NEWSLETTER : April 1998


Preparations for the 1998 AuSPEN Annual Scientific Conference are well underway. It is certainly shaping up to be an exciting and informative meeting. On Friday 23rd October the programme will be integrated with the Gastroenterological Society Meeting with two major joint Symposia/Plenary Sessions and one joint free paper session. The topics will focus on

Enteral and Parenteral Nutrition in Critical Illness, Trauma and Post-Surgery.

Intestinal Adaptation with an emphasis on the Role of Nutrition in this important process.

We have been extremely fortunate to have two excellent international speakers who are leaders in clinical and basic laboratory research in these areas. Ken Kudsk, President of the American Society of Parenteral and Enteral Nutrition, is a surgeon with a keen interest in the role of enteral nutrition following trauma and major surgery. Alan Walker is Professor of Nutrition at Harvard School of Public Health and has extensive clinical and research experience in intestinal development and adaptation. Both are engaging speakers .

The Social Programme is also shaping up very well with some terrific events planned.

Mark the 23rd and 24th of October in your diaries now ! Think about what you would like to present - it would be great to see you share your projects and experiences with us all.

I look forward to meeting with you all in Canberra.

Dr Julie Bines,

President of Auspen,

April 1998.


Dr Julie Bines, President of AuSPEN,

Dept. of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Melbourne.

Ph +61-3-9345-5060.

Fax +61-3-9345-6240


Dr Margaret Allman, Honorary Secretary of AuSPEN ,

Human Nutrition Unit, Biochemistry Dept.,The University of Sydney, Sydney 2006. Ph +61-2-9351-3758

Fax +61-2-9351-6022



June 1st - 6th : Medical Research Week organised by the Australian Society for Medical Research; events in all major centres

June 24th - 28th : 2nd International Conference on Natural Antioxidants and Anticarcinogens in Nutrition, Health and Disease. Helsinki, Finland. Contact Congress Team Fax 358-9-477-5811

September 16th - 19th : 20th ESPEN Congress on Clinical Nutrition and Metabolism will be held in Nice, France. Contact : Nice Acropolis, Development Dept., 1 Esplanade Kennedy, BP 83, 06302 Nice Cedex 4, France.

Ph 33-04-9392-8300 Fax 33-04-9392-8255

September 27th - 30th : 5th Conference of the International Society for Trace Element Research in Humans. Lyon, France. Contact Trace Element Institut for UNESCO, Immeuble Le Condorcet, 1 place de l'Ecole.

October 8th - 11th : The 23rd Australian & New Zealand Annual Scientific Meeting on Intensive Care, Adelaide Convention Centre. Prof Jonathan Cohen - Infection / Sepsis Dr Deborah Cook - Evidence Based Practice Prof Sergio Fanconi - Paediatric Intensive Care Prof Huda Huijer Abu-Saad - Nursing Research / Pain Assessment Prof Michael Matthay - Acute Lung Injury Ms Sandra Mattheson - Credentialling Prof Sander Van Deventer - Inflammation / Cytokines Ms Kathleen Vollman - Prone Positioning in Acute Lung Injury

Contact : Festival City Conventions, PO Box 949, KENT TOWN, South Australia 5071

Ph: 08-8363-1307 Fax: 08-8363-1604


October 19th - 22nd 1998 : The American Dietetic Association Annual Meeting and Exhibition, Kansas City Convention Center, Kansas City, MO. Contact The American Dietetic Association, 216 West Jackson Boulevard, Chicago, IL 60606-6995.

Tel 312- 899-0040. Fax 312-899-0008.




23rd and 24th OCTOBER 1998

National Convention Centre : Canberra

To be held in conjunction with Australian Gastroenterology Week.

The international faculty will include

Professor W. Allan Walker : Professor of Nutrition, Harvard Medical School, Harvard School of Public Health

Professor Ken Kudsk : Professor of Surgery at the University of Tennessee and current President of the American Society for Parenteral and Enteral Nutrition.

Features of this meeting will include :

The impact of nutrients and growth factors on gastrointestinal development and function.

The role of enteral and parenteral nutrition after severe trauma and surgery

For more information contact :

Dr Julie Bines Ph : +61-3-9345-5060

Fax +61-3-9345-6240


Dr Margaret Allman : Ph : +61-2-9351-3758

Fax +61-2-9351-6022

October 31st - November 3rd 1998 : Growth Factors and Nutrients in Intestinal Health and Disease. International GUT Symposium, Osaka, Japan. Contact : Dr Kinya Sando, Dept of Paediatric Surgery, Osaka University Medical School, 2-2 Yamadaoka , Sui ta, Osaka, 656, Japan.

