(Systematising parenteral nutrition without ritualising it!)

Most authorities will agree that it is vital to have written protocols for the management of total parenteral nutrition (TPN). What they will not agree on is the content of such protocols, although there is consensus on several points. The most important thing to remember with such protocols is that little or nothing should be cast in stone - there is still controversy about almost every aspect of TPN, especially when used in an intensive care (ICU) setting. Protocols must be open to regular review.

Initiating TPN

The major indication for total parenteral nutrition is failure of the gastrointestinal tract to perform its normal function of processing and absorbing food (although TPN has been used with varying success in severe Crohn's disease and with high-output enterocutaneous fistulae). Such "bowel failure" is often relative, rather than absolute, and 'ileus' is often invoked as a reason to start TPN. We now know that 'ileus' is a condition that affects mainly the stomach and colon. If food can be placed in the jejunum, it will usually be tolerated and absorbed, unless excessive amounts are given, or the jejunum is grossly ischaemic. This is so even with conditions such as pancreatitis, where TPN was formerly considered contra-indicated. In general enteral nutrition is to be favoured over TPN, a contention supported by recent studies 1. The problem is often to obtain adequate enteral access - a well-constructed jejunostomy is ideal, but a pre-requisite is a history of institutional success with this technique. Some have reported far-from-ideal outcomes with jejunostomies, especially using percutaneous techniques. 2. An alternative to a jejunostomy is a naso-jejunal tube. The length of tube required is about 150 cm, and the tube should be shot-weighted. Such tubes are often ridiculously expensive when compared to even slightly shorter tubes, although they still cost less than a single day of TPN. The real problem is placement, which is again user-dependent - although some have reported good success with endoscopic placement of such tubes (or even blind nasogastric placement and then administration of a 'prokinetic agent'), this has by no means been a universal experience. Pleas for intra-operative placement of such tubes 3 tend to be ignored.

Even with the best intentions to feed enterally, the intensivist will encounter many cases where enteral feeding fails (often due to poor access). In such circumstances, failure to feed the critically ill patient will cause severe compromise, and TPN is usually considered imperative. Nevertheless, a recent meta-analysis showed no benefit of TPN on mortality rates in surgical patients, although TPN may have reduced complication rates. 4.

The timing of initiation of TPN is a vexing question. The Veterans' study 5 provided substantial evidence that the patient who is already substantially malnourished benefits from pre-operative initiation of TPN, although the study design is open to criticism. It would seem to make sense to start TPN as soon as one appreciates that a patient (who cannot be fed enterally) is at risk, or indeed already nutritionally compromised. Assessment of risk using the 'Subjective Global Assessment'6 rating is as effective as a variety of other, expensive markers of nutritional depletion 7. Nevertheless, some studies 8 allege that vigorous, early administration of TPN (containing lipid) may actually be harmful, for example in the trauma patient. These studies should be read with caution, as inappropriate TPN regimens may have been used. In the opinion of the author, much depends on (a) severity of illness and (b) baseline nutritional status. In the severely ill patient who is already nutritionally compromised, it would seem foolhardy in the extreme to withhold adequate food for even a day. Conversely, in a patient who is well and has suffered a minor insult, nutritional deprivation is often well-tolerated, although this is little justification to withhold food!

What to give?

Concern has been expressed about the appropriateness of many current TPN regimens. A bewildering variety of options is often available. Unfortunately, there is little evidence that many 'specific' regimens (put forward as 'ideal' for renal failure patients, liver failure patients, and so on), are preferable to other formulations. We will briefly look at some of the controversies.

Energy provision v Requirements

Most intensivists would seem to have abandoned previously touted approaches of providing vast amounts of nutrition to critically ill patients, who were previously assumed to be "hypercatabolic". Overfeeding has been well-reviewed by Klein and colleagues.9 There are numerous reasons to beware of overfeeding:

Some have advocated the use of a 'metabolic cart' in determining energy requirements.12 There are several problems with such an approach, including:

A reasonable general recommendation (in the absence of better data) is to provide approximately 25 kCal/kg/day 13 . (Burns patients may require substantially more than this). This energy provision should be adjusted according to response, as indicated below.

One approach (favoured by the author) that has not been adequately investigated in the ICU setting, is to calculate energy requirements using three-quarter power scaling (a la Kleiber). This approach has been discussed elsewhere. Note that energy calculations based on "ideal weight" may grossly mis-represent the patient's needs. (Virtual weight should only be fed with virtual food)!


