192 J. P. FLATT, PHD
Department of Biochemistry University of Massachusetts Medical Center Worcester, MA 01655 GEORGE L. BLACKBURN, MD, PHD Nutrition and Metabolism Laboratory New England Deaconess Hospital Boston, MA 02215 BRUCE R. BISTRIAN, MD, PHD Laboratory of Nutrition and Infection New England Deaconess Hospital Boston, MA 02215 REFERENCES 1. Blackburn
GL, Bistrian BR, Maini BS, et al: Nutritional and metabolic assessment of the hospitalized patient. JPEN 1:11-27,
1977 2. Konstantinides FN, Konstantinides NN, Li JC, et al: Urinary urea nitrogen: Too insensitive for calculating nitrogen balance studies in surgical clinical nutrition. JPEN 15:189-193, 1991 3. Bistrian BR: A simple technique to estimate severity of stress. Surg Gynecol Obstet 148:675-678, 1979 4. Mackenzie TA, Clark NG, Bistrian BR, et al: A simple method for estimating nitrogen balance in hospitalized patients: A review and supporting data for a previously proposed technique. J Am Coll Nutr 4:575-581, 1985
Parenteral Nutrition in Bone Marrow Transplant Patients To the Editor: I have reviewed the article by Geibig et all with interest. I have several questions however, regarding their methods and conclusions. First, the authors actually compared two high-nitrogen formulations. I am surprised their &dquo;standard&dquo; total parenteral nutrition (TPN) formulation supplies 1.7 g/kg per day protein and the highnitrogen formulation supplied 2.1 g/kg per day. I wonder whether the increased blood urea nitrogen in both groups observed during the study was a reflection of protein &dquo;overload&dquo; despite negative nitrogen balances. It remains unclear to me whether the groups receiving these two protein levels were truly identical. Unfortunately the reader is given insufficient information. Only the initiation dose of methylprednisolone is given. Were any changes made in this dosage during the study? Were the doses similar in both groups? The only measure of visceral protein stores was the total iron-binding capacity, which may be affected by iron deficiency in addition to hepatic abnormalities, thereby failing to reflect actual nutritional status. One might expect some hepatic abnormalities from bone marrow conditioning or previous chemotherapy, yet no information was given with regard to liver function and serum aminotransferase values. It would also have been valuable to have compared additional visceral proteins, namely albumin or prealbumin. In addition, the anthropometric data provided appear inadequate. The &dquo;standard&dquo; group had a slightly lower
weight but slightly greater caloric requirement than did the high-nitrogen group, although the differences do not reach statistical significance. This suggests to me that perhaps the standard group may have been at a lower percent of ideal body weight than was the high-nitrogen group. It is difficult for
me
to conclude
on
the basis of
the data
presented that both study groups truly were comparable nutritionally. In addition, the authors failed were collected. Was it at admission or the day TPN was begun, for instance ? Were the steroids begun before or after the baseline? Finally, the greatest difficulty I have with this study is the primary method used to assess efficacy, that being the nitrogen balance. Certainly the literature is replete with studies criticizing the use of the urinary urea nitrogen (UUN) to calculate nitrogen balance in a research study, but even if one were to accept the UUN and nitrogen balance as an accurate and reproducible measure of nitrogen balance, one is still faced with a major problem specific to the patient group studied. The authors state that 50% of the subjects developed acute graft-vs-host disease (GVHD) and 50% developed chronic GVHD, all within the first hospital admission (which presumably occurred during the TPN). It is unclear whether all patients developed some form of GVHD or whether those with acute disease progressed to more chronic disease, leaving a substantial group without GVHD. Because GVHD is associated with massive protein-losing enteropathy,2 I should think the UUN, even with its correction constant, would be a very inaccurate method for assessing nitrogen losses in these subjects. I wonder why the authors chose not to measure, but to estimate stool nitrogen losses.
to state when the baseline data
hospital
ALAN L. BUCHMAN, MD Division of Digestive Diseases
Emory University School of Medicine Atlanta, GA 30322 REFERENCES 1.
