Abstract
Pressure ulcers (PUs) are a common problem in critically ill patients admitted to the intensive care units (ICUs) and they account for more than 70% of patients with low serum albumin at admission. The aim of this study was to test the efficacy of intravenous administration of albumin in patients with low serum albumin < 3·3 g/dl. In a 1‐year period, a total of 73 patients were admitted to the ICU (males 45, 61·64% and females 28, 38·36%); of these, 21 patients were admitted with hypoalbuminaemia (serum albumin < 3·3 g/dl) and randomised into two groups: 11 patients were treated with 25 g intravenous albumin for the first 3 days within the first week of ICU stay (group A) and 10 patients did not receive albumin (group B). Three patients (27·27%) showed the onset of PUs in group A, whereas seven patients (70%) showed the onset of PUs within the first 7 days of stay in group B. Moreover, ulcers of group B were more severe than those of group A. This study shows that intravenous administration of albumin reduces the onset of PUs in patients admitted to the ICU and in some cases it also reduces the risk of progression to advanced stages of PUs.
Keywords: Albumin, Intensive care unit, Pressure ulcers
Introduction
Pressure ulcers (PUs) are described as ‘localised injury to the skin and/or underlying tissue, usually over a bony prominence, as a result of pressure or pressure in combination with shear’ (National Pressure Ulcer Advisory Panel and the European Pressure Ulcer Advisory Panel, NPUAP/EPUAP, 2009) 1. They vary in size and severity of tissue layer affected, ranging from skin erythema to damage to muscle and underlying bone, and are classified based on this using the NPUAP/EPUAP classification system (2009) 2, 3.
PUs are a worldwide problem affecting hospital and community patient populations. In practice, the emphasis is on identifying patients at risk and implementing appropriate interventions to prevent PU occurrence [AHCPR (Agency for Health Care Policy and Research), 1992; NICE, 2003] 4.
PUs are common among hospitalised patients in intensive care units (ICUs). ICU studies providing prevalence and incidence figures are scarce and their reported incidence in critical care patients varies widely from 1% to 56% 2, 5, 6. Patients admitted to the ICUs, who are confined to bed for long periods, are at particularly high risk of developing PUs 1. PUs are associated with negative patient outcomes such as pain, loss of function and independence, increased risk of infection and sepsis 7 and additional surgical procedures.8.
Albumin plays a fundamental role in patients with acute events, which require a long‐term hospitalisation in the ICU. Its major physiological functions include maintaining colloid osmotic pressure, binding and transport of metabolically active molecules, serving as an antioxidant, use as a surrogate marker of nutritional status and predictor of outcome in elective surgical populations, having an antithrombotic influence on platelets, aiding in acid–base balance and having a protective influence on capillary membrane integrity. The clinical implications of hypoalbuminaemia as an indicator of surgical or ICU outcome or nutritional status are clearly disease‐ and organ‐specific.
Recent studies suggested that hypoalbuminaemia is able to increase the frequency of PUs 1, 2, 8, 9 in more than 70% of patients with a serum albumin level below 3·3 g/l 1, 8 A low serum albumin concentration correlates with increased length of stay in the ICU and with complication rates such as ventilatory dependency and development of new infections.
Methods
Institutional Review Board approval was obtained. All patients provided written informed consent before participating in the study.
All types of ICU patients such as surgical, internal medicine and cardiovascular were included. In a 1‐year period from 1 January 2012 to 31 December 2012, a total of 73 patients were admitted to the ICU (males 45, 61·64% and females 28, 38·36%). The ranges of age were <20 years (1, 0·73%); 20–40 years (4, 5·48%); 40–60 years (19, 26·03%); 60–80 years (37, 50·68%) and >80 years (11, 15·07%). Of these 73 patients, 21 patients were admitted to the ICU with hypoalbuminaemia (serum albumin concentration < 3·3 g/dl 8), and were randomised into two groups: 11 patients were treated with 25 g intravenous albumin for the first 3 days within the first week of ICU stay (group A) and 10 patients did not receive albumin (group B). Complete demographics are shown in Table 1.
Table 1.
Demographics
| Variable | Whole study group |
|---|---|
| n (male/female) | 21 (14/7) |
| Age (years) | 74 ± 12 |
| Body mass index (kg/m2) | 31·4 ± 5·9 |
| Systolic blood pressure (mmHg) | 134 ± 17 |
| Diastolic blood pressure (mmHg) | 83 ± 10 |
| Fasting glucose (mg/dl) | 178 ± 11 |
| Total cholesterol (mg/dl) | 200 ± 39 |
| High‐density lipoprotein (mg/dl) | 51 ± 14 |
| Triglycerides (mg/dl) | 129 ± 74 |
| Albuminaemia (mg/dl) | 2·9 ± 1·7 |
| eGFR (ml/minute per 1·73 m2) | 35 ± 20 |
| FE% (Simpson) | 30 ± 21 |
eGFR, estimated glomerular filtration rate, FE%, ejection fraction percentage.
