When and How to Start Parenteral Nutrition

TPN is a strange mixure of rather horrible corrosive chemicals which replace the normal nutritive output of the enteric circulation and the liver. It is the last resort among the choice of nutrition. In fact, in many cases it is better to starve than to eat though the vein. There are serious complications associated with TPN use. Furthermore, there are even more serious consequences associated with the use of too much TPN, and these are discussed in the chapter on the consequences of over-feeding the critically ill patient.

The following is a likely list of "hard" indications for total parenteral nutrition:

  • Any disorder in which enteral feeding is not an option:
    • Short bowel syndrome with malabsorption
    • Prolonged bowel rest
    • Gastrointestinal fistula
    • Bowel obstruction or ileus
  • Any disorder where enteral nutrition fails to meet the metabolic requirements of the organism

In short, one must resort to the use of parenteral nutrition in case where enteral nutrition is clearly contraindicated, or when the enteral nutrional intake is so clearly inadequate that the patient would otherwise starve. From the evidence, one can draw the conclusion that a well-nourished patient may safely remain off all nutrition (instead of resorting to early PN). The more malnourished one becomes, the more PN becomes indicated, and the earlier. For the worst of them, PN should precede surgical interventions, as it may actually reduce their mortality in those circumstances (eg. in the case of the severely malnourished pre-oesophagectomy patient). If enteral nutrition is poorly tolerated, one should probably supplement the deficient calories parenterally. The greater debate today is how long one should persist with the poorly tolerated EN, trying this trick or that. Do we keep escalating prokinetics and adjusting the tube position for seven days, or do we supplement early? The prevailing opinion locally seems to favour the latter approach.

The guidelines differ on their interpretation of the evidence, and there has been controversy regarding the timing of TPN.. Generally, both ESPEN and ASPEN guidelines recommend that some sort of nutrition be commenced within 24-48 hours if one predicts that the patient will not be eating within 3 days. ESPEN people recommend that TPN be commenced within 24-48 hours if anything longer than a 3-day fast is anticipated (these guidelines were published in 2009). ASPEN people recommend that TPN be withheld for 7 days, and that no nutrition is better than early parenteral nutrition.

The ASPEN approach to delaying PN was confirmed by a 2011 NEJM trial, which demonstrated that delaying TPN until day 8 results in earlier recovery. The trial even used "ASPEN vs ESPEN" in its title.  This matter is a subject of hot debate. Marik et al. published a scathing assessment of early TPN, shaming its use and casting doubt on earlier meta-analysis data. In turn, they attracted a vigorous response from the author of this earlier paper. This author (Gordon S Doig) then went on to produce a trial for ANZICS which supported the use of early TPN, suggesting that it did not increase mortality, and that its use was associated with fewer days of invasive ventilation. In contrast, a more recent (2014) attempt to sort the growing pile of contradictory RCTs concluded that early TPN is probably a bad idea. 

In short, in this climate of disagreement, one would be forced to conclude that TPN within the first 6 days of critical illness should be viewed as at best a necessary evil, and deployed with careful consideration of its risk-benefit ratio.

The well-nourished patient can wait for 7 days before starting PN

When enteral nutrition is contraindicated, one should wait 7 days before starting PN (unless the patient is malnourished). Of course, all of this assumes that before their critical illness, the patient was totally fit and well-nourished. This is frequently not the case. What of the Ivor Lewis oesophagectomy, who has been dysphagic for months prior to their operation? What of the 80 year old nanna, whose intake has for years consisted of tea and biscuits? What of the anorexic teenager? These questions are difficult to answer with prospective studies. Experts agree that if enteral nutrition is not available in this group, then PN should be commenced earlier, because the nutritional reserve will be depleted much sooner than the normal 7 days.

Which brings us to the next item: Yes, 7 days.

This may seem odd, but remember that TPN has a significant complication rate. You are, after all, infusing a couple of litres of fairly toxic chemicals into your patients bloodstream every 24 hours. This does not go unnoticed by their organ systems. The evidence, you ask? Braunschweig and Heyland both found that in situations when enteral nutrition is for some reason verboten, it is actually safer to starve your patient. Only after 7 days of starvation does the risk of starvation-related complications finally outweigh the risk of TPN. Between 7 and 14 days, there seems to be a ramp up to a higher mortality with starving patients. PN should probably start before the 14th day of starvation.

This paradigm was questioned by Doig et al (2013, the EPN study) who investigated the use of early PN in patients who had some sort of relative contraindications to early enteral nutrition. Surprisingly ittle difference was found with the aggressive use of parenteral nutrients. The early PN patients did a little better in getting off the ventilator and lost less weight, but there was no mortality difference. This is even in the context of the control group waiting an average of 3 days before any nutrition whatsoever.

The malnourshed patient will require immediate PN

When enteral nutrition is contraindicated in the malnourished non-surgical patient, TPN should commence as soon as is practical.  The malnourished group of patients benefit from TPN more than they are harmed by it. This group is defined by recent weight loss of 10-15% of their previous weight, or by a body weight less than 90% of the "ideal" body weight. The reviews by Braunschweig and Heyland confirm that starving these people is even more unsafe than TPN.

