While modulating intestinal bacteria with prebiotics, symbiotics and probiotics has gained favour over recent years, little is understood about intestinal microflora as they naturally occur during a critical illness experience. How and when intestinal microflora change during critical illness remains elusive. In this study, more
participants experienced a higher proportion of absent and 3+ colonisation of E. coli and absent, scant, 1+ and 2+ of Corynebacterium sp. collected from rectal swabs on admission to, and discharge from, the ICU. The total bacteria counts of other
intestinal microflora (LF, NLF, gram positive bacilli, yeasts and skin flora) remained relatively unchanged or recovered to normal or baseline concentrations. No previous studies have explored the aerobic intestinal bacteria reported in Study Two.
A noteworthy finding of this study was the significant associations between normal faecal flora at multiple time points (see Table 5.19) indicating that normal faecal flora are modulated throughout the critical illness experience. It is postulated that the diversity of normal faecal flora throughout a critical illness experience is associated with the patient’s severity of illness, the ICU LOS, the complexity of physiological responses to critical illness and the multiplicity of ICU treatments including ETF. Reasons explaining these aerobic intestinal microflora changes during a critical illness experience remain elusive. Intestinal microflora dysbiosis has previously been reported at one week following hepatectomy (Kanazawa et al., 2005) and changes in intestinal microflora have been detected at one to two weeks in critically ill patients with severe systemic inflammatory response syndrome (Shimizu et al., 2006). It is difficult, however, to compare the findings of the current study with the Kanazawa et al. (2005) and Shimizu et al. (2006) studies due to the heterogeneity of the current study’s sample, the different intestinal microflora that were cultured and examined in the current study, the different methods and timing of specimen collection and the different methods of specimen processing.
Only one other study (Hayakawa et al., 2011) has examined changes in intestinal microflora during the early phase of critical illness in ETF patients. Dissimilar to the current study, the Hayakawa et al. (2011) study collected faecal specimens by rectal
swab within six hours of admission to the emergency department, prior to the administration of the first dose of antibiotics and with serial collection on days, 1, 3, 4, 7, 10 and 14. Bacterial counts were significantly reduced on the day of admission while Pseudomonas and Enterococcus colonisation increased during the study. Findings of the Hayakawa et al. (2011) study and the current study are similar in that intestinal microflora counts reduced significantly immediately following a sudden physiological insult, such as critical illness. However, the current study differed in that Hayakawa et al. (2011) found Pseudomonas and Enterococcus concentrations increased during the study period. Significant differences were noted between the current study and the Hayakawa et al. (2011) study in that the current study
examined diarrhoea, enteral nutrition and aerobic intestinal microflora associations and the Hayakawa et al. (2011) study examined anaerobic intestinal microflora changes only during the early phases of severe and sudden critical illness. Further, all participants in the current study received enteral nutrition; however, some patients in the Hayakawa et al. (2011) study received enteral and parenteral nutrition that may have resulted in a higher proportion of those patients experiencing hyperglycaemia, intestinal oncotic pressure disequilibrium and infections of some description. Of note is that these aforementioned clinical complications were not reported in the
Hayakawa et al. (2011) study. The implications of pathogenic microorganism
overgrowth and diarrhoea were also not reported in the Hayakawa et al. (2011) study. Participants in the current study were more acutely ill (APACHE II scores Mdn = 27, range 17–49) compared with the Hayakawa et al. (2011) study population (Mdn = 21, range 18–26), which may have culminated with a longer duration of antibiotic
administration and longer actual ICU LOS. The ICU LOS was not specifically reported in the Hayakawa et al. (2011) study, making generalisation of findings across critically ill patient cohorts difficult. Finally, the Hayakawa et al. (2011) study used different methods and timing of specimen collection that may have resulted in dissimilarities to the current study.
