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Adult TPN – Industrial multichamber bags vs pharmacy bespoke bags

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If used correctly multichamber bags are suitable for the majority of patients but unfortunately they are not always used appropriately. This may be because their apparent simplicity may mislead prescribers into assuming their use requires limited consideration

Peter Austin
MRPharmS(IPresc),
DipClinPharm, MSc(PTQA)
Senior Pharmacist
Nutrition Support Team
Southampton University
Hospitals NHS Trust
United Kingdom

Patients who require intravenous feeding usually have a need for a complete range of nutrients (Box 1) with three main options for their practical provision. Firstly bags can be compounded from individual components (bespoke regimens), secondly pre-compounded bags can be purchased with subsequent additions made before administration (tailored regimens) or thirdly pre-compounded bags can be purchased and used without further additions (standard regimens).

More traditionally pre-compounded bags can be aseptically prepared from individual components in an appropriate aseptic facility. However, multichamber bags are a rapidly growing alternative. These are industrially manufactured and terminally sterilised bags with two or three individual chambers filled with both amino acids and glucose (‘dual chamber’ bags) or with amino acids, glucose and lipid (‘triple chamber’ bags). When required, these are rolled up mixing the individual chambers and effectively making a macronutrient regimen without the need to aseptically combine the individual macronutrients. This eliminates the need to compound macronutrient regimens locally and at the same time avoids the cost of purchasing a bespoke or aseptically prepared pre-compounded regimen.

With the growing availability and clinical use of multichamber bags, particularly triple chamber bags, in order to ensure best practice it is important to be aware of the issues surrounding their use along with their advantages and disadvantages compared with bespoke regimens.

Discussion
All aseptic manipulations must be carried out with the greatest care and certain products, specifically cytotoxics and intravenous feeds, should always be manipulated within dedicated aseptic facilities.[1] This is to limit the risk of errors, limit the risk of administering a contaminated product and, in the case of cytotoxics,limit the exposure risk to staff.

Aseptic manipulations to intravenous feeds in clinical areas are sometimes suggested to be safe[2] but this cannot be justified.[3] The risks of both errors and contamination are simply too high with administration of contaminated intravenous feeds making patients very sick as well as being directly responsible for deaths.[4]

Dedicated aseptic facilities require significant resources to operate to adequate standards[5],[6] and to deal with continuously increasing workloads. Multichamber bags therefore offer two obvious advantages: an attractive price compared to bespoke regimens and a more limited requirement for local aseptic facilities and manipulations. In addition, unrolled multichamber bags offer a prolonged shelf life at room temperature. This means that refrigerator space is not required for their routine storage and furthermore a selection of bags can be kept with limited risk of expiry and resulting wastage. Another benefit is the wide variety of commercially available bags making it simple to stock a range suitable for the majority of anticipated patients.

However, whilst multichamber bags clearly have advantages, the complete picture is not so simple and unfortunately their apparent convenience and simplicity are often deceptive.

The most obvious disadvantages are the often limited electrolyte content and the lack of any micronutrients.

Whilst some patients will have limited, or even zero electrolyte requirements, the majority will have typical needs above that inherent in the majority of multichamber bags. This is because the electrolyte content of multichamber bags tends to come from the amino acid source incorporated into the bag rather than from a consideration of typical patient requirements (Box 2). Therefore whilst some patients’ electrolyte requirements can be met with the inherent bag content it is likely that in the majority of cases aseptic electrolyte additions will be required to limit the potential for the commonly recognised complications of deranged blood electrolyte levels.

The National UK adult nutrition support guidelines from the National Institute for Clinical Excellence (NICE)[7] require full individual patient electrolyte requirements to be provided from the outset of feeding. Some try to argue that incorporating these (when required) into the feed is unnecessary, especially on intensive care wards, because separate electrolyte infusions can simply be given as an alternative. Whilst this may be appropriate in individual cases, there are several potential problems with this approach.

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Firstly, even if required they might not be given separately for any of a variety of reasons (Box 3). Secondly, the intravenous administration of electrolytes often requires a significant fluid load especially outside of high- or intensive-care wards. In some patients, fluid overloading leading to oedema has been shown to cause delayed recovery of gut function and impaired wound healing.[8],[9] This is likely to increase the required duration of intravenous feeding as well as increasing other costs. Thirdly, the more infusions a patient receives the greater the risk of costly catheter related sepsis.[10] Fourth, multiple additional infusions limit the available intravenous access for other intravenous doses. Fifth, the requirement for additional prescriptions requires clinician time away from other urgent
duties.

