Clinical question
Should supplementation with energy, protein and micronutrients versus no supplementation/standard supplements be used to promote healing in adults with PIs?
Context
Population:
Intervention:
Comparison:
Main Outcomes:
Setting:
Conflicts on Interest:
Adults who have a pressure injury
Energy, protein and micronutrient supplement
No supplement
Any clinical setting
Hierarchy of outcome measures:
Outcome 1: Time to healing
Outcome 2: Complete healing (total/percent healed)
Outcome 3: Change in wound size (% change)
Outcome 4: Pain
Outcome 5: If infected at baseline, changes in signs and symptoms of infection
No Guideline Governance Group members of Core Review Group members had a conflict of interest
Evidence to Decision Framework
(Click on the individual judgements for more information)
Summary of Judgements
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Yes
Moderate
Moderate
Low
No important uncertainty or variability
Probably favors the intervention
Moderate costs
No included studies
Probably favors the intervention
Probably increased
Varies
Varies
1. Problem:
Is the problem (pressure injuries) a priority?
JUDGEMENT
No
Probably No
Probably Yes
Yes
Varies
Don’t Know
RESEARCH EVIDENCE
Treating pressure injuries to achieve healing is a priority to most individuals who experience a PI. In 2021, the Guideline Governance Group undertook a stakeholder survey on priority issues to address in the guideline. Receiving clinical guidance on nutritional interventions for treating pressure injuries (PIs) was rated as the highest priority by clinicians (median ranking 5/5) and people with or at risk of PIs and their informal carers (median ranking 5/5). Clinical guidance on nutritional interventions for treating PIs was rated as a high priority by researchers (median ranking 4/5) and industry representatives (median ranking 4/5).
In an earlier survey conducted by the previous Guideline Governance Group in 2018 (Haesler, Pittman et al. 2022), 71.8% (275/383) of individuals with or at risk of PIs and 65.3% (555/850) of informal carers rated receiving information on diet and hydration as important or very important.
2. Desirable Effects:
How substantial are the desirable anticipated effects?
JUDGEMENT
Trivial
Small
Moderate
Large
Varies
Don’t Know
RESEARCH EVIDENCE
| Outcome | Energy, protein and, micronutrient supplement |
No supplement |
Difference | Relative effect |
|---|---|---|---|---|
| Number completely healed | 107/284 (37.7%) | 74/293 (25.3%) | 114 more per 1000 (from 35 more to 215 more) |
RR 1.45 (1.14-1.85) |
Outcome 1: Complete PI healing
A meta-analysis (Langer, Wan et al. 2024) of three RCTs (Ek, Unosson et al. 1991, Ohura, Nakajo et al. 2011, Ohura, Nakajo et al. 2013, Yu, Liu et al. 2015) provided evidence on the effectiveness energy, protein and micronutrient nutritional formulas for complete PI healing versus a standard hospital diet or standard supplements.** The supplements were taken for between 20 days and 26 weeks by individuals with diagnosed malnutrition or who had co-morbidities associated with malnutrition (e.g., cognitive impairment). The analysis showed that energy, protein and micronutrient supplementation might be associated with more PIs achieving complete healing (relative risk [RR] 1.45, 95% CI 1.14 to 1.85), which translates to 114 more per 1000 PIs (from 35 more to 215 more) achieving complete healing. This reflected a moderate effect size. However, there is low certainty in this result. The certainty was downgraded twice for risk of bias because all the included studies had an overall high risk of bias (Langer, Wan et al. 2024).
** Regimens are described in the data extraction tables. Product names may have changed.
3. Undesirable Effects:
How substantial are the undesirable anticipated effects?
