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Glutamine-enriched enteral nutrition in patients with multiple trauma
CORRESPONDENCE
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Kuroki K, Masuda A, Uehara H, Kuroki A. A new treatment for toxic megacolon. Lancet 1998; 352: 782. Sheth SG, LaMont JT. Toxic megacolon. Lancet 1998; 351: 509–13. Smith LDS, Williams BL. The pathogenic anaerobic bacteria, 3rd edn. Springfield, Illinois: Thomas, 1984. Tibbles PM, Edelsberg JS. Medical progress: hyperbaric-oxygen therapy. N Engl J Med 1996; 334: 1642–48. Hyperbaric oxygen therapy: a committee report, rev edn. Kensington, Maryland: Undersea and Hyperbaric Medical Society, 1996.
3000
Volume of daily feeding (mL)
1
Glutamine-enriched enteral nutrition in patients with multiple trauma Sir—Alexander Houdijk and colleagues (Sept 5 p 772)1 claim to have shown a reduction in the incidence of pneumonia, sepsis, and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition. However, their results are difficult to interpret. The investigators used the infection rate in bone-marrow transplant patients, who are not directly comparable with patients who have multiple trauma, and a historical group of trauma patients from 1985–89 to predict an infection rate of 43% in their control group. This rate is more than twice that reported in two large studies of infection in intensive care,2,3 thus, the observed rate of infection in the control group was inexplicably and inappropriately high. Moreover, in small groups with differing lengths of stay in the intensive care unit (ICU), the rate of infection needs to be corrected for the number of patient-days spent in the ICU (episodes of infections per 1000 patient-days). This omission alone may account for the differences of infection rates found between the two groups. The researchers provide no evidence that the volume of enteral feed delivered and absorbed in the first 3–5 days was equal in the two study groups. Previous studies have shown a dose response of some forms of immune-enhancing enteral nutrition.4 In addition, more than 80% of infections in the control group noted by Houdijk and colleagues occurred early, between the fifth and seventh day after admission to the ICU. No information is provided about the use of antimicrobial prophylaxis, specifically selective decontamination of the digestive tract, and no reduction in the use of antimicrobials in the glutamine group was reported. The differences in infection rates between the two groups did not influence the duration of mechanical ventilation and length of ICU stay.
THE LANCET • Vol 352 • November 7, 1998
2400
1800
1200
600 Glutamine Control
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Days of nutrition Amount of enteral nutrition in both groups
Thus, the reduction of infection in the treatment group neither reduced true morbidity nor influenced the main determinants of cost per patientepisode. In our view, other forms of immune-enhancing nutrition are more effective.5 *Imogen Mitchell, David Bihari *Intensive Care Unit, Royal Prince Alfred Hospital, Camperdown, Sydney NSW, Australia; and Intensive Care Unit, St George Hospital Kogarah, Sydney NSW 1
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3
4
5
Houdijk AP, Rigusburger ER, Jansen J, et al. Randomised trial of glutamine-entriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 1998; 352: 772–76. Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study. JAMA 1995; 274: 639–44. Cook D, Guyatt G, Marshall J, et al. A comparison of sucrulfate and rantidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. New Engl J Med 1998; 338: 791–97. Atkinson S, Seiffert E, Bihari D, on behalf of the Guy’s Hospital Intensive Care Group. A prospective, randomised, double blind, controlled clinical trial of enteral immunonutrition in the critically ill. Crit Care Med 1998; 26: 1164–72. Zaloga GP. Immune-enhancing enteral diets: where’s the beef? Crit Care Med 1998; 26: 1143–46.
Authors’ reply Sir—Imogen Mitchel and David Bihari’s interpretation of our results is obscured by inappropriate comparison with previously reported results. The rate of infection in a homogeneous group of trauma patients cannot be compared with that in a heterogeneous intensive care population.1 Furthermore, to predict morbidity from infection before undertaking a single centre randomised study, the best statistical precision is reached by the use of results
from that centre. In our study, both the control and glutamine group had similar length of ICU stay (16·5 [0·21] and 14·5 [1·9] days) and therefore different lengths of ICU stay does not explain the difference in infections. There were no differences in the volume of feeding per day between both groups. At the end of the third day, patients already received a mean of 1800 mL of nutrition (figure). Antimicrobial prophylaxis was given for 24 h perioperatively, selective decontamination of the gut was not used. Antimicrobial strategy was not predefined in the study. An important number of patients in both groups had chest trauma and long-term mechanical ventilation is frequent. The healing of fractured ribs and contused lungs in patients with chest trauma are independent factors in addition to pneumonia that prolong the duration of ventilation. Nutritional supplementation is not likely to speed up fracture healing. Our study shows that enteral glutamine lowers the rate of pneumonia, bacteraemia, and sepsis in trauma patients. The strength of the study is that the effect of a single nutritional supplement is studied in a homogeneous group and comparison to studies that use immunonutrition with multiple supplements in a heteregeneous population of patients is inappropriate.1 Conclusions as to whether one or the other form of immunonutrition is more effective in trauma patients cannot be based on present facts. *A P J Houdijk, P A M van Leeuwen, H J Th M Haarman Department of Surgery, De Boelelaan 1118, 1051 HV Amsterdam, Netherlands 1
Atkinson S, Sieffert E, Bihari D. A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Crit Care Med 1998; 26: 1164–72.
