Diarrhea induced by enteral feeding
Mobarhan, Sohrab
CASE 1
Ms. AT is an 18-year-old black female who was admitted to the Intensive Care Unit (ICU) following aggravation of her Guillain-Barre syndrome and requiring assisted ventilation. The patient was seen by the nutrition support team 24 hours later to start her on enteral feeding. She appeared to be in normal nutrition status without evidence of significant weight loss. However, her serum albumin was 2.5 g/dL. Her height was 163 cm, weight 65 kg, and her resting energy expenditure (REE) as measured by indirect calorimetry was 1470 kcal per 24 hours. The patient was started on 30 mL Osmolite(R) HN/ hour (Ross Laboratories, Columbus, OH) delivered via nasoenteral tube, and the feeding was increased progressively to 60 mL over the next 3 days. On the 6th day she began having frequent loose bowel movements. The abdominal examination was unremarkable. Prior to any laboratory work-up, a 24-hour stool collection showed a total weight of 150 g. Careful examination of Ms. AT’s medications showed that she had been started on 30 mL combination of magnesium hydroxide-containing antacid (450 mg/mL) every 3 hours 2 days prior to the onset of diarrhea. The discontinuation of this antacid medication resulted in prompt cessation of reported diarrhea.
CASE 2
Ms. HD is a 65-year-old white female with a history of coronary heart disease. She was well until 3 weeks prior to admission, when she developed symptoms of an upper respiratory tract infection, manifested by fever and cough productive of yellow-green sputum. She was empirically started on an antibiotic. After an initial response to this medication, the patient’s clinical status began to deteriorate such that she finally required an emergency room visit. On presentation to the emergency room, her respiratory rate was 36 and blood gases demonstrated hypoxia and hypercapnia. A chest X-ray revealed bilateral pulmonary infiltrates. Because of worsening respiratory distress, she was ultimately intubated and admitted to the ICU. After 4 days, with minimal improvement in her respiratory status, she was started on enteral feedings. During the next 3 days the patient began to complain of abdominal pain and cramping. This was followed by large volume, watery diarrhea up to 10 times per day. The patient was initially treated with fiber and bowel paralytics with little effect. Her abdominal examination at this time was significant for diffuse tenderness, worse in the left lower quadrant, but without peritoneal signs. A 24-hour stool collection showed a fecal weight of 620 g. A flexible sigmoidoscopy was performed and demonstrated an erythematous and edematous mucosa with multiple interspersed whitish plaques. A stool test for Clostridium difficile toxin was positive and the diarrhea responded rapidly to oral treatment with metronidazole.
CASE 3
Mr. TP is a 42-year-old year old white male with a negative medical history who was brought to the emergency room after being involved in a motor vehicle accident. Upon presentation in the emergency room, the patient was comatose with signs of trauma to the head and abdomen. The patient was taken to the ICU where he was intubated for shallow, sporadic respirations and supported with assisted ventilation. Within 3 hours of admission, his vital signs became unstable and a complete blood count showed a decreasing hemoglobin without obvious signs of external blood loss. The patient was taken to the operating room for an emergency laparotomy, and a ruptured spleen was removed. The patient did well postoperatively with stable vital signs and improving sensorium. On the second hospital day he spiked a temperature of 102deg F. A work-up failed to reveal an obvious source, and broad-spectrum antibiotics were started for a presumed abdominal infection. In addition, the patient was started on enteral feeding, initially at a low rate, which subsequently was increased to target calories over the next 3 days. Two days later the patient began having watery diarrhea, which was negative for hemoccult blood. The total daily fecal output was 240 g. Stool cultures, C difficile toxin, ova and parasites, and fecal leukocytes were obtained and were negative. A flexible sigmoidoscopy demonstrated a normal mucosa. The diarrhea persisted and was empirically treated with fiber, bowel paralytics, and finally, bile acid resin binders. On the eighth hospital day, control of the diarrhea was achieved.
