Abstract
In addition to the data reported in our systematic review and meta-analysis ‘Current Evidence on Omega-3 Fatty Acids in Enteral Nutrition in the Critically ill’ we present data on intensive care unit and hospital mortality, age distribution between included studies, tolerability and adverse events of enteral omega-3 supplementation compared with control interventions in the critically ill. Moreover, we report additional analyses on 28-day mortality comparing old versus new studies and high versus low quality trials. Finally, we report baseline and follow-up levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reported in the trials included in Koekkoek et al. (2018). For further interpretation and discussion we recommend reading our systematic review and meta-analysis Current Evidence on Omega-3 Fatty Acids in Enteral Nutrition in the Critically ill’.
Specifications table
| Subject area | Medicine |
| More specific subject area | Analysis of data on omega-3 fatty acids in critical care nutrition |
| Type of data | Tables and figures |
| How data was acquired | Data were acquired through meta-analysis of 24 RCT׳s on enteral omega-3 fatty acid supplementation in critically ill patients |
| Data format | Analyzed |
| Experimental factors | Critically ill patients receiving enteral omega-3 fatty acid supplementation included in randomized controlled trials were included |
| Experimental features | Forest plots were generated and relative risk ratio׳s calculated to show the effects of omega-3 fatty acid supplementation |
| Data source location | A systematic review was conducted to identify all relevant randomized clinical trials published before January 2018 in MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials. |
| Data accessibility | A systematic review was conducted to identify all relevant randomized clinical trials published before January 2018 in MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials. |
Value of the data
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The data on tolerability and adverse events are helpful in a risk-benefit analysis of omega-3 supplementation in the critically ill.
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Data on ICU and hospital mortality provide more information on safety of omega-3 interventions.
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Data on age distribution between studies may be helpful in interpretation of results and may give rise to specific treatment of age-groups.
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Data on EPA and DHA baseline and follow-up levels may be of value in interpretation of the effects of omega-3 supplementation as they may be related to serum levels.
1. Data
We share data regarding ICU and hospital mortality, age distribution between included studies in [1], tolerability and adverse events of enteral omega-3 supplementation compared with placebo in the critically ill. Fig. 1 shows the effects of fish oil supplementation on ICU mortality in different ICU populations. Fig. 2 shows the effects of fish oil supplementation on hospital mortality in different ICU populations. In Fig. 3 the effects of fish oil supplementation on 28-day mortality, comparing old versus new randomized controlled trials (RCTs) are reported. In Fig. 4 the effects of fish oil supplementation on 28-day mortality, comparing high versus low quality RCTs are shown.
Fig. 1.
The effects of fish oil supplementation on ICU mortality in different ICU populations. ARDS: Acute respiratory distress syndrome; ICU: Intensive Care Unit; CI: confidence interval.
Fig. 2.
The effects of fish oil supplementation on hospital mortality in different ICU populations. ARDS: Acute respiratory distress syndrome; ICU: Intensive Care Unit; CI: confidence interval.
Fig. 3.
The effects of fish oil supplementation on 28-day mortality, comparing old versus new RCTs. CI: confidence interval.
Fig. 4.
The effects of fish oil supplementation on 28-day mortality, comparing high versus low quality RCTs. CI: confidence interval.
Adverse events registered in the trials included in [1] are reported in Fig. 5.
Fig. 5.
Adverse events in RCTs comparing fish oil supplementation with control enteral feeding. CI: confidence interval.
Table 1 reports baseline and follow-up EPA and DHA levels. Furthermore, Table 2 reports on age distribution in the studies included in [1]. Additionally, tolerability of omega-3 supplementation in ICU patients is reported in Table 3.
Table 1.
