Intravenous citrulline generation test to assess intestinal function in intensive care unit patients

Figures & data

Figure 1 Physiologic pathway of glutamine into citrulline by the enterocyte.

Abbreviations: P5C, pyrroline-5-carboxylate; OCT, ornithine carbamoyltransferase.

Table 1 Basic characteristics of ICU patients included in this study

Patient	Age (years)	Sex	BMI (kg/m^2)	Daily intake (kcal)a	Diagnosis	APACHE II scoreb	SOFA scorec	Survivald
1	67	F	34.4	1943	Type A aortic dissection	26	4	Alive
2	64	M	15.9	975	ARF, pneumonia	27	6	Alive
3	64	M	31.1	1728	Post-CABG	21	3	Alive
4	63	F	44.1	3209	Multiple myeloma	16	3	Alive
5	52	F	23.4	1401	ARF, COPD	19	2	Died
6	62	F	23.1	1317	Post-CABG	28	4	Alive
7	53	M	16.4	1203	ARF, pneumonia	27	5	Alive
8	50	M	34.0	1784	OHCA	19	5	Died
9	73	F	31.1	1709	OHCA	39	4	Alive
10	54	F	26.3	1499	Intracranial bleeding	25	6	Alive
11	71	F	27.3	1554	Type A aortic dissection	26	3	Alive
12	59	M	23.3	1970	ARF, pneumonia	25	2	Alive
13	41	F	26.0	1750	Type A aortic dissection	24	4	Alive
14	68	M	23.5	1712	ARF, pulmonary embolism	24	1	Alive
15	54	F	22.9	1803	ARF, intoxication sedatives	19	3	Alive
16	79	M	23.9	1047	ARF, pneumonia	24	4	Alive
Mean ± SD	60.9±9.8	9 F 7 M	26.7±7.0	1663±510		24.3±5.3	3.7±1.4	2 Died 14 Alive

Notes:

a Mean caloric intake in kcal 24 h prior to the first CGT (corrected for 8 h fasting period);

b score indicating first 24 h after admission, not during CGT;

c SOFA score at day of first CGT;

d 30 days mortality.

Abbreviations: ICU, intensive care unit; BMI, body mass index; CGT, citrulline generation test; F, female; M, male; ARF, acute respiratory failure; CABG, coronary artery bypass grafting; OHCA, out of hospital cardiac arrest; APACHE, acute physiology and chronic health evaluation; SOFA, Sequential Organ Failure Assessment.

Table 2 Inclusion and exclusion criteria for CGT study in ICU patients

Inclusion criteria
• Age between 18 and 80 years
• Verbal informed consent
• Fecal output <250 mL per day
Definition of a “stable” ICU patient
1. Any ICU patient admitted for mechanical ventilation, with stable hemodynamics as judged by the intensivist and an expected ICU stay of >72 h
2. Ability to tolerate enteral nutrition, provided by either nasogastric or nasojejunal feeding tube, meeting full protein energy requirements based on indirect calorimetric measurements and further individualized according to an automated nutritional program^Citation23
Exclusion criteria
• Documented causes of small bowel malabsorption possibly interfering with intestinal absorptive function, eg, coeliac disease, Crohn’s disease of the small bowel, exocrine pancreatic insufficiency, radiation enteritis, or short bowel syndrome
• Small intestinal resections and/or extensive colonic resection (>2/3)
• Liver cirrhosis Child–Pugh B or C, acute liver failure or renal failure requiring artificial support (eg, CVVH)
• Urea cycle defects/citrullinemia
• Exogenous steroids in excess of 10 mg prednisolone equivalent (leading to P5C synthase induction leading to increased production of citrulline from glutamine in the enterocytes)
• Pregnancy (no long-term data are available on the effects of Dipeptiven^® during pregnancy or lactation)
• Use of (par)enteral glutamine/citrulline supplements

Abbreviations: CGT, citrulline generation test; ICU, intensive care unit; CVVH, continuous veno-venous hemofiltration; P5C, pyrroline-5-carboxylate.

Figure 2 Mean plasma citrulline changes of various citrulline generation test methods (enteral–intravenous, arterial–venous) in 16 stable intensive care unit patients.

Abbreviations: Cit, citrulline; art, arterial; IV, intravenous; Glu, glutamine; ent, enteral; ven, venous.

Figure 3 Incremental area under the curve after 90 min (iAUCT90) of various CGT methods (enteral–intravenous, arterial–venous) in 16 stable intensive care unit patients. Dots represent individual values versus box and whisker plot.

Abbreviations: CGT, citrulline generation test; Cit, citrulline; IV, intravenous; Glu, glutamine.

Table 3 CGT reference values (mean ± SD) based on different methodologies in stable ICU patients (n=16)

Citrulline sampling	CGT 1 enteral glutamine		CGT 2 IV glutamine
	Venous	Arterial	Venous	Arterial
Baseline citrulline (µmol/L)	29±7	31±8	29±9	31±9
Peak citrulline (µmol/L)	45±14	51±16	42±12	48±14
Time to peak (min)	99±39	94±37	82±20	72±24
Slopea	0.18±0.12*	0.24±0.16*	0.19±0.05*	0.28±0.16*
iAUCT90 (µmol/L/min)b	578±418*	772±585*	784±231*	982±283*

Notes:

a Slope from baseline to peak plasma citrulline concentration during CGT.

b Incremental area under the CGT curve between 0 and 90 min.

* p<0.05 (arterial vs venous within either CGT 1 or 2).

Abbreviations: CGT, citrulline generation test; SD, standard deviation; ICU, intensive care unit; IV, intravenous; iAUCT90, incremental area under curve after 90 min.

Figure 4 Correlation between the standard incremental area under curve after 90 min (iAUCT90; intravenous glutamine administration and arterial sampling) of citrulline generation test (CGT) and the simplified 2-point CGT in 16 stable intensive care unit patients.

Strack van SchijndelRJWeijsPJKoopmansRHSauerweinHPBeishuizenAGirbesAROptimal nutrition during the period of mechanical ventilation decreases mortality in critically ill, long-term acute female patients: a prospective observational cohort studyCrit Care200913R13219671136

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