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An overview of evidence from systematic reviews evaluating early enteral nutrition in critically ill patients: more convincing evidence is needed.

Up to 37% of critically ill patients are severely or moderately malnourished at the time of their admission to the intensive care unit (ICU) (1). Malnutrition in critically ill patients has been associated with decreased immune function, an increased incidence of nosocomial infections, impaired respiratory function and an increased risk of death (1-3). Recognition of the association between malnutrition and poor outcomes has led to the proposal that the provision of early nutritional support should be a benchmark of quality of care in critically ill patients (4).

Current high-profile international and national quality improvement initiatives promote the delivery of early enteral nutrition (EN) in critical illness. The internationally recognised 'Fast-Hug' mnemonic (Feeding, Analgesia, Sedation, Thrombo-embolic prophylaxis, Head of bed elevation, Ulcer prophylaxis, Glucose control) has been used to popularise early enteral feeding in many countries (5). In Australia, the Safer Systems--Saving Lives national campaign incorporates Fast-Hug (www.cec.health.nsw.gov.au/toolkits/SSSL.html Accessed January 2009). Despite these high-profile quality improvement initiatives, the delivery of early EN remains inconsistent and often inadequate.

An international survey of current practice has shown that up to 40% of critically ill patients receive no nutritional support during their ICU stay6. Furthermore, patients who received nutritional support frequently remained unfed for up to 48 hours after ICU admission (7-9). The standard care arm of a recent large study, conducted in 27 ICUs throughout Australia and New Zealand, showed that up to 60% of patients who remained in the ICU at least three days were unfed for up to 48 hours (10). One way to improve practice and eliminate inconsistencies in care is to provide clinicians with persuasive evidence that will convince them of the benefits of changing their practice (10).

The purpose of this overview is to identify and appraise the evidence currently available regarding the benefits attributable to the provision of early EN. The recent completion of two separate reviews focused on randomised controlled trials (RCT) has highlighted a lack of new evidence on this topic in the form of recent RCTs (11,12). We therefore focused this overview on identifying and appraising evidence from published systematic reviews.

MATERIALS AND METHODS

Literature search

Medline was searched with the medical subject heading "enteral nutrition", using the highly sensitive clinical queries filter for systematic reviews (13). EMBASE was searched with appropriate EMTREE headings mapped from medical subject heading terms, which were combined with strategies optimised to identify systematic reviews on EMBASE (14). Full details are available on request from the authors.

No restrictions were placed on patient population or language and the reference lists of major published guidelines were hand-searched for additional published systematic reviews. The final close-out date for the search process was 1 September 2008.

Study selection

Systematic reviews containing meta-analyses of RCTs conducted in acutely hospitalised adult patients were eligible for inclusion.

We considered only studies of early standard EN (i.e. not immuno-nutrition, macro- or micro-nutrient supplementation), delivered via any route, compared to delayed nutrition. 'Early' was as defined by the authors of the systematic reviews. Only the most recent version of a series of duplicate publications was included.

Methodological quality

Two authors (PH, GD) independently assessed three key areas of methodological quality: 1) the appropriateness of the literature search; 2) potential for bias in the inclusion of studies; and 3) reporting of validity appraisal of the included RCTs (15).

Outcomes assessed

All outcomes reported by the authors of the systematic reviews were considered.

RESULTS

Study selection

All stages of study selection were completed independently by three authors (PH, GD, ES). Any differences in opinion were resolved by discussion.

Figure 1 presents the detailed results of the study selection process using the flow-diagram recommended by the Quality of Reporting of Meta-Analyses (QUOROM) conference participants (16).

Literature search

The electronic search identified 475 unique abstracts. Independent review resulted in the retrieval of the full text publications of 43 systematic reviews for detailed evaluation.

Detailed evaluation

Thirty-five systematic reviews did not meet our predefined inclusion criteria (Figure 1). Of the eight remaining systematic reviews, two were duplicate publications (17,18) of more recent papers and one was a foreign language publication (Swedish) (19) which presented data from previously published systematic reviews.

Five systematic reviews containing meta-analyses met the predefined inclusion criteria and form the basis of this overview (20-24).