For these reasons, when indicated and physically stable, adequate electrolyte additions should be made to all intravenous feeding regimens. However, intravenous feeds should not be relied on for urgent or critical provision of electrolytes as a proportion (or even a whole bag) of prescribed feed might not be received by a patient due to a complication such as catheter related sepsis. Furthermore, there is also a delay between prescribing and administration of the feed. Therefore it should not be forgotten that additional infusions may still be required, the rate of intravenous feeds might need to be reduced or the feed stopped if reported electrolytes require. However, additional electrolytes  should never be added to any intravenous feed outside of a dedicated aseptic facility for the reasons described
above.

Both the direct and indirect costs of up to 5 electrolyte additions to each multichamber bag before use, together with pressures on staff, must be taken into consideration and these can at least in part offset financial savings compared to bespoke regimens.

Multichamber bags currently contain no micronutrients but the UK NICE guidelines require all patients to receive adequate micronutrients from the outset of feeding.[7] However, whilst some practitioners maintain electrolyte additions are never required, others argue that micronutrient additions are unnecessary because over a short period inadequate provision of micronutrients is unlikely to be clinically relevant and therefore providing macronutrients alone is both reasonable and “better than nothing”.

However, this is not reasonable because patients requiring intravenous feeds are likely to be micronutrient deficient and inadequate provision can lead to obvious complications sufficient to warrant admission to intensive care and/or lead to patient death.[11],[12] Even in cases where such obvious problems do not arise, more subtle complications such as impaired wound healing and compromised immune function can result.[13] It must be remembered that the initial provision of intravenous feeding is usually not intended to promote weight gain but rather to stabilise the patient with limited energy provision, adequate electrolyte provision and generous micronutrient provision. Therefore providing feeds without adequate micronutrients is both illogical and dangerous. It is extremely concerning that many prescribers consider these issues irrelevant and that even dedicated pharmacy facilities may have a similar attitude.[14]

The separate administration of intravenous micronutrients may be possible although this can be complicated by similar issues to the separate administration of electrolytes (above).

Whilst appropriate aseptic facilities are required for additions to multichamber bags, the availability of such facilities should not encourage unnecessary changes of limited clinical relevance (Box 4). Indeed, limiting amendments to prescriptions not only retains simplicity but may also support the reuse of correctly stored but un-used bags.

In addition to often requiring electrolyte additions and always requiring micronutrient additions, the most apparent strength of multichamber bags can actually be a further disadvantage; that is, their apparent simplicity.

This apparent simplicity means that hospitals may only keep one or two regimens rather than a more complete range and inadequate clinical consideration may be given to their practical use. Worse still, they may be kept on wards as stock or given in an ’emergency’ with inadequate additions (particularly micronutrients). As discussed above, inadequate additions simply transfer and increase risk and the need for more resources from the pharmacy to the clinical environment. The inappropriate use of multichamber bags without adequate additions may also limit local aseptic services capacity or the availability of responsive outsourced aseptic facilities for when bespoke regimens are required. Steps need to be taken to prevent this.

These issues are best resolved with education and training in clinical nutrition and aseptics together with experience of their appropriate practical application.

The emphasis is very much on the use of tailored multichamber bags for the majority of patients but there are occasions when these cannot be used. Examples may include very high or low volume requirements although it is often possible to add volume to multichamber bags and there are other techniques that can be used to avoid the need to prepare bespoke regimens (Box 5). Bespoke regimens may provide more specific requirements in terms of energy or protein, providing it is remembered that estimating energy equations only offer approximations and therefore rounding off (usually down) is reasonable in the majority of cases.[15] Longer-term needs are more likely to require bespoke regimens rather than tailored multichamber bags.

Whilst several major manufacturers offer a range of multichamber bags, it is unlikely that one offers a more appropriate range compared to another although each range may be best used in different ways. For example, a decision will need to be made on whether to use different bags for varying energy requirements or alternatively whether using a proportion of a bag would be more appropriate.

In addition to considering the local patient population, there are also some specific points to consider when choosing which multichamber bags to stock locally that also apply to designing bespoke regimens.

Those labelled as suitable for ‘peripheral’ use are of a relatively low osmolarity but may become ‘central’ use only if sufficient additions are made increasing the concentration. Furthermore, multichamber bags labelled suitable for ‘peripheral’ use assumes that all patients can tolerate the same concentration of feed peripherally whereas in clinical practice an elderly patient with a long history of venepuncture is rather more likely to suffer peripheral vein thrombophlebitis than a younger patient with more intact veins. Therefore it is necessary to consider each patient individually and not blindly follow guidelines without a comprehensive understanding of what they mean.