EPA and DHA levels before and after fish oil supplementation.
| Study | Baseline EPA levels | Baseline DHA levels | Reached EPA levels | Reached DHA levels | Remarks |
|---|---|---|---|---|---|
| Atkinson 1998 | NR | NR | NR | NR | |
| Bower 1995 | NR | NR | Intervention group: 97% increase, p < 0.01 | Intervention group: 72% increase, p < 0.01 | Subset of 72 random patients |
| Control group: NS difference | Control group: NS difference | ||||
| Elamin 2012 | NR | NR | NR | NR | |
| Gadek 1999 | Intervention group: 0.4% of plasma phospholipid fatty acids | NR | Intervention group day 4:6.9% of plasma phospholipid fatty acids, p < 0.001 | NR | Extracted from figures |
| Control group: 0.6% of plasma phospholipid fatty acids | |||||
| Intervention group day 7:8.4% of plasma phospholipid fatty acids, p < 0.001 | |||||
| Control group day 4 and 7:0.1% of plasma phospholipid fatty acids, NS | |||||
| Galban 2000 | NR | NR | NR | NR | |
| Grau-Carmo NR 2011 | NR | NR | NR | NR | |
| Hosny 2013 | NR | NR | NR | NR | |
| Jakob 2017 | NR | NR | NR | NR | |
| Kagan 2015 | Intervention group: 5.5 ± 1.5% | Intervention group day 4: 6.0 ± 1.2% | Omega-3 Index | ||
| Control group: 4.6 ± 0.9% | Intervention group day 8: 6.8 ± 1.0% | Analyzed only for patients completing 8 days of the study (n = 33 in the control group and n = 40 in study group) | |||
| Control group day 4: 4.4 ± 0.8% | |||||
| Control group day 8: 4.5 ± 0.8 % | |||||
| Kieft 2005 | NR | NR | NR | NR | |
| Kudsk 1996 | NR | NR | NR | NR | |
| Mendez 1997 | NR | NR | NR | NR | |
| Mesejo 2015 | NR | NR | NR | NR | |
| Parish 2014 | NR | NR | NR | NR | |
| Pontes-Arruda 2006 | NR | NR | NR | NR | |
| Pontes-Arruda 2011 | NR | NR | NR | NR | |
| Rice 2011 | Intervention group: 2 mg/L | NR | Intervention group day 3, 6 and 12: approximately 16 mg/L | NR | Extracted from text and figure. Levels were measured in the first 60 patients. Because of unavailable samples, actual measurements are from 24 n−3 and 30 control patients at baseline (24 in each group at day 3, 17 in each group on day 6, and 8 n−3 and 9 control patients on day 12). |
| Control group: 2 mg/L | |||||
| Control group day 3, 6 and 12: approximately 2 mg/L | |||||
| Shirai 2015 | NR | NR | NR | NR | |
| Singer 2006 | NR | NR | NR | NR | |
| Stapelton 2011 | NR | NR | Intervention group day 5: 31.9 mg/L (IQR 24.1–59.7) | Intervention group day 5: 24.1 mg/L (IQR 15.8–39.8) | |
| Control group day 5:2.4 mg/L (IQR 1.5–6.3) | Control group day 5: 12.8 mg/L (IQR 9.1–17.9) | ||||
| Thiella 2012 | NR | NR | NR | NR | |
| Tihista 2017 | NR | NR | NR | NR | |
| Weimann 1998 | NR | NR | NR | NR | |
| Van Zanten 2014 | Intervention group: (EPA+DHA):LCP ratio = 0.03 ± 0.01 | Intervention group day 4: (EPA+DHA):LCP ratio increase of 3.4%(95% CI, 3.0–3.8%) | LCP = long-chain polyunsaturated fatty acids | ||
| Control group: (EPA+DHA):LCP ratio = 0.03 ± 0.01 | Intervention group day 8: (EPA+DHA):LCP ratio increase of 5.1%(95% CI, 4.6–5.5%) | ||||
| Control group day 4: (EPA+DHA):LCP ratio increase of −0.3%(95% CI, −0.4% to 0.2%) | |||||
| Control group day 8: (EPA+DHA):LCP ratio increase of −0.5% (95% CI, −0.6% to 0.4%) | |||||
EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; NR: not reported; NS: non-significant; IQR: interquartile range; LCP: long-chain polyunsaturated fatty acids.
Table 2.
