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.

 

References

Rice, Todd W., et al. "A randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure." Critical care medicine 39.5 (2011): 967.

Heighes, Philippa T., Gordon S. Doig, and Fiona Simpson. "Timing and Indications for Enteral Nutrition in the Critically Ill." Nutrition Support for the Critically Ill. Springer International Publishing, 2016. 55-62.

McClave, Stephen A., et al. "Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN)." Journal of Parenteral and Enteral Nutrition 40.2 (2016): 159-211.

Mentec, Hervé, et al. "Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications." Critical care medicine 29.10 (2001): 1955-1961.

Heyland, Daren K., et al. "Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients." Journal of Parenteral and Enteral nutrition 27.5 (2003): 355-373.

Montejo, J. C., et al. "Gastric residual volume during enteral nutrition in ICU patients: the REGANE study." Intensive care medicine 36.8 (2010): 1386-1393.

Poulard, Fanny, et al. "Impact of Not Measuring Residual Gastric Volume in Mechanically Ventilated Patients Receiving Early Enteral Feeding A Prospective Before–After Study." Journal of Parenteral and Enteral Nutrition 34.2 (2010): 125-130.

Desachy, Arnaud, et al. "Initial efficacy and tolerability of early enteral nutrition with immediate or gradual introduction in intubated patients." Intensive care medicine 34.6 (2008): 1054-1059.

Juvé-Udina, Maria-Eulàlia, et al. "To return or to discard? Randomised trial on gastric residual volume management." Intensive and Critical Care Nursing 25.5 (2009): 258-267.

Bing, Guo. "Gastric residual volume management in critically ill mechanically ventilated patients: A literature review." Proceedings of Singapore Healthcare (2015): 2010105815598451.

Nguyen, Nam Q. "Pharmacological therapy of feed intolerance in the critically ills." World journal of gastrointestinal pharmacology and therapeutics 5.3 (2014): 148.

Marino, L. V., et al. "To determine the effect of metoclopramide on gastric emptying in severe head injuries: a prospective, randomized, controlled clinical trial." British journal of neurosurgery 17.1 (2003): 24-28.

Nguyen, Nam Q., et al. "Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness*." Critical care medicine 35.2 (2007): 483-489.

Fraser, R. J., A. M. Deane, and Marianne J. Chapman. "Prokinetic drugs for feed intolerance in critical illness: current and potential therapies." Critical Care and Resuscitation 11.2 (2009): 132.

Singer, Pierre, et al. "ESPEN guidelines on parenteral nutrition: intensive care." Clinical nutrition 28.4 (2009): 387-400.

van Zanten, Arthur RH, et al. "Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis." Critical Care 19.1 (2015): 1-16.

Oldani, Massimo, et al. "Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials." Medicine 94.31 (2015).

Wernerman, Jan. "How to understand the results of studies of glutamine supplementation." Critical Care 19.1 (2015): 1-3.

van Zanten, Arthur RH, Zandrie Hofman, and Daren K. Heyland. "Consequences of the REDOXS and METAPLUS Trials The End of an Era of Glutamine and Antioxidant Supplementation for Critically Ill Patients?." Journal of Parenteral and Enteral Nutrition (2015): 0148607114567201.

Heyland, Daren, et al. "A randomized trial of glutamine and antioxidants in critically ill patients." New England Journal of Medicine 368.16 (2013): 1489-1497.

Van Zanten, Arthur RH, et al. "High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial." Jama 312.5 (2014): 514-524.

Ridley, Emma, Dashiell Gantner, and Vincent Pellegrino. "Nutrition therapy in critically ill patients-a review of current evidence for clinicians." Clinical Nutrition 34.4 (2015): 565-571.

Singer, Pierre, et al. "The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients." Intensive care medicine 37.4 (2011): 601-609.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." N Engl J Med 365.6 (2011): 506-517.

Heidegger, Claudia Paula, et al. "Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial." The Lancet 381.9864 (2013): 385-393.

Doig, Gordon S., et al. "Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial." Jama 309.20 (2013): 2130-2138.

Davies, Andrew R., et al. "A multicenter, randomized controlled trial comparing early nasojejunal with nasogastric nutrition in critical illness*." Critical care medicine 40.8 (2012): 2342-2348.

Harvey, Sheila E., et al. "Trial of the route of early nutritional support in critically ill adults." New England Journal of Medicine 371.18 (2014): 1673-1684.

Andrews, Peter JD, et al. "Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients." Bmj 342 (2011): d1542.

Vassilyadi, Frank, Alkistis-Kira Panteliadou, and Christos Panteliadis. "Hallmarks in the History of Enteral and Parenteral Nutrition From Antiquity to the 20th Century." Nutrition in Clinical Practice 28.2 (2013): 209-217.

Fink's Textbook of Critical Care: Chapter 94: Critical Care Nutrition by JUAN B. OCHOA, DAREN K. HEYLAND, STEPHEN A. McCLAVE.

Singer, Pierre, et al. "ESPEN guidelines on parenteral nutrition: intensive care."Clinical Nutrition 28.4 (2009): 387-400.

Martindale, Robert G., et al. "Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive Summary*." Critical care medicine 37.5 (2009): 1757-1761.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." N Engl J Med 365.6 (2011): 506-517.

Marik, Paul E., and Michael Hooper. "Parenteral versus enteral nutrition in the critically ill patient: a re-analysis of a flawed meta-analysis." Intensive care medicine 39.5 (2013): 979-980.

Doig, Gordon Stuart. "Parenteral versus enteral nutrition in the critically ill patient: additional sensitivity analysis supports benefit of early parenteral compared to delayed enteral nutrition." Intensive care medicine 39.5 (2013): 981-982.

Doig, Gordon S., et al. "Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial." JAmA 309.20 (2013): 2130-2138.

Fremont, Richard D., and Todd W. Rice. "How soon should we start interventional feeding in the ICU?." Current opinion in gastroenterology 30.2 (2014): 178.