Nutritional Support: Timing (Early versus Delayed Enteral Feedings) (UPDATE IN PROCESS)

I. Statement of the Problem

Over the past two decades, the impact of nutrition support on critically injured patients has received significant attention with research focusing on the importance of route and type of nutrition, timing of nutrition, severity of injury, and clinical outcome. Comparative studies in laboratory animals have documented improved outcomes associated with early enteral feeding (2 hours post-injury) compared with feedings initiated at 72 hours post-injury. With the diverse patient populations of blunt and penetrating torso trauma, severe burns, and head injuries, the metabolic and clinical effects of nutritional support are significantly different. This document summarizes published data and makes recommendations regarding the relative advantages and disadvantages of early enteral feeding in these diverse populations.

II. Process

A. Identification of References

References were identified from a computerized search of the National Library of Medicine for English language citations between 1983 and 2000. We reviewed only articles that attempted to use specialized nutritional support as early as possible following injury and analyzed the data for clinical success with the therapies. The bibliographies of the selected references were reviewed for relevant articles not found in the computerized search. Literature reviews, case reports, and editorials were excluded. Twenty-five articles were identified.

B. Quality of the References

The quality assessment instrument applied to the references was developed by the Brain Trauma Foundation and subsequently adopted by the EAST Practice Management Guidelines Committee. Articles were classified as Class I, II, or III according to the following definitions:

Class I: A prospective, randomized clinical trial. Thirteen articles were chosen and analyzed.

Class II: A prospective, non-comparative clinical study or a retrospective analysis based on reliable data. Eight articles were chosen and analyzed.

Class III: A retrospective case series or database review. Two articles were chosen and analyzed.

III. Recommendations

A. Level I

In severely injured blunt/penetrating trauma patients, there appears to be no outcome advantage to initiating enteral feedings within 24 hours of admission as compared to 72 hours after admission.

B. Level II

1. In burn patients, intragastric feedings should be started as soon after admission as possible, since delayed enteral feeding (>18 hours) results in a high rate of gastroparesis and need for intravenous nutrition.
2. Patients with severe head injury who do not tolerate gastric feedings within 48 hours of injury should be switched to postpyloric feedings, ideally beyond the ligament of Treitz, if feasible and safe for the patient.

C. Level III

1. Patients who are incompletely resuscitated should not have direct small bowel feedings instituted due to the risk of gastrointestinal intolerance and possible intestinal necrosis.
2. In patients undergoing laparotomy for blunt and penetrating abdominal injuries, direct small bowel access should be obtained (via nasojejunal feeding tube, gastrojejunal feeding tube, or feeding jejunostomy) and enteral feedings begun as soon as is feasible following resuscitation from shock.

IV. Scientific Foundation

Several clinical trials have attempted to examine whether the benefit of “early” enteral feeding documented in the research laboratory extends into the clinical arena. Unfortunately, as is seen in the accompanying evidentiary tables, there is no consensus as to what is meant by “early”, ranging between 4 and 72 hours post-admission. In contrast, animal data demonstrating the superiority of an early enteral strategy initiated feeding within 2 hours of injury.^[1]Furthermore, very few of the clinical trials actually compare “early” enteral with “late” enteral feeding, the majority comparing early enteral feeding and TPN. Because the impact of an early enteral strategy may vary depending on the specific injury type, three specific trauma patient subsets (blunt/penetrating torso, burn, head injury) are examined in this section.

Only one prospective randomized study in blunt/penetrating trauma patients has actually compared early and late enteral feeding, finding no metabolic or clinical advantage to early enteral feeding.^[2]However, as the authors acknowledge, it may be that initiating enteral feeding at 39 hours post-injury was not early enough to demonstrate this advantage, or perhaps the metabolic advantages are not demonstrable until after the 10-day study period employed in this study. Regardless, the findings from this report are important for two reasons. First, it is unlikely, in this patient population, that enteral feeding can be consistently initiated much earlier than the 39 hours post-injury achieved by these authors, given their very aggressive approach to post-pyloric enteral access. Second, despite the small number of patients in this study, no clinical outcome advantage could be ascribed to initiating enteral feeding within 30 hours of admission compared with 80 hours from admission. Thus, in this particular patient population, there is no literature support for early enteral feeding, at least as defined by these authors.