Criteria for inclusion of patients in this study were to be hospitalised in one of the ICUs with a minimum stay of 24 hours and not to have PU when admitted. The variables such as age, sex, length of ICU stay, length of hospital stay, comorbidity and chronic diseases were studied. Patients admitted to the ICUs came mostly from the operating room (56·0%), followed by the emergency room (21·6%). The main reasons for hospitalisation in the ICU were the postoperative period (62·0%) and respiratory diseases (24·6%). For clinical classification and PU assessment, NPUAP Pressure Ulcer Stages/Categories were used 2, 3 Characterisation of patients according to the clinical and hospitalisation data is shown in Table 2. On admission to the ICU, the clinical record levels of serum albumin and other biochemical indices, such as serum calcium, phosphate, triglycerides, total cholesterol lipoprotein, low‐density lipoprotein and high‐density lipoprotein, were reviewed.
Table 2.
Hospitalisation data
| Main diagnosis at ICU admission | n | % |
|---|---|---|
| Complicated cardiac surgery | 6 | 28·57 |
| Subarachnoid haemorrhage | 4 | 19·05 |
| Cardiogenic shock | 3 | 14·28 |
| Complicated neurosurgery | 1 | 4·76 |
| Exacerbated COPD | 1 | 4·76 |
| Polytrauma | 2 | 9·52 |
| Adult respiratory distress syndrome | 0 | 0·0 |
| Haemorrhagic shock | 2 | 9·52 |
| Decompensated myasthenia gravis | 0 | 0·0 |
| Pancreatitis | 1 | 4·76 |
| Decompensated rheumatoid arthritis | 1 | 4·76 |
COPD, chronic obstructive pulmonary disease.
Results
No patients enrolled in both groups were dismissed from the study. They were followed up for a minimum period of 7 days.
Of the 11 patients of group A, 3 patients (27·27%) showed onset of PUs. Based on NPUAP/EPUAP classification system of ulcers, these lesions were classified into two lesions (66·66%) in stage I and one lesion (33·33%) in stage II (Table 3). Of the ten patients of group B, seven patients (70%) showed onset of PUs. These lesions were classified into one lesion (14·28%) in stage I, two lesions (28·57%) in stage II, two lesions (28·57%) in stage III and two lesions (28·57%) in stage IV (Table 3).
Table 3.
Results
| Group A, patients treated with albumin (%) | Group B, patients not treated with albumin (%) | |
|---|---|---|
| Number of patients | 11 | 10 |
| Evidence of pressure ulcers | 3 (27·27%) | 7 (70·0%) |
| NPUAP/EPUAP classification system | ||
| Stage I | 2 (66·67%) | 1 (14·28%) |
| Stage II | 1 (33·33%) | 2 (28·57%) |
| Stage III | 0 (0·0 %) | 2 (28·57%) |
| Stage IV | 0 (0·0%) | 2 (28·57%) |
This study shows that albumin administration in ICU patients reduces not only the number of PUs but also the severity of the lesions. Both conditions are responsible for the prolongation of hospitalisation in patients, deterioration of their psychosocial conditions and increase in public spending.
Discussion
Critical patients show peculiar characteristics because of the severity of their clinical conditions, association with complex therapies and the need for more frequent and rigorous surveillance and control. Thus, they are more exposed to invasive procedures causing them to be more susceptible to complications and resulting in greater length of hospital stay 8, 10 PUs are a common problem across all health care settings and the incidence of PU is one of the quality signs of health centres. PUs are localised areas of tissue necrosis that tend to develop when soft tissue is compressed between a bony prominence and an external surface for a prolonged period of time 2, 5, 6, 11 About 70% of PUs occur in adults who are older than 65 years; the most common sites are sacrum and heels. The rate at which new ulcers develop in acute care settings varies from 0·4% to 38%, with a mean incidence of about 7%. Immobility, malnutrition and lower body mass index increase the risk of PU. Anaemia and low mean arterial pressure due to decrease of oxygen transport capacity of the blood may cause PU by impairing reaction of the tissue. Recovery in patients who have PUs is delayed, as demonstrated by an increased length of hospitalisation and increased health care costs. Moreover, PUs have been described as one of the most expensive and physically debilitating complications nowadays 12 and they are the third most expensive disorder after cancer and cardiovascular diseases. 13.
