgkin’sLymphoma (NHL) with a production of 48% diseaseresponse.6 Rituximab is also indicated in CD 20positive diffuse large B-cell NHL in combination withCHOP chemotherapy. The combination of rituximaband CHOP (R-CHOP) has shown improvement inevent-free survival (EFS) and overall survival (OS)compared to CHOP alone in 399 advanced stagepatients with diffuse large B-cell lymphoma over 60years of age (EFS 57% vs. 38%, P=.002, and OS 70%vs. 57%, P=.0007 at 2 years).7 Similarly, for 326evaluable patients younger than 61 years, R-CHOPshowed improve-ment in time to treatment failure(TTF) and overall survival (OS) compared to CHOPalone (TTF 84% vs. 62%, P=.00003, and OS 95% vs.85%, P=.0036 at 15 months).8 These two studiesestablish R-CHOP as the standard regimen for newlydiagnosed patients with diffuse large B-cell lymphoma.

The side effects of rituximab are generally mildand some of these can be reduced with medicines.Side effects can begin during the first dose of the drugand may continue for a few hours afterwards, but areusually milder with following doses. The more commonones are flu-like symptoms, low blood pressure duringinfusion so patients are always advised to stop anti-hypertensives at least 12 hours before treatment,slight allergic reactions, flushing, nausea, vomiting.

Trastuzumab (Herceptin®) is a humanizedmonoclonal antibody that binds to the extracellulardomain of Human Epidermal Growth Factor 2(HER2/neu) receptor, which is expressed inapproximately 25% of patients with breast cancer. Byattaching itself to the HER2/neu, trastuzumab blocksthe binding of epidermal growth factor, which thereforestops the cells from dividing and growing. It isapproved by FDA for metastatic breast cancers, whichoverexpress HER2/neu. However, trastu-zumab onlyworks in women who have high levels of the HER2protein and therefore testing of the HRE2 level isusually done when it is thought to be a treatmentoption. When administered as a single agent,trastuzumab resulted in a response rate of 21%.9 In aprospective trial, patients with metastatic disease wererandomized to receive either chemotherapy alone(doxorubicin and cyclo-phosphamide or paclitaxel) orthe same chemotherapy and trastuzumab. Patientstreated with chemotherapy plus trastuzumab had abetter overall survival advantage than those receivingchemotherapy alone (25.1 months vs. 20.3 months,P=.05).10 As a result, patients with metastatic breastcancer with substantial over-expression of HER2/neuare candidates for treatment with the combination oftrastuzumab and paclitaxel or for clinical studies oftrastuzumab combined with taxanes and other

Palliative Medicine Doctors' Meeting____________________________HKSPM Newsletter 2005 April Issue 1 p 9

chemotherapeutic agents.11 Because trastuzumabworks specifically on breast cancer cells and does notaffect normal cells, the side effects appear to be mild.The common side effects experienced are flu-likesymptoms, mild pain of diseased sites, headache,diarrhoea. When combined with doxorubicin,trastuzumab is associated with significant cardiactoxicity.12 Therefore trastuzumab is not recommendedto be used with chemo-therapeutic agents ofanthracycline group.

Angiogenesis InhibitorsAngiogenesis inhibitors prevent the formation of

new blood vessels that surround and "feed" cancercells the oxygen and nutrients they need to grow. Bydepriving cancer cells of their blood supply,angiogenesis inhibitors may be able to reduce tumorcell growth and cause tumours to grow more slowly orto become smaller.

Bevacizumab is a recombinant humanizedmonoclonal antibody against vascular endothelialgrowth factor (VEGF) and hence prevents theinteraction of VEGF to its receptors (Flt-1 and KDR)on the surface of endothelial cells. The interaction ofVEGF and its receptors on endothelial cells leads toendothelial cell proliferation and new blood vesselformation in in vitro models of angiogenesis.Bevacizumab is the first anti-angiogenic clinicallyproven to extend survival. It is approved by FDA inDecember 2004. It is being used in the USA alongsidechemotherapy for advanced colon cancer.Bevacizumab enhances the effects of chemotherapy,but does not appear to be effective when given alonein patients with colorectal cancer.

At the American Society of Clinical Oncology2003 meeting, the results of a randomized trial thatcompared combination chemotherapy (IFLregimen) -placebo with IFL-bevacizumab, a monoclonalantibody, against the vascular endothelial growthfactor receptor in 925 patients with advancedcolorectal cancer were presented. Bevacizumab wasadministered at a dose of 5 mg/kg every other week.The median progression-free survival of patientstreated with IFL plus bevacizumab was 10.6, versus6.2 months (P=.00001) for patients treated with IFLand placebo, and the median overall survival was 20.3versus 15.6 months (P=.00003), respectively. Overallresponse rates were also superior for thebevacizumab-containing regimen (44.9 vs. 34.7%,P=.029).13 The serious side effects include GIperforation, wound dehiscence and haemorrhage. Theincidence of GI perforation for patients treated withbolus IFL and bevacizumab was 2%. Other morecommon side effects are hypertension, tiredness,thrombo-phlebitis, diarrhoea, lowered WBC,headache, loss of appetite and mouth sores.

Discussion & ConclusionAs more research is being done to disclose the

molecular events that take place in cancerdevelopment, more novel agents bearing unique anti-cancer effects with specific, precise anti-cancertargets will be expected. All these efforts help tocreate a scene of treating cancers with a morespecific, individualized and tailor-made anticancerstrategies, which in turn could maximise the benefit-risk ratio and bring about improvement in survival andquality of life.

However, the great resources input in all thesefascinating researches, the business profit required bymany stock-holding pharmaceuticals would on theother hand, create a financial challenge, as thesenovel therapeutic agents are all remarkably expensive.In addition, as the anticancer effects of some of thecurrently available agents are "tumour-static" ratherthan "tumour-cidal", prolonged, continuous usage ofthese expensive agents may be required. The costingof these drugs may become an inhibitory factor limitingthe availability of these novel agents in developingcountries. It is expected that In order to keep in pacewith various developments & the envisioned rapidrising cost in cancer treatment nowadays, an effectivefinancing policy is always required.

References:1. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety

of imatinib mesylate in advanced gastrointestinal stromal tumors.N Engl J Med.2002;347,7:472-480.

2. Kris MG, Natale RB, Herbst RS, et al.: Efficacy of gefitinib, aninhibitor of the epidermal growth factor receptor tyrosine kinase,in symptomatic patients with non-small cell lung cancer: arandomized trial. JAMA 290 (16): 2149-58, 2003.

3. Fukuoka M, Yano S, Giaccone G, et al.: Multi-institutionalrandomized phase II trial of gefitinib for previously treatedpatients with advanced non-small-cell lung cancer. J Clin Oncol21 (12): 2237-46, 2003.

4. Herbst RS, Giaccone G, Schiller JH, et al.: Gefitinib incombination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. J Clin Oncol22 (5): 785-94, 2004.

5. Giaccone G, Herbst RS, Manegold C, et al.: Gefitinib incombination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1. J Clin Oncol22 (5): 777-84, 2004.

6. McLaughlin P, Grillo-López AJ, Link BK, et al.: Rituximab chimericanti-CD20 monoclonal antibody therapy for relapsed indolentlymphoma: half of patients respond to a four-dose treatmentprogram. J Clin Oncol 16 (8): 2825-33, 1998

7. Coiffier B, Lepage E, Briere J, et al.: CHOP chemotherapy plusrituximab compared with CHOP alone in elderly patients withdiffuse large-B-cell lymphoma. N Engl J Med 346 (4): 235-42,2002.

8. Pfreundschuh MG, Trümper D, Ma A, et al.: Randomizedintergroup trial of first line treatment for patients <=60 years withdiffuse large B-cell non-Hodgkin's lymphoma (DLBCL) with aCHOP-like regimen with or without the anti-CD20 antibodyrituximab-early stopping after the first interim analysis. [Abstract]J Clin Oncol 22 (Suppl 14): A-6500, 558s, 2004.