Ph 81-06-8793-753 Fax 81-06-7893-759


Presenter : Dr Paul Woods

Panel : Drs Furst, Russell, Zaloga and Zlotkin


There is nothing like hands on experience to stimulate thought and gain the skills to care for a long term home parenteral nutrition patient. In the literature we read predominantly about scientific studies and hopefully adapt our practice to fall into line with their conclusions. However the style and content of the scientific literature necessarily excludes the day to day detail on either the TPN patients' management or the patients' feelings about the process. At the 1997 Conference Dr Paul Woods, PW, presented two very frank and full accounts of what was involved with the support for ten years of a home TPN patient. His accounts provided cameos of what has happened over this significant period of time in TPN's history and in addition provided the all important physician's and patient's perceptions of what was happening to their knowledge and understanding of 'Home TPN'. This article is based on the full transcript of the tape of the first case in the session and I have edited it as little as possible so that the reader can sense the atmosphere of the session as Dr Woods presented the case to a panel who had no fore-knowledge of the details or final outcome of the case. This is an account of Home TPN in the real world and the responses of experts to the dilemas as the case was unfolded before them.



PW: This is a case involving a 57 year old lady with Non Hodgkins Lymphoma the major feature of which was involvement of the small bowel. As a consequence in 1987 she had a resection of the upper small bowel mesentery, which led to extensive ischaemic injury to the small bowel and infarction, which had to be resected and a jejuno colono anastomosis formed. She was in hospital for about six months during which time her nutrition was intermittent and difficult. I think there is a general reluctance to provide nutritional support to this category of patient who have extensive malignancy and are generally not responding well to treatment. As a result her nutritional support was started a little late in the process. She was normally a seventy kilogram woman but she eventually settled at a weight between fortyfive and fiftyfive kilograms at the end of her initial hospital stay

The main features of her condition when we were initially asked to take her on for nutritional support were hypoproteinaemia and ankle oedema. Biochemically the main feature was a low albumin and this slowly responded to treatment. Once she had a Hickman Catheter inserted she commenced daily TPN eventually being discharged home on TPN five nights a week. I will come back to the reason why she was not on daily TPN; she was certainly still able to eat but this caused a certain amount of diarrhoea. She was pretty stable for a relatively long period of time but for social reasons wished to reduce the TPN to the absolute minimum and after several months we reduced her to four nights per week and she maintained a weight of fiftyfive to fiftyseven kilograms which she was reasonably happy with.

During the early part of her care at home there were a number of irritating complications which everybody runs into from time to time.The Hickman Catheter extruded and had to be replaced. She had a period of lymphadenopathy and bacteraemia which was worrying because it raised the possibility of recurrence of the lymphoma. She had a subclavian vein thrombosis and had to have the Hickman removed again and at this stage we convinced her, in spite of her needle phobia, to have an Infusa Port which might allow her a more normal lifestyle. At this stage TPN was reduced to three days per week, her weight having been stable and all other nutritional parameters that were being measured at the time showing very little change.

PANEL : Venous access post thrombosis is always a difficult management problem particularly when you are presented with a situation of SVC thrombosis. We recently had a case of SVC thrombosis in a patient withHickman Catheter which we stented with a metal stent and then reaccessed the SVC that way. Once you have lost your SVC things become very difficult. I have another patient with SVC thrombosis on whom we had to do a thoracotomy to insert a right atrial Hickman. We have now successfully stented two patients with the short 2.5 cm metal wall stents. We have inserted IVC Hickmans into patients with SVC thrombosis but experience with those has not been good and we now have a boy who has been on TPN for thirteen years who has both SVC and IVC thomboses.

Question from the Audience : Do you ever use thrombolysis to try and clear veins ?

PANEL : We have used urokinase and streptokinase but in my experience SVC thrombosis is associated with the situation where the tip of the catheter has extruded up into the innominate vein and it is out of the SVC. That is the usual reason why they thrombose or alternatively it is related to bacterial infection. Essentially once you have thrombosis then you have got to take the catheter out. We recently had a patient referred to us from Brisbane who had a subclavian thrombosis and they had a right femoral A-V fistula inserted. The patient did not like this particularly because she had to needle the groin to give herself Home TPN. However, the radiologists, through a collateral, were able to railroad a guide wire into the SVC and right atrium to insert a Hickman. So just because they have got a subclavian thrombosis does not exclude access to the SVC.