One recent study^[3] randomized multisystem trauma patients (ISS >25, GCS score =12) to early (< 6 hours after resuscitation from shock) or late (=24 hours after resuscitation from shock) gastric feeding using the same enteral diet for both groups. Parenteral feeding was provided to both groups to meet caloric demands. Within 4 days, the early fed group tolerated significantly more enteral feeding than the late-fed group, and by the end of 1 week, they were receiving 80% of their enteral feeding compared with 61% in the late-fed group (p <0.025). The early-fed group sustained significantly fewer incidents of late multiple organ dysfunction, but ICU length of stay, and duration of mechanical ventilation was similar between the two groups. The use of TPN in this study, and the use of shock resolution as a criterion for initiation of enteral feeding, makes the results of this trial difficult to compare to those of Eyer referred to above.^[2] However, the two studies taken together would seem to raise serious questions regarding the significance of early enteral feeding, even if feedings are initiated as early as 6 hours following resuscitation.

The remainder of the prospective, randomized trials of blunt and penetrating trauma has been limited to patients with direct small bowel access obtained at the time of surgery. Moore et al.^[4] randomized patients to either needle catheter jejunostomy feedings with a chemically defined diet started 18-24 hours postoperatively or to no early enteral nutrition and demonstrated a significant reduction in septic complications, primarily intra-abdominal abscesses. Patients were limited to an ATI between 15 and 40 because of previous work^{[5] [6]} which demonstrated decreased gastrointestinal tolerance in patients with an ATI >40 or direct viscus injury. In this study, enteral feedings were administered to a goal rate within 72 hours, which limited successful advancement in the more severely injured. A second study of early enteral feeding versus TPN^[7] confirmed a reduction in septic complications (primarily pneumonia with a trend toward reduced intra-abdominal abscesses) in a similar population with mild to moderately severe injuries. In another study recruiting patients with moderately severe injuries (i.e., ATI 18-40 or ISS 16-45),^[8] diets were started within 24 hours and advanced to goal by 72 hours with gastrointestinal intolerance in approximately 26% of patients but interruption or discontinuation in only 13.5% of study patients.

A randomized, prospective study of enteral feeding via jejunostomy versus parenteral feeding demonstrated a significant reduction in intra-abdominal abscesses and pneumonia in moderate to very severely injured patients receiving enteral nutrition.^[9] Four percent of enterally fed patients failed enteral feedings (defined as 50% of nutrient goal by 1 week) because of severity of injury. As a result, parenterally fed patients received more nutrition than the enterally fed population. Benefits of enteral feeding were only noted in patients sustaining an ATI >24 or an ISS >20. Feedings were successfully started within 24 hours in both groups. A subsequent study randomized severely injured patients with an ATI >24 or an ISS >20 to one of two enteral diets.^[10] Diets were started 1.5 to 2 days following surgery due to early hemodynamic instability in many of the patients. Gastrointestinal symptoms were common and occurred in 88% of enterally fed patients, which required slowing the feedings in 45%. The more severe the blunt and penetrating trauma to the torso in patients requiring laparotomy, the greater the intolerance to feeding, the longer the delay before institution of feeding, and slower rate of progression necessary to improve tolerance.

Intragastric feedings have been studied most closely in burn patients. In a population of pediatric patients with > 40% total body surface area (TBSA) burns, early intragastric feeding started soon after admission was highly successful.^[11] This was duplicated in a larger population of pediatric patients with burns greater than 10%^[12] TBSA, and confirmed again in a group sustaining 25% to 60% TBSA burn.^[13] Although diarrhea occurred in 40%, early intragastric feeding following burn was well tolerated. In a population of patients with burns of 40% to 70% TBSA^[14], intraduodenal feeding was started within 48 hours and was well tolerated. Fifty-five intubated, ventilated patients with burns of approximately 45% were started on intragastric feedings with gastric stimulatory agents.^[15] When diets were started within 15 hours, goals were reached in 82% of patients within 72 hours, but when feedings were delayed to 18 hours or greater, the majority of patients failed. A study in patients with 35% TBSA burn of intra-duodenal feeding started within 48 hours also was well tolerated with rare episodes of distension, reflux, or diarrhea.^[16] In a retrospective study of 106 patients with burns of 20% or greater,^[17] tolerance of intragastric feedings was >90% in patients started within 6 hours of burn.

