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Published on 20 September 2010

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Parenteral nutrition in oncology

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Patients with cancer are at high risk of malnutrition, as a result of both their underlying condition and its treatment

Rebecca White
Nutrition Support Pharmacist
Oxford Radcliffe Hospitals NHS Trust

Unexplained weight loss is one of the most common presenting symptoms leading to further investigation and a diagnosis of cancer. Weight loss in cancer patients is a prognostic indicator of poor outcome and it can be due to reduced intake caused by physical symptoms such as obstruction or dysphagia or, in advanced cancer, due to cancer cachexia.
Cancer cachexia is more complex than simple anorexia and weight loss alone, and there are several contributing factors including a pro-inflammatory response which promotes weight loss and reduces responsiveness to nutritional support. General improvement in nutritional status can affect quality of life through influence on fatigue, activity levels, pain control and sense of well being. The impact of quality of life on a patient’s ability to tolerate both the physical and mental demands of medical treatment cannot be underestimated.
Early identification of patients who may benefit from nutritional intervention can be achieved through the effective use of screening tools.[1] Timely provision of oral nutritional supplements and the pro-active use of enteral tube feeding in high-risk patients is continuing to increase as available evidence indicates the specific patient groups that will benefit from such interventions.
Due in part to the cost and risk of complications, parenteral nutrition (PN) is now reserved for patients who cannot tolerate oral or enteral nutrition and for whom the benefits of nutrition support outweigh the burden of care and the potential risk of metabolic, vascular and septic complications.[1–3]
There are three predominant indications for short term use of PN in cancer patients: bowel obstruction secondary to solid tumours, and mucositis[4] and graft-versus-host-disease (GVHD) as a result of treatment strategies in haematological malignancies. Longer-term PN may be indicated in patients with severe radiation enteritis.[2]

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Bowel obstruction and peri-operative parenteral nutrition
Bowel obstruction is a common indication for PN, which is usually provided until an appropriate intervention such as stenting, resection or bypass can be undertaken. There is evidence that demonstrates reduction in post-operative complications if nutrition support is provided prior to surgery in malnourished patients.[5]
A full medical and nutrition history must be undertaken prior to initiating parenteral nutrition. This patient group is at particular risk of re-feeding syndrome if the PN prescription is excessive (See Box 1). These patients are likely to have had minimal nutritional intake prior to presentation and a significant history of weight loss. NICE, ASPEN and ESPEN all make specific recommendations on the initiation of parenteral nutrition in these high risk patients.[1,2,5] PN should be delivered by the most appropriate venous access route. If short-term PN is required to optimise the patient prior to surgery then the peripheral route may be appropriate.
Enteral feeding tube placement during surgery will speed the transition to enteral feeding in the postoperative period – this is now considered routine practice in surgery for head and neck, and upper gastrointestinal tumours.

Complications of treatment of haematological malignancies
Bone marrow transplantation (BMT) consists of a conditioning regimen of high-dose chemoradiotherapy followed by intravenous infusion of haemopoietic stem cells, aimed at re-establishing normal bone marrow function. Irrespective of the type of BMT the conditioning regimen administered pre-transplant has a deleterious effect on the rapidly replicating cells of the GI tract.
Mucositis is caused by the effect of chemotherapy on the rapidly replicating cells of the GI tract. Over 40% of patients receiving chemotherapy will suffer from some degree of mucositis, but those receiving bone marrow or stem cell transplants or those undergoing radiotherapy are even more likely. Although the increased use of growth factors has reduced the duration of neutropenic mucositis, some patients require artificial nutrition support to maintain them during this period.
Mucositis causes pain and significantly reduced oral intake. Enteral feeding tubes have been placed safely in patients with grade 2 mucositis but when mucositis is severe and enteral access cannot be achieved safely, the use of PN is appropriate. As for all patients a full nutritional and medical history should be undertaken prior to initiating PN. In general, patients are well nourished at the time of BMT.
A complication of the BMT itself that has nutritional consequences is GVHD. GVHD is caused by the donor T-lymphocytes attacking the host cells, which predominantly affects the skin, liver and GI tract. Improved immunosuppressive regimens post-transplant have reduced the incidence of GVHD, however if GVHD develops, artificial nutrition support is required to maintain the patient through what can be a protracted period of reduced nutrient intake and absorption.
PN is indicated if nutritional intake cannot be maintained orally for a reasonable period of time (seven days recommended by ASPEN) and if diarrhoea is excessive, resulting in fluid and electrolyte imbalances. Managing PN in these patients can be difficult due to the fluid shifts and electrolyte imbalances caused by the diarrhoea and the complications and consequences of the drug therapy used to treat the GVHD.