Question from the Audience : Do you use prophylactic anticoagulation for Home TPN patients who have not had a thrombotic episode

PANEL : No I do not, but one of the patients I referred to earlier, the one with the SVC and IVC thrombosis, actually has Antithrombin III supplements prescribed twice weekly for the past five years. In general terms we do not give long term anticoagulants and long term Heparin has a major association with the development of osteoporosis. Whether the low molecular weight Heparin taken long term causes osteoporosis, well the data is not yet in. Most of these patients cannot take Warfarin. They cannot absorb it in a reliable fashion. So patients who have underlying hypercoagulability and whom you want to anticoagulate on Home TPN are a real problem. Nevertheless we try and avoid long term Heparin even if it is the 'sub-cut' fragments preparation.

Question : PW : Do you use low dose Warfarin

PANEL : In the patient I have on Home TPN, Warfarin absorption is so variable that I have not used it. The patient's INR can go all over the place, you have got changes in bowel transit time, you have got alterations in bacterial flora and endogenous Vitamin K production. I think it is really risky.

PANEL : We would probably not agree with that. In any patient who has thrombosis we would anticoagulate. The patient in this case presentation is probably not going to be a problem. This patient has reasonable gut function because she is must be maintaining her gut cells if she is down to four days of TPN. We have a lady with only 60cm of gut but we treat her with oral drugs. For example her Thyroxine dose is 1mg. This is very high by normal standards but she is able to absorb sufficient of that. You would put these patients on a combination of Aspirin with some Warfarin and just monitor them periodically. You know the INR is not like a value or that you have to keep way way down. The moment you put a patient's coagulation time up you have already dropped the coagulation factors by 70 - 80%. In fact with Heparin you can get an anticoagulant effect without the laboratory ever being able to detect an anticoagulant effect and that is because you drop the coagulation factors down. I do not know what this patient's total life expectancy is but if this was somebody who you feel is going to get into trouble again, and they all do, then you do everything possible to protect those veins so I would try anticoagulation. I would do it gently but I certainly would do it

Actually some of these people you can recannulate after a year or so. We had a lady who clotted off her right side and we went down to her femoral and interestingly enough, a year or so later when that clotted we went back and did an angiogram and the previously thrombosed

vesssel had reopened backup. And I agree, as has just been said, the radiologists can find some vessel to cannulate and throw up a wire there and do sometimes some very creative things.

My other comment on her would have been to try and manipulate her nutrition so that she got some gut hypertrophy. We have been using the same protocol as Doug Willmore which involves treatment with growth hormone and high dose glutamine. I do not know if it really causes hypertrophy or not, but a lot of our patients that were on Home TPN for seven days a week, are now down to one day or two days per week with this regimen. Whether they would achieved that anyway, it is hard to tell, but certainly I think that some of these people you can actually get down to minimal days on TPN. And what is interesting, once you get them down to one or two days per week, you are tempted to think that the patients no longer need it. But the moment you remove those two days per week, then the patients start losing weight. So it is clear that you can get them down to low levels, but sometimes you cannot remove all of it, they need that little amount of TPN to maintain balance.

PANEL: Just a quick comment. In paediatrics we do have some of our patients on long term TPN. For us, perhaps two years is long term, so if we do have children with thrombosis, we do use low molecular weight heparin. We routinely do bone densitometry on an annual basis, but because our long term is shorter than your long term, we are willing to put up with it in children.

PANEL: Do you have any data on low molecular weight Heparin and osteoporosis? Unfractionated Heparin long term seems to cause osteoporosis.

PANEL: I am not aware of any data.

PANEL: I do not think there is any data. The point is if you are worried about it you do densitometry. And in this patient I would not be particularly worried about it. If you have a patient who does not have a very long term outlook, then I would not be particularly worried about it. I think her more life threatening event would be the clotting off of her veins and not having nutritional access then that would become a higher risk than would osteoporosis. But with densitometry, you can just follow this until it were rapidly deteriorating. You could put her on extra capsules of supplements and some of the other things - even Calcitonin if you were wanting to try to maintain bone status.

PW: She did in fact get a brief period of anticoagulation, had a new line in and only had one more thrombotic episode in the next eight years, and on that ocassion the line had to be replaced. So in fact so she did very well in spite of our apprehension and concern about future access.