Case 1Madam Lee was a 78 years old lady who

suffered from diabetes mellitus, hypertension,ischaemic heart disease, gout, and had beendiagnosed end stage renal disease by renalphysician since January 2004 with mutual decisionon conservative therapy (i.e. not for renalreplacement therapy). She was admitted to acutegeriatric ward in September 2004 for fluid retentioncausing generalized edema including acutepulmonary edema. Palliative care physician wasasked for advice on symptom control. Hersymptoms were mainly nausea and dyspnoeawhich were satisfactory controlled with oralhaloperidol and lasix infusion. She then developedsymptoms and signs of uraemic encephalopathyand was controlled with subcutaneous midazolamand she passed away peacefully few days later.

Case 2Madam Wong was a 72 years old lady who

suffered from hypertension, atrial fibrillation,diabetes mellitus, ischaemic heart disease, andcongestive heart failure (New York HeartAssociation Classification IV) and was under thecare of cardiologist. In 2002, although she wasinserted an Implantable Cardioverter Defibrillator(ICD) for ventricular arrhythmia, biventricular pacingfor heart failure was attempted with failure. She hadmultiple hospital admissions since then. During herlast admission in Dec 2003, palliative carephysician was consulted for symptom control. Hermain symptoms were easy fatigue, dyspnoea atrest with orthopnoea and insomnia. Low dosemorphine was tried with no effect. Benzodiazepine

was prescribed with modest improvement in sleepand dyspnoea condition. She died suddenly athome one month later.

DiscussionThe hospice movement was initially developed

in response to the perceived need of terminally illcancer patients. However, the emergence ofAIDS/HIV in the 1980s presented a major challengeto palliative care, and increasingly, more people inthe developed world die from chronic diseasesother than cancer. Hence, palliative care should notonly be considered as part of cancer care, but alsothroughout medical care.

Data collected by the United Kingdom (UK)National Council for Hospice and SpecialistPalliative Care Services showed that over the last 4years (1999 – 2003), the number of in-patients withnon-malignant conditions had varied somewhatfrom 4.4 to 5.4% among all palliative care units inUK. 1 There is, also, anecdotal evidence thatincreasing numbers of patients with non-malignantdisease are now being referred to palliative careservices in some parts of UK. 2

In Hong Kong, we do not have any local dataon this issue. The impression is that only a few non-malignant terminally ill patients are directlyreceiving care from palliative care services,although the un-met needs are perceived high. Thereasons for this are complex. The prognosticuncertainties, a lack of relevant expertise, fear of‘flooding’ of caseload, boundary dispute betweenprofessionals and between services, and issue onfunding and human resources may all contribute.

Palliative Care for Non-malignant PatientsDr. Lam Po Tin, Senior Medical Officer, United Christian HospitalE mail: [email protected]


9. Cobleigh MA, Vogel CL, Tripathy D, et al.: Multinational study ofthe efficacy and safety of humanized anti-HER2 monoclonalantibody in women who have HER2-overexpressing metastaticbreast cancer that has progressed after chemotherapy formetastatic disease. J Clin Oncol 17 (9): 2639-48, 1999.

10. Slamon DJ, Leyland-Jones B, Shak S, et al.: Use ofchemotherapy plus a monoclonal antibody against HER2 formetastatic breast cancer that overexpresses HER2. N Engl JMed 344 (11): 783-92, 2001.

11. Burstein HJ, Kuter I, Campos SM, et al.: Clinical activity oftrastuzumab and vinorelbine in women with HER2-

overexpressing metastatic breast cancer. J Clin Oncol 19 (10):2722-30, 2001.

12. Seidman A, Hudis C, Pierri MK, et al.: Cardiac dysfunction in thetrastuzumab clinical trials experience. J Clin Oncol 20 (5): 1215-21, 2002.

13. Hurwitz H, Fehrenbacher L, Cartwright T et al.:Bevacizumab (amonoclonal antibody to vascular endothelial growth factor)prolongs survival in first-line colorectal cancer (CRC): Results ofa phase III trial of bevacizumab in combination with bolus IFL(irinotecan, 5-fluorouracil, leucovorin) as first-line therapy insubjects with metastatic CRC. Pro Soc Clin Oncol 2003 (abstr3646)

Two large epidemiological studies were carried outin UK and USA respectively to assess the needs onpalliative and terminal care of non-malignantpatients. The first study was the Regional Study ofCare for the Dying (RSCD) which was a populationbased retrospective survey of a random sample ofpeople who died in UK in 1990.3 The second onewas the Study to Understand Prognoses andPreferences for Outcomes and Risks of Treatment(SUPPORT) which was a prospective controlled trialto improve end of life care for seriously illhospitalized patients in USA. 4, 5 Based on datafrom these 2 large studies, several recent papers6,7,8,9,11 have emphasized the un-met needs ofpatients with advanced disease with conditionsother than cancer. Most of the advanced diseasesbeing studied were congestive heart failure (CCF)7,8,10,14,15,16 and chronic obstructive pulmonarydisease (COPD). 9,11,12,13 There was evidence thatdyspnoea was more common inpatients with COPDthan lung cancer patients 9 while fatigue andtiredness in patients with CCF was as common as incancer patients 10

For patients with non-malignant disease,palliative care specialist can provide i) expertise indealing with complex psychological or spiritualproblems in the face of death, ii) expertise in thecare of actively dying patients, iii) familiarity intalking about death and dying, iv) familiarity inthinking through the difficult ethical issues at the endof life, v) skilled symptom control. However, howshould local palliative care service respond to thehigh un-met needs? The first challenge is to getpalliative care specialist to recognize that they havea role in managing patients with progressive non-malignant conditions. Education should be bi-directional. While those physicians currently caringfor non-malignant patients should be educated thephilosophy of palliative care, we ourselves shouldlearn about prognosis and management of variousprogressive non-malignant diseases. It is importantto identify the most appropriate time for palliativecare to be involved and to understand needs invarious local patient groups. We may need to set upa dialogue with different subspecialties about howwe can best explore a partnership to help with theoptimization of patient care during the course oftheir illness. The second challenge is to test outways of responding to these needs and to exploredifferent models of service provision. Whether oneoff consultation between referring team andpalliative care team or short term interventions withre-referral if needed, or a continuing commitmentfrom specialist palliative care unit is better deserve

further research and exploration. Last but not least,while many treatments and strategies for managingadvanced cancer will be applicable to non-malignant patients, innovative methods will also berequired. For example, development of appropriateprognostic models for various non-malignantdiseases and research on clinical management ofvarious difficult symptoms should be furtherencouraged and enforced.

Hopefully, we shall see improvement in carefor non-malignant patients in future.

