Skip to main content

Systematic review: The relation between nutrition and nosocomial pneumonia: randomized trials in critically ill patients

Abstract

Objective

To review the effect of enteral nutrition on nosocomial pneumonia in critically ill patients as summarized in randomized clinical trials.

Study identification and selection

Studies were identified through MEDLINE, SCISEARCH, EMBASE, the Cochrane Library, bibliographies of primary and review articles, and personal files. Through duplicate independent review, we selected randomized trials evaluating approaches to nutrition and their relation to nosocomial pneumonia.

Data abstraction

In duplicate, independently, we abstracted key data on the design features, population, intervention and outcomes of the studies.

Results

We identified four trials of enteral vs total parenteral nutrition, one trial of early enteral nutrition vs delayed enteral nutrition, one trial of gastric vs jejunal tube feeding, one trial of intermittent vs continuous enteral feeding, and three trials evaluating different enteral feeding formulae. Sample sizes were small, pneumonia definitions were variable and blinded outcome assessment was infrequent. Randomized trial evidence is insufficient to draw conclusions about the relation between enteral nutrition and nosocomial pneumonia.

Conclusions

Nutritional interventions in critically ill patients appear to have a modest and inconsistent effect on nosocomial pneumonia. This body of evidence neither supports nor refutes the gastropulmonary route of infection.

Introduction

Nosocomial pneumonia is an important cause of morbidity and mortality in hospitalized patients. Diagnosis and treatment continues to challenge clinicians and stimulate investigators. Prevention of this serious infection has been the focus of numerous studies, conferences and professional documents. Nosocomial pneumonia prevention strategies may be directed at the ventilator circuit (frequency of tubing circuit changes and gas humidification strategies), the endotracheal tube (intubation orifice, secretion drainage and suctioning) or body position (kinetic bed therapy and semirecumbancy). Other nonpulmonary approaches are pharmacologic (selective digestive decontamination and stress ulcer prophylaxis) or nutritional (the type, site and timing of enteral feeds).

The largest number of published randomized trials in intensive care medicine have evaluated selective digestive decontamination and stress ulcer prophylaxis. Five meta-analyses [1,2,3,4,5] suggest that selective digestive decontamination confers a large, clinically important and statistically significant reduction in nosocomial pneumonia rates (common odds ratio approximately 0.30, 95% CI 0.28–0.48). Nevertheless, selective digestive decontamination is not widely used, in part due to concern about long-term microbial resistance patterns and antibiotic costs [6]. Stress ulcer prophylaxis trials have been recently summarized in a meta-analysis suggesting that sucralfate, as compared with histamine-2-receptor antagonists or antacids, is associated with a trend toward a lower rate of nosocomial pneumonia (common odds ratio 0.78, 95% CI 0.60–1.01) [7]. Other experiments show that modifying gastric pH with acidified enteral feeds decreases gastric colonization, thereby supporting this underlying biologic rationale [8]. However, sucralfate is not considered of proven benefit due to the possibility that sucralfate confers a protective effect only when compared with gastric pH-altering drugs (which themselves are associated with a modest increase in nosocomial pneumonia compared to control) [7].

Kinetic bed therapy has been reviewed in a meta-analysis of six trials in seriously and critically ill patients, which indicated a significantly lower rate of pneumonia and atelectasis in patients receiving continuous postural oscillation [9]. A less expensive and adaptable pneumonia prevention strategy focussing on body position has been studied in three randomized trials [10,11,12]. Torres et al [10] found that after instillation of radioactive technetium sulfur colloid into the stomach, radioactive counts in endobronchial secretions were significantly higher in samples obtained while patients were supine than when they were semirecumbent. In another study, scintigraphic evidence of esophageal reflux was found in 81% of patients in the supine position compared to 64% in the semirecumbent position [11]. Orozco-Levi et al administered nasogastric technetium sulfur colloid and found that radioactive counts in endobronchial secretions increased over time, but were higher in the supine than the semirecumbent position [12]. Although a causal relationship between pneumonia and this secondary endpoint of aspiration of gastric contents has not been convincingly demonstrated, these trials are in keeping with the gastropulmonary route of infection.