Now I will go on to summarise some of the major problems over the next four or five years. There were recurrent episodes of erosive gastritis with GI bleeding, which was quite profuse on one or two occasions leading to urgent admission and the need for transfusion. She had problems with fluid overload and presented in congested cardiac failure on a couple of occasions and needed to have her fluids adjusted accordingly. She certainly noticed on the TPN regime that she was on - and this may not be a problem in Toronto - but certainly over here in the summer, we needed to give her an extra litre of saline in addition to her TPN to keep her hydration up because of the heat.

She also developed 'biochemical' carnitine deficiency. We checked her minor trace elements from time to time along with a number of other parameters and she turned up with quite a profound carnitine deficiency on serum levels. Her levels were about 16 with our reference range being about 30 - 50. We had to go to some lengths to get approval to administer supplements of carnitine. Initially, this was done orally and after six months of oral therapy, the carnitine level had fallen by a further 3. So we then got Federal Dept. of Health approval to supplement the TPN with intravenous carnitine and within three months it was well up into the normal range. I would be quite interested in the Panel's opinion whether her episodes of cardiac failure and general malaise and feeling of weakness may have been due to carnitine deficiency. I guess it is a complex problem and it is pretty hard to isolate one factor, but how relevant does the Panel consider this fairly profound loss of serum carnitine?

PANEL: People debate whether carnitine is an essential in home TPN. I think there have been a couple of reports that one in JPEN of the Test cricketer who was on home TPN in Adelaide who developed carnitine deficiency. My understanding is that they get markedly abnormal liver functions, fatty liver, fatty deposits in muscle. We had one case which we thought might have carnitine deficiency and we imported, I think from Japan, intravenous carnitine. But even in the case report in JPEN, I am not convinced that the alteration in hepatic function and fatty liver was all due to carnitine deficiency. That patient was very septic, glucose intolerant and there were a lot of other candidate causes. So I, personally, have never supplemented carnitine specifically in home TPN. I would be interested to know what the other members of the panel think.

PANEL: I think that the message should not be here that we go back and suggest that carnitine should be measured in every patient. I think that carnitine deficiency is extremely rare and I might even argue that a definition of carnitine deficiency simply based on low plasma levels may not be particularly meaningful. You did say that the patient had other symptoms which may or may not have been due to carnitine deficiency. Did the symptoms change when she received adequate carnitine?

PW: Very difficult to say.

PANEL: Did she have abnormal liver function, fatty infiltration?

PW: She had abnormal liver function right from the outset as soon as TPN was commenced - nothing unexpected and comparable to what we see with all patients that we have on TPN.

PANEL: All these patients will have a bit of cholestasis in the liver. They get bacterial over growth in their small bowel, because they have a short gut and they have lost the ileocaecal valve, so they go on to get endotoxaemia in the portal vein and they will have slightly abnormal LFT's. But to say that they have carnitine deficiency is a different thing. You have got to do a muscle biopsy, is my understanding, and show the histological changes of the fat within the muscle cells.

PANEL: Yes I agree. I think the message has to be that it is very rare and probably need not be added to TPN, and probably should never be measured unless you specifically think you need to measure it.

PW: I think you will see from the next slide that there are certain characteristic features about this patient that were at this stage making us fish for something to treat, and I guess the concern in retrospect is the temptation to treat serum levels, as you suggest, rather than treat a disease process.

PANEL: May I ask you, were the short chain and long chain acid carnitines measured in this patient?

PW: No.

PANEL: I very much agree with the others on the Panel - carnitine deficiency is really so rare in TPN patients compared to what we see in other groups of patients, like say in chronic uraemics. Even in those patients there is good compensation by conjugated carnitines and the total carnitine is usually approaching normal levels. So it would be very interesting in such situations of long term TPN to measure the whole carnitine pattern, not only the free carnitine.

PW: Well another episode which was a little interlude that she could have done without was the concern of recurrence of lymphoma with abdominal pain and the possibiliy of lymphadenopathy. She had a short course of chemotherapy without a tissue diagnosis, and that knocked her back for a short while, but she certainly seemed to improve after that. Then we had the last episode of thrombosis of the Infusaport which was then changed and new one survived I think for the rest of her days.