References

1. National Council’s E-mail, August 2004. Minimum Data SetsProject. National Council for Hospices and Specialist PalliativeCare Service. www.ncpc.org.uk. 2. Kite S, Jones K, Tookman A.Specialist palliative care and patients with non-cancerdiagnoses; the experience of a service. Pall Med 1999; 13: 477 –484

3. Addington-Hall JM, McCarthy M. Regional study of care for thedying: methods and sample characteristics. Pall Med 1995; 9:27-35

4. The SUPPORT Principal Investigators. A controlled trial toimprove care for seriously ill hospitalized patients. The study tounderstand prognoses and preferences for outcomes and risksof treatment (SUPPORT). JAMA 1995; 274(20): 1591-8

5. Connors AF, Dawson NV, Lynn J. Decision making in SUPPORT:Introduction. J Clin Epidemio 1990; 43 Suppl: 47S – 49S

6. Lynn J, Teno JM, Phillips RS, et al. Perceptions by familymembers of the dying experience of older and seriously illpatients. Ann Int Med 1997, 126(2): 97-106

7. McCarthy M, Lay M, Addington-Hall JM. Dying from heartdisease. Journal of the Royal College of Physicians of London1996; 30(4): 325 -8

8. McCarthy M, Addington-Hall JM. Communication and choice indying from heart disease. JRSM 1997; 90(3): 128-131

9. Edmonds P, Karlsen S, Kham S, et al. A comparison of thepalliative care needs of patients dying from chronic respiratorydiseases and lung cancer. Pall Med 2001;15:287-295

10. Anderson H, Ward C, Eardley A. The concerns of patients underpalliative care and a heart failure clinic are not being met. PallMed 2001;15:279-286

11. Claessens MT, Lynn J, Zhong Z, et al. Dying with lung cancer orchronic obstructive pulmonary disease: insights from SUPPORT.Journal of American Geriatric Society 2000,48(5): S146-S153

12. Gore JM, Brophy CJ, Greenstone MA. How well do we care forpatients with end stage COPD? A comparison of palliative careand quality of life in COPD and lung cancer. Thorax2000;55:1000-1006

13. Skilbeck J, Mott L, Page H, et al. Palliative care in chronicobstructive airways disease: a needs assessment. Pall Med1998; 12: 245-254

14. Rogers AE, Addington-Hall JM, McCoy ASM, et al. A qualitativestudy of chronic heart failure patients’ understanding of theirsymptoms and drug therapy. Eur J Heart Failure 2002; 4:283-287

15. Rogers AE, Addington-Hall JM, Abery AJ, et al. Knowledge andcommunication difficulties for patients with chronic heart failure:qualitative study. BMJ 2000 ; 321: 605-607.

16. Murray SA, Boyd k, Kendall M, et al. Dying of lung cancer orcardiac failure: prospective qualitative interview study of patientsand their carers in the community. BMJ 2002; 325:929-934.


The hospital mortuary is often depicted as alarge freezer where dead bodies are stored anddreadful feelings are buried. The idea of the freezer,which is due to the hygienic consideration ofkeeping the dead, seems to have taken up thewhole meaning of this particular space. Physically,it freezes the deceased; psychologically, it freezesthe emotions; and spiritually, it freezes the meaningof existence. It seems that facing the ultimateconcern of our own existence, we have no idea howto deal with it except for bringing the space andourselves to a standstill. This understanding, thoughcomprehensible, has rendered us vulnerabletowards our own mortality.

The freezer effectLast offices are always seen as the hospital’s

last duty to the patient, with nurses officiating in thefinal act of care and responsibility. But in fact, it isnot the final stage of death that the patient and thebereaved people have to go through during thehospitalization period. The bereaved familymembers have to come back to the hospital to meetthe deceased again for identification and discharge.This last encounter is often ignored; even the lastoffices fail to acknowledge and incorporate it. Theplace where this last encounter takes place oftencarries the freezer effect which manifests itself ascool, unfurnished and disoriented, but most of usaccept it and take it for granted because theencounter with this space often arouses a fear ofmortality that one tries to avoid or escape from.

Since 1997, there has been a rapid increase inturnover rate and a pressing demand for dead bodystorage space in Haven of Hope Hospital. Thehospital therefore planned to install a new storageunit, and redesign the space. The presence of art inhospital care is understood to be important, tocreate an environment of healing.1 Firstly, areas ofimprovements and objectives were identifiedthrough observations and interviews with variousparties. Design criteria were then derived anddeveloped. Input from service users, healthcareworkers, designers and architect was sought andprocessed to formulate the design solutions.Research into the topic of dying and bereavement,

the psychology of color and design also contributedto the formation of the mortuary in Haven of Hopetoday. Finally, donation funding was sought tosupport the cost of the renovation project, and themortuary renovation project was completed in 2002.

Redefining the mortuary spaceBirth and death define a human life, they are

the two requirements for a human life to becomplete.2 They reinforce each other to makehuman life meaningful; without birth, there will be nolife; and without death, life loses its value. Themortuary, a place where lives and deaths meets, isplaying a crucial and provocative role in deatheducation. Despite the transcendental nature of themisty of death, a healthy attitude towards deathcontributes to the provision of a functional andunderstanding mortuary environment.

The objectives of the renovation project notonly aim to solve the environmental issues of theold mortuary, but also try to explore variousdimensions of the mortuary space within the publichospital setting. From a psychological perspective,an oriented containing space and the family reunionconcept contribute to better coping mechanism;from a humanistic perspective, a well furnished andbetter equipped mortuary reflects our respect forbasic human existence; spiritually speaking, theinstillation of hope restores the value of being.

Oriented space to acknowledge disorder andconfusion

In bereavement, a person is literally lost in hisor her own grief, and the more disorganized one’sthinking, the more difficult it is to step aside from thedisorganization.3 This is why the mortuaryenvironment should carry a clear space allocation.When people are better oriented, internal confusionis better contained by well-defined externalstructure and the sense of loss is more likely to beperceived as manageable. Clear definition of themortuary space was enabled by new sinages,partitions, clocks, sliding doors and variousfunctional settings. Since green is most frequentlyassociated with sickness and nausea 4, the colorscheme of the mortuary will be changed from light

Last Office Service in Palliative Care:Experience Sharing from the mortuary renovation project in Haven Of Hope HospitalAmy IP, Assistant Hospital Administrator (Community Relations), Haven of Hope HospitalEmail: [email protected] C.T. LEUNG, Hospital Chief Executive, Haven of Hope HospitalEmail: [email protected]


green to peach, which helps to create a warm andreceptive transitional space.

Containing space to support private mourningThe loss of a loved one arouses pain, sorrow

and grief. A better mortuary design should providea chance for mourning, to enable family membersto acknowledge their thoughts and feelings. Thesuggestion of a home-like setting offers a naturalsharing space for ’family reunion’. The familymembers shall be allowed time to identify thedeceased body and to say their final goodbyes withreference to the time frame stated in the infectioncontrol guidelines. To support these privatemoments, an extra viewing room is required. Thesemoments give loved ones time to adjust to what hashappened. So instead of the routine, process-oriented identification, the reunion concept wouldbe more able to facilitate expression, which mayhelp the bereaved family members to accept andaffirm their own feelings and thoughts. A supportiveenvironment, which provides enough private spaceand a sense of restfulness for ventilation of feelings,is more able to contain pre-verbal feelings andemotions.

Caring atmosphere to work with defensesA number of coping mechanisms are usually

called on help to reduce the level of tension oranxiety when people find themselves in a helplessor vulnerable situation. The psychological defencesare regarded as important essential means bywhich the individual is prevented from beingoverwhelmed by the anxiety and psychic pain ofgrief.5 A caring atmosphere therefore shall be inline with the psychological defences of thebereaved because it helps to increase copingcapacities.6 In this case, the bereaved familymembers may be helped to modulate grief andmourning through recognizing that the one theyloved was resting in peace in the bedroom. Thoughthe defenses may delay the relearning process ofthe individual, they often succeed in preventinganxiety from rising and protect the bereaved fromfurther emotional and psychological threat and helpthem to cope with their own anxiety towards deathin such a dramatic moment.

Comforting agents to instill hopeIn most societies, death is viewed as a stage

of transition, a transition to some other state ofbeing. Death is often perceived not as the end oflife, but the beginning of a new one. Despite theending of the physical and psychosocial being,most people believe there is a prospect of spiritual

life after death. When there is a prospect of life afterdeath, physical life will not end hopelessly. In thisconnection, signs and symbols about the quality ofthe continual existence could be introduced ascomforting agents. Symbols of love, peace hopeare good suggestions for the remembrance ofeverlasting relationships, and quality of life afterdeath.