DISCUSSION
The majority of nutritionists agree that enteral feeding (EF) is the preferred type of nonvolitional nutritional treatment. However, it is also associated with multiple metabolic, respiratory, and gastrointestinal complications.(1,2) Among such complications, diarrhea is probably the most troublesome, with a reported incidence up to 68%. Diarrhea causes nursingcare-related problems and metabolic problems, and frequently compounds nutrient deficiencies by disrupting the EF.(3) The understanding of the pathogenesis and treatment of EF-related diarrhea is hampered by the fact that there is considerable controversy about the definition of this type of diarrhea. A recent study and extensive review by Zimmaro and colleagues(4) highlights this difficulty. Their literature review suggests that at least 14 different definitions of diarrhea can be found. Moreover, it appears that while some authors consider even one single loose or nonformed stool as evidence of diarrhea, others require the clinical evidence of four or more liquid stools per day to support this diagnosis.(5,6) Based on these reported impressions and their own experience, Zimmaro et al.(4) analyzed the data on the frequency and consistency of diarrhea collected prospectively during a period of 3 months on all patients receiving EF. They employed eight different descriptions to define diarrhea, which were: >=1 liquid stool/day, >=2 liquid stools/day, >=3 liquid stools/day, >=4 liquid stools/ day, >=3 stool/day, >=4 stools/day, >=4 stools/day for 2 days, and >=5 stools/day.
During a period of 3 months, a total of 29 patients 41-86 years old were monitored for 13.0 days. The extent of diarrhea was assessed in relation to the incidence of diarrhea and the percentage of days with diarrhea. The latter was calculated by the number of days with diarrhea divided by the number of days monitored, multiplied by 100.
The authors noted significant differences in the incidence of diarrhea, ranging from 72% to 21%, depending on which definition of diarrhea was used. Similarly, the definition of diarrhea influenced the calculated percentage of days with diarrhea. When the definition of >=1 liquid stool/day was used, the percentage of days with diarrhea was 25.6 +/- 4.8%. Yet, when the definition of diarrhea was >=5 stools/ day the average percentage was reduced to 1.7% +/0.8%. As was expected, the duration of monitoring showed a significant positive relationship to the incidence of diarrhea. However, when diarrhea was reported as a percentage of days with diarrhea, the relationship disappeared. This work, as well as several other studies and reviews(1,2) shows the inaccuracy of commonly used definitions of diarrhea. In 1991, Benya et al.(7) designed a carefully conducted study that determined the fecal output of nine malnourished patients who received the same iso-osmolar formula during the first 6 days of tube feeding.(7) The patients and/or nurses were interviewed daily on the frequency of patients’ defecation and to see whether they thought diarrhea was present. The frequency of defecation was recorded and all stool from the patients were carefully collected and weighed. On a subjective basis, the incidence of diarrhea rose from 11% on day 1 to 25% on day 4 and to 43% by day 6. The group complaining of diarrhea averaged 3.0 bowel movements per day, while those denying diarrhea (n = 5) averaged fewer than 0.2 bowel movements per day (p > 0.01). Stool weight, however, plateaued for all patients by day 6 at 52.7 +/- 35.7 g of stool per day. Interestingly, no patient had in excess of 250 g of stool per day. This study showed that both patients and nurses mistakenly interpret frequent small amounts of loose stool as diarrhea.
The inadequacy in defining diarrhea through subjective claims and frequency of defecation was also shown by data from NHANES I, reported by Everhart et al.(8) In a survey of 14,407 healthy adults, between 1.6% and 5.2% claimed to suffer frequent diarrhea. Interestingly, 22.8% of black men over 60 years of age reported having two or more bowel movements per day.(8) In a study of daily stool output of 20 normal volunteers, Wyman et al.(9) noted a mean stool weight of 128.5 g per subject per day with a standard deviation of 41 g. Two to three standard deviations from mean (200-250 g) stool per day would represent a statistically legitimate point for separation of clinically significant diarrhea from daily normal stool output.
The human gastrointestinal system is highly efficient in digestion and absorption of a variety of foods, including enteral formulas. Zarling et al.(10) showed that normal subjects tolerate complete and elemental enteral formulas very well. Using a nasoduodenal feeding route they infused either elemental formulas (Criticare HN, Bristol Myers/Mead Johnson, Evansville, IN) or complex formulas (Isocal HCN, Bristol Myers/Mead Johnson, Evansville, IN) in 20 healthy volunteers. The infusion rate ranged between 50 and 150 kcal/hour and the osmolality ranged between 323 and 690 mOsm/kg of water. Even at the maximum flow rate and osmolality, both enteral formulas were tolerated well. There was no evidence of diarrhea and no carbohydrate malabsorption was detected as measured by breath hydrogen test.