Geibig CB, Owens JP, Mirtallo JM, et al: Parenteral nutrition for marrow transplant recipients: Evaluation of an increased nitrogen dose. JPEN 15:184—188, 1991
2. Cornelius EA:
reaction.
Protein-losing enteropathy in the graft-versus-host Transplantation 9:247—252, 1970
Tube
Feeding-Related Diarrhea
To the Editor: In their study on tube feeding-related diarrhea Guenter et all examine the association of various factors with diarrhea in acutely ill patients. For several reasons we question the validity of their findings. Fifty patients were &dquo;assigned&dquo; to each diet group. It is not clear whether randomization was used in this assignment. Without proper randomization the potential for bias exists. No mention is made of medications the subjects may
Downloaded from pen.sagepub.com at NANYANG TECH UNIV LIBRARY on April 24, 2015
193 have received other than antibiotics. There have been reports,2,3 including the article by Hill et al4 in that same issue of JPEN, that have documented the association of sorbitol-containing medications in tube-fed patients with diarrhea. Conversely, a recent study found a very low incidence of diarrhea in tube-fed patients when controlling for sorbitol-containing elixirs .5 Magnesium-containing antacids also have been implicated as a contributing factor to diarrhea in tube-fed patients.’ As discussed by Hill et al,4 manufacturers are not required to put the sorbitol content on the list of ingredients in medications. Moreover, sorbitol content may vary widely among manufacturers of the same generic drug. We compiled a list of the sorbitol contents of the various elixir preparations on our hospital formulary. Sorbitol was present in more than 45 of these preparations. For example, the acetaminophen elixir on our formulary contains 160 mg of acetaminophen and 2.5 g of sorbitol in 5 mL. One standard dose of acetaminophen (640 mg) would therefore deliver 10 g of sorbitol (or 15 g if they should receive an extra-strength dose of 1000 mg). This amount has been shown to cause gastrointestinal discomfort in healthy persons, whereas about 20 g usually causes diarrhea. It is easy to see how a patient on
multiple medications could ingest of sorbitol
over
Finally, and
the
course
most
of a
a
significant quantity
day.
importantly, association does
prove causation. Guenter et
al’ did
not not show that tube
feeding was responsible for the diarrhea in the first place. To prove tube feeding was responsible would have required that they discontinue the feeding and find that the diarrhea resolves, and/or that they include a group of similar but non-tube-fed patients. In addition, all other of diarrhea, such as sorbitol-containing medications, would have to be excluded. This was done in the causes
et al2 and in one recently conducted by both for diarrhea in a small percentage of ourselveS,5 patients in which it developed. Similarly, although they have confirmed the findings of some other studies associating antibiotic usage with diarrhea, they have not shown that antibiotics caused the diarrhea, although 50% of the cases were indirectly related to antibiotics based on a positive test for stool Clostridium difficile toxin. Both administration of antibiotics and lower serum albumin levels were found to be associated with diarrhea. It is not stated whether the antibiotics were given orally or intravenously. In further analyses, antibiotics were associated with lower serum albumin levels, and after controlling for antibiotic usage serum albumin was not significantly associated with diarrhea. An explanation for the relationship between antibiotics and serum albumin can be found in looking at the body’s metabolic response to injury.’ Sepsis or severe infection can initiate a number of processes modulated by hormones or monokines. As part of this response there is both a decrease in the production of albumin and an increase in its catabolism, leading to lower serum albumin levels. Because patients who have sepsis or severe infections are likely to be receiving antibiotics, an association between antibiotics and lower serum albumin levels is to be expected. Although the
attempted to control for severity of illness through disease classification, the above association authors