Training and other improvement measuresThe renovation is not limited to the event of

arrangements for identification and body collection,but also extends to the system as a whole. Literally,the original name of the ‘viewing room’ was basedon functional considerations. After renovation, theroom was renamed the ‘Serenity Room’ ,suggesting a place for rest in peace. To promoteservice delivery, mortuary attendants should beprovided with training in dying and bereavementcare, to be trained as a ‘companion’, not just a‘guide’. Knowledge of different cultures, religionsand rituals could also empower the mortuary staff indelivering the service.

ConclusionProper handling of the deceased reflects our

beliefs about death and dying. As death and lifereinforce each other to make human lifemeaningful, it is only by acknowledging the value ofdeath and being respectful about it that we wouldbe able to enforce positive values of life. Dignity isimportant for those alive and even more importantfor those who witness dying because it has aprofound effect on their perception and judgment onthe value of life. We try to explore other dimensionsof the mortuary space through treating thedeceased not as just a dead body, but as arespected being. When we broaden our view andgain awareness of human existence, the freezingeffect could be diminished and transformed, and weare able to redefine this space with a potential formeanings.References1. Behrman P., Art in hospitals: why is it there and what is it

for? Lancet, 1997, 350:584-85.2. Kessler D., The Rights of the Dying – a companion for life,

Harper Collins, 1997.3. Parkes, Laungani and Young, Death and Bereavement

Across Cultures, Routledge, London, 1997.4. Sharpe D.T., The Psychology of Color and Design,

Nelson-Hall Co., Chicago, 1974.5. Wood M IN Pratt M., and Wood M.J.M. ed Art Therapy in

Palliative Care: The Creative Response, Routledge,London, 1998.

6. Bateman A., Brown D., Pedder J., Introduction toPsychotherapy: An outline of psychodynamic principlesand practice, Routledge, London, 2000.

Original article_____________________________________________HKSPM Newsletter 2005 April Issue 1 p 14

Original article_____________________________________________HKSPM Newsletter 2005 April Issue 1 p 15

The ‘bedroom’ environment in the new Serenity Roomconveys a sense of peacefulness and restfulness.Infection control measures has been integrated into thespecifically designed bed, drawer and linen items.Equipment with intrusive implications are stored in drawers.

With an additional Serenity Room, family members could spend time with theirbeloved ones privately without being hastened to make room for others.

The corridor and the doors were decorated with landscape paintingsand natural wood patterns to create a warm and rhythmic environmentfor emotional support and orientation.

Clear definition of space was enabled by new signages, partitions,clocks, sliding doors and different functional settings (entrance,waiting area, bed room, toilet and exit)

Soft lighting from aboveto symbolize ‘hope’

Signs and symbols of love,peace and hope introduced as comforting agents.

Geometric patterns and well-defined objects are used to provide amore structured environment, air ventilation facilities are installed

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Free Paper Abstracts - 6th Asia Pacific Hospice Conference

Free Paper Abstracts_______________________________________HKSPM Newsletter 2005 April Issue 1 p 18

Introduction: Although the length of survival of advanced COPD patients is difficultto predict, palliative care is increasingly being advocated as a better option foroptimizing the quality of life of COPD patients in the end of life. This study aimed tocompare the quality-of-life concerns of patients with advanced COPD with theterminal cancer patients, and to explore their need for palliative care.

Method: 108 advanced COPD patients and 100 terminal cancer patients wereinterviewed using the Quality-of-Life Concerns in the End-of-Life Questionnaire(QOLC-E). QOLC-E comprises four positive and four negative subscales. Thepositive subscales are support, the value of life, food-related concerns, andhealthcare concerns; the negative subscales are physical discomfort, negativeemotions, a sense of alienation, and existential distress. The overall QOL, 8 QOLC-E subscale scores, and P-ADL and I-ADL scores of the two patient groups werecompared using independent t tests.Results: The advanced COPD patients were more dependent in activities of dailyliving than the terminal cancer patients (t = -6.2, -4.7, P < 0.01). They had a loweroverall QOL evaluation than cancer patients (t = -2.1, P < 0.05). No significantdifference was found in the mean QOLC-E score between COPD and cancerpatients (t = -1.6, P > 0.05). The COPD patients scored lower in 3 out of 4 negative

Introduction: Considerable controversy over the justifications for forgoing life-sustaining treatment to patients with advanced dementia (AD) exists. Based on anethnographic study, the decision-making practices for forgoing tube feeding andantibiotic treatment for AD patients in the U.S. and Hong Kong is examined.

Methods: Prospective case studies were undertaken in long term care settings inthe U.S. and Hong Kong over a period of six months. Data sources included clinicalobservation notes from 20 patients, interview notes from their family members andhealthcare providers. Three strategies were used to manage the data: eventanalysis, content analysis and cross-case analysis. The American Caucasianculture, Chinese Confucian culture, hospice care culture and biomedical careculture provided the contexts for analysis.

Results: Three patterns of decision-making are delineated: (1) advance decision-making with respect paid to the patient’s wished, (2) advance decision-makingfocused on what is best for the patients, and (3) clinical decision-making withreference to biomedical parameters. The values, beliefs and experiences of thepatient-family-healthcare provider tripartite that shapes the practices are examined.

Conclusions: Forgoing life-sustaining treatment decision is difficult to make withinthe clinical context. Underpinning these difficulties are the predominant values incurrent medical practice that support the biological determinants of life and medicaltechnology for enhancing the quality of life. In resolving these difficulties, a moralparadigm shift in two respects is required for framing the care of patients dying withAD. They are a shift from the medical protraction of life and a shift towards forms ofcare that enhance quality of life within the natural-organic framework of emotional,relational, esthetic and spiritual well-being.

Acknowledgment: Funded by University Central Research Grants (GY-D44) & FulbrightScholarship

Samantha Pang,Betty Chung,Ivan Chung,Amanda Leung,Ladislav Volicer,Peter White

An empirical analysis of the decision-making of forgoing life-sustaining treatments for patients withadvanced dementia

Comparing the quality-of-life concerns of patients with advanced chronic obstructive pulmonarydisease and terminal cancer

Samantha Pang,KS Chan,Betty Chung,KS Lau,Edward Leung,Amanda Leung,Helen Chan


subscales, while the cancer patients scored lower in the value of life subscale(p<0.05) among the 4 positive subscales.Conclusions: The results showed that both advanced COPD and terminal cancerpatients bore similar quality-of-life concerns. However, the advanced COPDpatients assessed their quality of life worse than that of the terminal cancerpatients. The results highly suggest that palliative care should be extended topatients with advanced COPD, taking into account the unique characteristics ofCOPD patients.

Acknowledgement: Funded by the Research Grants Council of HKSAR (PolyU7257/00H)

Comparing the quality-of-life concerns of patients with advanced chronic obstructive pulmonarydisease and terminal cancer

Introduction:Tuen Mun Hospital is a 1600-bed acute regional hospital in New Territories West ofHong Kong and the only oncology centre in the region, providing service to apopulation of around one million. Many patients with advanced cancer werediagnosed, treated and subsequently died in our hospital. To cater for the needs ofthese patients, the hospice service was established in 1994 under the Departmentof Clinical Oncology and provides in-patient, day care, home care, consultation and

Specialist hospice service in an acute regional hospital: a ten-year review

K. K. Yuen

Background and Objective: Infection is common and is a major cause of mortalityand morbidity in patients with terminal malignancy. However, there is not muchinformation describing the judicious use of antibiotics at the end of life. This studywas taken to review the pattern of use of antibiotics and to identify potential factorsthat could affect outcomes after infection.

Study design: Medical records of all patients with terminal malignancy who wereenrolled into the palliative care service of a district hospital during the periodJanuary 2002 to July 2002 were retrospectively reviewed. The definition of infectionwas defined. A cut off of survival at 14 days after infection was chosen as theoutcome measure in this study.