Age of study population of included RCTs.
| Study | Age intervention | Age control |
|---|---|---|
| Atkinson 1998 | 63 (18–99)* | 62 (18–87)* |
| Bower 1995 | 39 ± 18.2 | 39.9 ± 18.2 |
| Elamin 2012 | 50.0 ± 22.2 | 55.2 ± 16.5 |
| Gadek 1999 | 51 ± 2 | 51 ± 3 |
| Galban 2000 | 53.9 ± 18.5 | 57.7 ± 16.9 |
| Grau-Carmona 2011 | 62 (40–71)^ | 65 (51–76)^ |
| Hosny 2013 | 52.8 ± 18.87 (intervention group A) | 50.5 ± 14.77 |
| 53.1 ± 12.47 (intervention group B) | ||
| Jakob 2017 | 65.3 (52.6–75.3)^ | 61.6 (48.6–71.3)^ |
| Kagan 2015 | 42.9 ± 18.6 | 38.4 ± 16.8 |
| Kieft 2005 | 66.0 (49–74)^ | 68.0 (55–74)^ |
| Kudsk 1996 | 34.3 ± 3.1# | 31.8 ± 2.3# |
| Mendez 1997 | 28.2 ± 1.2# | 35.3 ± 2.3# |
| Mesejo 2015 | 57 (43–70)^ | 60 (45–71)^ |
| 58 (46–68)^ | ||
| Parish 2014 | 64.4 ± 10.2 | 62.7 ± 13.7 |
| Pontes-Arruda 2006 | 64.3 ± 18.7 | 66 ± 20 |
| Pontes-Arruda 2011 | 70 (64–78)^ | 72 (65–82)^ |
| Rice 2011 | 55.5 ± 17.0 | 52.9 ± 16.5 |
| Shirai 2015 | 71 (66–77)^ | 74 (60–80)^ |
| Singer 2006 | 57.0 ± 18.7 | 62.3 ± 17.2 |
| Stapelton 2011 | 49.0 ± 16.5 | 50.7 ± 16.5 |
| Thiella 2012 | 49.3 ± 20.7 | 53.1 ± 19.3 |
| Tihista 2017 | 38.7 ± 16.2 | 41.6 ± 16.6 |
| Weimann 1998 | 34.8 ± 16.9 | 31.0 ± 11.8 |
| Van Zanten 2014 | 57 ± 19 | 59 ± 18 |
Age is reported in mean ± standard deviation unless otherwise specified. * median with range ^ median with interquartile range # mean ± standard error of the mean.
Table 3.
Tolerability of enteral fish oil supplementation.
| Study | Nausea/ vomiting | Dyspepsia | High GRV | Aspiration | Diarrhea | Constipation | Abdominal distention | Ileus | Pancreatitis | Calories delivered | Replace tube | Achieved feeding target | Triglycerides | Prokinetics | Overall GI complications | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Atkinson 1998 | Intervention | NR | NR | NSD | NR | NSD | NR | NR | NR | NR | 14 (0–32)a kcal/kg/day | NR | 50/197 | NR | NR | NR | |
| Control | NR | NR | NSD | NR | NSD | NR | NR | NR | NR | 13 (0–32)a kcal/kg/day | NR | 51/193 | NR | NR | NR | ||
| Bower 1995 | Intervention | NSD | NR | NR | 1/147 | NSD | NR | NR | NSD | NR | NR | NSD | 100/147 | NR | NR | NR | |
| Control | NSD | NR | NR | 1/132 | NSD | NR | NR | NSD | NR | NR | NSD | 100/132 | NR | NR | NR | ||
| Elamin 2012 | Intervention | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 9/9 | NR | NR | NR | |
| Control | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 8/8 | NR | NR | NR | ||
| Gadek 1999 | Intervention | 1/70 | 0/70 | NR | 1/70 | 5/70 | NR | 2/70 | 1/70 | 2/70 | NR | 1/70 | 50/70 | 28% decrease on day 7 | NR | NR | |
| Control | 1/76 | 1/76 | NR | 0/76 | 5/76 | NR | 4/76 | 1/76 | 1/76 | NR | 5/76 | 43/76 | 19% decrease on day 7 | NR | NR | ||
| Galban 2000 | Intervention | NR | NR | NR | NR | 20/89 | NR | NR | NR | NR | 1231 ± 411 kcal/day | NR | NR | NR | NR | 48/89 | |
| Control | NR | NR | NR | NR | 12/87 | NR | NR | NR | NR | 1414 ± 471 kcal/day | NR | NR | NR | NR | 56/87 | ||