Study characteristics

The five included systematic reviews identified 30 unique trials with a total of 1736 patients. Eleven of these trials were included in more than one systematic review. Table 1 presents detailed characteristics of the five included systematic reviews.

Patient populations

The five systematic reviews included in this overview were conducted in the following patient populations: acutely ill hospitalised patients (24), critical illness (23), burns (20), elective intestinal surgery (21) and pancreatitis (22).

Marik and Zaloga24 defined 'acute illness' to include adult postoperative patients, trauma of any type, any form of head injury, any degree of thermal injury or any patient admitted to a medical ICU. No RCTs of medical ICU patients were included in the Marik and Zaloga meta-analysis.

Heyland et al (23) defined a 'critically ill' patient as a patient who had an urgent or life-threatening complication (high baseline mortality rate) and was cared for in an ICU environment. Elective surgery patients admitted to ICU were excluded.

Wasiak et al (20) defined a 'burn' injury as any burn injury to the epidermis, subcutaneous tissues, vessels, nerve, tendons or bone.

Lewis et al (21) were initially interested in colerectal surgery but were unable to identify trials with a specific focus on these patients. Although the paper's introduction indicates the focus on colerectal surgery, the meta-analysis included trials of elective surgery of either the upper or lower gastrointestinal tract, including hepatobiliary surgery and non-specific intestinal resection. We therefore refer to this patient population as 'elective intestinal surgery'.

[FIGURE 1 OMITTED]

McClave et al (22) addressed a question regarding the benefits of early EN in a patient population undergoing surgical intervention for complications of 'acute pancreatitis'. It is difficult to determine any other details of patients, as selection criteria for the patient population are not reported.

Timing of EN

Two systematic reviews included trials where 'early' EN was commenced within 24 hours of injury or surgery (20,21), one included trials where 'early' EN was commenced within 36 hours (24) and one included trials where 'early' EN was commenced on the day after surgery (22).

The final systematic review23 reported including trials where 'early' EN was commenced within 24 to 48 hours; however one trial (25) included by these authors defined 'early' EN as up to 60 hours after ICU admission.

Comparison intervention

Two systematic reviews defined the comparison group as delayed EN (20,24). One defined the comparison as delayed nutrient intake, including EN, parenteral nutrition or oral diet (23). One defined the comparison as no caloric oral intake or tube feeding within 24 hours postoperatively and specifically excluded parenteral nutrition (21). The final one defined the comparison group as 'standard care', which included fluid resuscitation and analgesia only (22).

Methodological quality

1) Appropriateness of the literature search

All five included systematic reviews reported details on their search strategy, including search terms and restrictions. All five reported searching Medline with only one of five not additionally searching EMBASE or Cochrane (24). Two placed no restrictions on language (20,23) and one placed no restrictions on publication status (20).

Attempts to identify additional studies by contacting experts in the area, manufacturers or known authors were reported by all five systematic reviews. Only one study did not explicitly report searching reference lists or bibliographies of identified review articles (20).

2) Potential for bias in inclusion of studies

Details on inclusion and exclusion criteria were reported by all five systematic reviews and all reported the involvement of two or more authors in the study selection process.

None of the five systematic reviews reported detailed results of the selection process in the text or in the form of a QUOROM flow diagram (see Figure 1 as an example). We were therefore unable to judge whether the results of the study selection process were reproducible. There may be bias present in the inclusion of studies in all five systematic reviews.

3) Reporting of validity appraisal of the included

RCTs

All five systematic reviews outlined an intended process for assessing the validity of the included trials, however only one reported detailed results of their validity appraisal (20).

Outcomes assessed

Table 2 provides a complete listing of all results reported by each included systematic review.

Mortality

All five systematic reviews conducted a meta-analysis on mortality.

In elective intestinal surgery, meta-analysis demonstrated a statistically significant reduction in mortality associated with early EN (relative risk [RR] 0.41, 95% confidence interval [CI] 0.18 to 0.93, P=0.03, I2=0.0%) (21).

In critical illness and acute pancreatitis, trends towards a reduction in mortality associated with early EN were observed: critical illness (RR

0.52, 95% CI 0.25 to 1.08, P=0.08, heterogeneity P=0.67) (23) and acute pancreatitis (RR 0.26, 95% CI 0.06 to 1.09, P=0.06, I2=0.0%) (22).

