A Retrospective Study of the Impact of Pressure Ulcers on Survival in Elderly Persons With Chronic Diseases
Medical advancements are extending the lives of persons with chronic diseases, increasing their risk for pressure ulcer (PU) development. A retrospective chart review of 192 patients (49.48% male, mean age 9.7 ± 10.9 years) admitted to a skilled nursing department between 2008 and 2013 was performed to determine whether PUs and comorbidities, singly and combined, affect patient survival.
Characteristics abstracted and assessed included sociodemographic factors (age, gender), diseases/comorbidities (eg, chronic renal failure, dementia, Parkinson’s disease [PD], ischemic heart disease, and diabetes mellitus), persistent vegetative state (PVS), type and quantity of PUs (excluding Stage I and PUs that developed during the study), body mass index (BMI) <22, and laboratory data (serum albumin, total protein level, and hemoglobin [Hg] <10). Results were expressed as proportion or mean ± standard deviation. All statistical tests were 2-sided. A P value <.05 was considered significant. Hazard ratios (HR) and statistical significance for survival by risk factors were calculated by the Cox proportional hazards model. Univariate survival models were fitted for all risk factors. Statistical and clinical considerations were used to choose a subset of significant factors to include in a multivariate survival model; all chosen factors were fitted at the first step of the univariate survival models. Age, gender, and BMI were included in the model due to their known clinical effects on survival and their influence on other prognostic factors. In assessing anemia and Hg, only anemia was included due to multicollinearity. From the chosen factors fitted at the first step, a backward elimination was used to successively remove nonsignificant factors until all factors were significant at the 0.10 level. Patients were followed from hospitalization date until death or censoring of study. Median survival time was 122 days (CI: 82-192 days). The median survival time of patients with PUs was 72 days. Every increase in the number of PUs increased mortality by 14% (P <.001, HR = 1.14, CI: 1.07-1.20). In univariate analysis, PUs, anemia, dementia, and PD were found to have a significant association with decreased survival (P = .0001, .003, .001, and .004, respectively). In multivariate analysis, significant risk factors for decreasing survival time were the presence of PUs (HR = 1.14, P = .0001) and dementia (HR = 1.585, P = .009). Anemia (HR = 1.345, P = .09) and PVS (HR = 0.51, P = .09) were determined not to be significant. Anemia was found to decrease survival time and PVS was found to increase survival time. When number of PUs was combined with anemia, advanced dementia, or BMI, the median survival decreased from 72 days to 52, 63, and 63 days, respectively. These findings suggest that PUs in this population are not an isolated health problem but are 1 indicator of systemic deterioration and decreased survival time. The significance of knowing the survival time of patients with PUs has clinical and ethical implications for the comprehensive treatment of elderly patients, particularly those with advanced dementia and other associated medical conditions.
According to a retrospective analysis of the national Medicare Patient Safety Monitoring System database,1 awareness and management of pressure ulcers (PUs) are improving, but PU prevalence continues to increase. This is due, in part, to advancements in the treatment of chronic diseases, which extend the period of limited patient functionality and increase the number of persons with PUs and comorbidities. Understanding the relationship between long-term multiple disease conditions and PU development is critical in explaining the underlying etiology of PUs. Traditionally, the pathogenesis of PUs was based on local extrinsic factors such as pressure, loading, shearing forces, friction, and moisture. However, despite the presence of these extrinsic factors not all immobile, bedridden patients develop PUs. At the same time, elderly patients with multiple advanced comorbidities and disabilities appear to develop PUs despite preventive interventions. This implies PUs are a final pathway of an intrinsic pathological process.2 In a meta-analysis3 of 33 studies of health conditions (28 involving hospitalized persons and 5 involving nursing home residents), PUs were found to be 1 of 7 conditions (physical dysfunction, cognitive impairment, malnutrition, disease diagnosis, laboratory values, PUs, and shortness of breath) associated with short-term mortality. In a retrospective study4 of 174 patients with PUs in a skilled nursing facility, patients with PUs died sooner than patients with the same comorbidities without PUs (94 days versus 414 days, P = .005).