Several risk factors have been identified for the development of PUs and they are classified into extrinsic and intrinsic factors. Extrinsic factors include interface pressure, shearing forces, friction and moisture. Intrinsic factors are the nutritional status of the patient, patient age, immobility, incontinence, circulatory factors and neurological disease. Three main mechanical factors are thought to contribute to the development of PUs: pressure, friction and shear 1, 2, 3, 4 Patients with PU could have both medical and psychosocial complications. 14.
The strong point of this study is the detailed screening of risk factors of PUs on admission to the ICU, and with strict preventive treatment it has been shown that it would be possible to decrease the incidence of PUs through albumin administration. On the basis of the statistical results of previous studies, 8, 9, 15 which have clearly shown that values of serum albumin of less than 3·3 g/dl are associated with a very high incidence of PUs, this study has shown that albumin administration (25 g intravenous human albumin for 3 days within the first week of ICU stay) significantly reduces the onset of PUs in ICU patients. Furthermore, it also reduces the risk of progression to advanced stages of PUs.
The reason why albumin administration would benefit patients with low serum albumin concentration might be that plasma oncotic pressure is maintained at a suitable level so as to maintain homeostasis. If the patient's plasma albumin concentration has declined below that level, then the administration of exogenous albumin might have positive effects on the restoration of homeostasis.
Human serum albumin is a 66·5‐kDa, negatively charged, elliptically shaped protein that constitutes 50% of the total plasma protein and contributes up to 80% of the intravascular oncotic pressure.
Currently, there are more than 50 variants of the 585‐amino acid sequence described. 16 The normal serum concentration of albumin is approximately 4 g/dl. Under normal circumstances, albumin synthesis occurs in only 20–30% of hepatocytes, and hepatocyte synthetic rates are regulated by changes in plasma colloid pressure, metabolic and inflammatory state of the host and various anabolic and catabolic hormones. The body has no capacity for storage of albumin or any protein; therefore, once synthesised, it is secreted into the intravascular space, and there is a normal circulation of albumin between the intravascular and interstitial space. Albumin transverses the intravascular space, a phenomenon known as ‘transcapillary filtration’, into the interstitial space at a rate of 6–7 g/h via both passive filtration at areas with large gaps in the endothelium and active filtration via the receptor albondin. 17.
Albumin functions as a transport protein for a large number of metabolites including ions (calcium and copper), fatty acids, amino acids, thyroxine and bilirubin. It also serves as an important antioxidant. 16.
Reduced albumin levels will result in not only an alteration of intravascular and extravascular fluid flux, but will also decrease all the secondary functions of albumin, including drug and nutrient transport, maintaining capillary integrity and its function as an antioxidant affecting extracellular matrix integrity.
The increased stress response leads to increased systemic inflammatory response and elevated levels of tumour necrosis factor‐alpha and interleukin‐6. With the release of the proinflammatory cytokines, the liver undergoes ‘hepatic reprioritisation’. This results in an increase in the synthetic rate of acute‐phase proteins, such as C‐reactive protein, haptoglobin, complement‐3, fibrinogen and amyloid, at the expense of visceral proteins. Other factors decreasing albumin synthesis include a reduction in intravascular oncotic pressure and the deficiency of amino acids such as leucine, arginine, isoleucine and valine. These amino acids can be rate‐limiting steps leading to reduced albumin synthesis. 16.
In the hospitalised patient population, multiple studies have shown that albumin levels are inversely proportional to mortality and complication risk, and hypoalbuminaemia is an independent risk factor for poor outcomes. 8 Thus, low albumin levels are associated with worse outcomes in both elective and emergent operations, regardless of the organ system involved. 8 The use of albumin is common across the world but is relatively expensive, accounting for up to 30% of the pharmacy budget in many hospitals.
In future studies, it would be interesting to assess the utility of wound healing markers such as metalloproteinases (MMPs) and the therapeutic use of MMP inhibitors, already studied in other kinds of chronic wounds 18, 19, 20 and also in PUs.
In conclusion, this study shows that intravenous administration of albumin for a period of 3 days reduces the onset of PUs in patients admitted to the ICU.
Acknowledgement
The authors declare that they have no competing interests.