Infectious complications

All five systematic reviews conducted a meta-analysis on infectious complications. Four of the meta-analyses pooled all types of infections and one provided a breakdown by type of infection21.

In acutely ill hospitalised patients, meta-analysis demonstrated a significant reduction in pooled infectious complications associated with early EN24 (RR 0.45; 95% CI 0.3 to 0.66, P=0.00006, heterogeneity P=0.049).

In acute pancreatitis22, a subgroup analysis addressing EN delivered on the day after surgery versus standard care showed a trend towards reduced postoperative peritonitis with early EN (28.2% vs 9.3%, RR = 0.33, P=0.07, heterogeneity P value not reported).

Length of stay (hospital or ICU)

Two systematic reviews reported a reduction in length of stay associated with early EN: elective intestinal surgery (length of stay weighted mean difference -0.60 days, 95% CI -0.66 to -0.54, heterogeneity P=0.09) (21) and acutely ill hospitalised patients (length of stay weighted mean difference -2.2 days, 95% CI -3.63 to -0.81, P=0.004, heterogeneity P=0.0012) (24).

Other complications

In elective intestinal surgery, risk of vomiting was significantly increased with early EN (RR 1.27, 95% CI 1.01 to 1.61, P=0.04, [I.sup.2]=0.0%) (21).

DISCUSSION

We identified five published meta-analyses that evaluated the benefits attributable to the provision of early EN in five different acutely hospitalised patient populations (20-24). Only one of these publications met all three key methodological quality criteria appropriate for meta-analyses (20).

In elective intestinal surgery patients, we found the provision of early EN significantly reduced mortality (21), while in acutely ill patients, early EN resulted in a significant reduction in infectious complications (24). Although early EN may reduce hospital length of stay in acutely ill and elective surgery patients, both meta-analyses contained evidence of heterogeneity and should be interpreted with caution. Furthermore, the provision of early EN was associated with increased vomiting in elective surgery patients, however it was not associated with an increase in hospital-acquired pneumonia in these patients. The meta-analysis of acutely ill hospitalised patients contained a significant number of studies that were also included in the metaanalysis of elective intestinal surgery patients.

In summary, although there was no direct evidence of significant benefit attributable to early EN from meta-analysis of trials conducted in focused critically ill patient populations, there was no evidence of clinically important harm. This overview found that there is a need to improve the methodological quality of future published systematic reviews and there may be a need for better evidence on this topic.

Current practice mirrors current evidence

The delivery of early EN is not uniformly achieved in all patients, with 40 to 60% of eligible critically ill patients failing to receive early EN (6,7,9,10). The evidence of benefit from early EN, as summarised in this overview, is also not uniform. Evidence of benefit was not seen in critically ill patient populations and was not consistent across other patient populations. Practice change in the ICU is often reported to be a complex and challenging task (9,10). It is possible that current practice is inconsistent due to the variable nature of the evidence of benefit attributable to early EN. It is unlikely that quality improvement initiatives will achieve universal uptake of recommendations for early EN without more convincing evidence.

Quality of the current evidence and future improvements

The purpose of a systematic review is to summarise a body of evidence in order to provide a useful answer to a clinical question (26). A recent survey of 1900 physicians in clinical practice showed that systematic reviews were accessed more frequently than original clinical trials because they were regarded to be 'more clinically relevant' (27). Unfortunately, the results of our overview found that systematic reviews of early EN may not be well conducted.

The QUOROM initiative provides a series of recommendations for the conduct and presentation of systematic reviews (16). Amongst other recommendations, the QUOROM statement advises authors to explicitly report details of the search that was undertaken and the results of the article selection process. QUOROM also recommends formal validity appraisal of all trials that are included. Our overview found deficits in the reporting of the trial selection process and in validity appraisal.

The QUOROM flow diagram is a figure that can be used to present explicit information about both the numbers of papers identified by the literature search and the results of the study selection process (16). None of the systematic reviews included in our overview presented the results of their study selection process. Presentation of the study selection process using a QUOROM flow diagram can improve a reader's confidence that some form of bias has not influenced the study selection process (see Figure 1 for example). We strongly recommend that all future systematic reviews include a QUOROM flow diagram.