The gastropulmonary route of infection is a concept at least two decades old [13], support for which is derived from multiple human observational studies and experimental evidence [14, 15]. Enteral nutrition, compared to parenteral nutrition, is associated with decreased translocation in animals and decreased infectious morbidity in critical illness in humans [16]. Accordingly, it holds the promise of affording protection against nosocomial pneumonia. However, enterally feeding critically ill patients is often associated with intolerance, thereby predisposing them to aspiration pneumonia. The goal of this systematic review is to critically appraise and summarize the randomized trials of nutritional strategies and their influence on nosocomial pneumonia in critically ill patients.

Methods

Study identification

To identify randomized trials, we searched two computerized databases from 1980 onwards. For MEDLINE, we used the following text words and keywords: critical care, intensive care units, pneumonia, respiratory tract infection, mechanical ventilation, gastropulmonary, enteral nutrition, randomized controlled trials, prospective studies. For EMBASE, we used: pneumonia, prevention, control. Frequently cited articles were identified and SCISEARCH (Science Citation Index online) was used to locate any additional relevant randomized trials. We also used the Cochrane Library, searching the Clinical Trials Registry for randomized trials, and the Cochrane Database of Systematic Reviews (CDSR) as well as the Database of Abstracts of Reviews (DARE) for systematic reviews containing relevant primary studies. We confined our search to studies enrolling non-neutropenic adult humans without the human immunodeficiency virus. We had no language restrictions.

The titles (and the abstracts, when available) in the MEDLINE and EMBASE printouts, and the reference lists of all primary and review articles were reviewed independently in duplicate. Any additional relevant articles were thereby identified and retrieved.

Study selection

The following selection criteria were applied to the full manuscripts by two reviewers independently:

  1. 1.

    Population: critically ill adults, including trauma and burn patients.

  2. 2.

    Interventions: nutritional support.

  3. 3.

    Outcomes: nosocomial pneumonia.

  4. 4.

    Design: published randomized trials in humans.

A priori, we excluded relevant nutritional interventions in seriously but not necessarily critically ill patients, studies examining surrogate endpoints for pneumonia [8], studies which did not report how pneumonia was diagnosed [17,18,19], studies which evaluated or reported composite infectious outcomes [20], and duplicate publications [21].

Study characteristics and data abstraction

Two reviewers abstracted data from the randomized trials to describe the method of treatment allocation, the proportion of patients who were excluded post-randomization, whether cointerventions were described, whether the endpoints were assessed by investigators blinded to the intervention, and the outcome definitions employed. Disagreements between reviewers on design characteristics and raw data abstraction were resolved by discussion and consensus.

Analysis

We measured agreement between reviewers on the selection of articles for inclusion in the review. We standardized presentation of the randomized trial results using relative risk, and calculated 95% confidence intervals using the log transformation method. Since study questions and trial designs differed, we did not statistically pool results of these trials, or subgroups of them, in a meta-analysis.

Results

Study identification and selection

The search yielded four trials of enteral vs total parenteral nutrition [22,23,24,25], one trial of early enteral nutrition vs delayed enteral nutrition [26], one trial of gastric vs jejunal tube feeding [27], one trial of intermittent vs continuous enteral feeding [28], and three trials evaluating different enteral feeding formulae [29,30,31]. Agreement was 100% for selection of these trials and systematic reviews.

Study characteristics

Study characteristics are reported in Table 1. Patients were medical or surgical ICU patients, burn, or trauma victims. Two studies were explicit about concealment of randomization using sealed envelopes [26,28]. The nature of some of these comparisons precluded blinding of patients and caregivers. Patients were unlikely to be aware of the details of their care and were not participating in assessment of the presence of nosocomial pneumonia. However, lack of blinding could have affected the care delivered by bedside nurses, respiratory therapists and intensivists, which could have affected the development of lung infection. In one trial, the neurosurgeon evaluating outcomes was blinded [22]; in another, confirmation of outcome was conducted by a second blinded surgeon [24]. Two of the three studies comparing different feeding products employed blinded outcome assessment [29,31].

Cointerventions are interventions which are unrelated to the study question, yet may impact on the outcome, and could be unequally distributed across groups. These include stress ulcer prophylaxis and selective digestive decontamination (Table 1). Other cointerventions not mentioned, but potentially important to standardize or report, might include chest physiotherapy and position of the patients.

In two trials, the pneumonia definition incorporated but did not require invasive bronchoscopic techniques [24,28]; in a third trial, a positive bronchoalveolar lavage was required for the diagnosis [31].

