Table 2.
Effect of supplements on therapy of pressure ulcers
| References | Number of subjects (n) | Patient population characteristics | Intervention; additional intake of nutrient/day | Period of supplementation (days) | Study design | Parameters of pressure ulcer healing | Results |
|---|---|---|---|---|---|---|---|
| Taylor et al.18 | 20 | Surgical patients with PUa Age: 75 (mean), 54–88 (range) BMI: n.d. |
Verum Vit C, 1,000 mg (Merck) Placebo n.d. |
30 | Double blind, placebo controlled | PU area reduction Healing rate |
V>P V>P |
| ter Riet et al.19 | 88 | Patients with PU (82% stage II/III), 23% with diabetes Age: n.d. BMI: V: 21.5, P: 20.7 (medians) |
Verum Vit C, 1,000 mg (Roche) Placebo Vit C, 20 mg (Semperit) |
84 | Block-randomized, double-blind, placebo-controlled, multicenter study (11 nursing homes, 1 hospital) | Healing rate Healing velocity Healing volume reduction |
V=P V=P V=P |
| Frias Soriano et al.23 | 39 | Patients with PU, stage III/IV, partly with dementia, paralysis, fracture, diabetes, infection, and pneumonia Age: 75±13 BMI: 22.9±5.9 |
Verum ONS (Cubitan®; Nutricia) Intakeb Energy: 475 kcal Protein: 38 g Vit C: 474 mg Vit E: 71 mg Zinc: 17 mg |
21 | Not randomized, not controlled, multicenter study (10 hospitals) | PU area Healing rate Wound ground Granulation tissue Sphacelus Necrotic tissue Wound infection Wound malodour Infected ulcers Exsudation Wound pain PUSH score |
V↓ (week 0 vs. week 3) V ø (week 0 vs. week 1, 2, 3) V↑ (week 0 vs. week 1) V↓ (week 0 vs. week 3) V↓ (week 0 vs. week 2, 3) V↓ (week 0 vs. week 1, 2) V↓ (week 0 vs. week 1, 2, 3) V↓ (week 0 vs. week 2) V↓ (week 0 vs. week 3) V ø (week 0 vs. week 1, 2, 3) V1 ø, V2↓, C↓, ΔC<ΔV1, ΔV2 (week 3) |
| Desneves et al.20 | 16 | Inpatients with PU, stage II–IV, from aged care or spinal injury wares, without osteomyelitis, diabetes, and parenteral nutrition support Age: 73±3, 37–92 (range) BMI: 23.6±1.2, 16.4–28.1 (range) |
Verum 1 ONS (Resource®; Novartis) Energy: 500 kcal Protein: 18 g Vit C: 72 mg Zinc: 7.5 mg Verum 2 ONS (Resource® Arginaid™ Extra; Novartis) Energy: 500 kcal Protein: 21 g Arginine: 9 g Vit C: 500 mg Zinc: 30 mg Control No ONS |
21 | Randomized, double blind, placebo controlled | PUSH score | V1 ø V2↓ (week 0 vs. week 2, 3) C↓ (week 0 vs. week 3) |
| Raffoul et al.24 | 9 | Patients with deep limb ulcers or PU, unresponsive for conservative treatment, without wound infections and renal failure Age: 71±3 BMI: 23.3±1.0 |
Verum ONS (Clinutren®; Nestlé), 1–4 servings/day, one multivitamin tablet (Supradyn®; Roche), 500 mg Vit C (Redoxon®; Roche) Intakec Energy: 720 kcal Protein: 27 g Vit A: 4.04 mg RE Vit C: 752 mg Vit E: 19.6 mg Zinc: 10.2 mg Iron: 11.5 mg Selenium: 36 μg |
15 (5 days before until 10 days after surgery) | Not controlled | Wound healing by d10 Days needed to complete healing Hydroxyproline on d10 in subcutaneous tissue |
90% (median) 20 days (median) 11 mmol/cm (median) |
| Heyman et al.25 | 245 | Patients with PU, stage II–IV, 40% diabetes, 35% cerebrovascular accident, 51% dementia, 44% multiple diagnoses, 78% wheelchair, and/or chair-bound Age: 82±1 BMI: n.d. |
Verum ONS (Cubitan®; Nutricia), three servings/day Energy: 575 kcal Protein: 46 g Arginine 6.9 g Vit C: 575 mg Vit E: 87 mg Zinc: 21 mg |
63 | Not randomized, not controlled, multicenter study (61 long-term care facilities) | PU area Patients with complete wound closure Exsudate |
V↓ (week 3, 9 vs. week 0) 7% (week 16), 20% (week 49) V↓ |
| Cereda et al.21 | 28 | Patients with PU, stage II–IV, without chronic disease (e.g., diabetes mellitus, peripheral vascular disease, autoimmune, and neoplastic disorders) Age: 82±2 BMI: 22.0±1.8 |