would indicate otherwise. This association between antibiotic usage and lower serum albumin levels was correctly noted, but they did not exclude the possible association of both of these with more severe illness. More severe illness may be associated with the use of larger numbers of other medications, such as those listed above, which are probably the real cause of most cases of diarrhea in tube-fed patients. DON HENSRUD, MD, MPH DOUGLAS C. HEIMBURGER, MD Division of Clinical Nutrition Departments of Nutrition Sciences and Medicine University of Alabama at Birmingham Birmingham, AL 35294 REFERENCES 1. Guenter
PA, Settle RG, Perlmutter S, et al: Tube feeding-related diarrhea in acutely ill patients. JPEN 15:277-280, 1991 2. Edes TE, Walk BE, Austin JL: Diarrhea in tube-fed patients: Feeding formula not necessarily the cause. Am J Med 88:91-93, 1990 3. Edes TE, Walk BE: Nosocomial diarrhea: Beware the medicinal elixir. South Med J 81:S31, 1988 4. Hill DB, Henderson LM, McClain CJ: Osmotic diarrhea induced by sugar-free theophylline solution in critically ill patients. JPEN 15:332-336, 1991 5. Heimburger DC, Sockwell DG, Geels WJ: Does tube feeding cause diarrhea? (Abstr). Am J Clin Nutr 53:P-19, 1991 6. Hyams JS: Sorbitol intolerance: An underappreciated cause of functional gastrointestinal complaints. Gastroenterology 84:30-33, 1983 7. McMahon MM, Bistrian BR: The physiology of nutritional assessment and therapy in protein-calorie malnutrition. Disease-aMonth 36, 1990
study by Edes
Measurement of
Resting Metabolic Expenditure
To the Editor: I have read with interest the article &dquo;A Single, Accurate Measurement of Resting Metabolic Expenditure&dquo; by Drs Stokes and Hill that appeared in JPEN.1 Although the paper presents some additional findings concerning resting metabolic expenditures (RMEs), there is nothing new relative to the measurements of patients at rest or in a postprandial state or conditions concerning how long the single measurement needs to be made. The authors should have indicated that the reference to my paper in JPEN (3:452-456, 1979) (their reference 14) and otherS2-4 describes similar conditions. The authors also indicated that I used a 5- to 10-minute measurement of RME to estimate the 24-hour total energy requirements of patients (ref 14). All my published data on RME measurements have been with mv ventilated hood system over a 20- to 30-minute period in the morning before breakfast or intake. In earlier years I did employ a 5-minute measurement of expired breath using the Ilrly-
Downloaded from pen.sagepub.com at NANYANG TECH UNIV LIBRARY on April 24, 2015
299 TABLE I Documentation relevant to Pharmacia Deltec
matic representation of the LifePort Lo-Profile Port provided by the manufacturer. To confirm the correct identity of the other implanted catheters, we again reviewed the medical records and xrays of the
PORT-A-CATH System explain the misidentification. Searching prior medical records, examining several infusion systems, and speaking with manufacturers has subsequently allowed us to identify the catheter in Figure 1 as a LifePort Lo-Profile Port (Strato Medical Corporation). The earlier records identified the catheter and included other more precise descriptors (Cat. no.
LPS1055; Lot
no.
80978). Further, the radiographic
pearance of the infusion
cases. We report here that the other catheters have been correctly identified to the best of our knowledge. The supporting documentation for the cases relevant to Pharmacia Deltec appears in Table I. We wish to thank Ms Copeland for bringing the catheter misidentification to our attention. We appreciate the opportunity to enhance the accuracy of our earlier
report.
ap-
system matched the diagram-
MICHAEL H. ZAROUKIAN, MD, PHD Michigan State University East Lansing, Mich WILLIAM R. JACOBS, MD
Raleigh, NC
Correction In the letter
by Hensrud and Heimburger (Vol. 16, No. 2, 1992) the last sentence of the fourth paragraph is incorrectly stated, as a result of a printing error. The correct sentence should read as follows: This was done in the study by Edes et al~ and in one recently conducted by ourselves,’ both of which found that tube-feeding was responsible for diarrhea in a small percentage of patients in which it developed.