Study results

The results of these randomized trials are presented in Table 2. The four trials evaluating total parenteral vs enteral nutrition yield inconsistent results. In one, there was a trend toward a lower rate of pneumonia associated with enteral nutrition [23], in another study the pneumonia rate was significantly lower in the enteral nutrition group [24], and in the remaining two studies, the pneumonia rate was slightly higher in patients receiving enteral nutrition [22,25].

One study examined early enteral nasoduodenal nutrition begun within 24 h vs nasoduodenal enteral nutrition delayed for 72 h. In patients receiving early feeds, there was a trend toward increased pneumonia (8/19 vs 4/19, respectively) [26].

Considering the potential for enteral nutrition to cause aspiration pneumonia, one study tested the effect of proximal vs distal delivery sites [27]. Two cases of pneumonia were identified amongst those 19 patients receiving prepyloric gastric feeds and no cases were observed in the 19 patients receiving post-pyloric feeds through a jejunal tube.

To avoid continuous alkalinization and intragastric Gram-negative growth associated with enteral feeding, intermittent enteral nutrition was compared with continuous enteral nutrition in one trial [28]. Five of 30 patients in each group developed nosocomial pneumonia.

Three studies examined different enteral feeding formulae and their relation to lung infection. The first compared modular tube feeds (a high protein, low fat, linoleic acid-restricted formulation enhanced with arginine, cysteine, vitamin A, zinc, omega-3-polyunsaturated fatty acids, and ascorbic acid) against Osmolite and Traumacal and found a trend toward lower pneumonia rates in the modular tube feed patients [29]. There was no difference in pneumonia between trauma patients fed Immun-Aid (containing glutamine, arginine, omega-3-polyunsaturated fatty acids, nucleotides, and branched chain amino-acids) vs Vivonex (standard enteral formulae) [30]. In another study of trauma patients, Immun-Aid was associated with a trend toward a lower pneumonia rate than patients fed with Promote (an isonitrogenous, isocaloric diet) [31].

Table 1 Nutrition and nosocomial pneumonia: study characteristics
Table 2 Results of randomized trails of nutrition and nosocomial pneumonia

Discussion

The results of these 10 trials of feeding strategies, either individually or in aggregate, provide inconclusive evidence about the relation between enteral nutrition and nosocomial pneumonia. These studies enrolled a total of 582 patients and contribute 117 cases of pneumonia. The single trial showing a significantly lower pneumonia rate associated with jejunal enteral nutrition over parenteral nutrition [24] has not been translated into widespread clinical policy, perhaps due to the inconvenience and expertise required for jejunostomy tubes. Aside from concerns about type I and II error when interpreting the trials in this review, there are other relevant outcomes addressed by some, but not all of these studies, including effects on nutritional markers and adverse outcomes such as catheter sepsis and patient comfort. Readers are referred to the original articles for these important details.

Factors such as cost, and ease with which the feeding strategy can be employed, are additional issues that bear on the interpretation and application of these trial results in practice. Intensivists also consider evidence from observational studies when making clinical decisions. Given these provisos, it is not surprising that definitive statements about enteral nutrition and lung infection are not forthcoming. Some guidelines from the Center for Disease Control on the prevention of nosocomial pneumonia [32] focus on gastropulmonary approaches. Stress ulcer prophylaxis with an agent that does not increase gastric pH was `suggested for implementation in many hospitals and supported by suggestive clinical and epidemiologic studies and a strong theoretical rationale'. Other interventions labelled as `unresolved for which no recommendations were made' included jejunal feeding, intermittent enteral feeding and selective digestive decontamination. In the American Thoracic Society statement on prevention of hospital-acquired pneumonia in adults [33], some prophylactic interventions were classified as having `probable effectiveness, used widely in some clinical settings', such as distal enteral nutrition, semi-erect positioning, and sucralfate. Selective digestive decontamination was considered `of unproven value used on a limited investigational or clinical basis'.