Results: Among the eligible 87 patients, 70 had at least one infective episode andaccounted for a total of 120 episodes. Sixty eight episodes resulted in survival for >14 days while fifty two episodes survived equal to or less than 14 days. The mostfrequent sites of infection were chest (n=63, 52.5%), followed by urinary tract (n=35,29.2%) and skin /wound (n=6, 5%). 97.5% (n=117) episodes were prescribedantibiotics. Most of the antibiotics were prescribed empirically (n=72, 61.5%). Theuse of second line antibiotics was 16.2% (n=19). By multivariate logistic regressionanalysis, dyspnoea [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.1 -6.3],antibiotics utilization pattern [empirical therapy (OR = 4.8, 95% CI =1.7 -13.2)versus therapy according to antibiotic sensitivity] and route of administration[parenteral route (OR = 3.3, 95% CI = 1.3 – 8.2) versus oral route] were identifiedas independent determinants affecting survival after infection.Conclusion: Most infections were treated with empirical antibiotics. Dyspnoea waspossibly associated with poor prognosis in infections in palliative care whileantibiotics therapy according to sensitivity was associated with better prognosis.Further studies are encouraged to verify this. The bioethical principles on the use ofantibiotics as a life-sustaining treatment should always be followed.

Retrospective analysis of the use of antibiotics and survival difference in palliative care patients withinfections

PT Lam,KS Chan,CY Tse,MW Leung


bereavement services. The objective of this review is to describe the developmentand utilization of hospice service during the past ten years since its establishment.

Method: Patient and administrative data were retrospectively collected from ourpatient and administrative databases. The outcomes assessed include referral andutilization parameters.Results: During the period from September 1994 to November 2004, a total of4502 referrals were received. Among these, 3078 patients were included in theservice. The reasons for exclusion were patient’s refusal, residence outside ourservice area, death on waiting and diseases amendable to radical treatment. Therewere on average 500 hospital admissions per year and the number of in-patientbeds was increased from 8 beds in 1994 to 35 beds in 2004. The mean intervalfrom start of hospice service to patient death was 70 days.Conclusions: The large number of referrals reflected a genuine need for hospiceservice in the acute hospital setting. Hospital-based hospice service facilitatescontinuity of patient care and provides support to other hospital teams. We believethis mode of operation is the best way to meet our local needs.

Introduction: Studies on what is helpful for Chinese bereaved persons are hard tofind. Death and widowhood are still taboo topics. This study is a qualitative studyon what helps in the bereavement experience among Chinese widows in HongKong. Method: This is an exploratory phenomenological study on the bereavementexperiences of seven Chinese widows recruited from a hospice ward in a localhospital in Hong Kong. The informants shared stories about their relationship withthe deceased in the past, at the moment of death as well as the ongoingrelationship after the death. The data was analyzed by the grounded theoryapproach.

Findings: The Chinese widows attributed their adjustment to the bereavementexperience to the different domains in the relationship with the deceased. TheChinese norms on social role, gender identity and expectations on marital bondingeven after death of husband are revealed. The discussions will focus on the issuesof the role of awareness of the impending death, provision of hospice and palliativecare, care for carers, creation of legacies as well as sensitivity towards culturalembedded practice.

Conclusion: From the above findings, postulations on "what helps" for bereavedpersons are being developed. Suggestions for practice in hospice, palliative andbereavement care will be proposed. It is hoped that the discussion of these hiddenvoices can help ignite further research to verify the postulations, to further improvethe hospice and palliative care for the Asian population.Acknowledgement : The work described in this article was partially supported by a grant from theResearch Grants Council of the Hong Kong Special Administrative Region, China (Project No.HKU 7110/01H).

Specialist hospice service in an acute regional hospital: a ten-year review

What helps in bereavement ? – qualitative study of Chinese widowers in Hong Kong

Cecilia L.W. ChanAmy Y.M. ChanSamuel M.Y. Ho

Introduction: "Good death" has gained more attention in the Chinese population.To promote good death of dying patients becomes an important goal in end of lifecare. Previous discussions mainly focused on dying patients, but recent findingsshow that it may be crucial for bereaved persons as well. Thus, this paper aims atdiscussing "good death" from the views of bereaved Chinese older adults and itsimplications on bereavement care.

Good death and good life: we need both for good bereavement

Wallace Chan


Method: Fifteen bereaved Chinese older adults who experienced spousal deathafter the age of sixty five were interviewed. Interviews were transcribed andanalyzed according to grounded theory.

Results: Bereaved older adults seemed to perceive "good death" as different from"good dying", and thus tended to positively evaluate spousal death as "good" inspite of difficult situations experienced in the dying process. Inappropriate care andtreatment received in the hospital was perceived to cause unnatural sufferings tothe deceased spouse. This affected the perception of quality of dying, and in turnaroused anger, sense of powerlessness and made bereaved older adults difficult tomake sense of the death. Findings also showed that "good death" might be goodfor the deceased but not for the bereaved sometimes. It might be good for thedying spouse to die in short time to minimize sufferings, but it also implied the lackof time for the remaining spouse to prepare for the death. Death of spouseinevitably happened, and there is no guarantee that "good death" can be ensured.Instead, bereaved older adults expressed that "good life" could assure goodbereavement. The good use of time in daily life and the sense of meaningfulness inthe whole life ensured better adjustment. Meaning and time seemed to be apossible direction in developing proactive bereavement care in old age.

Introduction: Spirituality, the core of the individual person, is regarded as theessence of the person which influences/leads to the choice of his/her copingattitude while facing impending death. Encountering the spirit of the patient doesrequire sensitivity, courage and the spirituality of the staff herself. It is so often feltas the most difficult and time-consuming piece of work as well as the awareness ofher own vulnerability and that of the patient.

Method: This is a freely randomized retrospective review of 4 spiritual relatedquestions in the patients’ documentation which had to be completed within 3 daysafter patients were admitted to the In-patient unit; or within 3 home visits of thoseadmitted to the Home Care Services.

Objectives:1. To see the percentage of completion of the relevant questions2. The possible reason of the default

Results: Out of 118 case notes in the month of May and June 2004, there were 8%of patients was unable to be assessed due to critical condition such as too drowsyor confusion. 84% of completion of the first question relating to patient’s ownreligious ritual. 20% completion of the second question relating to patient’sperception of God/Destiny in relating to own illness. There were 35% completion onquestion three addressing his feelings towards spiritual beliefs and finally only 27%completion rate on question four regarding their view on meaning of life.

Conclusion: Such a percentage was clearly low and prompt improvement actionshould be worked out and carried through otherwise, the quality of holistic careprovided to patients is questionable. A new designed questionnaire based on theresult generated from the previous study on "Genuine Needs of Patient and Family"was under trial in the In-patient unit and the result is pending.

A retrospective review of the document on the 4 questions related to spiritual support to patients ofBradbury Hospice

Clare Lai

Good death and good life: we need both for good bereavement

Case HistoryMr. To was a seventy-nine year old gentleman,

a non-smoker and a non-drinker who hadhepatocellular carcinoma first diagnosed in March2002. In December 2000, he was found to haveelevated alpha fetoprotein (AFP) of 25.8 iu/mlduring his follow up for his medical problems(diabetes mellitus, hepatitis B related cirrhosis,paroxysmal atrial fibrillation). He has ultrasound andsubsequently CT scan of abdomen performedwhich showed no evidence of malignancy. Magneticresonance imaging (MRI) was suggested for followup. In March 2002, he has MRI done which showedtumour at lateral segment of left lobe. Laparoscopicradiofrequency ablation (RFA) was performed inApril. Unfortunately, the tumour recurred in August2002. Despite repeated RFA, there was diseaseprogression with ascites, pleural and pericardialeffusion. Management plan was discussed withpatient and relatives and they agreed that furtheraggressive treatment would unlikely to be helpful.Tamoxifen was added.