Department of Biochemistry University of Massachusetts Medical Center Worcester, MA 01655 GEORGE L. BLACKBURN, MD, PHD Nutrition and Metabolism Laboratory New England Deaconess Hospital Boston, MA 02215 BRUCE R. BISTRIAN, MD, PHD Laboratory of Nutrition and Infection New England Deaconess Hospital Boston, MA 02215 REFERENCES 1. Blackburn
GL, Bistrian BR, Maini BS, et al: Nutritional and metabolic assessment of the hospitalized patient. JPEN 1:11-27,
1977 2. Konstantinides FN, Konstantinides NN, Li JC, et al: Urinary urea nitrogen: Too insensitive for calculating nitrogen balance studies in surgical clinical nutrition. JPEN 15:189-193, 1991 3. Bistrian BR: A simple technique to estimate severity of stress. Surg Gynecol Obstet 148:675-678, 1979 4. Mackenzie TA, Clark NG, Bistrian BR, et al: A simple method for estimating nitrogen balance in hospitalized patients: A review and supporting data for a previously proposed technique. J Am Coll Nutr 4:575-581, 1985
Parenteral Nutrition in Bone Marrow Transplant Patients To the Editor: I have reviewed the article by Geibig et all with interest. I have several questions however, regarding their methods and conclusions. First, the authors actually compared two high-nitrogen formulations. I am surprised their &dquo;standard&dquo; total parenteral nutrition (TPN) formulation supplies 1.7 g/kg per day protein and the highnitrogen formulation supplied 2.1 g/kg per day. I wonder whether the increased blood urea nitrogen in both groups observed during the study was a reflection of protein &dquo;overload&dquo; despite negative nitrogen balances. It remains unclear to me whether the groups receiving these two protein levels were truly identical. Unfortunately the reader is given insufficient information. Only the initiation dose of methylprednisolone is given. Were any changes made in this dosage during the study? Were the doses similar in both groups? The only measure of visceral protein stores was the total iron-binding capacity, which may be affected by iron deficiency in addition to hepatic abnormalities, thereby failing to reflect actual nutritional status. One might expect some hepatic abnormalities from bone marrow conditioning or previous chemotherapy, yet no information was given with regard to liver function and serum aminotransferase values. It would also have been valuable to have compared additional visceral proteins, namely albumin or prealbumin. In addition, the anthropometric data provided appear inadequate. The &dquo;standard&dquo; group had a slightly lower
weight but slightly greater caloric requirement than did the high-nitrogen group, although the differences do not reach statistical significance. This suggests to me that perhaps the standard group may have been at a lower percent of ideal body weight than was the high-nitrogen group. It is difficult for
me
to conclude
on
the basis of
the data
presented that both study groups truly were comparable nutritionally. In addition, the authors failed were collected. Was it at admission or the day TPN was begun, for instance ? Were the steroids begun before or after the baseline? Finally, the greatest difficulty I have with this study is the primary method used to assess efficacy, that being the nitrogen balance. Certainly the literature is replete with studies criticizing the use of the urinary urea nitrogen (UUN) to calculate nitrogen balance in a research study, but even if one were to accept the UUN and nitrogen balance as an accurate and reproducible measure of nitrogen balance, one is still faced with a major problem specific to the patient group studied. The authors state that 50% of the subjects developed acute graft-vs-host disease (GVHD) and 50% developed chronic GVHD, all within the first hospital admission (which presumably occurred during the TPN). It is unclear whether all patients developed some form of GVHD or whether those with acute disease progressed to more chronic disease, leaving a substantial group without GVHD. Because GVHD is associated with massive protein-losing enteropathy,2 I should think the UUN, even with its correction constant, would be a very inaccurate method for assessing nitrogen losses in these subjects. I wonder why the authors chose not to measure, but to estimate stool nitrogen losses.
to state when the baseline data
hospital
ALAN L. BUCHMAN, MD Division of Digestive Diseases
Emory University School of Medicine Atlanta, GA 30322 REFERENCES 1.
