Therapy L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study.
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Summary
Posted By:	K Havill
E-Mail:	khavill@hnehealth.nsw.gov.au
Posted Date:	5/04/07
Title:	L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study.
Authors:	Dechelotte P, Hasselmann M, Cynober L, Allaouchiche B, Coeffier M, Hecketsweiler B, Merle V, Mazerolles M, Samba D, Guillou YM, Petit J, Mansoor O, Colas G, Cohendy R, Barnoud D, Czernichow P, Bleichner G.
Reference:	Crit Care Med. 2006 Mar;34(3):598-604.
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	OBJECTIVE: Glutamine (Gln)-supplemented total parenteral nutrition (TPN) improves clinical outcome after planned surgery, but the benefits of Gln-TPN for critically ill (intensive care unit; ICU) patients are still debated. DESIGN: Prospective, double-blind, controlled, randomized trial. SETTING: ICUs in 16 hospitals in France. PATIENTS: One-hundred fourteen ICU patients admitted for multiple trauma (38), complicated surgery (65), or pancreatitis (11). INTERVENTIONS: Patients were randomized to receive isocaloric isonitrogenous TPN via a central venous catheter providing 37.5 kcal and 1.5 g amino acids.kg-1.day-1 supplemented with either L-alanyl-L-glutamine dipeptide (0.5 g.kg-1.day-1; Ala-Gln group, n=58) or L-alanine+L-proline (control group, n=56) over at least 5 days. MEASUREMENTS AND MAIN RESULTS: Complicated clinical outcome was defined a priori by the occurrence of infectious complications (according to the criteria of the Centers for Disease Control and Prevention), wound complication, or death. The two groups were compared by chi-square test on an intention-to-treat basis. The two groups did not differ at inclusion for type and severity of injury (mean simplified acute physiology score II, 30 vs. 30.5; mean injury severity score, 44.9 vs. 42.3). Similar volumes of TPN were administered in both groups. Ala-Gln-supplemented TPN was associated with a lower incidence of complicated outcome (41% vs. 61%; p<.05), which was mainly due to a reduced infection rate per patient (mean, 0.45 vs. 0.71; p<.05) and incidence of pneumonia (10 vs. 19; p<.05). Early death rate during treatment and 6-month survival were not different. Hyperglycemia was less frequent (20 vs. 30 patients; p<.05) and there were fewer insulin-requiring patients (14 vs. 22; p<.05) in the Ala-Gln group. CONCLUSIONS: TPN supplemented with Ala-Gln dipeptide in ICU patients is associated with a reduced rate of infectious complications and better metabolic tolerance.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
	Yes: The randomization envelopes were held by the pharmacist and were assigned in strict chronological order in each treatment group. A potential crtiscism is that the envelopes were not described as opaque however since the study was 'pharmacy randomised' this may not have been a major problem.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	Yes: Figure 1 shows all patients accounted for and follow up was complete.114 patients were enrolled and randomised and the ITT analysis was conducted on all 114.
2b. Were patients analyzed in the groups to which they were randomized?
	Yes: All patients wre analysed in the group originally assigned, regardless of how much TPN was received.
3. Were patients, health workers, and study personnel blind to treatment?
	Yes:The two TPN solutions were labeled identically and the two solutions were indistiguishable. Stated that all patients and coworkers were unaware of tretment allocation and remained blinded to the treatment allocation until the final statistical evaluation was completed
4. Were the groups similar at the start of the trial?
	Apppears so: Tables 1 & 2 appear that the groups were similar and stated data statisticall compared but p values not supplied. Also in text gave numbers for diabetic and alcoholic patients respectively 8 and 7 - small numbers but evenly distributed.
5. Aside from the experimental intervention, were the groups treated equally?
	Unsure: They received isonitogenous and isocaloric TPN the only difference was substituion al-glut with Ala-pro. No other information was provided on other procedures or numbers in each hospital.
What are the Results?
1. How large was the treatment effect?
	Primary outcomes were 'Complicated outcome' defined as a nosocomial infection and/or wound infection(according to criteria of the centers for disease control and prevention, Atlantis 1988)and/or death over the duration of the TPN. Table 3 P less than 0.05 for all patients with complicated outcome on ITT ala-Gln 41% and control 61% - this however was 40% and 58% patients with nosocomial infectiosn and only reached significance when the two deaths in the study period in each group are added. RRR of 32% Secondary outcomes: death over 6 months, ICU LOS, hospital LOS there was no difference. However there was a weak trend towards more deaths in the ala-Gln group (27% vs 16%, p=0.2)
2. How precise was the estimate of the treatment effect?
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	The patient groups were narrow critical care group who could not be enterally fed for at least 5 days. Multiple trauma, complications after surgery and panceatitis. Patients were critically ill based on their SAPS and ISS. The difference appeared to be mainly due to a reduction in pneumonia, but despite this had no observed improvement in mortality or ICU stay - there does appear to be more deaths in the glutamine group at 6 months.
2. Were all clinically important outcomes considered?
	I believe all important outcomes, except complete costs, were considered. Complete costing would include the cost of TPN, cost of GLU, increased ICU stay and antibiotic use.
3. Are the likely treatment benefits worth the potential harms and costs?
	Although reduction in infectious complications may be considered important, I am concerned that this result is not translated into other important outcomes such ICU LOS and mortality. Also the trend to increased deaths in the treatment group is of concern. Glutamine will increase the cost of TPN and this study may not justify its addition.
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