Success with enteral feeding of patients with severe head injuries is less encouraging. In two studies of patients with GCS scores between 4 and 10,^{[18] [19]} patients randomized to intragastric feeding received <500-600 kcal/day over the first 2 days, < 800 cal/day on days 3-5, and <1,500 cal/day on days 6-8 due to gastroparesis. However, no attempts were made to feed patients until nasogastric drainage had dropped below 100 cc. Similar results were noted in 23 patients sustaining blunt and penetrating trauma to the head with GCS scores between 4 and 10.^[20] Although feedings were not initiated unless nasogastric drainage was <200 cc per day and bowel sounds were present, only one-third of patients tolerated feedings within 7 days of injury, and 12 never tolerated feedings. Resolution of gastroparesis occurs on days 3 to 4 in many patients although it may occur sooner than the studies above since gastric emptying may occur despite higher nasogastric drainage and prior to return of bowel sounds.^[21] In another study,^[22] nasojejunal feedings approached nutrient needs within 3 days but did not approach nutrient goals until day 5 to day 7 in patients receiving intragastric feeding due to high gastric residuals. Similar delays were noted in a study of 48 evaluable head-injured patients.^[23] Recently, 82 patients sustaining head injury were randomized to either intragastric feeding or to intestinal feeding using a pH sensor tube. All patients required mechanical ventilation on the first day of hospitalization, had a GCS score >3, and had at least one reactive pupil. Intestinal tube placement was confirmed by abdominal radiography. Patients receiving the small intestinal tube had a higher percentage of energy and nitrogen administration during the study. Within 3 days of injury, the intestinal-fed patients achieved 70% of their nutrient goal and by 6 days achieved 90% of their nutrient requirements. Intragastric-fed patients achieved 30% of nutrient goals by day 3 and 55% by day 6. The intestinally fed patients sustained fewer complications and had an associated reduction in acute-phase protein production.^[24] The Cochrane Library has recently summarized the available data concerning the timing of nutritional support in head-injured patients.^[25]

V. Summary

Direct small bowel access is necessary to successfully feed patients via the gastrointestinal tract who have sustained severe blunt and penetrating torso and abdominal injuries as well as severe head injuries. Intragastric feeding becomes successful in the majority of head-injured patients at approximately day 3 or 4, at the earliest, due to gastroparesis. Small bowel feedings are tolerated in this patient population with small bowel access. In patients with penetrating and blunt injuries to the abdomen who have small bowel access, enteral feeding can be instituted in most patients after resuscitation is complete and hemodynamic stability has been gained. Advancement to goal rate is slower in patients with higher ATI scores, in particular if ATI >40. In addition, gastrointestinal injury below the site of access may slow advancement of tube feedings but is not a contraindication to direct small bowel feedings. Intragastric feeding in patients with severe burns should be instituted as soon as possible during resuscitation to prevent or minimize the onset of gastroparesis that appears to occur with increasing incidence if feedings are delayed, particularly if delayed beyond 18 hours. In all patient populations, total parenteral nutrition can be instituted soon after injury, ideally after hemodynamic stability has been gained and resuscitation is complete.

VI. Future Investigation

Several obstacles limit the successful use of early enteral nutrition. First, access to suitable sites in the gastrointestinal tract for the delivery of nutrition support requires clinical vigilance and planning. Although many patients can be successfully fed intragastrically, critical illness and critical injury often mandate placement of the tube beyond the ligament of Treitz. Unless access is obtained at the time of celiotomy, methods to successfully advance tubes beyond the ligament of Treitz are limited, and further research for solutions to this problem is warranted. Methods are needed to recognize dislodgment into the stomach and to keep the tube beyond the ligament of Treitz, particularly those advanced through the stomach. Second, protocols or markers which promote successful, safe advancement of feeding rate are needed, especially markers which identify patients who will be intolerant of enteral feeding due to distension, bloating, diarrhea, and the rare complication of intestinal necrosis. Third, development of pharmacologic or nonpharmacologic means to reverse or eliminate gastroparesis or ileus may minimize progressive calorie deficits and maximize the benefits of early enteral delivery of nutrients. Finally, authors do not agree about what constitutes “early” or “delayed” enteral feeding. In some studies, early is defined in hours, and in others, it is defined in terms of days. Until there is consensus regarding these definitions, it is impossible to determine whether the theoretic benefits ascribed to early enteral feeding truly outweigh the additional effort and potential complications associated with this approach to nutritional support. Well designed, prospective, randomized studies, employing a precise definition of early feeding, together with clinically relevant outcome parameters (morbidity, infectious morbidity, neurologic outcome, etc.) in a well-defined patient population (burns, head injury, or torso trauma) are needed to adequately resolve this important issue.