For the family situation, Mr. To has fourchildren (three sons and the youngest daughter)who were all married. His second son lived inMauritius and his daughter in Canada. He lived withhis wife and his third son, who was divorced.Knowing of her father’s condition, the daughterquitted her job and returned to Hong Kong tosupport the family.

Mr. To was admitted to our hospital in May2004 for progressive increase in shortness ofbreath and abdominal distension. Physicalexamination and investigations (including CXR andechocardiogram) revealed right pleural effusion,pericardial effusion, gross ascites and rapid atrialfibrillation. During this admission, Mr. To wasreferred to our palliative care unit for management.Mr. To was very worried and asked specificallywhether his pericardial fluid needed to be tappedout. We consulted our cardiologist to assess hiscondition. There was no evidence of cardiactamponade and they suggested to treat his heartfailure with diuretic, herbesser and digoxin.Pericardial tapping was not indicated. Mr. To feltless breathlessness afterwards.

He also had an episode of pneumonia with low

grade fever. Antibiotic was given and his condition(including dyspnoea) improved after two days. Hewas in satisfactory condition with good appetite,receiving limb mobilization training and has minimalbreathlessness.

He developed mild increase in abdominaldistension and was equivocal for abdominaltapping. Eventually tapping was attempted but nofluid was tapped out. He remained in good mood.Few days later, he had mild shortness of breath andankle swelling. CXR showed increase in rightpleural effusion. Chest tapping was done with190ml of fluid tapped out. The pleural fluid wastransudative in nature. His breathing was betterafterwards. Mr. To asked again whether hispericardial fluid needed to be tapped or not. In viewof his deep concern, an echo-cardiogram wasrepeated and the decision was seriously consideredand finally it was decided not to performpericardiocentesis in view of low platelet count,impaired clotting profile and no evidence oftamponade. Mr. To agreed to the decision after ourexplanation.

Since early June 2004, Mr. To’s physicalcondition was gradually downhill. He was sleepyand tired. His appetite decreased. He appeared tohave more acceptance of his disease and talkedopenly with our hospice nurse about his condition.He said that he accepted his gradual deteriorationand understood that he would die as the diseaseprogressed. He expressed happiness as he wouldreach heaven. He believed in and believed inall gods. He believed that he was a good personand would reach heaven after his death. He alsoplanned his funeral arrangement and discussedwith his family. He would have Buddhist ceremonyat night and follwoed by Catholic ceremony in themorning as most family members were Catholics.

During this period, he had markedly increasein jaundice and also increase in abdominaldistension. He was undecisive whether to haveabdominal tap again. In the middle of one night, Mr.To felt he was deteriorating and asked his son, whowas accompanying him, to call all family membersto come to see him. His wife and other childrenarrived and rushed into the ward. The night nurse,not informed and totally unprepared, was surprised

A Patient with Fluid in the Wrong SpacesDr Lau Kam-shing,Senior Medical Officer, Palliative Care Unit, Department of Respiratory Medicine, Ruttonjee Hospital.Correspondence: [email protected]

Palliative Medicine Grand Round______________________________HKSPM Newsletter 2005 April Issue 1 p 22

and stopped their entrance as she did not find Mr.To’s condition was deteriorated and she was afraidthat the visitors would disturb other patients in thesame cubicle. There was some tension initially buteventually the night nurse allowed them to enterand to accompany Mr. To that night. In the nextmorning, Mr. To agreed to have abdominal tappingand four liters of fluid were tapped out and he feltmuch better.

On another night, Mr. To frequently pressedthe call bell for the nurse to see him. Two patientsnearby passed away in the last two days. Afterattending him few times, night nurse reassured himand placed his bed in the corridor opposite thenurse station that night and no need for similararrangement in subsequent nights.

Mr. To further deteriorated with weak voice,poor eating and generalized discomfort on directquestioning. There was no particular complaint ofshortness of breath. After communication with Mr.To and his family, syringe driver with morphine wassetting up and Mr. To passed away peacefully twodays afterwards with all family membersaccompanying him in the night time.

DiscussionMr. To was unfortunate to have fluids in the

wrong spaces (pleural, pericardial and peritoneal)during his course of illness. The management wassummarized in table 1.

The management of the fluids reflects that thereis more than physical component in the situation.Despite only 190 ml of pleural fluid was tapped out,Mr. To felt improved in his breathless. It is likely thatthe support and concern from the staff for hisbreathlessness and did something (tapping) torelieve his symptom which played a significant partin his improvement more than the physical removalof fluid. Similarly, he was very concerned about hispericardial fluid as he expressed several times onwhether the fluid needed to be tapped. Patients withmalignant pericardial effusion have poor prognosisand limited life-expectancy. The median survival isof 2 to 3 months.1 Though Mr. To may not know the

grave prognosis, he was very concern about thefluid indeed. In Chinese term, he mentioned ‘heartwater’ for the pericardial fluid and heart is a majorvital organ and it is likely that he feared that the‘water’ was threatening to his heart and wished usto do something. The physical presence of the fluidbrought about psychological fear and threat to thepatient. As the procedure was risky and notabsolutely indicated, we did not advise him for theprocedure. However, we had attended to hisconcern by repeating investigations and tocommunicate with him about the decision.Emotional support and reassurance is important.2The process itself (without getting rid of the fluid)reduced the fear and threat of Mr. To and heaccepted it peacefully.

For the peritoneal fluid, he was equivocalabout tapping again after the first dry tap. Mostlikely, the ascites was causing much discomfort tohim as reflected in his decision to call all familymembers to come (despite no objectivedeterioration) at midnight as if he was dying. Thissuggestion was also supported by the fact that fourlitres of fluid were tapped out the next day withmuch improvement.

Fear vs acceptanceDuring his course of illness, Mr. To gradually

accepted his condition and was able to talk openly.He was even able to plan for his funeralarrangement with his family and expecting hisspiritual journey after death. However, he would stillhave fearful moments when death appearedimminent (when he felt he was dying of discomfortfrom marked ascites and when his nearby patientsdied and death was so real to him). This wouldreveal only a small portion of the much neededstrength and energy consumed by the patient infacing death.

In order to have a better understanding of ourpatients, it would be useful if we can understandmore than just the observed behaviour which canbe considered as the tip of an iceberg. We can usethe Personal Iceberg Metaphor of the Satir Modelas a tool to understand more.3 (see disgram)

Type of Fluid Intervention Result

Peritoneal Dry TapPleural 190 ml tapped Dyspnoea improvedPericardial Discussed, not tappedPeritoneal 4 litres tapped Felt better

Table 1:Body fluids and management


'ss

The Iceberg Metaphor illustrated that one’smanifested behaviour reflected one’s deeperemotions and values and with one self at the veryfundamental base of one’s ‘iceberg’. We can takethe example of the event of Mr. To calling his familymembers to accompany him in the middle of thenight. The following table attempts to describe thepersonal iceberg of Mr. To and the iceberg of hisfamily member at that moment.

With better understand of the patient andfamily members, it would be easier to showempathy to them and to work out a solutiontogether. During the process, we must also beaware of our own ‘iceberg’ (our feelings,perceptions, expectations etc…) in dealing with thesituation.Cure vs Care

In the management of Mr. To’s pericardial fluid,I have described the traditional ‘cure’ model basedapproach as we assess the indication for tappingand the complications and risks involved. Inpatients with terminal illness, cure is not possibleand caring is important. We have to understand thefear & concern of Mr. To with relation to hispericardial fluid. Table 2 illustrates the differentperspectives in dealing with the medical problem.