There are some key regimen ratios that need to be taken into consideration (Box 6) and calculating them should be straightforward.[16] In some cases a nonnitrogen to nitrogen ratio of 100:1 is recommended for intensive care patients[17] but this does not appear to be evidence based and seems to stem from the idea that catabolic patients need more protein to maintain or build up their muscle tissue. This concept is generally inappropriate[18] and the usual recommended ratio
of 150 to 250:1 is likely to remain reasonable in this cohort.

Other differences between manufacturers of multichamber bags include the type of lipid and whilst the more modern variants have a certain appeal the evidence for their use needs to be strengthened.[19]

With these ideas in mind it should be possible to intravenously feed the vast majority of adult patients with a tailored multichamber bag or, if absolutely necessary and with the limitations described above, by using a multichamber bag with seperate infusions. A limited number of patients will still require bespoke regimens and adequate provision should be made for this when the situation arises.

Conclusion
Providing an adequate range is stocked and they are used appropriately, multichamber bags are suitable for the majority of patients requiring intravenous feeding providing the bags are individually tailored. This requires responsive dedicated aseptic facilities either locally or off-site. If this cannot be achieved then the centre should have a system in place to refer patients requiring intravenous nutrition to another centre where it can be prescribed and administered safely.

The use of multichamber bags is not simple and it is not ‘cheating’ rather it requires the prescriber to have the clinical skill to use them appropriately and the pharmacy to be aware of the issues surrounding their appropriate use. To support these aims, appropriate prescribing policies are needed to enforce safe clinical practice and the appropriate use of multichamber bags.

Future investment in the training of prescribers, pharmacists and aseptics staff as well as the development of aseptic facilities to enable the pharmacy to maintain a clinical service supporting the appropriate use of intravenous feeds in the most efficient and safe manner, is essential.

References
1. National Patient Safety Agency. Patient Safety Alert 20 Promoting safer use of injectable medicines NPSA/2007/20. London: 2007.
2. Driscoll D. Safety issues during the compounding and dispensing of PN admixtures. Hospital Pharm Eur 2007;31:39-41.
3. Austin P. Safe use of intravenous feeding (feedback). Hospital Pharm Eur 2007;33:5.
4. News. Two children die after receiving infected TPN solutions. Pharm J 1994;252:596.
5. Beaney A, ed. Quality Assurance of Aseptic Preparation Services, 4th edn. London: Pharmaceutical Press 2006.
6. Medicines and Healthcare Products Regulatory Agency. Rules and Guidance for Pharmaceutical Manufacturers and Distributors. London: Pharmaceutical Press, 2007.
7. National Institute for Clinical Excellence. Nutrition Support for Adults Oral Nutrition Support, Enteral Tube Feeding and Parenteral Nutrition. London: National Health Service, 2006.
8. Dileep L, Bostock K, Neal K, Perkins A, Rowlands B, Allison S. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet 2002;359(9320):1812-1818.
9. Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lindorff-Larsen K, et al. Effects of intravenous fluid restriction on postoperative complications. Comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 2003;238:646-646.
10. Clark-Christoff N, Watters V, Sparks W, Snyder P, Grant J. Use of Triple-Lumen Subclavian Catheters for Administration of Total Parenteral Nutrition. JPEN 1992;16(5):403-407.
11. Chadda K, Raynard B, Antoun S, Thyrault M, Nitenberg G. Acute lactic acidosis with Wernicke’s encephalopathy due to acute thiamine deficiency. Intens Care Med 2002;28: 1499.
12. Kitanura K, Yamaguchi T, Tanaka H, Hashimoto S, Yang M, Takahashi T. TPN-induced fulminant beriberi: a report on our experiKitaence and a review of the literature. Surg Today 1996;26(10):769-776.
13. Austin P, Stroud M. Prescribing Adult Intravenous Nutrition. London: Pharmaceutical Press 2007. p129-131.
14. Newton R, Hardy G. Meeting report. Does one size fit all? Hosp Pharm 2004;11:346.
15. Austin P, Stroud M. Prescribing Adult Intravenous Nutrition. London: Pharmaceutical Press 2007. p162-164.
16. http://www.nutritionsupportteam.co.uk/calculations. html
17. Hawker F. How to feed patients with sepsis. Curr Opin Crit Care 2000;6(4):247-252.
18. Austin P, Stroud M. Prescribing Adult Intravenous Nutrition. London: Pharmaceutical Press 2007. p82-84.
19. Wanten G. An update on parenteral lipids and immune function: only smoke, or is there any fire? Curr Opin Clin Nutr Metab Care 2006;9:79-83.



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