References

1. Mochizuki H, Trocki O, Dominioni L, et al: Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding. Ann Surg 200:297, 1984.
2. Eyer SD, Micon LT, Konstantinides FN, et al. Early enteral feeding does not attenuate metabolic response after blunt trauma. J Trauma. 1993;34:639-644.
3. Kompan L, Kremzar B, Gadzijev E, Prosek M. Effects of early enteral nutrition on intestinal permeability and the development of multiple organ failure after multiple injury. Intensive Care Med 1999;25:157-161.
4. Moore EE, Jones TN. Benefits of immediate jejunostomy feeding after major abdominal trauma: a prospective, randomized study. J Trauma. 1986;26:874-881.
5. Moore EE, Dunn EL, Jones TN. Immediate jejunostomy feeding. Its use after major abdominal trauma. Arch Surg. 1981;116:681-684.
6. Jones TN, Moore FA, Moore EE, McCloskey BL. Gastrointestinal symptoms attributed to jejunostomy feeding after major abdominal trauma: a critical analysis. Crit Care Med.1989;17:1146-1150.
7. Moore FA, Moore EE, Jones TN, McCroskey BL, Peterson VM. TEN versus TPN following major abdominal trauma: reduced septic morbidity. J Trauma. 1989;29:916-923.
8. Moore FA, Moore EE, Kudsk KA, et al. Clinical benefits of an immune-enhancing diet for early postinjury enteral feeding. J Trauma. 1994;37:607-615.
9. Kudsk KA, Croce MA, Fabian TC, et al. Enteral versus parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg. 1992;215:503-513.
10. Kudsk KA, Minard G, Croce MA, et al. A randomized trial of isonitrogenous enteral diets after severe trauma. An immune-enhancing diet reduces septic complications. Ann Surg.1996;224:531-543.
11. Alexander JW, MacMillan BG, Stinnet JD, et al. Beneficial effects of aggressive protein feeding in severely burned children. Ann Surg. 1980;192:505-517.
12. Gottschlich MM, Jenkins M, Warden GD, et al. Differential effects of three enteral dietary regimens on selected outcome variables in burn patients. J Parenter Enteral Nutr. 1990;14:225-236.
13. Chiarelli A, Enzi G, Casadei A, Baggio B, Valerio A, Mazzoleni F. Very early nutrition supplementation in burned patients. Am J Clin Nutr. 1990;51:1035-1039.
14. McArdle AH, Palmason C, Brown RA, Brown HC, Williams HB. Early enteral feeding of patients with major burns: prevention of catabolism. Ann Plastic Surg. 1984;13:396-401.
15. Raff T, Hartmann B, Germann G. Early intragastric feeding of seriously burned and long-term ventilated patients: a review of 55 patients. Burns. 1997;23:19-25.
16. Saffle JR, Wiebke G, Jennings K, Morris SE, Barton RG. A randomized trial of immune-enhancing enteral nutrition in burn patients. J Trauma. 1997;42:793-802.
17. McDonald WS, Sharp CW Jr, Deitch EA: Immediate enteral feeding in burn patients is safe and effective. Ann Surg. 1991;213:177-183.
18. Rapp RP, Young B, Twyman D, et al. The favorable effect of early parenteral feeding on survival in head injured patients. J Neurosurg. 1983;58:906-912.
19. Young B, Ott L, Twyman D, et al. The effect of nutritional support on outcome from severe head injury. J Neurosurg. 1987;67:668-676.
20. Norton JA, Ott LG, McClain C, et al. Intolerance to enteral feeding in the brain-injured patient. J Neurosurg. 1988;68:62-66.
21. Hadley MN, Grahm TW, Harrington T, Schiller WR, McDermott MK, Posillico DB. Nutritional support in neurotrauma: A critical review of early nutrition in forty-five acute head injury patients.Neurosurgery. 1986;19:367-373.
22. Grahm TW, Zadrozny DB, Harrington T. The benefits of early jejunal hyperalimentation in the head-injured patient. Neurosurgery. 1989;25:729-735.
23. Borzotta AP, Pennings J, Papasadero B, et al. Enteral versus parenteral nutrition after severe closed head injury. J Trauma. 1994;37:459-468.
24. Taylor, SJ, Fettes SB, Jewkes C, Nelson RJ. Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury. Crit Care Med 1999; 27:2525-2531.
25. Yanagawa T, Bunn F, Roberts I, Wentz R, Pierro A. - Nutritional support for head-injured patients. [Review] Cochrane Database of Systematic Reviews [computer file] 2000;(2):CD001530.

Tables

Early versus Delayed Enteral Feedings Evidentiary Tables

Table 1. Blunt/Penetrating Trauma

Early versus Delayed Enteral Feedings Evidentiary Tables

Table 2. Burns

Early versus Delayed Enteral Feedings Evidentiary Tables

Table 3. Head Injury