The strength of the conclusions of a systematic review are directly reliant on the quality of trials it contains (28). It is essential that authors adhere to review standards and ensure they identify and base their primary findings on valid trials (29). Only one systematic review reported the specific results of their validity assessment. Without explicit reporting of key trial validity features, it is impossible to determine whether the conclusions of a systematic review are based on flawed or unsound studies (http://clinicalevidence.bmj.com/ceweb/about/appraisal.jsp Accessed March 2009). Authors of systematic reviews should always report individual validity elements for all included trials (30).

Limitations and strengths of this overview

The findings of this overview are based on a thorough and extensive literature search. Although the primary search focused on Medline and EMBASE, it did not extend to secondary electronic sources such as CINAHL or conference abstract databases. Hand-searching the reference lists of recently published guidelines and contacting experts in the field helped identify systematic reviews published in other sources. It is also important to note that neither the search nor the article selection process was limited by language. Non-English articles were translated upon identification and included or excluded as appropriate.

As with any systematic review, the primary limitation of this overview is the fact that the strength of the conclusions reached is directly reliant upon the papers it includes. Only one included paper satisfactorily addressed all three key measures of methodological quality appropriate for a systematic review.

Summary

The provision of early nutritional support has been proposed as a quality benchmark for critically ill patients4 and recent quality improvement initiatives, such as the Safer Systems--Saving Lives campaign, are emphasising its importance. However, between 40 and 60% of eligible critically ill patients still do not receive early nutritional support (6,7,9,10).

We performed an extensive literature search and identified five systematic reviews focused in five different patient populations that evaluated the benefits attributable to early EN. Early EN was found to significantly reduce mortality in elective intestinal surgery and to significantly reduce infectious complications in acutely ill hospitalised patients. However, all but one of the five identified systematic reviews had key methodological quality deficiencies.

In summary, although we found evidence of benefit with no evidence of clinically significant harm, the consistency and quality of the current evidence may not be good enough to convince more clinicians to provide early EN to more critically ill ICU patients. Better evidence may be needed to reduce the variability in the provision of early EN to critically ill patients.

Accepted for publication on June 4, 2009.

REFERENCES

(1.) Sungurtekin H, Sungurtekin U, Oner O, Okke D. Nutrition assessment in critically ill patients. Nutr Clin Pract 2008; 23:635-641.

(2.) Giner M, Laviano A, Meguid MM, Gleason JR. In 1995 a correlation between malnutrition and poor outcome in critically ill patients still exists. Nutrition 1996; 12:23-29.

(3.) Kuzu MA, Terzioglu H, Genc V, Erkek AB, Ozban M, Sonyurek P et al. Preoperative nutritional risk assessment in predicting postoperative outcome in patients undergoing major surgery. World J Surg 2006; 30:378-390.

(4.) Nutrition intervention in ICU improves outcomes. Healthc Benchmarks 1998; 5:175-176.

(5.) Vincent JL. Give your patient a fast hug (at least) once a day. Crit Care Med 2005; 33:1225-1229.

(6.) Heyland DK, Schroter-Noppe D, Drover JW, Jain M, Keefe L, Dhaliwal R et al. Nutrition support in the critical care setting: current practice in Canadian ICUs--opportunities for improvement? JPEN J Parenter Enteral Nutr 2003; 27:74-83.

(7.) Heyland DK, Dhaliwal R, Day A, Jain M, Drover J . Validation of the Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients: results of a prospective observational study. Crit Care Med 2004; 32:2260-2266.

(8.) Martin CM, Doig GS, Heyland DK, Morrison T, Sibbald WJ. Multicentre, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT). CMAJ 2004; 170:197-204.

(9.) Jain MK, Heyland D, Dhaliwal R, Day AG, Drover J, Keefe L et al. Dissemination of the Canadian clinical practice guidelines for nutrition support: results of a cluster randomized controlled trial. Crit Care Med 2006; 34:2362-2369.

(10.) Doig GS, Simpson F, Finfer S, Delaney A, Davies AR, Mitchell I et al. Effect of evidence-based feeding guidelines on mortality of critically ill adults: a cluster randomized controlled trial. JAMA 2008; 300:2731-2741.