Nutrition is integral to the care of an ICU patient. The method, site and timing of enteral nutrition may have a protective or predisposing influence on the risk of nosocomial infection [34], though strong proof from experiments in humans does not currently exist. Although a meta-analysis of published and unpublished trials of general surgical and trauma patients suggested a lower pneumonia rate in patients receiving enteral nutrition vs total parenteral nutrition [35], published data from ventilated medical ICU patients are sparse, and generalizing to other populations may not be reasonable. Interventions requiring further investigation with large rigorous studies of ICU patients include those discussed in this review, as well as the size of feeding tubes [36], their insertion site, where the tubes are located in the gastrointestinal tract [37], feeding advancement schedules, and the effect of prokinetic drugs [38].

References

  1. Vandenbrouke CM, Vandenbrouke JP: Effect of selective decontamination of the digestive tract on respiratory tract infections and mortality in the intensive care unit. Lancet 1991, 338: 859-862.

    Article  Google Scholar 

  2. Selective Decontamination of the Digestive Tract Trialist's Collaborative Group : Meta-analysis of randomized controlled trials of selective decontamination of the digestive tract. Br Med J 1993, 307: 525-532.

    Article  Google Scholar 

  3. Kollef MH: The role of selective digestive tract decontamination on mortality and respiratory infections: a meta-analysis. Chest 1994, 105: 1101-1108.

    Article  PubMed  CAS  Google Scholar 

  4. Heyland DK, Cook DJ, Jaeschke RZ, Griffith LE, Lee HN, Guyatt GH: Selective decontamination of the digestive tract: an overview. Chest 1994, 105: 1221-1229.

    Article  PubMed  CAS  Google Scholar 

  5. Hurley JC: Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection ? Antimicrob Agents Chemother 1995, 39: 941-947.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Verwaest C, Verhaegen J, Ferdinande P, et al.: Randomized controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit. Crit Care Med 1997, 25: 63-71.

    Article  PubMed  CAS  Google Scholar 

  7. Cook DJ, Reeve BK, Guyatt GH, et al.: Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA 1996, 275: 308-314.

    Article  PubMed  CAS  Google Scholar 

  8. Heyland DK, Bradley C, Mandell LA: Effect of acidified enteral feedings on gastric colonization in the critically ill patient. Crit Care Med 1992, 20: 1388-1394.

    Article  PubMed  CAS  Google Scholar 

  9. Choi SC, Nelson LD: Kinetic therapy in critically ill patients: combined results based on meta-analysis. J Crit Care 1992, 79: 57-62.

    Article  Google Scholar 

  10. Torres A, Serra-Battles J, Ros E, et al.: Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992, 116: 540-543.

    Article  PubMed  CAS  Google Scholar 

  11. Ibanez J, Penafiel A, Raurich JM, Marse P, Jorda R, Mata F: Gastroesophageal reflux in intubated patients receiving enteral nutrition: effect of supine and semirecumbent positions. J Parent Enteral Nutr 1992, 16: 419-422.

    Article  CAS  Google Scholar 

  12. Orozco-Levi M, Torres A, Ferrer M, et al.: Semirecumbent postion protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients. Am J Resp Crit Care Med 1995, 152: 1387-1390.

    Article  PubMed  CAS  Google Scholar 

  13. Atherton ST, White DJ: Stomach as source of bacteria colonizing respiratory tract during artificial respiration. Lancet 1978, ii: 1968-1971.

    Google Scholar 

  14. Heyland D, Mandell LA: Gastric colonizaiton by Gram-negative bacilli and nosocomial pneumonia in the intensive care unit patient: evidence for causation. Chest 1992, 101: 87-93.

    Article  Google Scholar 

  15. Bonten MJM, Gaillard CA, de Leeuw PW, Stobberingh EE: Role of colonization of the upper intestinal tract in the pathogenesis of ventilator associated pneumonia. Clin Infect Dis 1997, 24: 309-319.

    Article  PubMed  CAS  Google Scholar 

  16. Heyland D, Cook DJ, Guyatt GH: Enteral nutrition in the critically ill patient: a critical review of the evidence. Intensive Care Med 1993, 19: 435-442.

    Article  PubMed  CAS  Google Scholar 

  17. Hadley MN, Grahm TW, Harrington T, Schiller WR, McDermott MK, Posillico DB: Nutritional support and neurotrauma: a critical review of early nutrition in forty-five acute head injured patients. Neurosurgery 1986, 19: 367-373.

    Article  PubMed  CAS  Google Scholar 

  18. Adams S, Dellinger EP, Wertz MJ, Oreskovich MR, Simonowitz D, Johansen KAJ: Enteral versus parenteral nutritional support following laparatomy for trauma: a randomized prospective trial. J Trauma 1986, 26: 882-891.