| Grau-Carmona 2011 | Intervention | NR | NR | 220 episodes/1000 days of EN | NR | 271 episodes/1000 days of EN | NR | NR | NR | NR | 1718 (1189–1956) kcal/day | NR | NSD | 120.3 ± 40.3 mg/dL | NR | NR | |
| Control | NR | NR | 279 episodes/1000 days of EN | NR | 302 episodes/1000 days of EN | NR | NR | NR | NR | 1599 (1351–1976) kcal/day | NR | NSD | 106.9 ± 41.9 mg/dL | NR | NR | ||
| Hosny 2013 | Intervention | NR | NR | NR | NR | 5/25 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Control | NR | NR | NR | NR | 4/25 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | ||
| Jakob 2017 | Intervention | NR | NR | NR | NR | 29/45 | NR | NR | NR | NR | 18.0 (12.5–20.9) kcal/kg/day | NR | NR | NR | 15/45 | NR | |
| Control | NR | NR | NR | NR | 31/44 | NR | NR | NR | NR | 19.7 (17.3–23.1) kcal/kg/day | NR | NR | NR | 15/44 | NR | ||
| Kagan 2015 | Intervention | NR | NR | NR | NR | 1.1 ± 2.3 episodes | NR | NR | NR | NR | 1612.8 ± 532.6 kcal/day | NR | 52/62 | NR | NR | NR | |
| Control | NR | NR | NR | NR | 1.6 ± 4.4 episodes | NR | NR | NR | NR | 1622.9 ± 728 kcal/day | NR | 52/58 | NR | NR | NR | ||
| Kieft 2005 | Intervention | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Control | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | ||
| Kudsk 1996 | Intervention | NR | NR | NR | NR | NSD | NR | NSD | NR | NR | 18.03 ± 1.62 kcal/kg/day | NR | NR | NSD on day 7 | NR | 13/16 | |
| Control | NR | NR | NR | NR | NSD | NR | NSD | NR | NR | 18.29 ± 1.60 kcal/kg/day | NR | NR | NSD on day 7 | NR | 16/17 | ||
| Mendez 1997 | Intervention | NR | NR | NR | NR | 150-400 mL/day | NR | NR | NR | NR | 29.5 ± 2.6 kcal/kg/day | NR | NR | NR | NR | NR | |
| Control | NR | NR | NR | NR | 300-700 ml/day | NR | NR | NR | NR | 26.5 ± 3.2 kcal/kg/day | NR | NR | NR | NR | NR | ||
| Mesejo 2015 | Intervention | NR | NR | 1/52 | NR | 2/52 | NR | 0/52 | NR | NR | 22.2 ± 4.1 kcal/kg/day | NR | NR | NSD | NR | NR | |
| Control | NR | NR | 3/105 | NR | 4/105 | NR | 1/105 | NR | NR | 21.7 ± 4.8 kcal/kg/day | NR | NR | NSD | NR | NR | ||
| Parish 2014 | Intervention | NR | NR | NSD | NR | NSD | NR | NR | NR | NR | NSD | NR | NR | NR | NR | NR | |
| Control | NR | NR | NSD | NR | NSD | NR | NR | NR | NR | NSD | NR | NR | NR | NR | NR | ||
| Pontes-Arruda 2006 | Intervention | 0/55 | 1/55 | NR | NR | 9/55 | NR | NR | NR | 0/55 | 1621 ± 48 kcal/day | 2/55 | 14/55 | NR | NR | NR | |
| Control | 1/48 | 0/48 | NR | NR | 7/48 | NR | NR | NR | 1/48 | 1647 ± 74 kcal/day | 4/48 | 23/48 | NR | NR | NR | ||
| Pontes-Arruda 2011 | Intervention | 2/53 | NR | NR | NR | 4/53 | NR | NR | NR | NR | 1538 (1295–1890) kcal/day | NR | NR | NR | NR | NR | |
| Control | 3/53 | NR | NR | NR | 7/53 | NR | NR | NR | NR | 1523 (1370–1950) kcal/day | NR | NR | NR | NR | NR | ||
| Rice 2011 | Intervention | 3.8% | NR | 3.2% | NR | 28.7% | NR | 9.3% | NR | NR | NR | NR | NR | NR | NR | NR | |