PN should start preoperatively in the malnourished surgical patient

When enteral nutrition is contraindicated in the malnourished surgical patient, TPN should have started pre-operatively. This is the abovementioned situation of the massive horrendoplasty performed in a nutritionally disadvantaged person. The typical setting is an oesophagectomy for oesophageal carcinoma, but there are many other examples. The Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient recommend that these preoperatively malnourished patients be fattened up before surgery. That's right: the malnourished Ivor Lewis patient should receive TPN for 7-10 days preoperatively, if they are to derive any benefit from it.

timing of TPN in perioperative malnourished patients

Patients started on PN should start at 80% of goal rate.

"Permissive underfeeding" is an intentional way of decreasing the risks from TPN while maximising the benefits. How long do you keep this 80% rate? According to the Canadian Guidelines, 100% rate may commence "once the patient stabilizes". Furthermore, one controversial study recommends the first week of TPN be devoid of soy-based lipids. This is not a widely-supported stance.

Weirdly, the benefit of TPN is lost in this group if it s only started post-operatively, and though they may be malnourished, it is still safer to starve them for 5-7 days post op than to start TPN. Furthermore, the benefit of TPN only outweighs the risk in the group which is destined to receive TPN for a prolonged period of time, something longer than 7 days.

Add TPN to inadequate enteral nutrition

Patients poorly tolerant of enteral nutrition should receive PN as a supplement. Once again the reviews by Braunschweig and Heyland support the idea that after 7 or so days of poor nutrition the benefits of TPN outweigh the risks. Poor nutrition may still occur with enteral nutrition if the nasogastric feeds are poorly tolerated. The TPN should continue as supplementation until at least 50-60% of nutritional needs are met by enteral nutrition.

The exact time of supplementation is unclear, but it seems that early TPN supplementation is probably a good idea.

The 2011 study of early TPN (Caesar et al, NEJM - the EPaNIC trial) found that "late initiation of parenteral nutrition was associated with faster recovery and fewer complications, as compared with early initiation". However, of the studied patients (4640 of them) the majority (60%) were cardiac surgical patients who do not routinely require TPN,  the investigators used a "strict" BSL target for their insulin therapy (which we know is harmful), and 5% dextrose was used as a maintenance fluid (which is bizarre and is not practiced in Australian ICUs).

The more recent (smaller, but better designed) trial by Heidegger et al (2013) demonstrated a decreased rate of infections in the group of patients who had received supplemental PN together with their (inadequate) EN. The supplemented group also had better nutrition (103% of the goal was met, as opposed to 77% in the control group). In view of this, both ESPEN and the Alfred authors recommend PN be added to EN after two days of struggling with feed tolerance.

A practical approach to starting TPN

Question 28 from the second paper of 2006 asked the candidates to "outline how you would initiate a regime for Total Parenteral Nutrition in a critically ill septic malnourished 60kg man". This question closely resembles Question 7 from the first paper of 2015, which asked the candiates to write a TPN prescription. This question was not about the need or indication for TPN, nor was it asking the candidates to debate the relative merits of parenteral and enteral routes of nutrition. The decision was made for the candidates: TPN is required.

If such a question is asked again, the following stereotypical rote-learned answer should be regurgitated for maximum effect:

  • Assess daily metabolic requirements
    • Use predictive equations to make educated estimates
    • Measure energy expenditure with indirect calorimetry or reverse Fick equation
    • Apply coefficients to the findings to establish daily energy requirments in the context of a specific disease state, weg. whether one would need to contribute extra protein for a hypercatatbolic trauma patient, or extra lipid for a hypecapneic patient with COPD.
  • Establish the indications for TPN, and confirm that commencement of TPN is the ideal step to take (given that in many circumstances, it is actually better to wait for 7-10 days without nutrition)
  • Establish central access
  • Supply macronutrients by infusing a mixture of fat protein and carbohydrate, according to the proportions established by abovementioned methods.
    • Carbohydrate: fat ratio: 70:30.
    • Protein is also required: 1.5-2g/kg/day
      • Fat is supplied as 10% lipid emulsion, at  1.1 kcal/ml
      • Carbohydrate is supplied as 50% dextrose, at 1.7 kcal/ml
      • Protein is supplied as 10% amino acid solution, as 100g/L
  • Ensure regular contibution of trace elements, vitamins and micronutrients
  • Ensure regular monitoring of the following parameters:
    • BSL: to prevent hyperglycaemia
    • EUCs to watch for uraemia and hypokalemia
    • CMPs to watch for the hypophosphataemia of refeedig syndrome
    • LFTs to observe for steatohepatitis and acalculous cholecystitis
  • Ensure good thromboprophylaxis in view of prothrombotic effects of lipid emulsion
  • Ensure regular monitoring of the central venous access site, in view of the increased risk of CVC-associated infection associated with TPN.



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