Relationships between diarrhoea, diet and aerobic intestinal microflora have been insufficiently examined in the critical illness context. Changes in western diets have demonstrated insignificant changes in the intestinal microflora in healthy individuals (Schneider et al., 2000). The relationships between extreme dietary changes such as those associated with ETF, aerobic intestinal microflora and a critical illness have,
however, yielded different outcomes (Schneider et al., 2000). In this study, changes in intestinal microflora were not associated with a change of pre-hospital diet and enteral nutrition in newly admitted critically ill patients. The results of this study confirm the conflicting associations between extreme dietary changes and
adaptations in participants’ normal faecal flora in the Schneider et al. (2000) study. Only one other study (Whelan et al., 2009) has examined diarrhoea, enteral nutrition and intestinal microflora relationships; however, the Whelan et al. (2009) study was conducted in non-critically ill patients. Similar to this study, Whelan and colleagues (2009) found that there were very few changes in intestinal microflora in ETF patients; however, significant individual variation was noted between the participants’ intestinal microflora in faecal samples. Higher concentrations of
Clostridia (p =.026), and lower concentrations (p =.069) and proportions (p =.029) of Bifidobacteria were found in the Whelan et al. (2009) study. A notable finding of the Whelan et al. (2009) study was that the proportion of Bifidobacteria was
significantly different (Mdn = 0.4%, p =.035) in those participants who did not develop diarrhoea. This finding suggests that other unknown factors may be associated with diarrhoea. Diarrhoea was experienced by 50% (n = 10) of their sample. Consistent between the current study and the Whelan et al. (2009) study is that critically ill and non-critically ill hospitalised and ETF patients displayed
significant diversity in their intestinal microflora. This GIT microflora dysbiosis may predispose the patient to an array of pathological states that might be minimised or avoided with more effective management of the GIT microflora.
Significant differences are evident between the findings of diarrhoea and aerobic intestinal microflora in the current study and intestinal microflora in other studies (Hayakawa et al., 2011; Kanazawa et al., 2005; Schneider et al., 2000, Shimizu et al., 2006). Each of these studies used a different set of intestinal microflora to examine as a primary outcome measure. No rationale was provided in any of these studies for this choice and thus it is difficult to see why there would be such diversity. The choice of intestinal microflora that have been examined in these studies is possibly associated with the fact that anaerobic bacteria colonisation outnumbers aerobic bacteria colonisation in the large intestine by a proportion of 1000:1 (Engelkirk & Burton, 2007; Forbes et al., 2007; Guarner, 2008). Consequently, anaerobic bacteria
counts are easier to measure. Of note between the Hayakawa et al. (2011), Kanazawa et al. (2005), Schneider et al. (2000) and Shimizu et al. (2006) studies is that the relationship between intestinal microflora, diet and critical illness just has not been established.
Of the medication and clinical indicator variables examined in this study, only the duration of hypoalbuminaemia was associated with changes in intestinal microflora. This was not expected as some medications (H2-receptor antagonists and PPI medications) have previously been associated with modulating gastric acidity and therefore the gastric and intestinal tract’s microflora (Beaugerie, 2004; Cunningham & Dial, 2008; Gorkiewicz, 2009; Leonard, Marshall, & Moayyedi, 2007). The longer duration of hypoalbuminaemia was associated with greater diversification in aerobic intestinal microflora, further supporting the association between the ICU patient with diarrhoea and medications, clinical indicators and aerobic intestinal microflora depicted within the revised conceptual framework (see Figure 6.1, page 170). The absence of any association between the ICU patient with diarrhoea, aerobic intestinal microflora and medications, and clinical indicators examined in the current study might be attributed to the small study sample or the small number of participants who received the medications and experienced a derangement of clinical indicators. Alternatively, a relationship between the aforementioned variables simply did not exist. For these reasons, caution is required when generalising the findings of this study to the broad ICU population until further studies corroborate or refute the findings of the current study.
This is the first study to report the association between aerobic intestinal microflora and the time to ETF commencement following ICU admission. In the current study, the time from ICU admission to the commencement of ETF was significantly associated with changes in the colonisation counts of normal faecal flora collected from the rectal swab at ICU admission and also the first faecal sample.
Gastrointestinal tract disuse is reflected through delay to ETF commencement. Longer periods of GIT disuse disrupt intestinal epithelial cell homeostasis.
Gastrointestinal tract disuse has been associated with intestinal epithelial apoptosis, which may result in intestinal bacteria translocation (Marshall et al., 2012), release of inflammatory mediators (Chapman et al., 2007) and intestinal reperfusion injury
(Marshall, 2009; Marshall et al., 2012; Putensen, Wrigge, & Hering, 2006) in critical illness. More change in normal faecal flora colonisation counts were observed when there was a longer timeframe from ICU admission to the commencement of ETF reconfirming the association between the ICU patient with diarrhoea, ETF
(commencement, duration, delivery and formula) and aerobic intestinal microflora (see Figure 6.1, page 170).