| Control | 2.4% | NR | 4.0% | NR | 20.9% | NR | 7.4% | NR | NR | NR | NR | NR | NR | NR | NR | ||
| Shirai 2015 | Intervention | 0/23 | NR | NR | NR | 6/23 | NR | 0/23 | NR | NR | 18.78 (18.12–20.21) kcal/kg/day | NR | NR | 110 (94–131) mg/dL on day 14 | NR | NR | |
| Control | 0/23 | NR | NR | NR | 4/23 | NR | 0/23 | NR | NR | 19.48 (15.73–20.68) kcal/kg/day | NR | NR | 92 (79–123) mg/dL on day 14 | NR | NR | ||
| Singer 2006 | Intervention | NR | NR | NR | NR | NR | NR | NR | NR | NR | 1624 ± 512 kcal/day | NR | 46/46 | NR | NR | NR | |
| Control | NR | NR | NR | NR | NR | NR | NR | NR | NR | 1420 ± 437 kcal/day | NR | 49/49 | NR | NR | NR | ||
| Stapelton 2011 | Intervention | NR | NR | NR | NR | NR | NR | NR | NR | NR | 7362 ± 3800 kcal/week | NR | NR | NR | NR | NR | |
| Control | NR | NR | NR | NR | NR | NR | NR | NR | NR | 7495 ± 3831 kcal/week | NR | NR | NR | NR | NR | ||
| Thiella 2012 | Intervention | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Control | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | ||
| Tihista 2017 | Intervention | NR | NR | 4/47 | NR | 2/47 | 45/47 | NR | NR | NR | 16 ± 4 kcal/kg/day | NR | NR | NR | NR | NR | |
| Control | NR | NR | 15/45 | NR | 7/45 | 40/45 | NR | NR | NR | 17 ± 3 kcal/kg/day | NR | NR | NR | NR | NR | ||
| Weimann 1998 | Intervention | NR | NR | 466 ± 262 mL | NR | 4/16 | 3/16 | NR | NR | NR | 561 ± 266 kcal/day | 1 (1–4) | NR | NR | NR | NR | |
| Control | NR | NR | 513 ± 154 mL | NR | 4/13 | 6/13 | NR | NR | NR | 520 ± 342 kcal/day | 1 (1–3) | NR | NR | NR | NR | ||
| Van Zanten 2014 | Intervention | NR | NR | NR | NR | 1/152 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Control | NR | NR | NR | NR | 0/149 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | ||
GRV: gastric residual volume; GI: gastro-intestinal; NR: not reported; NSD: non-significant difference; IQR: interquartile range; EN: enteral nutrition.
IQR with range; NR = not reported; NSD = no significant difference, no absolute numbers reported in article.
2. Experimental design, materials and methods
The search strategy, study identification and selection criteria used to acquire the data presented in this article are reported in [1].
Acknowledgements
None.
Footnotes
Transparency data associated with this article can be found in the online version at https://doi.org/10.1016/j.dib.2018.10.017.
Contributor Information
W.A.C. Koekkoek, Email: koekkoekk@zgv.nl.
V. Panteleon, Email: vasilianna.panteleon@gmail.com.
A.R.H. van Zanten, Email: zantena@zgv.nl.
Transparency document. Supplementary material
Supplementary material
.
References
- 1.Koekkoek W.A.C., Panteon V., Van Zanten A.R.H. Current Evidence on Omega-3 Fatty Acids in Enteral Nutrition in the Critically ill – a systematic review and meta-analysis. Nutrition. 2018 doi: 10.1016/j.nut.2018.07.013. (In this issue) [DOI] [PubMed] [Google Scholar]
Associated Data
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Supplementary Materials
Supplementary material