Verum ONS (Cubitan®; Nutricia), two servings/day, or enteral formula (Cubison®; Nutricia), 1,000 mL/day Intaked by Cubitan® vs. Cubison® Energy (kcal): 475 vs. 950 Protein (g): 32 vs. 52 Arginine (g): 5.7 vs. 8.1 Vit C (mg): 475 vs. 361 Zinc (mg): 17 vs. 19 Control No supplement |
84 | Randomized, controlled, multicenter study (four long-term care facilities) | PU area Reduction in PU area PUSH score |
V=C (week 2, 4, 6, 8, 12) V=C (week 2, 4, 6); V>C (week 8) V=C (week 2, 4, 6, 8); V<C (week 12) Regression model: Inverse association between PUSH score and arginine intake and the use of a disease-specific formula |
| van Anholt et al.22 | 43 | Patients with PU, stage III–IV, life expectancy≥6 months, without undernutrition and palliative care Age: 75±2 BMI: 24.7±0.7 |
Verum ONS (Cubitan®; Nutricia), three servings/day Intaked Energy: 569 kcal Protein: 45 g Arginine: 6.8 g Vit A: 541 mg RE Vit C: 569 mg Vit E: 86 mg TE Folic acid: 455 μg Carotenoids: 4.5 mg Zinc: 20 mg Selenium: 145 μg Copper: 3.0 mg Placebo n.d. |
56 | Multicenter, multicountry, randomized, controlled, double blind | PU area PUSH score Tissue type Ulcer closed or epithelialized (%) Ulcer Granulated or necrotic (%) |
V<P (week 3, 5) V<P (week 4) V>P (week 4) V<P (week 4) |
| Brewer et al.26 | 35 | Spinal-cord–injured patients with PU, stage II–IV, partly with diabetes, but without sepsis, chronic renal failure, metabolic disease, and diabetic food ulcers Age: 51±2 BMI: n.d. |
Verum ONS (Arginaid®; Nestlé Nutrition), two servings/day Energy: 33 kcal Carbohydrates: 8 g Arginine: 9 g Vit C: 310 mg Vit E: 120 mg TE Control (historical group) No ONS |
Time until wound closure | Not randomized, controlled | Time for wound closure Healing rate |
V<C V>C |
| Ohura et al.28 | 50 | Patients with PU, stage III–IV, 48% cerebral infarctions, 35% dementia, but without liver or renal disorders, severe diabetes mellitus, malignant tumor, unmanageable severe general condition, and unevaluable presssure ulcer wounds Age: 81±1 BMI: 17.7±0.5 |
Enteral formula (Racol®; EN Otsuka Pharmaceutical) Verum vs. Control Energy (kcal): 1,384 vs. 1,092 Protein (g): 61 vs. 48 Fat (g): 31 vs. 24 Carbohydrates (g): 216 vs. 171 Vit A (mg RE): 1.6 vs. 1.2 Vit C (mg): 289 vs. 307 Vit E (mg TE): 9 vs. 7 Zinc (mg): 9 vs. 7 Copper (mg): 1.7 vs. 1.4 |
84 | Randomized, controlled | PU area | V=C (week 0, 2, 4, 6); V<C (week 8, 10, 12) |
| Leigh et al.27 | 23 | Inpatients with PU, stage II–IV, without sepsis, acute gastrointestinal surgery, and dialysis Age: 69±4 (range: 31–92) BMI: 26.8±1.6 |
ONS (Arginaid®; Nestlé Medical Nutrition), V1: one serving/day, V2: two servings/day Intake Verum 1 vs. Verum 2d Energy (kcal): 15 vs. 30 Carbohydrates (g): 4 vs. 7 Arginine (g): 4.1 vs. 8.3 Vit C (mg): 143 vs. 285 Vit E (mg TE): 37 vs. 75 |
21 | Randomized | PUSH score | Effects by time, not by treatment, No impact from initial nutritional status assessed by SGA |
Data on age (years) and on BMI (kg/m2) are means±SEM. Means were calculated as weighted means from the data of individual groups if not provided by the authors. Missing SEMs were calculated by SDs or SEMs of individual groups.
a
Diagnoses: fractured neck of femur, rheumatoid arthritis, cerebrovascular accident, fractured pelvis, peripheral vascular disease, paraplegia, gastric ulcer, benign prostatic hypertrophy, diverticular disease, aortic aneurysm.
b
Mean ingestion of 1.9 servings/day.
c
Considering mean intake from target dose.
d
Based on a mean intake of 75% of target dose; PUSH, Pressure Ulcer Scale for Healing; RE, retinol equivalent; SGA, subjective global assessment; ↓, significant decrease; ø, no significant changes; Δ, changes; ↑, significant increase.