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PN composition
Evidence is inconsistent on the impact of malignancy on energy requirements, and therefore nutritional requirements should be calculated using standard predictive equations. Once initiated, the patient should be monitored closely for tolerance and adequacy of nutrition support. For short-term peri-operative PN (1–2 weeks) a standard regimen composition is reasonable.
Most clinical guidelines recommend initiating PN at 50% of requirements and titrating to target rate over 48–72 hours, thus minimising the effect of re-feeding.
In any patient on PN, excessive glucose provision can lead to fluid and sodium retention due to the anti-diuretic action of insulin and in oncology patients this can compound the fluid retention already experienced by patients on high-dose steroids. Glucose oxidation rate can be calculated and should not be exceeded. Usually 50–70% of energy requirements are provided as glucose.
There is increasing evidence that cancer patients, particularly those with cachexia, tolerate higher levels of lipid provision due to an increase in lipid oxidation rate. However, due to concerns about the consequences of long-term excessive lipid provision it is recommended that a 1:1 ratio of glucose to lipid be used. There is some evidence that a higher ratio of lipid to glucose may be beneficial in the resolution of GVHD, however further work is required in this area.
Sufficient amino acids should be provided to meet requirements. ESPEN guidelines recommend a minimum of 1g/kg/day. There is an increasing body of evidence that glutamine supplementation of PN may be beneficial in patients with haematological malignancy; however an optimal dose has yet to be determined.

Impact of concurrent drug therapy on PN composition
Patients undergoing treatment for haematological malignancies can be on a considerable array of therapeutic and prophylactic drug therapy which can all impact on the PN prescription.
Prophylaxis against infection in neutropenia will usually involve antibacterial, antiviral and possibly antifungal therapy. Not only do these contribute to the fluid volume infused on a daily basis but also on electrolyte provision.
Treatment of GVHD will usually include high-dose steroid therapy, ciclosporin, interleukin-II receptor antibodies and other immunosuppressant therapy.

Minimising complications of PN therapy
Many patients within this group will have existing venous access in place as a result of ongoing chemotherapy regimens. Decisions to use any existing vascular access device should be taken on a case-by-case basis; device colonisation should be excluded before use for PN. Consideration should be given to all the other therapy that may need to be administered and a regimen developed to allow the safe administration of all therapy including the PN; additional vascular access devices or additional lumens may be required to achieve this. The pharmacist has a key role in advising on compatibility, infusion volumes and timing.
As with all patients, a strict adherence to protocols for connection and disconnection of the PN is essential in minimising the risk of developing catheter-related sepsis. This is a particular concern in neutropenic patients, where identification of the source of sepsis can be particularly difficult. Close monitoring of fluid balance is essential as fluid retention can result in complications if not identified and managed promptly.
Monitoring of clinical chemistry on a daily basis is usually required in these patients to ensure that any deficiencies are corrected promptly. Communication between the nutrition support team should include the limitations of PN as a means of correcting acutely depleted electrolytes, particularly magnesium.

The role of the pharmacist
The pharmacist plays a significant role not only in the determination of PN composition but also in the optimisation of all drug therapy. His/her knowledge of drug-related side effects, infusion composition and therapeutics makes his/her input into the care of these patients essential. He/she is a key member of both the nutrition support team and the ward-based clinical team.

Summary
Patients with cancer are at high risk of malnutrition, as a result of both their underlying condition and its treatment. Early identification and optimisation of nutritional intake can minimise complications and the need for PN. However, concerns regarding the cost and complications of PN should not preclude its use in those patients who will benefit. The involvement of the multidisciplinary nutrition team will minimise the risk of complications associated with this complex therapy.

References
1. DA Allen et al. JPEN J Parenter Enteral Nutr 2009 33(5):472–500.
2. F Bozzetti et al. Clinical Nutrition 2009 28:445–454.
3. J Arends et al. GMS Ger Med Sci 2009 7:Doc09.
4. P Niscola et al. Haematologica 2007 92(2):222–231.
5. National Collaborating Centre for Acute Care, February 2006. Nutrition support in adults Oral nutrition support, enteral tube feeding and parenteral nutrition. National Collaborating Centre for Acute Care, London.



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