    Article  PubMed  CAS  Google Scholar 

  19. Moore EE, Jones TN: Benefits of immediate jejunostomy feeding after major abdominal trauma — a prospective, randomized study. J Trauma 1986, 26: 874-881.

    Article  PubMed  CAS  Google Scholar 

  20. Bower RH, Cerra FB, Bershadsky B, et al.: Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective randomized clinical trial. Crit Care Med 1995, 23: 436-449.

    Article  PubMed  CAS  Google Scholar 

  21. Kudsk KA: Gut mucosal nutritional support: enteral nutrition as primary therapy after multiple system trauma. Gut 1994, 35 (suppl 1): S52-S54.

    Article  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. 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: 503-511.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Borzotta AP, Pennings J, Papasadero B, et al.: Enteral versus parenteral nutrition after severe closed head injury. J Trauma 1994, 373: 459-468.

    Article  Google Scholar 

  26. 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.

    Article  PubMed  CAS  Google Scholar 

  27. Montecalvo MA, Steger KA, Farber HW, et al.: Nutritional outcome and pneumonia in critical care patients randomized to gastric versus jejunal tube feedings. Crit Care Med 1992, 20: 1377-1387.

    Article  PubMed  CAS  Google Scholar 

  28. Bonten MJ, Gaillard CA, van der Hulst R, et al.: Intermittent enteral feeding: the influence on respiratory and digestive tract colonization in mechanically ventilated intensive-care-unit patients. Am J Respir Crit Care Med 1996, 154: 394-399.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  CAS  Google Scholar 

  30. Moore FA, Moore FF, Kudsk KA, et al.: Clinical benefits of an immune-enhancing diet for early postinjury enteral feeding. J Trauma 1994, 37: 607-614.

    Article  PubMed  CAS  Google Scholar 

  31. 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. 10.1097/00000658-199610000-00011

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Tablan OC, Anderson LJ, Arden N, Breiman RF, Butler JC, McNeil MM: Guideline for prevention of nosocomial pneumonia. Part I. Issues on prevention of nosocomial pneumonia. Am J Infect Control 1994, 22: 247-292.

    Article  PubMed  CAS  Google Scholar 

  33. American Thoratic Society Ad Hoc Committee of the Scientific Assembly on Microbiology, Tuberculosis and Pulmonary Infections : Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy and preventive strategies: a consensus statement. Am J Resp Crit Care Med 1995, 153: 1711-1725.

    Google Scholar 

  34. Heyland DK, Cook DJ, Guyatt GH: Does the formulation of enteral feeding products influence infectious morbidity and mortality in the critically ill patient? A critical review of the evidence. Crit Care Med 1994, 22: 1192-1202.

    Article  PubMed  CAS  Google Scholar 

  35. Moore FA, Feliciano DV, Andrassy RJ, et al.: Early enteral feeding compared with parenteral reduces postoperative septic complications. The results of a meta-analysis. Ann Surg 1992, 216: 172-183.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  36. Metheny NA, Eisenberg P, Spies M: Aspiration pneumonia in patients fed through nasoenteral tubes. Heart Lung 1986, 15: 256-261.

    PubMed  CAS  Google Scholar 

  37. Strong RM, Condon SC, Solinger MR, Namihas BN, Ito-Wong LA, Leuty JE: Equal aspiration rates from post-pylorus and intragastric-placed small-bore nasoenteric feeding tubes: a randomized, prospective study. J Parenter Enteral Nutr 1992, 16: 59-63.

    Article  CAS  Google Scholar 

  38. Heyland DK, Tougas G, Cook DJ, Guyatt GH: Cisapride improves gastirc emptyting in mechanically ventilated critically ill patients: a randomized double-blind trial. Am J Resp Crit Care Med 1996, 154: 1678-1683.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Barbara Hill for her help with the manuscript preparation and Lauren Griffith for her help with the analyses.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cook, D., Jonghe, B.D. & Heyland, D. Systematic review: The relation between nutrition and nosocomial pneumonia: randomized trials in critically ill patients. Crit Care 1, 3 (1997). https://doi.org/10.1186/cc1

Download citation

  • Received:

  • Published:

  • DOI: https://doi.org/10.1186/cc1

Keywords