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Oliver Arkell wrote 07-07-2011 10:48:53 am
To be fair though, the results of NICE-SUGAR weren't available when this trial was being designed...

Neil Orford wrote 07-07-2011 02:02:43 pm
All the points raised seem to point a concern about applicability of this result in the Australian context, and that there are a lot of unknowns regarding feeding (late vs early PN, top up PN, permissive underfeeding, etc).

It appears more information regarding this, designed in keeping with Australian/ NZ feeding practices is needed. Gordon Doig's Early PN trial has just completed recruitment (n=1400ish), so should add to the landscape later this year or early next year, once followup and manuscript preparation is complete. There is also talk of Aust/NZ topup PN and permissive hypocaloric EN trials, so we may get closer to understanding this area over the next 5 years.

Oliver Arkell wrote 08-01-2011 12:23:46 pm
Is this really an early PN vrs Late PN trial? Or a PN-to-top-up-EN trial? This isn't the way its used in most places at present.

Todd Fraser wrote 08-16-2011 06:00:01 pm
There are certainly some perculiarities in this trial!

One that stands out is the lack of documentation of hyperglycaemia. Given that many have argued that the reason the old TPN trials did not show a benefit was because they caused uncontrolled hyperglycaemia, I would have thought this was tracked and reported. It is possible that the early group had less well controlled sugars and the infectious complications followed.

Another interesting feature is the effect on CRP - it was higher in the late group, who had fewer infections. Is it possible that CRP is a marker of immune competency in this sense - that they had higher CRPs because their immune system worked better (hence the lower infectious complication rate)?

Neil Orford wrote 07-06-2011 06:13:56 pm
The early management of nutritional support in ICU patients remains controversial. The European (ESPEN) guidelines recommend practitioners consider initiating PN within 2 days after ICU admission if EN cannot be instituted. The US and Canadian guidelines recommend PN not be delivered concurrently with EN for a week after ICU admission, unless the patient was previously malnourished. This study, a prospective, parallel grouped, multicenter, RCT, aimed to compare the 2 approaches.

4640 patients were randomised over 40 months in 7 ICUs in Belgium. The early PN group received 20% glucose IV for 2 days, then PN was commenced aiming for 100% of caloric goals through combined EN/PN. The late group received 5% glucose for 7-days then PN if EN was not at target. The delivered energy was clearly different for the first 7-days. They all got the same vitamins and trace elements, and they all had tight glucose control (Leuven investigators).

There was no difference in mortality between the 2 groups. The late group had a significantly higher discharge alive from ICU at day 8 (75.2% vs 71.7%, p=0.007), lower complication rate, less inflammation, shorter duration of ventilation, hospital stay, ICU stay, and lower health-care cost (approx 1,100 Euro). Overall the authors conclude there is no benefit in early PN in ICU patients that are not already malnourished.

Is there anything else we should consider;

1. Does the issue of early high dextrose vs low dextrose that was protocolised in thi

Alex McKenzie wrote 07-06-2011 06:16:28 pm
I can't help but think that the glucose load given in the first 24-48 hours is unhelpful, and when coupled with the intensive insulin therapy that would be required to control sugars in this period (remembering the results of NICE-SUGAR), I wonder if this explains the results

Neil Orford wrote 07-06-2011 06:46:52 pm
I agree Alex, the criticisms and controversy generated by the glucose management at the start of the 2 Van den Berghe IIT trials made interpretation difficult from an Australian perspective, were we would not consider giving so much. Some harsher critics commented that the IIT trials showed that insulin offset the harm of high glucose load.

I don't know, but it certainly muddies the waters

Neil Orford wrote 07-06-2011 06:46:59 pm
I agree Alex, the criticisms and controversy generated by the glucose management at the start of the 2 Van den Berghe IIT trials made interpretation difficult from an Australian perspective, were we would not consider giving so much. Some harsher critics commented that the IIT trials showed that insulin offset the harm of high glucose load.

I don't know, but it certainly muddies the waters

Benjamin Moran wrote 07-06-2011 06:50:49 pm
A couple of things that are highlighted by this study:

1. The use of dextrose infusions for the first 48 hours is not in either of the European or US guidelines, and is not current practice in Australia. I worry this practice may predispose to refeeding syndrome.
2. It is an interesting regime of nutritional support, given that there is concomitant commencement of EN + PN to achieve nutritional goals. The most common practice I have come across is to institute EN and then add or switch to PN if goals are not met at 72 hours.
3. This is a predominately surgical ICU, where approx 60% were cardiac surgery pts. This raises the issue of applicability to a general ICU.
4. The use if IIT has already been highlighted, and seems to be a regional (Leuven) protocol that they are unwavering on.
5. Given the methodology, the results of decreased infectious rates, mechanical ventilation and cost associated with late-PN I interpret with caution, as the feeding protocol is not one that is used frequently.
6. Looking at the ANZICS Nutritional Guidelines article (Doig et al, JAMA 2008), the population that required supplementation with PN after failed EN was approx 10-15%, so this represents a minority of patients, and this paper does not answer the question of whether to supplement patients on EN with PN or the time-frame with which this should occur (i.e. early Vs late PN).