In another study, Benya et al.(11) investigated the efficiency of intestinal absorption of protein and carbohydrates in malnourished and well-nourished patients requiring enteral feeding. Twenty-one subjects requiring tube feeding without significant edema or major organ failure and not on antibiotics (well-nourished controls = 7; malnourished = 7; malnourished with nongastrointestinal malignancy = 7) received 56 kcal/hour Osmolite (Ross Laboratories, Columbus, OH) continuously for 72 hours. Twelve of these subjects completed an additional 48 hours of study when they received 125 kcal/hour continuously. The hydrogen breath tests were performed serially to assess carbohydrate absorption, and stool nitrogen content was measured to assess protein absorption. The frequency of defecation, stool weight, and stool moisture content were also measured.
The analysis of these data failed to reveal statistically significant differences between the three groups in terms of protein and carbohydrate absorption, as well as failing to demonstrate the presence of diarrhea. It was concluded that malnourished patients receiving an iso-osmolar diet absorb carbohydrate and protein as well as well-nourished patients during enteral feeding.
Kandil et al.(12) studied the tolerance of healthy subjects to increasing rates of enteral formula tube feeding. This well-designed and rather complex study was conducted in a metabolic unit, where five normal volunteers with a history of normal daily bowel movements were fed Osmolite HN via enteral tube starting at 314 kJ/kg body weight/day (continuous feeding). The feedings were progressively increased each 24 hours (63 kJ/kg body weight/day) until the stool weight exceeded 300 g/ 24 hours or intolerable clinical symptoms developed. The results of the study showed that the subjects were able to tolerate a maximum of 24 hours infusion of 331-511 kJ/kg body weight/day (198-340 mL/hour). Despite large amounts of infused formula per day, which in some cases exceeded 67 L per day, diarrhea was noted in only three subjects. The mean fecal carbohydrate, fat, and nitrogen content of patients were not different. However, the diarrhea stools had significantly higher concentrations of magnesium as compared to nondiarrhea stool (192 +/- mmol/L vs. 139 +/- 17 mmol/L, p
Overall review of clinical data indicates that diarrhea associated with EF is often multifactorial and can be caused by antibiotics, with subsequent changes in the carbohydrate salvage pathway, C difficile infection, antacids containing magnesium hydroxide, or sorbitol, used as a vehicle for some medications.(2) Although the small intestine develops some degree of atrophy during starvation, and this may be aggravated by the administration of total parenteral nutrition support, it is not clear whether such changes may induce diarrhea. However, in the presence of massive edema and concurrent hypoproteinemia, the small intestine may become intolerant to EF. There are several lines of evidence available in experimental animal studies to suggest that volume expansion is diarrheagenic, resulting in net intestinal secretion of water and electrolytes.(13,14) In fact, in our opinion, patients with multiple organ failure and/or those affected by massive edema do not tolerate EF and need parenteral nutrition support.
The three cases presented here show the importance of both the initial clinical evaluation of the patient and a 24-hour stool collection prior to subsequent work-up. Our recent unpublished clinical studies have also shown that cholestyramine may be an important tool in reducing the prevalence of EF-induced frequent stooling and diarrhea.
Our concern regarding EF-induced diarrhea is that enteral formulas are often unjustly blamed as the culprit. Consequently, frantic attempts are undertaken to replace one formula by another, often more expensive one. Only as a last resort should the EF itself be reduced, changed, or discontinued. Furthermore, if we assume that EF-associated diarrhea is mainly a frequent defecation of small amounts of loose stool, then research and clinical attempts should be directed toward improving colonic absorption and providing bulk to patients in the form of fiber additive or the use of other agents such as cholestyramine in order to reduce the frequency of defecation.
It seems logical that investigators in the areas of enteral feeding need to agree on a standardized definition of diarrhea. Perhaps investigators should do as their gastroenterologist colleagues have done for decades; collect the stool, weigh it, analyze it, and then define it as either diarrhea or normal stool.
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