JUDGEMENT
Trivial
Small
Moderate
Large
Varies
Don’t Know
| Outcome | Energy, protein and, micronutrient supplement |
No supplement |
Difference | Relative effect |
|---|---|---|---|---|
| Adverse GI tract events | 8/30 (26.7%) | 5/30 (16.7%) | 100 more per 1000 (from 68 fewer to 555 more) |
RR 1.60 (0.59-4.33) |
Outcome: Adverse GI events
The forest plot (Langer, Wan et al. 2024) included one RCT (Ohura, Nakajo et al. 2011, Ohura, Nakajo et al. 2013) reporting adverse gastrointestinal (GIT) effects associated with an energy, protein and micronutrient supplement. Compared to not taking a supplement, there was a non-significant higher rate of GIT events associated with the intervention (26.7% vs 16.7%, RR 1.60, 95% CI 0.59 to 4.33, p=0.36). This translated to 100 more individual per 1,000 experiencing an adverse GIT event (from 68 fewer to 555 more). However, there is very low certainty in this result. The certainty was downgraded once for the high overall risk of bias of the included study.(Langer, Wan et al. 2024) The certainty was also downgraded twice for imprecision because the confidence interval (CI) overlaps the null effect and includes potential benefit (RR<0.75) and potential harm (RR>1.25), and because there was a low number of events and participants (Langer, Wan et al. 2024)..
4. Overall certainty of evidence: What is the overall certainty of the evidence of effects?
JUDGEMENT
Very low
Low
Moderate
High
No included studies
RESEARCH EVIDENCE
| Outcome | Relative Importance | Certainty of Evidence |
|---|---|---|
| Complete healing | CRITICAL | LOW |
Outcome 1: PI occurrence
There is no core outcome set specific to pressure injury healing. To determine the relative importance of outcome measures, the GGG reviewed literature (Gottrup, Apelqvist et al. 2010, Augustin, Schmitt et al. 2014, Driver, Gould et al. 2017, Driver, Gould et al. 2019, Miranda, Deonizio et al. 2021, Raepsaet, Alves et al. 2023, Gupta, Goldstone et al. 2024, Zhang, Zhang et al. 2024), on PI and wound healing outcome measures and, in 2021, undertook a survey of stakeholders regarding their perspective on the importance of commonly reported wound healing outcomes. Based on the review and survey, the GGG prioritized consideration of the following five outcome measures of interest when evaluating evidence for interventions to support PI healing. These clinical outcomes were supported by all surveyed stakeholder groups as critically important to making decisions about the evidence, and are wound agnostic (Gupta, Goldstone et al. 2024), frequently reported in PI research (Miranda, Deonizio et al. 2021), and relevant to both clinical practice and quality of life for individuals with a PI (Driver, Gould et al. 2017, Driver, Gould et al. 2019).
Priority for outcome measures was:
Time taken to heal
Complete healing
Percent change in wound size
Wound-related pain
Change sin signs and symptoms of infection (if infected at baseline)
Certainty of evidence for complete PI healing was low. The certainty was downgraded twice due to all studies having a high overall risk of bias (Langer, Wan et al. 2024).
5. Values:
Is there important uncertainty about or variability in how much people value the main outcomes?
JUDGEMENT
Important uncertainty or variability
Possibly important uncertainty or variability
Probably no important uncertainty or variability
No important uncertainty or variability
RESEARCH EVIDENCE
In a Delphi survey (Lechner, Coleman et al. 2022) that developed a core outcomes et for PI prevention trials, the outcome of PI occurrence was rated as being of critical important (score of 7-9) by all types of stakeholders (health professionals, people with or at risk of a PI and their informal carers, industry representatives and researchers). Greater than 90% of the 158 participants rated this outcome measure as critically important (Lechner, Coleman et al. 2022).
6. Balance of Effects:
Does the balance between desirable and undesirable effects favour the intervention or the comparison?
JUDGEMENT
Favors the comparison
Probably favors the comparison
Does not favor either the intervention or the comparison
Probably favors the intervention
Favors the intervention
Varies
Don’t know
RESEARCH EVIDENCE
Moderate desirable and moderate undesirable (GIT adverse events that resolved quickly).
7. Resources Required:
How large are resource requirements (costs) of the intervention?