The purpose of this study was to investigate the impact of various combinations of comorbidities and PUs on patient survival.
Setting and patient population. The records of all patients admitted to the Skilled Nursing Department of Herzog Hospital in Jerusalem, Israel between July 1, 2008 and December 31, 2013 were assessed. Inclusion criteria for admittance to the Department included being bedbound and having 1 or more of the following: extensive and a deep PU (grade III or IV according to the National Pressure Ulcer Advisory Panel5 [NPUAP] staging system), terminal cancer requiring palliative care, renal failure requiring hemodialysis, oxygen dependence, noninvasive ventilation (continuous positive airway pressure use), and tracheostomy.
Ethical approval for the study was received from the Helsinki Committee of Herzog Hospital. Patient confidentiality was ensured by encoding all data according to patient identification numbers without the name of the patient.
Procedures and variables. A retrospective chart review was conducted of all patients who met the inclusion criteria for the skilled nursing unit. Relevant medical data were extracted, and patients were followed until death or the end of the study period (December 31, 2013).
The following data, recorded in the medical charts by the attending physician upon admission, were abstracted: sociodemographic characteristics (age, gender), diseases/comorbidities (eg, chronic renal failure, dementia, Parkinson’s disease [PD], ischemic heart disease, diabetes mellitus), persistent vegetative state (PVS), quantity of PUs, body mass index (BMI) <22, and laboratory data (serum albumin, total protein level, and hemoglobin [Hg] <10). New PUs that developed during the study and Stage I PUs were not included.
Data collection. Data were extracted from the patients files to Excel files by the authors.
Statistical analyses. Results were expressed as proportion or mean ± standard deviation. All statistical tests were 2-sided. A P value <.05 was considered significant. Hazard ratios (HR) and statistical significance for survival by risk factors were calculated using the Cox proportional hazards model. Univariate survival models were fitted for all risk factors. Statistical and clinical considerations were used to choose a subset of significant factors to include in a multivariate survival model: all chosen factors were fitted at the first step of the univariate survival models. Other factors (age, gender, and BMI) were included in the model due to their known clinical effects on survival and their influence on other prognostic factors. In assessing anemia and Hg, only anemia was included due to multicollinearity. From the chosen factors fitted at the first step, a backward elimination was used to successively remove nonsignificant factors until all factors were significant at the 0.10 level. Only quantity of PUs and BMI remained in the final model. When gender and age were forced into the model and rerun, the same result was reached so gender, age, quantity of PUs, and BMI remained in the final model. All data were analyzed using SAS software version 9.4 (SAS Institute, Inc, Cary, NC).
Among the 192 patients assessed (95 [49.48%] male, 97 [50.5%] female), the mean age was 79.7 ± 10.9 years and the median age was 81.5 years. Median survival time was 122 days (CI: 82-192 days); 76% of all patients had died by the end of the study.
Age was found to be a statistically significant factor in decreasing survival (HR 1.03, CI: 1.014-1.050, P = .0004); gender was not found to be a significant factor affecting survival (HR 1.09 95% CI: 0.78-1.51, P = .61).
Effects of individual comorbidity plus PU. The mean survival time for 192 patients (the entire sample) was 263 ± 339 days. For the 94 (49%) persons with PUs, the mean survival time was 182 ± 255 days and for the 98 (51%) patients without PUs the mean survival time was 341 ± 390 days.
In univariate analysis, the number of PUs (HR 1.14, 95% CI: 1.07-1.20, P <.001), advanced dementia (HR 1.76, 95% CI: 1.25-2.47, P = .001), PD (HR 1.728, 95% CI: 1.02-2.91, P = .04), and anemia (HR 1.638, 95% CI: 1.17-2.28, P = .003) were found to be statistically significant factors in decreasing survival. In contrast, PVS (HR 0.42 95% CI: 0.19-0.90, P = .02) and serum albumin (HR = 0.98 95% CI: 0.974-1.00, P = .05) were found to be statistically significant factors in longer survival. Comorbidities not found to be statistically significant risk factors in survival included chronic renal failure, ischemic heart disease, diabetes mellitus, BMI, total protein level, and Hg (see Table 1 and Table 2).