Although previous recommendations for the critically ill have endorsed administration of approximately 1g/kg/day of high-quality protein (or amino acids, as in TPN) to the critically ill, current trends seem to favour approximately 1.5g/kg/day. Note that the proportions of various amino acids in most TPN solutions have only a passing resemblance to normal physiological requirements, and probably differ substantially from an "ideal" formulation for the critically ill, although we are still pretty ignorant about what should constitute such an "ideal".

If you calculate the nitrogen to 'non-protein' energy ratios of local 'standard', premixed, 'three in one' TPN solutions, you will find that for many, if you are giving adequate amounts of amino acids, then you are providing too much energy. Traditional ratios of 1 g Nitrogen to ~150 kCal are commonly encountered, although current recommendations are in the order of 1:100. (The situation is not quite as dismal as with many 'standard' enteral feeds)!

We will not here discuss the use of Glutamine containing TPN, nor will we examine the notable deficiency of sulphur-containing amino acids in most commercial TPN solutions.

Carbohydrate v Fat

It is likely that many, possibly even most ICU patients on TPN are receiving excessive quantities of carbohydrate.14 In general, any patient who receives over four to five mg/kg/min of glucose will tolerate this poorly, and become hyperglycaemic. At particular risk are diabetic patients (common in ICU), and those with impaired glucose tolerance, often as a consequence of stress and/or administration of corticosteroids. Other patients who may poorly tolerate a glucose load are those with hepatic disease.15

In many circumstances, energy provision may be improved by providing more of the patient's energy requirements as fat, although provision of excess amounts of energy in any form may be deleterious. Monitoring of glycaemia and lipaemia is discussed below.

Electrolytes and water!

It is vitally important to keep track of electrolyte and water balance in the critically ill. Unfortunately, this is easier said than done, and in some intensive care units, even regular weighing is honoured more in the breach than the observance! Water, sodium, chloride, potassium, magnesium, phosphate, and calcium requirements should all be attended to meticulously. Balancing these may be difficult, and failure to appropriately adjust calcium and phosphate may be life-threatening, as discussed below.

Minerals, Vitamins, 'Micronutrients'

Prescription of 'minerals' and vitamins in ICU are unlikely to be appropriate if based on recommended daily requirements, although good evidence as to what we should be prescribing is sorely lacking! Many intensivists err on the side of over-provision of some 'trace elements' and water-soluble vitamins, arguing that provision of large amounts of vitamin C, thiamine and perhaps zinc is unlikely to be deleterious. This is not necessarily correct, as vast amounts of vitamin C may (suprisingly) actually increase oxidative stress!16 It is extremely important to be on the alert for evidence of overt mineral or vitamin deficiency, although with current formulae, such deficiency is unlikely. More worrying is the possibility of subclinical deficiency adversely affecting outcome. Note that concurrent dialysis may grossly deplete the patient of vitamins such as thiamine.

Special circumstances?

We have already mentioned the paucity of evidence for "organ-specific" or "disease-specific" nutritional therapy. Probably far more important (in the opinion of the author) is to administer appropriate nutritional therapy to the individual patient, paying attention to baseline nutritional state, scaling appropriate to mass, and most importantly, observing their response to feeding. Monitoring of this response is covered in the next section.


Administration of total parenteral nutrition should be seen as a continuous cycle of evaluating the need for TPN, adjusting TPN components, and observing the response (with appropriate adjustment and re-evaluation).

Each unit will have its own well-defined protocols, but generally they will share common features. We consider monitoring of the following to be vital:

  1. Metabolic indicators
  2. Evidence of complications, notably infection but also line-related thrombosis, and other line complications.
  3. Surveillance for adverse drug interactions!

In many protocols, surveillance of each parameter is prescribed at rigidly fixed intervals. This is often inadvisable for several reasons. On the one hand, important metabolic abnormalities may be missed, while on the other, costs may increase due to inappropriately frequent testing.

Metabolic Surveillance


Perhaps the most important metabolic parameter of all is glycaemic control. Although hard evidence is lacking, we suspect that even moderate degrees of hyperglycaemia may result in increased incidence of infection, and adverse outcomes. 17 The frequency of glucose monitoring should be tailored to the patient - in a patient who is unstable and has impaired glucose tolerance, monitoring may need to be performed hourly until glycaemic control has been achieved. Conversely, thrice daily monitoring may be adequate in other, stable patients.

Inadequate glycaemic control should be seen as a marker of overfeeding, and excessive carbohydrate administration. There are two possible approaches to this problem. One may administer insulin in order to achieve euglycaemia, or decrease carbohydrate administration. What is not acceptable is to allow hyperglycaemia to persist!