Geibig CB, Owens JP, Mirtallo JM, et al: Parenteral nutrition for marrow transplant recipients: Evaluation of an increased nitrogen dose. JPEN 15:184—188, 1991
2. Cornelius EA:
reaction.
Protein-losing enteropathy in the graft-versus-host Transplantation 9:247—252, 1970
Tube
Feeding-Related Diarrhea
To the Editor: In their study on tube feeding-related diarrhea Guenter et all examine the association of various factors with diarrhea in acutely ill patients. For several reasons we question the validity of their findings. Fifty patients were &dquo;assigned&dquo; to each diet group. It is not clear whether randomization was used in this assignment. Without proper randomization the potential for bias exists. No mention is made of medications the subjects may
Downloaded from pen.sagepub.com at NANYANG TECH UNIV LIBRARY on April 24, 2015
193 have received other than antibiotics. There have been reports,2,3 including the article by Hill et al4 in that same issue of JPEN, that have documented the association of sorbitol-containing medications in tube-fed patients with diarrhea. Conversely, a recent study found a very low incidence of diarrhea in tube-fed patients when controlling for sorbitol-containing elixirs .5 Magnesium-containing antacids also have been implicated as a contributing factor to diarrhea in tube-fed patients.’ As discussed by Hill et al,4 manufacturers are not required to put the sorbitol content on the list of ingredients in medications. Moreover, sorbitol content may vary widely among manufacturers of the same generic drug. We compiled a list of the sorbitol contents of the various elixir preparations on our hospital formulary. Sorbitol was present in more than 45 of these preparations. For example, the acetaminophen elixir on our formulary contains 160 mg of acetaminophen and 2.5 g of sorbitol in 5 mL. One standard dose of acetaminophen (640 mg) would therefore deliver 10 g of sorbitol (or 15 g if they should receive an extra-strength dose of 1000 mg). This amount has been shown to cause gastrointestinal discomfort in healthy persons, whereas about 20 g usually causes diarrhea. It is easy to see how a patient on
multiple medications could ingest of sorbitol
over
Finally, and
the
course
most
of a
a
significant quantity
day.
importantly, association does
prove causation. Guenter et
al’ did
not not show that tube
feeding was responsible for the diarrhea in the first place. To prove tube feeding was responsible would have required that they discontinue the feeding and find that the diarrhea resolves, and/or that they include a group of similar but non-tube-fed patients. In addition, all other of diarrhea, such as sorbitol-containing medications, would have to be excluded. This was done in the causes
et al2 and in one recently conducted by both for diarrhea in a small percentage of ourselveS,5 patients in which it developed. Similarly, although they have confirmed the findings of some other studies associating antibiotic usage with diarrhea, they have not shown that antibiotics caused the diarrhea, although 50% of the cases were indirectly related to antibiotics based on a positive test for stool Clostridium difficile toxin. Both administration of antibiotics and lower serum albumin levels were found to be associated with diarrhea. It is not stated whether the antibiotics were given orally or intravenously. In further analyses, antibiotics were associated with lower serum albumin levels, and after controlling for antibiotic usage serum albumin was not significantly associated with diarrhea. An explanation for the relationship between antibiotics and serum albumin can be found in looking at the body’s metabolic response to injury.’ Sepsis or severe infection can initiate a number of processes modulated by hormones or monokines. As part of this response there is both a decrease in the production of albumin and an increase in its catabolism, leading to lower serum albumin levels. Because patients who have sepsis or severe infections are likely to be receiving antibiotics, an association between antibiotics and lower serum albumin levels is to be expected. Although the
attempted to control for severity of illness through disease classification, the above association authors
