Therapy Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients
This review may be edited
Summary
Posted By:	Elizabeth Sweetman
E-Mail:	easweetm@nsccahs.health.nsw.gov.au
Posted Date:	20/1/09
Title:	Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients
Authors:	Kuhls DA, Rathmacher JA, Musngi MD, Frisch DA, Nielson J, Barber A, MacIntyre AD, Coates JE, Fildes JJ
Reference:	J Trauma. 2007 Jan;62(1):125-31; discussion 131-2
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	BACKGROUND: Negative nitrogen balance and skeletal muscle loss are common in critically injured patients and may contribute to morbidity, mortality and resource utilization. Juven, an enteral supplement which is a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine (ARG), and glutamine (GLN) has been shown to restore muscle in cachetic acquired immunodeficiency syndrome (AIDS) and cancer patients. More recently HMB has been shown to attenuate cancer-induced muscle loss by decreasing muscle proteolysis. The purpose of this study was to analyze whether HMB alone or in combination with ARG and GLN would have a similar effect on critically injured trauma patients. We hypothesized that nitrogen balance would be improved and muscle proteolysis decreased with HMB and HMB/ARG/GLN supplementation. METHODS: There were 100 adult trauma patients with Injury Severity Score (ISS) >18 were enrolled in this prospective, randomized, blinded study. All patients received standard tube feeds and one of three iso-nitrogenous supplements; HMB, HMB/ARG/ GLN, or placebo (PLAC) for 28 days. Urine, serum, and clinical data were collected for 72 patients receiving at least 7 days of supplementation during the first 14 days of treatment. Urinary 3-methylhistidine (3-MH) was used as a proxy for muscle proteolysis. RESULTS: The three groups were similar in age, gender, mechanism, and severity of injury, with the average ISS being 31.9. Utilizing covariant (ISS) repeated measure (days 1-14) mixed model (SAS) analysis, there was a significant treatment effect (p = 0.05) on nitrogen balance (g/d). Change in nitrogen balance from the first 7 days to the last 7 days was -4.3 for the HMB and -5.6 g/d HMB/ARG/GLN groups compared with -8.9 g/d for the PLAC group. 3-MH to creatinine ratios were not different in the PLAC group as compared with the HMB/ARG/GLN and HMB groups (Treatment Effect, p = 0.80). CONCLUSIONS: These data suggest that supplementation with HMB alone may improve nitrogen balance in critically injured adult patients and that this effect is not a result of lowered muscle protein turnover as originally hypothesized.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
	Unclear. In this trial, patients were randomized to one of three treatment groups. On page 126, the authors reveal that a "randomized number generator was utilized before the study start date". In spite of a randomized number generator being used in this trial, readers must keep in mind that the technique used to implement the randomization sequence was not fully described so allocation concealment may not have been maintained.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	No. On page 127, the authors of this paper state that from the 100 critically ill trauma patients enrolled in the study, only 72 patients were used for statistical analysis (a 28% loss to follow-up). This is excesssive. Outcomes for these loss to follow-up patients are not reported and we do not know which groups they were originally assigend to. The investigators of this study developed additional statistical exclusion criteria for patients in the study (for the period after the time of enrolment). If patients following enrolment failed to meet the 50% compliance for supplementation during the initial 14 days of the study and full 28 days of the study, they were excluded from analysis. The 28 patients who did not meet the 50% compliance for supplementation did so for the following reasons; 3 patients died while on the supplementation protocol, 2 patients withdrew from the study and died within the 28 day study protocol, 3 patients were removed from the study for renal insufficiency medical concerns and a total of 19 patients withdrew consent during the 28 day study period.
2b. Were patients analyzed in the groups to which they were randomized?
	Yes however there was a significant loss to follow-up (patients who did not met the 50% compliance for supplementation were excluded from the final analysis; see results section, p. 127).
3. Were patients, health workers, and study personnel blind to treatment?
	Yes. Within this trial a double-blinded design was used (pg. 126, methods section). All study personnel with the exception of the clinical pharmacist were blinded to the study treatments and all nutritional supplements used in the study were packaged the same and were all orange flavoured.
4. Were the groups similar at the start of the trial?
	Essentially yes. The pre-injury weight of those patients in the HMB was lower(74.9 +/- 2.9) compared with those patients in the Juven group (84.8 +/- 4.8) and the Control group (90.1 +/- 6.1).
5. Aside from the experimental intervention, were the groups treated equally?
	Yes all trial groups were treated the same.
What are the Results?
1. How large was the treatment effect?
	Hypothesis of the trial: Nitrogen balance would be improved and muscle proteolysis decreased with HMB + HMB/ARG/GLN supplementation. Note: No statistically significant differences between trial groups in the following outcomes; Mortality, 28 day antibiotic use, hospital LOS, ICU LOS, ventilator days or no. of infections per patient. Other results of this 3 armed trial: Nitrogen Intake for the 14 day collection did not differ between groups (p = 0.63). Control group - 248 +/- 16g HMB/ARG/GLU group - 268 +/- 17g HMB group - 270 +/- 14g Nitrogen balance was affected by treatment (p = 0.05). HMB/ARG/GLN group had a more negative nitrogen balance than the HMB group over days 1-7 and 8-14 (p = < 0.05). Control group had a trend towards a more negative nitrogen balance compared to the HMB group over days 8-14 (p = 0.08). Nitrogen Balance of first 7 days compared with last 7 days of the trial was greater in the HMB group compared with the control group (p = <0.05). Muscle proteolysis was not affected by treatment.
2. How precise was the estimate of the treatment effect?
	Precision was expressed as standard errors. See above.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	Due to both the unclear nature of randomisation and the significant loss to follow-up (28%)within this trial, the results presented in this paper should be considered with caution.
2. Were all clinically important outcomes considered?
	Yes.
3. Are the likely treatment benefits worth the potential harms and costs?
	A cost analysis for each trial group has not be performed within this trial.
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