Monitoring of the lipid response to TPN is often ignored or underplayed, yet such monitoring is vital. 18 There is currently much debate about the nature of lipids that should be administered, and whether such innovations as structured lipids and triglycerides of varying chain lengths are of any benefit.


As a minimum, a daily determination of urea, creatinine, and electrolytes is necessary. In addition, attention should be paid to abnormalities of calcium, magnesium, and phosphate, particularly the latter. Here again, rather than monitoring according to a rigid protocol, testing should depend on the nature and severity of the patient's illness. For example, a patient who shows evidence of the "refeeding syndrome" may require daily (or more frequent) phosphate determination, and a grossly hypomagnesaemic diabetic on diuretics might require several serum magnesium levels during the course of a single day. Conversely, weekly determination of these may be quite adequate in a patient stable on longer-duration TPN.

Other parameters

Perhaps the most important 'parameter' to watch is the overall clinical wellbeing of the patient! Appreciation that a patient is subtly deteriorating may be the first clue that a TPN-related complication is present, rather than some specific metabolic parameter being abnormal. In addition, abnormalities of other less-specific tests such as International Normalised Ratio (INR), "liver function tests", or even arterial blood gas analysis, may signal a problem.

Those who administer TPN should also be aware of a host of potential metabolic complications, especially with prolonged therapy. These include deficiencies of micronutrients, hyperosmolarity, hyperammonaemia (especially associated with liver dysfunction), chronic metabolic bone disease, and managanese overload (with accumulation of Mn in the basal ganglia).

In addition, hepatic complications are a major source of worry. These include intrahepatic cholestasis (in infants and children), hepatic steatosis (due to overfeeding, mainly in adults), and biliary sludge (in both children and adults).

We are still not certain about the value of monitoring "indices of nutritional status" such as pre-albumin, ferritin and so on, especially in acute critical illness. Certainly the time honoured use of serum albumin seems most inappropriate in the critically ill, as this parameter may vary dramatically in a fashion completely unrelated to nutritional status.

Surveillance for Infection

One of the major determinants of outcome in ICU is nosocomial infection, which is excessively common. Although frequently related to mechanical ventilation, as well as inappropriate, excessive or prolonged antibiotic therapy, infection is often temporally related to administration of TPN. Infection in such circumstances may be related to:

Every unit should have a formal protocol for TPN hang times, management of connections, and aseptic management of intravascular lines. But in addition, there should be protocols for management of and surveillance for evidence of systemic infection, and aggressive management of hyperglycaemia. Differentiation between the 'systemic inflammatory response syndrome' and actual infection remains a difficult task, although preliminary evidence suggests that new markers such as procalcitonin may be valuable in some circumstances.19

Drug Interactions

This is a woefully neglected aspect of TPN administration The general rule should be that nothing is added to TPN solutions. The rule is frequently flouted. Unfortunately, precipitation in TPN solutions may be obscured by the lipid component, even resulting in the death of the patient! Precipitation of calcium and phosphate has been reported even with no additions to TPN mixes 20. The problem is not confined to the 'TPN bag' - TPN solution should never be co-administered via the same port as other medication. A dedicated line is imperative.


The individual patient

As already mentioned, TPN therapy should initially be tailored according to the needs of the specific patient. Even more important, however, is to adjust provision of nutrients according to the patient's response to therapy, particularly the patient's glycaemic control and insulin requirements.

The TPN 'cohort'

In the ideal ICU, there should not only be surveillance of individual patients, but also monitoring of overall outcomes in patients receiving TPN. It is only by doing this, and comparing the results to standardised outcomes in other units, that ICU administrators can be sure that they are not harming patients through inappropriate TPN management techniques. The whole process of TPN administration should be under the continual spotlight of patient outcomes and also costs. We must remember that there is an order of magnitude difference in the cost of enteral and parenteral food. An appropriate data-base management system (with diligent and comprehensive data entry and analysis) should be an invaluable asset. Once a problem has been identified (for example, excessive incidence of line-related sepsis), immediate corrective action can then be instituted.


We have briefly touched on some often controversial aspects of TPN administration. This talk was not intended to provide an exhaustive review, nor to provide an inflexible and rigorous protocol. We hope that we have stimulated at least a few people to return to their ICUs and re-evaluate their current practices. One thing the author finds extremely regrettable is the lack of availability of detailed TPN protocols on the Internet. ASPEN however appear to have made a good start by recently publishing clinical protocols on the Web! 21


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