(11.) Doig GS, Simpson F. Early enteral nutrition in the critically ill: do we need more evidence or better evidence? Curr Opin Crit Care 2006; 12:126-130.

(12.) Doig GS, Simpson F, Sweetman EA. Evidence-based nutrition support in the intensive care unit: an update on reported trial quality. Curr Opin Clin Nutr Metab Care 2009; 12:201-206.

(13.) Shojania KG, Bero LA. Taking advantage of the explosion of systematic reviews: an efficient MEDLINE search strategy. Eff Clin Pract 2001; 4:157-162.

(14.) Wilczynski NL, Haynes RB. EMBASE search strategies achieved high sensitivity and specificity for retrieving methodologically sound systematic reviews. J Clin Epidemiol 2007; 60:29-33.

(15.) Delaney A, Bagshaw SM, Ferland A, Manns B, Laupland KB, Doig CJ. A systematic evaluation of the quality of meta-analyses in the critical care literature. Crit Care 2005; 9:R575-582.

(16.) Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 1999; 354:1896-1900.

(17.) Lewis SJ, Egger M, Sylvester PA, Thomas S. Early enteral feeding versus "nil by mouth" after gastrointestinal surgery: systematic review and meta-analysis of controlled trials. BMJ 2001; 323:773-776.

(18.) Andersen H K, Lewis SJ, Thomas S. Early enteral nutrition within 24h of colorectal surgery versus later commencement of feeding for postoperative complications. Cochrane Database Syst Rev 2006; 4:CD004080.

(19.) Thorell A, Nygren J, Ljungqvist O. [Is fasting after gastrointestinal surgery necessary? Meta-analysis of early enteral nutrition versus traditional nutritional therapy]. Lakartidningen 2002; 99:1786-1790.

(20.) Wasiak J, Cleland H, Jeffery R. Early versus delayed enteral nutrition support for burn injuries. Cochrane Database Syst Rev 2006; 3:CD005489.

(21.) Lewis SJ, Andersen HK, Thomas S. Early enteral nutrition within 24 h of intestinal surgery versus later commencement of feeding: a systematic review and meta-analysis. J Gastrointest Surg 2008; 13:569-575.

(22.) McClave SA, Chang WK, Dhaliwal R, Heyland DK. Nutrition support in acute pancreatitis: a systematic review of the literature. JPEN J Parenter Enteral Nutr 2006; 30:143-156.

(23.) Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 2003; 27:355-373.

(24.) Marik PE, Zaloga GP. Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med 2001; 29:2264-2270.

(25.) Minard G, Kudsk KA, Melton S, Patton JH, Tolley EA. Early versus delayed feeding with an immune-enhancing diet in patients with severe head injuries. JPEN J Parenter Enteral Nutr 2000; 24:145-149.

(26.) Oxman AD, Guyatt GH, Singer J, Goldsmith CH, Hutchison BG, Milner RA et al. Agreement among reviewers of review articles. J Clin Epidemiol 1991; 44:91-98.

(27.) McKinlay RJ, Cotoi C, Wilczynski NL, Haynes RB. Systematic reviews and original articles differ in relevance, novelty, and use in an evidence-based service for physicians: PLUS project. J Clin Epidemiol 2008; 61:449-454.

(28.) Juni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 2001; 323:42-46.

(29.) Egger M, Juni P, Bartlett C, Holenstein F, Sterne J. How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. Health Technol Assess 2003; 7:1-76.

(30.) Cook DJ, Sackett DL, Spitzer WO. Methodologic guidelines for systematic reviews of randomized control trials in health care from the Potsdam Consultation on Meta-Analysis. J Clin Epidemiol 1995; 48:167-171.

Address for correspondence: Dr G. S. Doig, gdoig@med.usyd.edu.au Reprints will not be available from the authors.

P. T. HEIGHES *, G. S. DOIG ([dagger]), E. A. SWEETMAN ([double dagger]), F. SIMPSON ([section])

Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia

* M.P.S. (Education), B.N., Research Fellow.

([dagger]) Ph.D., Associate Professor Intensive Care.

([double dagger]) M.H.M., B.N., Research Fellow.