would indicate otherwise. This association between antibiotic usage and lower serum albumin levels was correctly noted, but they did not exclude the possible association of both of these with more severe illness. More severe illness may be associated with the use of larger numbers of other medications, such as those listed above, which are probably the real cause of most cases of diarrhea in tube-fed patients. DON HENSRUD, MD, MPH DOUGLAS C. HEIMBURGER, MD Division of Clinical Nutrition Departments of Nutrition Sciences and Medicine University of Alabama at Birmingham Birmingham, AL 35294 REFERENCES 1. Guenter
PA, Settle RG, Perlmutter S, et al: Tube feeding-related diarrhea in acutely ill patients. JPEN 15:277-280, 1991 2. Edes TE, Walk BE, Austin JL: Diarrhea in tube-fed patients: Feeding formula not necessarily the cause. Am J Med 88:91-93, 1990 3. Edes TE, Walk BE: Nosocomial diarrhea: Beware the medicinal elixir. South Med J 81:S31, 1988 4. Hill DB, Henderson LM, McClain CJ: Osmotic diarrhea induced by sugar-free theophylline solution in critically ill patients. JPEN 15:332-336, 1991 5. Heimburger DC, Sockwell DG, Geels WJ: Does tube feeding cause diarrhea? (Abstr). Am J Clin Nutr 53:P-19, 1991 6. Hyams JS: Sorbitol intolerance: An underappreciated cause of functional gastrointestinal complaints. Gastroenterology 84:30-33, 1983 7. McMahon MM, Bistrian BR: The physiology of nutritional assessment and therapy in protein-calorie malnutrition. Disease-aMonth 36, 1990
study by Edes
Measurement of
Resting Metabolic Expenditure
To the Editor: I have read with interest the article &dquo;A Single, Accurate Measurement of Resting Metabolic Expenditure&dquo; by Drs Stokes and Hill that appeared in JPEN.1 Although the paper presents some additional findings concerning resting metabolic expenditures (RMEs), there is nothing new relative to the measurements of patients at rest or in a postprandial state or conditions concerning how long the single measurement needs to be made. The authors should have indicated that the reference to my paper in JPEN (3:452-456, 1979) (their reference 14) and otherS2-4 describes similar conditions. The authors also indicated that I used a 5- to 10-minute measurement of RME to estimate the 24-hour total energy requirements of patients (ref 14). All my published data on RME measurements have been with mv ventilated hood system over a 20- to 30-minute period in the morning before breakfast or intake. In earlier years I did employ a 5-minute measurement of expired breath using the Ilrly-
Downloaded from pen.sagepub.com at NANYANG TECH UNIV LIBRARY on April 24, 2015
299 TABLE I Documentation relevant to Pharmacia Deltec
matic representation of the LifePort Lo-Profile Port provided by the manufacturer. To confirm the correct identity of the other implanted catheters, we again reviewed the medical records and xrays of the
PORT-A-CATH System explain the misidentification. Searching prior medical records, examining several infusion systems, and speaking with manufacturers has subsequently allowed us to identify the catheter in Figure 1 as a LifePort Lo-Profile Port (Strato Medical Corporation). The earlier records identified the catheter and included other more precise descriptors (Cat. no.
LPS1055; Lot
no.
80978). Further, the radiographic
pearance of the infusion
cases. We report here that the other catheters have been correctly identified to the best of our knowledge. The supporting documentation for the cases relevant to Pharmacia Deltec appears in Table I. We wish to thank Ms Copeland for bringing the catheter misidentification to our attention. We appreciate the opportunity to enhance the accuracy of our earlier
report.
ap-
system matched the diagram-
MICHAEL H. ZAROUKIAN, MD, PHD Michigan State University East Lansing, Mich WILLIAM R. JACOBS, MD
Raleigh, NC
Correction In the letter
by Hensrud and Heimburger (Vol. 16, No. 2, 1992) the last sentence of the fourth paragraph is incorrectly stated, as a result of a printing error. The correct sentence should read as follows: This was done in the study by Edes et al~ and in one recently conducted by ourselves,’ both of which found that tube-feeding was responsible for diarrhea in a small percentage of patients in which it developed.