I have alluded to some of the factors which contributed to this lady's problems and some of these are quite understandable. She was a very introspective personality. She expressed great fear both of her disease and of its treatment. Throughout her period of time in hospital and on TPN, she never really came to accept that she had a disease that was not necessarily curable or a loss of bowel that was so great that she would never be able to come off TPN completely. I think that these feelings aggravated the problems and contributed to a lifestyle that was governed by the episodes of diarrhoea that she had. She would eat as much as possible to avoid being on more TPN than necessary. At the same time the amount she could eat was limited by the number of diarrhoeal stools. She seemed to settle out at about seven stools a day, but her life, certainly during the first three or four years, was governed by "was there a toilet nearby". Naturally she was very embarrassed about all of this, so really it was a major impact on her well-being, and her day to day life.

The other thing that I found very difficult as her physician was that every time she saw other health professionals, and there were many to see because of her involvement with the gastroenterologists, the surgeons and other specialists, was that if they could not explain what was wrong with her, then they always blamed the TPN. And I am sure you have all experienced the reasoning - this solution is going in every night, and that has got to be responsible for some of the symptoms !

About this time we were blessed with a visit from a specialist from the USA who reviewed the case with us and gave us a number of suggestions which included intravenous glutamine supplementation. We were able to administer glutamine intravenously for a relatively short period of time before it was removed from our formulary. We increased the sodium content of the TPN, in spite of normal serum levels and we also increased zinc and biotin.

We also dealt with another curious problem which she seemed to have. She noticed after the TPN session that she would get a sort of hangover effect and that on some days she would also get terrible cramps particularly in the feet. Eventually she realised that the days she got cramps were the days that she did not have fat in her TPN, and the days when she got the hangover were the days when she did get the fat in her TPN. So in the end, we had to put it to her as a choice, and she chose to have hangovers and no cramps so in fact we went along with giving fat during every TPN session. Is this a common symptom and problem?

PANEL: Did you measure her blood sugars when she came off TPN?

PW: We brought her in a couple of times and did studies throughout the twentyfour hour period looking at exactly those types of problems, and we never once found any great fluctuation in any of these things.

PANEL: The only thing I can suggest is to tell your patient to slow the infusion rate down for the last two hours. The obvious question is - Is she is having symptoms of some type of reactive hypoglycaemia ?

PW: We certainly suspected that.

PANEL: Did you measure her arterial blood gases and assess her acid basis status?

PW: Acid basis status whenever measured was normal except during one or two episodes of congestive failure and when she was admitted more acutely unwell with fever and sepsis.

PANEL: I ask the question because we had a couple of children with bacterial overgrowth who developed lactic acidosis, and the children appeared to be drunk. I do not know if they have hangovers, but in their acidosis state they are wobbly and acidotic.

Comment from the Audience: I have also had experience of home TPN patients who have had cramps, and I actually have one patient who swears by Vitamin E. Now she takes lots of Vitamin supplementation and she finds this helps a lot with her cramps. Her serum Vitamin E is normal. We have done nerve conduction studies and all sorts of investigations on this child without finding any explanations for her cramps. She is still on oral Vitamin E supplements and she swears by them for relieving her cramps.

PW: I thought I would show you this table of data at this stage just to show a fairly typical TPN formulation and programme that she was receiving. We had, in fact, been persuaded by the patient to cut her down to two days a week and she would have gone further if possible, but exactly as the Panel suggested earlier on, the moment we got down below two nights a week her weight started to drop off rapidly. She seemed to settle around about fifty kilosgrams. If she got sick or if we reduced the TPN any further, she dropped to fortyfive kilograms, started to feel very unwell and looked terrible.

PANEL: Paul, did you make some assessment of her zinc status? I know you said that on advice from your US visitor you increased her zinc prescription. Some of these patients actually require even more than that particularly those with such extensive small bowel resection. If you look at Steve Waldron's study published in the American Journal of Clinical Nutrition, some of these patients can need fifteen to twenty milligrams per day. Did you measure her serum and urinary zinc status?

PW: We did not and I suppose being the only home TPN patient we have ever had, we still feel fairly much a novice at this, and we have learnt a few things from that. Now I would look a lot more carefully at clearance of some of these elements rather than just their serum levels in the future.

PANEL: This is the sort of patient that I would give 10 milligrams of zinc a day. I do not know what the others think about that, but in Waldron's paper they did a statistical regression analysis, and calculated a formula which said that basically you multiply the ostomy output by about fifteen milligrams per litre of output whether it be fistular or diarrheal losses. Steve Waldron did all those balance studies and we now just use those formulae to calculate how much the daily requirement is rather than measure it. I do not know if others on the Panel would like to comment on that ?