([section]) M.N.D., Senior Research Fellow.
Table 1
Summary of characteristics of the five included systematic reviews

Study       Patient population    Included trials     Patient
            number of included                       numbers in
            trials                                   individual
                                                       trials

Wasiak      Burn injuries         Peck (2004)             27
et al       (3 RCTs)              Peng (2001)             22
2006 (20)                         Wang (1997)             21

Lewis       Elective intestinal   Mulrooney (2004)        73
et al       surgery (13 RCTs)     Smedley (2004)          79
2008 (21)   * 8 lower GI          Stewart (1998)          80
              surgery             Heslin (1997)          195
            * 3 predominantly     Hartsell (1997)         58
              lower GI surgery    Watters (1997)          31
            * 1 upper and         Beier-Holgersen         60
              hepatobiliary       (1996)
              surgery             Ortiz (1996)           190
            * 1 not specified     Carr (1996)             28
                                  Reissman (1995)        161
                                  Binderow (1994)         64
                                  Schroeder (1991)        32
                                  Sagar (1979)            30

McClave     Acute pancreatitis    Pupelis (2001)          60
et al       * 2 RCTs included     Pupelis (2000)          29
2006 (22)     in subgroup
              analysis

Heyland     Critically ill        Pupelis (2001)          60
et al       patients              Minard (2000)           27
2003 (23)   * 8 RCTs included     Kompan (1999)           28
              in analysis of      Singh (1998)            43
              timing              Chuntrasakul            38
                                  (1996)
                                  Eyer (1993)             38
                                  Chiarelli (1990)        20
                                  Moore (1986)            63

Marik       Acutely ill           Heslin (1997)          195
and         hospitalised          Watters (1997)          31
Zaloga      patients (15 RCTs)    Beier-Holgersen         60
2001 (24)   * 9 abdominal         (1996)
              surgery             Carr (1996)             28
            * 3 trauma            Schroeder (1991)        32
            * 2 head injury       Sagar (1979)            30
            * 1 burns             Kompan (1999)           28
                                  Singh (1998)            43
                                  Chiarelli (1990)        20
                                  Moore (1986)            63
                                  Taylor (1999)           82
                                  Schilder (1997)         94
                                  Hasse (1995)            31
                                  Grahm (1989)            32
                                  Seri (1984)             18

Study       Patient population    Primary outcomes    Secondary
            number of included       assessed         outcomes
            trials                                    assessed

Wasiak      Burn injuries         Mortality.          Weight.
et al       (3 RCTs)              Length of           Nutritioinal
2006 (20)                         hospital stay.      markers.
                                  Frequency of        Metabolic
                                  infection.          markers.
                                  Number of           Biochemical
                                  adverse event       markers.
                                                      Hormonal
                                                      markers.

Lewis       Elective intestinal   Pneumonia.          Nausea and
et al       surgery (13 RCTs)     Wound infections    vomiting
2008 (21)   * 8 lower GI          Intra-abdominal
              surgery             abscess.
            * 3 predominantly     Anastamotic
              lower GI surgery    leakage.
            * 1 upper and         Length of
              hepatobiliary       hospital stay.
              surgery             Mortality 30 days
            * 1 not specified     postoperatively.

McClave     Acute pancreatitis    Mortality.
et al       * 2 RCTs included     Infection.
2006 (22)     in subgroup         Hospital length
              analysis            of stay.

Heyland     Critically ill        Mortality.          Nutritional
et al       patients              Infectious          endpoints
2003 (23)   * 8 RCTs included     complications.
              in analysis of      Length of stay.
              timing

Marik       Acutely ill           Infections.
and         hospitalised          Non-infectious
Zaloga      patients (15 RCTs)    complications.
2001 (24)   * 9 abdominal         Length of
              surgery             hospital stay.
            * 3 trauma            Mortality.
            * 2 head injury
            * 1 burns

Study       Patient population    Intervention/     Comparison
            number of included    defined time
            trials                of early EN

Wasiak      Burn injuries         Within 24 h of    Delayed EN:
et al       (3 RCTs)              injury            >24 h after
2006 (20)                                           injury