1553
2 3
4
5
Kuroki K, Masuda A, Uehara H, Kuroki A. A new treatment for toxic megacolon. Lancet 1998; 352: 782. Sheth SG, LaMont JT. Toxic megacolon. Lancet 1998; 351: 509–13. Smith LDS, Williams BL. The pathogenic anaerobic bacteria, 3rd edn. Springfield, Illinois: Thomas, 1984. Tibbles PM, Edelsberg JS. Medical progress: hyperbaric-oxygen therapy. N Engl J Med 1996; 334: 1642–48. Hyperbaric oxygen therapy: a committee report, rev edn. Kensington, Maryland: Undersea and Hyperbaric Medical Society, 1996.
3000
Volume of daily feeding (mL)
1
Glutamine-enriched enteral nutrition in patients with multiple trauma Sir—Alexander Houdijk and colleagues (Sept 5 p 772)1 claim to have shown a reduction in the incidence of pneumonia, sepsis, and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition. However, their results are difficult to interpret. The investigators used the infection rate in bone-marrow transplant patients, who are not directly comparable with patients who have multiple trauma, and a historical group of trauma patients from 1985–89 to predict an infection rate of 43% in their control group. This rate is more than twice that reported in two large studies of infection in intensive care,2,3 thus, the observed rate of infection in the control group was inexplicably and inappropriately high. Moreover, in small groups with differing lengths of stay in the intensive care unit (ICU), the rate of infection needs to be corrected for the number of patient-days spent in the ICU (episodes of infections per 1000 patient-days). This omission alone may account for the differences of infection rates found between the two groups. The researchers provide no evidence that the volume of enteral feed delivered and absorbed in the first 3–5 days was equal in the two study groups. Previous studies have shown a dose response of some forms of immune-enhancing enteral nutrition.4 In addition, more than 80% of infections in the control group noted by Houdijk and colleagues occurred early, between the fifth and seventh day after admission to the ICU. No information is provided about the use of antimicrobial prophylaxis, specifically selective decontamination of the digestive tract, and no reduction in the use of antimicrobials in the glutamine group was reported. The differences in infection rates between the two groups did not influence the duration of mechanical ventilation and length of ICU stay.
THE LANCET • Vol 352 • November 7, 1998
2400
1800
1200
600 Glutamine Control
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Days of nutrition Amount of enteral nutrition in both groups
Thus, the reduction of infection in the treatment group neither reduced true morbidity nor influenced the main determinants of cost per patientepisode. In our view, other forms of immune-enhancing nutrition are more effective.5 *Imogen Mitchell, David Bihari *Intensive Care Unit, Royal Prince Alfred Hospital, Camperdown, Sydney NSW, Australia; and Intensive Care Unit, St George Hospital Kogarah, Sydney NSW 1
2
3
4
5
Houdijk AP, Rigusburger ER, Jansen J, et al. Randomised trial of glutamine-entriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 1998; 352: 772–76. Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study. JAMA 1995; 274: 639–44. Cook D, Guyatt G, Marshall J, et al. A comparison of sucrulfate and rantidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. New Engl J Med 1998; 338: 791–97. Atkinson S, Seiffert E, Bihari D, on behalf of the Guy’s Hospital Intensive Care Group. A prospective, randomised, double blind, controlled clinical trial of enteral immunonutrition in the critically ill. Crit Care Med 1998; 26: 1164–72. Zaloga GP. Immune-enhancing enteral diets: where’s the beef? Crit Care Med 1998; 26: 1143–46.
Authors’ reply Sir—Imogen Mitchel and David Bihari’s interpretation of our results is obscured by inappropriate comparison with previously reported results. The rate of infection in a homogeneous group of trauma patients cannot be compared with that in a heterogeneous intensive care population.1 Furthermore, to predict morbidity from infection before undertaking a single centre randomised study, the best statistical precision is reached by the use of results
from that centre. In our study, both the control and glutamine group had similar length of ICU stay (16·5 [0·21] and 14·5 [1·9] days) and therefore different lengths of ICU stay does not explain the difference in infections. There were no differences in the volume of feeding per day between both groups. At the end of the third day, patients already received a mean of 1800 mL of nutrition (figure). Antimicrobial prophylaxis was given for 24 h perioperatively, selective decontamination of the gut was not used. Antimicrobial strategy was not predefined in the study. An important number of patients in both groups had chest trauma and long-term mechanical ventilation is frequent. The healing of fractured ribs and contused lungs in patients with chest trauma are independent factors in addition to pneumonia that prolong the duration of ventilation. Nutritional supplementation is not likely to speed up fracture healing. Our study shows that enteral glutamine lowers the rate of pneumonia, bacteraemia, and sepsis in trauma patients. The strength of the study is that the effect of a single nutritional supplement is studied in a homogeneous group and comparison to studies that use immunonutrition with multiple supplements in a heteregeneous population of patients is inappropriate.1 Conclusions as to whether one or the other form of immunonutrition is more effective in trauma patients cannot be based on present facts. *A P J Houdijk, P A M van Leeuwen, H J Th M Haarman Department of Surgery, De Boelelaan 1118, 1051 HV Amsterdam, Netherlands 1
Atkinson S, Sieffert E, Bihari D. A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Crit Care Med 1998; 26: 1164–72.
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