JUDGEMENT
Large costs
Moderate costs
Negligible costs and savings
Moderate savings
Large savings
Varies
Don’t know
RESEARCH EVIDENCE
In the Panel Group’s expert opinion, nutritional supplementation can be expensive, particularly for homeless people, people living in the community, people in long term institutional settings, and those without access to health insurance. This is a particular concern for people who require supplementation for longer duration. In acute care settings, particularly intensive care, nutritional supplements are usually funded within the costs of health care.
In the Guideline Governance Group’s expert opinion, the above costs represent moderate costs of implementing the nutritional supplementation
8. Certainty of evidence of required resources:
What is the certainty of evidence of resource requirements (costs) of the intervention?
JUDGEMENT
Very low
Low
Moderate
High
No included studies
RESEARCH EVIDENCE
There is no research evidence.
9. Cost Effectiveness: Does the cost-effectiveness of the intervention favour the intervention or the comparison?
JUDGEMENT
Favors the comparison
Probably favors the comparison
Does not favor either the intervention or the comparison
Probably favors the intervention
Varies
No included studies
RESEARCH EVIDENCE
Analysis of the costs associated with energy, protein and micronutrient supplementation was made(Hisashige and Ohura 2012) based on the findings of one of the included RCTs (Ohura, Nakajo et al. 2011, Ohura, Nakajo et al. 2013). The cost analysis showed a cost savings of approximately $37,000–$44,000 (USD in 2010) per quality adjusted life years (QALY) gained (Hisashige and Ohura 2012, Wong, Walia et al. 2018). The incremental cost-effectiveness ratio (ICER) was –$32,532 (USD in 2017) for 12 weeks of treatment and –$38,726 (USD in 2017) for 14 weeks of treatment.(Wong, Goh et al. 2019) The economic analysis was considered to have several significant limitations and was not included in the Cochrane review analysis of cost effectiveness of nutritional interventions for treating PIs (Langer, Wan et al. 2024).
10. Inequity:
What would be the impact of recommending the intervention on health inequity?
JUDGEMENT
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
RESEARCH EVIDENCE
In the Panel Group’s expert opinion, people who are at higher risk of nutritional deficits are also more likely to be unable to access nutritional supplementation due to their social circumstances and the cost of interventions. This includes barriers to accessing a dietitian to evaluate the person’s nutritional needs. In the Guideline Governance Group’s expert opinion, recommending nutritional supplementation would likely increase health inequity. There are barriers to accessing supplementation for many people depending on their geographic location and the clinical context.
11. Acceptability:
Is the intervention acceptable to key stakeholders?
JUDGEMENT
No
Probably no
Probably yes
yes
Varies
Don’t know
RESEARCH EVIDENCE
In the Panel Group’s expert opinion, a wide range of factors influence acceptability of nutritional supplements. These include palatability of thickened supplements and altered foods (e.g. pureed or thickened) and the person’s ability to consume the volume of fluid required for some supplements.
In the Guideline Governance Group’s expert opinion, recommending nutritional supplementation would having varying acceptability from stakeholders.
12. Feasibility:
Is the intervention (limiting sitting time) feasible to implement?
JUDGEMENT
No
Probably no
Probably yes
yes
Varies
Don’t know
RESEARCH EVIDENCE
In the Panel Group’s expert opinion, barriers to implementation include access to a dietitian to ensure the intervention can be individualized to the person’s needs. Nutritional supplementation is not available in many clinical and geographic contexts, and in some contexts there are rigid referral mechanisms to access dietitians and nutritional interventions.
In the Panel Group’s expert opinion, people living in the community may be unable to implement the recommendation due to lack of relevant knowledge to select an appropriate supplement.
In the Guideline Governance Group’s expert opinion, the feasibility of implementing a recommendation to provide nutritional supplementation varies. In some contexts (e.g. most acute care settings) access to nutritional supplementation and the processes that support implementation (e.g. screening for nutritional deficits, dietician review, access to products) is highly feasible. In other contexts (e.g., community settings, low resource communities) implementing a recommendation to provide nutritional supplementation would not be feasible.
References
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