Lewis       Elective intestinal   Within 24 h of    Delayed EN:
et al       surgery (13 RCTs)     surgery.          >24 h after
2008 (21)   * 8 lower GI          4 studies         surgery
              surgery             commenced
            * 3 predominantly     EN within 6 h
              lower GI surgery    of surgery
            * 1 upper and
              hepatobiliary
              surgery
            * 1 not specified

McClave     Acute pancreatitis    Day after         Standard
et al       * 2 RCTs included     surgery           care (IV
2006 (22)     in subgroup                           fluids and
              analysis                              analgesia)

Heyland     Critically ill        Within 24-48 h    Delayed EN:
et al       patients              of admission to   48 h after
2003 (23)   * 8 RCTs included     ICU               admission to
              in analysis of                        ICU
              timing

Marik       Acutely ill           Within 36 h of    Delayed EN:
and         hospitalised          admission to      >36 h after
Zaloga      patients (15 RCTs)    the hospital or   admission to
2001 (24)   * 9 abdominal         within 36 h of    the hospital
              surgery             surgery           or surgery
            * 3 trauma
            * 2 head injury
            * 1 burns

EN=enteral nutrition, RCT=randomised control trial,
GI=gastrointestinal, ICU=intensive care unit, IV=intravenous.
Bold: Indicates clinical trial included in more than one systematic
review.

Table 2
Results reported in the five included systematic reviews

Outcome          Systematic review paper   Results

Mortality        Acute illness (24)        RR 0.74 (95% CI 0.37-1.48,
                                           P=0.40, heterogeneity
                                           P=0.92)
                 Critical illness (23)     RR 0.52 (95% CI 0.25-1.08,
                                           P=0.08, heterogeneity
                                           P=0.67)
                 Burns (20)                RR 0.74 (95% CI 0.25-2.18,
                                           P=0.59) *
                 Intestinal surgery (21)   RR 0.41 (95% CI 0.18-0.93
                                           P=0.03, [I.sup.2]=0.0%)
                 Pancreatitis (22)         RR 0.26 (95% CI 0.06-1.09,
                                           P=0.06, [I.sup.2] 0.0%)
Infectious       Acute illness (24)        RR 0.45 (95% CI 0.30-0.66
                                           P=0.00006, heterogeneity
                                           P=0.049)
complications    Critical illness (23)     RR 0.66 (95% CI 0.36-1.22,
                                           P=0.19, heterogeneity
                                           P=0.22)
                 Burns (20)                WMD number of infections
                                           0.0 (95% CI -1.94-1.94,
                                           P=1.0) *
                                           WMD number of antibiotic
                                           days 0.0 (95% CI
                                           -19.67-19.67, P=1.0) *
                 Intestinal surgery (21)   Wound infections RR 0.77
                                           (95% CI 0.48-1.22, P=0.26
                                           [I.sup.2]=42.2%)
                                           Intra-abdominal abscess RR
                                           0.87 (95% CI 0.31-2.42,
                                           heterogeneity P=0.84)
                                           Pneumonia RR 0.76 (95% CI
                                           0.36-1.58, P=0.46,
                                           [I.sup.2]=0%)
                 Pancreatitis (22)         28.2% vs 9.3%, RR 0.33 (CI
                                           not reported P=0.07)
Length of stay   Acute illness (24)        WMD reduced by 2.2 days (95%
                                           CI -0.81- -3.63, P=0.002,
                                           heterogeneity P=0.002)
                 Critical illness (23)     No differences in length of
                                           stay--results not reported
                 Burns (20)                WMD acute stay 0.0 days
                                           (95% CI -30.95-30.95
                                           P=1.0) *
                                           WMD ICU stay increased by
                                           3.0 days (95% CI
                                           -21.55-27.55, P=0.8) *
                 Intestinal surgery (21)   WMD reduced hospital stay by
                                           0.60 days (95% CI -0.66-
                                           -0.54 heterogeneity P=0.09)
                 Pancreatitis (22)         No reported data

RR=risk reduction, CI=confidence interval, WMD=weighted mean
difference. * heterogeneity not applicable - only one trial.
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Author:Heighes, P.T.; Doig, G.S.; Sweetman, E.A.; Simpson, F.
Publication:Anaesthesia and Intensive Care
Article Type:Report
Geographic Code:8AUST
Date:Jan 1, 2010
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