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Question 9  from the second paper of 2001 presents us with the scenario of a trauma patient whose nutritional needs are not being met. Why are they not being met? There are a series of potential reasons. A tabulated response is offered, listing potential causes against their solutions. Following this, a long and pointless rant takes place, discussing the various finer points. The time-poor exam candidate is invited to explore the CCC of LITFL (Intolerance to enteral nutrition is particularly helpful).

In brief,

  • Make sure the nutritional goal is sensible
  • Make sure its really not being met
  • Minimise interuptions to enteral nutrition, and use higher make-up rates
  • Return higher gastric aspirates than you'd normally be comfortable with
  • Sit the patient up to 45º
  • Start some pro-kinetic agents (metoclopramide and erythromycin)
  • Advance the NGT into the jejunum (may not help)
  • If goals remain unmet after ~48 hours, add PN as a supplement
Causes and Solutions for Problems with Nutritional Support
Problem Cause Solution
The calculated energy requirement was wrong The predictive equation was inaccurate -  for example, the patient belongs to a special population - severe burns, multi-trauma, hypothermia, etc.
Or, the dietitian assessing the intake is wrong because of some basic misunderstanding.
Recalculate the goal rate using a more accurate method, eg. indrect calorimetry. Discuss basic mathematics with the dietitian.
There are numerous interruptions to feeding,
but feeds are well tolerated
Frequent trips to the operating theatre or CT scanner Either rationalise the travel time, or continue feeding during the transfers.
Alternatively, increase the rate of feeds to contribute 100% of nutritional needs in a decreased timeframe
Frequent interruptions of NG feeds due to high gastric aspirates Ensure some of the aspirated gastric residual volume is returned.
Instruct staff not to stop feeds unless the residual volume is in excess of 500ml
There is genuine feed intolerance There could be numerous reasons; among them:
-  "chemical ileus " (eg. due to opiates)
- poor gut perfusion, eg. shock
- poor gastric emptying due to ANS dysfunction
- post-operative gut damage
-

- Adjust the patient's posture to semi-upright
- Advance the NGT into a post-pyloric position
- Administer prokinetics:
   - metoclopramide or domperidone
   - erythromycin
   - oral naloxone
   - neostigmine

- Consider a PEG or jejunostomy tube

If all else fails, contribute the additional calories via TPN (if after trying for 2 days nothing is helping)

The feeds are well tolerated, in terms of gastric aspirates being low,  but the nutrients are poorly absorbed The gut is ischaemic, or the villi are denuded, or there is no enough gut (short gut), or the gut transit is too fast (eg. the diarrhoea is very severe). Antimotility agents (eg. loperamide) may be required for the fast transit; otherwise, one has little recourse other than to rely on TPN.
 

Tolerate gastric aspirates of up to 500ml

Generally, healthy adults are thought to produce from 2-3 up to 5-6 litres (if being fed) of gastric juices per day, which averages out to 100-250ml or so every hour; of this the vast majority is reabsorbed by the gut. Of the total gastric content, some is gastric secretions (maybe 1500-2500ml per day) and some is swallowed saliva (maybe 1000ml/day)

The fasted person has only about 100ml of gastric content (maybe significantly less).

Lets say you infuse a goal rate of 60ml/hr of feeds, and aspirate 4-hourly. A patient whose pylorus is tightly closed will absorb nothing, and 240ml of feeds will collect in their stomach. Additionally there might be from 400ml up to 1000ml of gastric secretions, and 160ml of saliva. This hypothetical patient would end up with 800-1400ml of stomach content. From ones ICU experience one can recall that this sort of 4th hour residual volume is never seen in practice. Thus, some gastric emptying is almost always occurring.

Ab initio, a study by McClave from 1992 had investigated 38 patients, and settled on 200ml in 2 hours as the upper limit of residual volume. Most textbooks on this subject cite this study, so it must have some influence over the hearts and minds of those who are passionate about gastric residual volumes. However, Stephen McClave later headlined the position statement which recommended 500ml as the upper limit.