PANEL: Actually, I think that is quite a reasonable comment. It is hard to overdose on zinc, so probably if you are not sure, it is better to give more rather than little. I was going to ask you why the biotin supplements were suggested ?

PW: That is a difficult question to answer. Biotin is not something we could measure at our hospital. We could not measure the levels or monitor it in any way. I think it was suggested because of its role as a cofactor and with possible increased zinc supplementation, this was something else which might well be deficient.

PANEL: I ask the question because we actually did this for probably the first and only patient who had biotin deficiency; they have a very distinctive rash.

PANEL: Why was the increased sodium suggested?

PW: I think for perhaps the same reasons as one of the other Panel members has alluded to in relation to zinc. Perhaps that although the serum level appeared to be satisfactorily maintained, the body pool might still be reduced, and she might be better off with a higher intake of salt. This was certainly neccessary during the hot weather period of the year, but I do not think there was any great science behind it.

Comment from the Audience: This woman is on two days per week TPN and presumably was getting very little in the way of oral enteral energy or nutrient intake during the week. Would the Panel like to comment on the implications for substrate utilisation of having only twelve hours twice a week of lots of calories and lots of other nutrients and then almost none on the other days. What are the consequences of this 'feast then famine' sort of regimen ?

PANEL: Well although twelve hours of TPN twice a week is not a lot it appeared to be adequate in this patient because she was maintaining her weight. That means that she must have been absorbing a reasonable amount of the other material. I have got three patients like this who are on one or two days of TPN and they are eating 3500 Calories as well. The problem is that you are not quite sure how much they are absorbing. Obviously they are not absorbing all of that because their weight stays down low. We just monitor weight closely and periodically we will do a nutritional profile, which includes some of the micronutrients. We probably do this every six months or once a year if they are doing well. And as long as they are maintaining their weight and they feel well, we just leave them like that. But it is astonishing to see that if you remove that one day of TPN then their weight starts dropping. So what happens is that they are probably just maintaining their balance by maintaining their oral intake but they cannot do without that extra TPN. We have had some of them record everything they ate, and then we ran the data through a computer program, which calculated out all the essential requirements. It turns out that they are eating quite a lot, and they are probably absorbing a reasonable amount of it.

Comment from the Audience: I suppose my question is - Is it more efficient, given a set number of Calories, to give those at one point in time or is it more efficient to have them divided into a number of times, or does it not matter?

PANEL: I think it is more efficient to have it divided. It depends on which way you want to look at it. If you look at a protein synthesis and this is the main interest of weight lifters and other people, then it is the nutrient profile that the cells are being exposed to which is the main consideration. Now if there is also a big rise and a fast drop in available nutrients to the cell then it is not as efficient as if the rise is up and stays up over a more prolonged period of time. Now when you eat enterally, your body does just that, you absorb over a longish period of time. But even when you give TPN, you are giving that over a reasonable period of time; it is not like you are running that in over an hour, and then the patient gets nothing for twenty three hours. So I would say that actually the patient here is probably getting exposed, not to an acute period, but actually getting exposed to the nutrient profile over a significantly long period of time. And then it is probably good to be in a fasting period for some of that time to allow the receptors to upgrade before more nutrients are given.

PANEL: Zinc is an important example of two factors which may be prerequisites for proper substrate utilisation. One is the bioavailability of nutrients and from this clinical history we can be quite sure that this she did pretty well at utilising what was infused or orally administered. The second factor and one which is very important is the intracellular energy status. It is possible that these patients can have essentially a decreased energy status because of low intracellular energy stores. This could arise, for example, if the substrates are very rapidly infused and so I agree that you should give time for the body to utilise the substrate. We have assessed intracellular energy status by measuring adenines and creatine phosphates etc. in both muscle and liver. The results would indicate that it is possible for this kind of patient to have a decrease of up to 20-30% in intracellular energy reserves and this situation could become a limiting factor in substrate utilisation.

PANEL: I would like to add another comment : one of the issues in this patient that concerns me is not only nutrition but also hydration. These patients are prone to a phenomenon called oxalosis. They have still got a colon and one of the things that these people can get is recurrent kidney stones or a glomerulo nephritis with a crystalline oxalosis and we have had two patients die in renal failure with this syndrome. What I would be doing in this case is measuring the patient's 24 hour urinary oxalate excretion firstly because that may have some dietary implications as to which foods to avoid. And secondly it is very important on days when she is not on TPN and particularly during periods of hot weather that she is not concentrating her urine predisposing to a glomerulo nephritis. These people can die of renal failure so I would take that into the equation and then maybe select another night of the week where I would have just given her hydration and checked her electrolytes. So just in the back of my mind in this case I am worried about hydration and I think a lot of people forget to monitor hydration in these people. I would like to know what the others think about this.