The Last Journey – Good DeathFinally, despite Mr. To’s disease could not be

cured, we have supported him during his lastmoments of life. During his death, he expected allfamily members accompanying him. In fact all hisfamily members returned from other parts of theworld and gathered around his bedside when hepassed away. He was also not in distress and waspeaceful while on subcutaneous morphine andhaloperidol.

References:1. Allen KB, Faber LP, et al. Pericardial effusion:

subxiphoid pericardiostomy versus percutaneouscatheter drainage. Ann Thorac Surg. 1999Feb;67(2):437-40.

2. Mangan CM. Malignant pericardial effusions:pathophysiology and clinical correlates. Oncol NursForum. 1992 Sep;19(8):1215-21.

3. Banmen J. Satir’s systemic brief therapy trainingprogram: Counselling practicum workbook forprofessionals. Shiuh-Li Liuh Memorial Foundation.2003.

Behaviour

Coping

Feelings

Feelings about feelings

Perception

Expectations

Yearnings

Self: I am

Diagram: The Personal Iceberg Metaphor of the Satir's Model

Indication for tapping

Complications & Risks

The meaning of having ‘heart water’ to Mr. To

What is the expectation of tapping the ‘heart water’ to him:Symptom relief? Something threatening to be removed?

Table 2: Cure Vs Care

Ask the family to come inthe middle of the night

Insist seeing patients evenstopped by night nurse

Congruent Placcating

Fear, Lonely

His condition is critical

Angry (towards staff),Worried (towards patient)

Patient want to see relatives and theyshould be allowed to see patient

Relatives to be aroundat this moment

Nurses to be caring andwelcome them to patient

Mr. To Family members


Case HistoryMadam S was a 71 year-old lady who suffered

from carcinoma of rectum with Hartman’s operationperformed in 2000. Unfortunately she wasdiagnosed to have lung cancer with bonemetastasis in 2003. She was admitted into thePalliative Care Ward of Caritas Medical Centrebecause of severe left hip pain. She rated her hippain as 8 out of 10 in VRS; and the pain wasstabbing in nature, and exacerbated by bodymovement. The hip pain persisted throughout dayand night, and sleep was severely disturbed. Herpain was not relieved by oral methadone 5mg bidand breakthrough doses of morphine at 2.5mgorally hourly prn.

Madam S had eight children, but they all livedapart. As she moved around at home alone, shehad to hop on her right leg in order to avoid pain inleft hip. Being an obese lady, this was not easy forher to cope. As her hip pain worsened, she movedto a private old age home, though she disliked theenvironment there. Madam S was fully aware of herillness and showed acceptance. She expressed herwish to attend the wedding ceremony of hergrandson in 2 weeks’ time.

On physical examination, she was mentallyalert. She had a colostomy bag in situ with brownishstool. Her left lower limb had limited range ofmovement because of severe left hip pain. CXRshowed a left lung mass with no rib fracture.(Fig.1) X ray both hips showedsevere osteolytic bone lesions inleft iliac crest and pathologicalfracture of left femoral head.(Fig.2)Her blood results were as follows:Urea 3.2mmol/L, Cr 56 mol/L,Na 134mmol/L, K 3.5mmol/L,Corrected Ca 2.39 mmol/L,Alkaline Phosphatase 232IU/L,Spot sugar 5.6mmol/L

HerHer complete blood picture andliver function test were normal.Our goal of management at thattime was to control her bone pain,and hopefully with less pain, shecould attend the wedding of hergrandson.

The dose of methadone was increased to10mg bid, and Naproxen 250mg bid was added asadjuvant. Breakthrough dose of syrup morphine at5mg was given half hour before bathing andturning. A total of 3 to 4 doses of breakthroughmorphine were required per day. Palliativeradiotherapy for pain control was also suggested.She refused the intervention as she could nottolerate the supine position during the procedure.This was her experience not long ago while shewas admitted into the Clinical Oncology Unit.

A Lady with Severe Left Hip PainDr Kwok Oi-Ling, Dr. Tse Man-Wah,Palliative Care Unit, Department of Medicine & Geriatrics, Caritas Medical Centre.Correspondence: [email protected]


Fig. 1: CXRshowing theleft lung mass

Fig. 2: X ray pelivs and hip showing osteolytic lesionsin plevis and facture of left femur

ProgressHer pain control was poor despite increased

dose of methadone to 15mg bid. She developedconfusion on day 8. The mean daily dose ofmethadone in these 8 days of admission was 25mg.She also developed severe constipation withvomiting on day 9 despite concomitant use oflactulose 10ml tid and senokot 15mg Nocte. Bloodtests were performed again to investigate for othercauses of confusion. The results were as follows:

Urea 2.5 mmol/L, Cr 48 mol/L, Na 134mmol/LK 3.6mmol/L, Corrected Ca 2.49 mmol/LAlkaline phosphatase 246IU/LSpot sugar 6.0mmol/L

Oral methadone was then switched totransdermal fentanyl 25 g/hr on Day 9 for theadverse side effects of constipation and confusion,inadequate pain control and intolerance of oralmedication. The dose of transdermal fentanyl wastitrated to 50 g/hr on Day 13. With the rotation ofopioid, pain control was much improved. The painVAS score decreased from 8 to 3 out of 10 at restwith subsidence of confusion and constipation. Asher general condition improved, Madam S was ableto enjoy some of the creational activities, such aswatching video shows in her bed. Unfortunately, shecould not join the wedding ceremony of hergrandson because of the great difficulty in transferof positions. A special wedding ceremony was thenarranged in the Day Care Centre of our PalliativeCare Ward to fulfill her last wish.

On Day 25, she experienced increasing left hippain with numbness of left lower limb. SodiumValproate 200mg tid was added to transdermalfentanyl 50 g/hr as adjuvant. However, she stillreported a VAS pain score of 7 out of 10.Subcutanecous infusion of ketamine at 50mg perday was commenced at Day 27, as adjuvant totransdermal fentanyl. Ketamine was stepped up to75mg per day at Day 32 and further increased to100mg per day at Day 35.

Her pain was well controlled by then, and herVAS pain score improved from 7 to 2 out of 10 atrest. She did not report any side effects such ashallucination or delirium. She could still enjoygathering and chatting with her relatives. Sheremained in satisfactory pain control until Day 75,when her general condition slowly deteriorated withincreasing general weakness. Ketamine wascontinued together with transdermal fentanyl50 g/hr till patient died peacefully at Day 90 ofadmission.

DiscussionIn summary, this was a patient with hip pain

secondary to bone invasion by tumour resulting infracture, soft tissue infiltration, and likely to haveinvolvement of the nerve plexus. Although palliativeradiotherapy could be a useful treatment, patientdeclined this option as she considered it tooburdensome. Pain control by methadone ishindered by the dose limiting side effects. Shebecame confused and unable to tolerate oral drugs.As the side effect of confusion subsided withdiscontinuation of methadone, and that othercommon causes of confusion had been ruled out, itwas likely that methadone was the cause of theconfusion.

The rotation of methadone to fentanyl in thispatient served three purposes: to reduce sideeffects, to improve pain control, and to administeropioid in alternative route when oral route was notfeasible. Fortunately these purposes were fulfilledas the dose of transdermal fentanyl was titrated to50 g/hr. Although Mdm S cvould not presentherself in the wedding ceremony of her grandson,she was well enough to attend a specially arrangedone in our Palliative Care Unit.

However, as the disease progressed, theregime was no longer able to control her pain.Disease progression, emergence of opioidtolerance, predominance of neuropathic pain couldall contribute to the poor pain control. Her pain waslater adequately controlled by adding ketamine asadjuvant. Ketamine is being used in palliative carefor alleviation of cancer pain due to variousunderlying mechanisms. The pharmacology ofketamine helps us to understand its role asanalgesia.