References
- 1. Coleman S, Gorecki C, Nelson EA, Closs SJ, Defloor T, Halfens R, Farrin A, Brown J, Schoonhoven L, Nixon J. Patient risk factors for pressure ulcer development: systematic review. Int J Nurs Stud 2013;50:974–1003. DOI: 10.1016/j.ijnurstu.2012.11.019.0. [DOI] [PubMed] [Google Scholar]
- 2. Shahin ES, Dassen T, Halfens RJ. Incidence, prevention and treatment of pressure ulcers in intensive care patients: a longitudinal study. Int J Nurs Stud 2009;46:413–21. [DOI] [PubMed] [Google Scholar]
- 3. Black J, Baharestani M, Cuddigan J, Dorner B, Edsberg L, Langemo D, Posthauer ME, Ratliff C, Taler G, National Pressure Ulcer Advisory Panel . National pressure ulcer advisory panel's updated pressure ulcer staging system. Dermatol Nurs 2007;19:343–9. [PubMed] [Google Scholar]
- 4. Keller BPJA, Wille J, Van Ramshorst B, van der Werken C. Pressure ulcers in intensive care patients: a review of risk and prevention. Intensive Care Med 2002;28:1379–88. [DOI] [PubMed] [Google Scholar]
- 5. Boyle M, Green M. Pressure sores in intensive care: defining their incidence and associated factors and assessing the utility of two pressure sore risk assessment tools. Aust Crit Care 2001;14:24–30. [DOI] [PubMed] [Google Scholar]
- 6. Jiricka MK, Ryan P, Carvalho MA, Bukvich J. Pressure ulcer risk factors in an ICU population. Am J Crit Care 1995;4:361–7. [PubMed] [Google Scholar]
- 7. Chou CD, Yien HW, Wu DM, Kuo CD. Albumin administration in patients with severe sepsis due to secondary peritonitis. J Chin Med Assoc 2009;72:243–50. [DOI] [PubMed] [Google Scholar]
- 8. Serra R, Caroleo S, Buffone G, Lugarà M, Molinari V, Tropea F, Amantea B, de Franciscis S. Low serum albumin level as an independent risk factor for the onset of pressure ulcers in intensive care unit patients. Int Wound J 2012. DOI: 10.1111/iwj.12004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Neel DR, McClave S, Martindale R. Hypoalbuminaemia in the perioperative period: clinical significance and management options. Best Pract Res Clin Anaesthesiol 2011;25:395–400. [DOI] [PubMed] [Google Scholar]
- 10. Allman RM, Laprade CA, Noel LB, Walker JM, Moorer CA, Dear MR, Smith CR. Pressure sores among hospitalized patients. Ann Intern Med 1986;105:337–42. [DOI] [PubMed] [Google Scholar]
- 11.The National Pressure Ulcer Advisory Panel. Pressure ulcers prevalence, cost and risk assessment: consensus development conference statement—the National Pressure Ulcer Advisory Panel. Decubitus 1989;2:24. [PubMed]
- 12. Burdette‐Taylor SR, Kass J. Heel ulcers in critical care unit: a major pressure problem. Crit Care Nurs Q 2002;25:41–53. [DOI] [PubMed] [Google Scholar]
- 13.Health Council of the Netherlands. Pressure ulcers. The Hague: Optimum Healthcare, 1999, Publication No. 1999/23; ISBN: 90‐5549‐302‐3.
- 14. Perneger TV, Helliot C, Raë AC, Borst F, Gaspoz JM. Hospital‐acquired pressure ulcers. Risk factors and use of preventive devices. Arch Intern Med 1998;158:1940–5. [DOI] [PubMed] [Google Scholar]
- 15. Hommel A, Bjorkelund KB, Thorngren KG, Ulander K. Nutritional status among patients with hip fracture in relation to pressure ulcers. Clin Nutr 2007;26:589–96. [DOI] [PubMed] [Google Scholar]
- 16. Margarson MP, Soni N. Serum albumin: touchstone or totem? Anaesthesia 1998;53:789–803. [DOI] [PubMed] [Google Scholar]
- 17. Caironi P, Gattinoni L. The clinical use of albumin: the point of view of a specialist in intensive care. Blood Transfus 2009;7:259–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Serra R, Buffone G, Falcone D, Molinari V, Scaramuzzino M, Gallelli L, de Franciscis S. Chronic venous leg ulcers are associated with high levels of metalloproteinases‐9 and neutrophil gelatinase‐associated lipocalin. Wound Repair Regen 2013;21:395–401. [DOI] [PubMed] [Google Scholar]
- 19. de Franciscis S, Gallelli L, Battaglia L, Molinari V, Montemurro R, Stillitano DM, Buffone G, Serra R. Cilostazol prevents foot ulcers in diabetic patients with peripheral vascular disease. Int Wound J 2013. DOI: 10.1111/iwj.12085. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Serra R, Gallelli L, Buffone G, Molinari V, Stillitano DM, Palmieri C, de Franciscis S. Doxycycline speeds up healing of chronic venous ulcers. Int Wound J 2013. DOI: 10.1111/iwj.12077. [DOI] [PMC free article] [PubMed] [Google Scholar]