PANEL: Actually hydration is a common problem with the long term TPN patients that we have had that. What we do is use hydration formulas and we use Gatorade but they can get sick of the Gatorade after a while ! Anyway you really just want to supply the fluid, electrolytes well I am not so sure about them. Often they can maintain those but you just want them to be able to absorb some volume. Of couse if you put too much electrolytes and too much glucose into their oral rehydration fluids then you run the risk that they will get diarrhoea.

PANEL: I believe Gatorade HIgh Performance has seventeen millimoles sodium per litre, which may not be enough - we try and give them fluids with at least thirty to forty millimoles. Something like Gastrolyte or Repalyte and even those can fall short of what you want to supply because if you look at the WHO recommendations for rehydration of high risk individuals then they are recommending sixty to ninety millimoles. This is probably equivalent to Gatorade plus a teaspoonful of salt !

PANEL: The problem is that they will not drink salt water !

PW: In spite of the story that has unfolded she had quite prolonged periods of being well but remaining introspective. And then one day she turned up almost in a wheelchair and there was a dramatic change in her appearance. She looked hunched over, she was in pain and she had developed severe pain particularly in the hips and also in spots in the ribs and so on. Obviously this raised the possibility of recurrence of lymphoma. We decided in fact that she was suffering from some form of metabolic bone disease and we referred her to the Endocrinologists who did a complete evaluation of her bone status and decided that she did in fact have a form of metabolic bone disease which was not typically osteoporosis or osteomalacia. Their recommendation was a course of treatment with calcium, vitamin D and oestrogen principally on the basis of her biochemical results. She had a very rapid and good biochemical improvement with almost no symptomatic improvement in the early stages. Nevertheless we continued therapy over several months and she did in fact improve clinically to the point where she was again fully mobile and seemed to return to a period of reasonable health which, apart from minor problems and the appearance of increasing ecchymoses over the skin, lasted for a period of two to three years.

Over the last year of her life she became repeatedly and increasingly admitted to hospital with malaise, fatigue, and eventually a recurrence of bone pain. Several of these episodes of unwellness were associated with a rise in creatinine and as the Panel may have predicted, she progressed terminally to multi organ failure of which renal failure was a principal feature although there were a number of other things going on including this vasculitic rash. This rash was extremely prominant and was biposied to show a rather non-specific inflammation of a vasculitic type. She died earlier this year in multi-organ failure and again I would be interested in the Panel following up some of their comments made earlier as to which were the most relevant to this patient's clinical course.

PANEL : Well the other thing I can think of with this patient's demise is sepsis originating from the central line in. Very sub-acute sepsis can present like this so presumeably you did a lot of blood cultures and white cell counts etc. and made quite sure she did not have sepsis originating from the central line ? Did you echo the line ?

PW: Yes, we echoed her heart and saw the line as well and saw nothing abnormal.

PANEL: Tricuspid valve was alright ?

PW: She had trivial mitral incompetance but nothing else.

PANEL: White cell count - did she have a septic clinical picture ?

PW: There were a number of occasions when she had fevers and raised white cell counts. Repeated evaluations and courses of antibiotics did not really support the idea that ongoing sepsis was a cause.

PANEL: I would probably have pulled the line out. It is a dilema - even though you try hard to document sepsis on the line first - you look for a clot, - you look for tricuspid valve regurgitation, you do all the right things but even so I would probably have pulled the line out.

Whether she got oxalosis in her kidney I do not know. Did you ever measure her 24 hour urinary oxalate excretion ? She could have had oxalosis of the kidney and sepsis would have been be the other thing.

And I suppose another cause could be ectopic PTH and hypercalcaemia. This can present very much like this particularly in patients with lymphoma they can get ectopic PTH secretion - it is one of the classical presentations of ectopic PTH. Were you able to document whether or not she had recurrent disease and hypercalcaemia at this stage ?

PW: We always wondered but unfortunately we did not get consent for an autopsy so we do not know.

PANEL: Particularly when supplementing with calcium and vitamin D together you have just got to monitor their calcium levels to make sure they are not going too high.