Ketamine is a mixture of R(-) and S (+) isomer.It is S isomer that is responsible for the anestheticand analgesic effects. Ketamine is metabolised inliver to produce the pharmacologically activemetabolite norketamine, which is one-third aspotent as ketamine. Ketamine is the most potent N-methyl-D-aspartate (NMDA) receptor antagonist.Animal studies have shown the capability of NMDAreceptor antagonist to inhibit the development ofopioid tolerance. Hence, in addition to treatingopioid-resistant pain, ketamine may also reverseopioid tolerance. Psychotomimetic side effects,such as hallucinations, delirium, and vivid imagery,should be observed for; which can be remedied byconcomitant administration of benzodiazepine orhaloperidol. Cardio-vascular side effects such as


tachycardia and hypertension may also occur, andhence ketamine should be used with caution inpatients with ischaemic heart disease, heart failure,hypertension, or history of stroke.1 Apparently,Mdm S tolerated ketamine well without significantadverse effects.

In Hong Kong, oral preparation of ketamine is notavailable for use as medication. Therefore ketamine isadministered via parenteral route. Ketamine is notuncommonly used by palliative care physicians asadjuvant for cancer pain, and has been administeredvia different routes. However, in a recent CochraneReview on using ketamine as adjuvant to opioid incancer pain, it was concluded that current evidencedid not lead to a robust recommendation on its useand the route of administration.2 Two randomisedcontrolled cross over studies and thirty-two casereports or open label uncontrolled trials weresystemically analysed in this review.

In one randomised controlled trial in 20003, tencancer patients with neuropathic pain unrelieved bymorphine were included. Patients were exposed tothree arms of treatment: (1) 0.25mg/kg ketamine ivbolus (2) 0.5mg/kg ketamine iv bolus and (3)placebo. The cross over and wash out period wasat least 2 days. Results showed that ketamine ivbolus significantly reduced pain intensity in allpatients at both doses of 0.25mg/kg and 0.5mg/kg.Four out of ten patients had side effects includinghallucinations, drowsiness and confusion, whichwere reversed by giving diazepam 1mgintravenously.

Another randomised controlled trial wasreported by Yang et al in 1996.4 Twenty patients (10men, 10 women), aged 22-68 years with cancerpain were recruited and randomised into twotreatment arms: (1) intrathecal ketamine 1mg/kgtogether with intrathecal morphine and (2)intrathecal morphine only. The dose of morphinewas titrated and when pain relief had been stablefor 48 hours, patients were crossed over. Resultsshowed that co-administration of low dose ketaminecould reduce the amount of intrathecal morphinerequired to control cancer pain. Adverse effectsreported included pruritis, constipation, urinaryretention, difficulty in urination, nausea andvomiting, hallucination and respiratory depression.However, there was no withdrawal or drop outreported.4

Apart from these two randomised controlledtrials, there were 32 case reports or openuncontrolled trials studies reporting improvement ofopioid analgesia with ketamine. Reported routes of

administration of ketamine included oral,intramuscular bolus, subcutaneous bolus, sub-cutaneous infusion, intravenous bolus, intravenousinfusion, epidural bolus and intrathecal infusion. Thedose of ketamine used ranged from subcutaneousinfusion at 1mg/kg per day to intravenous infusionat 600mg per day and to intrathecal infusion at67.2mg daily. Treatment duration ranged from fourhours to one year. The most common occuringadverse effects were sedation and hallucination.Other side effects reported included evokednystamus, inflammation of subcutaneous infusionsite, generalised hyperalgesia and allodynia afterabrupt termination.

Based on the above studies, the reviewersopined that larger studies and more information areneeded before one can conclude whether the routeof administration of ketamine has an impact on itseffectiveness as an analgesic.

Recently, intranasal route of administration ofketamine has been investigated. It was arandomised, double-blinded, placebo-controlled, 2-period cross-over trial performed to evaluate thesafety and efficacy of intranasal ketmaine to treatbreakthrough pain in patients with chronic pain. Thestudy included patients referred from pain clinicswith age older than 18 years old; with stable painpattern of 2-7 episodes of daily breakthrough paindespite taking stable and regular analgesic; withbreak-through pain intensity greater than or equal to5 by numerical pain intensity scale; and patientswho were able to use nasal spray properly. Tenpercent aqueous solution of ketamine hydrochloridewith 0.002% benzalkonium chloride (vehicle) in anasal spray pump was used and each spray wasequivalent to 10mg ketamine.

A total of 20 patients completed the study, with10 patients in each arm. They crossed over after awash out period of 48 hours. These 20 patients hada variety of chronic painful conditions. Four out oftwenty patients had cancer pain and thirteenpatients had back pain. All patients had used strongopioids for more than 6 weeks before study,including morphine, methadone and fentanyl.

When breakthrough pain developed, with painscore >/=5, patient was given ketamine or placebonasal spray. Self administration of 1-5 sprays atinterval of 90 seconds was allowed. If pain was notrelieved after 5 sprays, patient should take theusual breakthrough pain medications. Pain scorewas repeated at 5, 10, 15, 20, 25, 30, 40, 50 and 60minutes after the first spray and adverse effects


was documented. Blood were checked at 0, 2, 30and 60 minutes for analysis of ketamine andnorketamine levels.

Results showed a reduction in pain score of2.65 for the ketamine treated group (vs 0.81 inplacebo group; p<0.0001). Statistically significantpain relief occurred within 10 min of delivery of thefinal intranasal spray of ketamine and the statisticaldifference remained up to 50 min after the lastspray. Ketamine reached the highest mean plasmaconcentration at 30 min after the nasal spray, butwas first detected in plasma at as early as 2 min.No serious side effects or death were reported. Halfof the patients in treatment group reported minorside effects including fatigue, dizziness, feeling ofunreality, change of vision and nausea (vs 10% inplacebo group). All were transient and resolved in60 minutes. None of these side effects hadsignificant difference between the treatment and theplacebo group, except for fatigue. Thirteen out oftwenty patients in the placebo group required usualbreakthrough medications, while none in thetreatment group made such request. The authorsconcluded that intranasal ketamine was safe andeffective for breakthrough pain.

ConclusionSubcutaneous ketamine infusion was effective

and safe when used as adjuvant for pain control inthis lady. The intranasal route has its attractivenessas a convenient route of administration for suitablepatients. More studies and information are requiredto determine the convenience, efficacy, and safetyof various routes of administration.

References1. McQueen AL and Baroletti SA. Adjuvant ketamine analgesic for

the management of cancer pain. The annual ofpharmacotherapy, 2002;6:1614-1619.

2. Bell R, Eccleston C and Kalso E. Ketamine as an adjuvant toopioids for cancer pain (Review). The Cochrane database ofsystematic reviews, 2004;2.

3. Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effect ofintravenous ketamine in cancer patients on morphine therapy: arandomized, controlled, double-blind, crossover, double-dosestudy. Journal of Pain & Symptom Management 2000;4:246-51.

4. Yang CY, Wong CS, Chang JY. Intrathecal ketamine reducesmorphine requirements in patients with terminal cancer pain.Canadian Journal of Anaesthesia 1996; 43 (4);379-83.

5. Carr DB, Goudas LC, Denman WT, Brookoff D, et al. Safety andefficacy of intranasal ketamine for the treatment of breakthroughpain in patients with chronic pain: a randomized, double-blind,placebo-controlled, crossover study. Pain;108;17-27.


Picture quiz: What is the nationality of this bird?

Answer:Montreal,Canada-seethemapleleaveinherheart

Correspondence to:Dr. Doris Tse Man Wah, Dept of Medicine & Geriatrics,

Caritas Medical Centre, 111, Wing Hong Street, Shamshuipo, Kowloon, Hong Kong.Tel : 34087454 Fax : 2148 4399

Email : [email protected] Homepage : http://www.fmshk.com.hk/hkspm

AcknowledgmentThis Newsletter is sponsored by

Society for the Promotion of Hospice Care

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