How large a gastric aspirate is too large? Experts disagree. A good review article from 2000 confirms that there is confusion among the literature, with volumes from 150 to 500ml quoted. The most recent consensus statement suggests that while anything in the range of 200-500 should be investigated (i.e., one should submit for some cognitive processing the question, "does my feed-intolerant patient have something seriously wrong with them?"), only a gastric aspirate in excess of 500ml should be a reason to stop feeds. The rationale for this answer is that inappropriate feed cessation is the most common reason for why one may not reach their goal rate of nutrition, and when the goal rate drops below 50-65%, one loses the benefits of enteral nutrition.

Return up to 250ml of gastric residual volume

So, lets say the aspirate was in excess of 500ml, and you have decided to act in response to this. How will you act? You have the choice of stopping the feeds or continuing them, and you have this bucket full of undigested stomach content (shall we pump it back into the patient, doctor?) The consequence of having a low threshold for stopping feeds and discarding the residual volume is unmet nutritional goals. Predictably, nobody can agree about how long the feeds should be held for, what rate to restart them at, and what to do with the aspirated residual volume. A recent review (Guo, 2015) could not find any grounds for firm recommendations among seventeen studies on the subject. If one needed some guidance,  Juvé-Udina et al (2009)  tested a sane compromise, and found that it was safe to return 250ml of the residual volume, discarding the rest. This seems to be a sensible approach, as it protects the patient from both malnutrition and regurgitation.

Start prokinetic agents

A curiously autotranslated-looking article by Nam (2014) reviews the current evidence and the pharmacological arsenal available; a concise summary is also offered by LITFL. It is a summary of the CCR article by Frazer et al (2009), which is a definitive resource on the subject. A local homage to prokinetics also exists in the chapter on the management of constipation and poor gut motility in the ICU.

The conventional prokinetic agents are:

  • Metoclopramide
  • Domperidone
  • Erythromycin
  • Enteral naloxone
  • Methylnaltrexone
  • Neostigmine

The exotic drugs:

  • Alvimopan (an opiate antagonist)
  • Mitemcinal (an erythromycin-like motilin agonist)
  • Ghrelin (an enteric hormone)
  • Dexloxiglumide (a cholecystokinin receptor agonist)

In short, metoclopramide, erythromycin and enteral naloxone all seem to be good prokinetic agents. The dose of naloxone via the NG tube is 8mg 4 times a day, which means you require a special enteric formulation (the IV ampoules only contain 400mcg). Cisapride and tegaserod were once available, but their tendency to kill people with cardiovascular toxicity has seen them removed from the market. Neostigmine and methylnaltrexone are agents which influence lower gastrointestinal motility more than upper, and are probably poor first line choices.

Which drug to start as first line therapy? It seems both metoclopramide and erythromycin should be used together. Erythromycin is the more potent agent of the two (Nguyen et al, 2007), and there is evidence that metoclopramide may have no effect on gastric emptying alltogether (Marino et al, 2003). There is the threat of tachyphylaxis: both agents lose their effectiveness over the first week of therapy.

Try post-pyloric feeding

If the NG aspirate volumes are too high, it is sensible to advance the feeding tube into the small bowel (beyond the ligament of Treitz). Post-pyloric feeding ( typically into the 3rd portion of the duodenum) is well studied - there are 3 big meta-analysis articles. Generally, they all agree that post-pyloric feeding is a good idea in patients whose gastric emptying rate is sub-par, or those who are at a particularly high risk of aspiration (e.g.. somebody who has to be nursed in a flat supine position). Does this really work? Probably not. The ENTERIC study (Davies et al, 2013) compared nasogastric and nasojejunal feeding and could not find any difference in complication rate (particularly, frequency of pneumonia), efficiency of nutrient delivery or mortality.

Add TPN to inadequate enteral nutrition

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.

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.

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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.

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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.

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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.

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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.

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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.