PANEL: With regard to the vitamin D and the calcium Jeejeebhoy's group probably did the initial work which suggested that the bone pain could be related to excessive vitamin D in the TPN. In a normal indivdual the role of the vitamin D is to promote the absorption of oral or enteral calcium. However, if you happen to be someone who is not taking anything by mouth and you give reasonable doses of vitamin D then Jeejeebhoy's suggestion was that the calcium would be leached out of the bone. These patients would have fractures as these patients did, they would have bone pain, they would have hypercalcaemia and hypercalciuria. We do annual bone densitometry on our patients and we do in fact see bones that are somewhat osteopaenic. We are only measuring urinary calcium excretion while they are on parenteral nutrition, that is during on the twelve hour TPN period, and we observe that they have extreme hypercalciuria. But during the twelve hours when they are off TPN they no longer have the hypercalciuria. So I am not sure that this issue is settled - should we or should we not give vitamin D with parenteral nutrition if the patient is NPO ? I would like to know what the other people think.

PW: Well we certainly remove it whenever anybody goes into renal failure.

PANEL: You need vitamin D to also mineralise your bone so it has two effects. Too high a concentration will activate the osteoclasts and these will start demineralising bone. But not enough vitamin D will create just as much of a problem. Osteomalacia obviously is a vitamin D deficiency problem and if you do a bone biopsy you are meant to be able to pick that up. Or you can use the bone labelling technique and repeat bone biopsies to make sure of what you are dealing with. It becomes very difficult to know whether you should give vitamin D or not. Two things I would have done. First of all fluoride works great in these people. You do not have to give calcium and vitamin D and I would have worried about giving her oestrogens particularly chronically. What fluoride is going to do it is not make her bones any better but it will make them harder. Frequently the pain is relieved and the bone can be stronger but more brittle if that makes some sense. The other thing to do would be if you really thought she was mobilising bone then diphosphonates would probably be the agents of choice rather than using calcium and vitamin D.


I am often asked how and where can you access Medline on the Internet. There are a number of free links into Medline usually associated with another web page. is a commercial medical information site however visitors can use their direct link into Medline.

As an example I searched for Cholestasis on this link and amongst the several ‘finds’ this was probably the most interesting and relevant for the readership of this Newsletter :

Use of cholecystokinin to prevent the development of parenteral nutrition-associated cholestasis.

Teitelbaum DH; Han Markey T; Drongowski RA; Coran AG; Bayar B; Geiger JD; Uitvlugt N; Schork MA

Department of Surgery, University of Michigan Medical Center, Ann Arbor, USA.

JPEN , 1997 Mar, 21:2, 100-3 Abstract

BACKGROUND: Neonates are at high risk for the development of parenteral nutrition-associated cholestasis when receiving a prolonged course of total parenteral nutrition (TPN). Although this cholestasis is of unknown etiology, it may result from a lack of gastrointestinal hormone formation, including cholecystokinin, which normally occurs after enteral feedings.

METHODS: Two groups of neonates were studied. The treatment group consisted of 21 consecutive, prospectively enlisted neonates receiving TPN for > 14 days. The nontreatment group consisted of 21 infants from the 2 years preceding the study who were matched to the treatment group by gestational age, diagnosis, and duration of TPN. The major outcome determinant was direct bilirubin. Cholestasis was defined as a direct bilirubin > 2.0 mg/dL and was considered severe if the direct bilirubin was > 5.0 mg/dL after other causes were ruled out.

RESULTS: The mean direct bilirubin levels in the nontreated group progressively rose over time, whereas the mean direct bilirubin in the treated group remained level. The incidence of infants with a direct bilirubin > 2.0 mg/dL was 24% and 43% in the CCK+ and CCK- groups, respectively, and was not significant (p = .14). The percentage of infants with a direct bilirubin > 5.0 mg/dL was 9.5% and 38% in the treatment and nontreatment groups, respectively, and was significant, p = .015.

CONCLUSIONS: Levels of direct bilirubin were lower in the treated compared with the nontreated group. These findings suggest that cholecystokinin prophylaxis in high-risk neonates may help prevent the development of parenteral nutrition-associated cholestasis.


The views and opinions expressed in this Newsletter are not necessarily the views and opinions of the Australian Society of Parenteral and Enteral Nutrition. Reports and articles on techniques, procedures and products are provided for the information of the Members of the Society and their inclusion does not imply any endorsements from the Australian Society of Parenteral and Enteral Nutrition. No liability can or will be accepted by AuSPEN or its agents for the third party use of information in this Newsletter.

Dr Tom Hartley, Editor, 26/04/98.