In multivariate analysis, only PUs (HR = 1.14, P = .0001) and dementia (HR = 1.58, P = .009), were found to be statistically significant factors leading to shorter survival time when combined with PU. Anemia (HR = 1.34, P = .09) and PVS (HR = 0.51, P = .09) were not determined to be significant. Anemia was found to decrease survival time, and PVS was found to increase survival time (see Table 3).
Effects of multiple comorbidities and PU. When the presence of PUs was combined with anemia, survival decreased from 72 days with PU alone to 52 days with anemia. When the number of PUs was combined with advanced dementia or with BMI <22, the survival time decreased from 72 days with PU alone to 63 days with either of the comorbidities. In the backward elimination model, only the number of PUs and BMI were significant and remained in the final model.
The results of this study demonstrated a significant association between PUs, comorbidities (particularly advanced dementia), and decreased survival.6 This confirms that the presence as well as the number of PUs are indicative of shorter survival time. The study results show each additional PU (above and beyond 1 ulcer) increased mortality by 14% (P <.001, HR = 1.14, CI: 1.07-1.20).
In multivariate analysis, the combination of PUs (HR = 1.14, P = .0001) and dementia (HR = 1.58, P = .009) significantly decreased survival time. Anemia (HR = 1.34, P = .09), and PVS (HR = 0.51, P = .09) were not determined to be significant. Backward elimination showed combining PU and anemia reduced the median survival from 74 days to 52 days. Combining PU and dementia reduced the median survival time from 82 days to 63 days. Combining PU with low BMI reduced the median survival time from 96 days to 63 days.
It is important to consider why advanced dementia was significantly associated with decreased survival when combined with PUs. Also associated with decreased survival were anemia, PD, and BMI when combined with PUs. PVS was associated with increased survival when combined with PUs. The Coleman et al7 conceptual framework cites 3 direct risk factors associated with development of a PU: immobility, skin status, and poor perfusion. These risk factors associated with PU development highlight the influence of increased health deterioration and susceptibility to early death.
Anemia. In the case of anemia, poor perfusion of blood can cause local ischemia and tissue breakdown, contributing to PU development. In a systematic review of 54 studies that included 34 449 acute care and community patients, Bouten et al8 and Coleman et al9 found poor perfusion to be 1 of 3 primary risk factors for PU development. The study by Jaul and Calderon-Margalit4 comparing 174 patients with multiple comorbidities with and without PUs, hospitalized in the Skilled Nursing Department for 3.5 years, found anemia of chronic disease was significantly associated with PUs in univariate (71.5% versus 28.5%, P = .01; OR: 2.16, 95% CI: 1.14-4.08) and multivariate analysis (63% versus 37%, P = .004; OR: 0.73, 95% CI: 0.58-0.90). In results from a cross-sectional study in medical and surgical wards in India, Chauhan et al10 reported anemia was a significant risk factor for the development of a PU. A a 4-case review11 of patients with extensive PUs and anemia of chronic diseases due to the negative effect of inflammatory cytokines on erythroid progenitor cells showed treatment involving recombinant human erythropoietin resulted in improvement of the wounds. The retrospective study by Fuoco et al12 among 40 patients with sacral PUs concluded both anemia and serum protein alteration depend on the chronic inflammatory state related to the presence of PUs.
Hepcidin. Hepcidin is a peptide hormone secreted by the liver during inflammation. It induces macrophage and liver cell trapping and decreases intestinal iron absorption, resulting in anemia of chronic disease. A review13 found that in the inflammatory state associated with nonhealing wounds, the hepcidin hormone rate is accelerated, decreasing iron absorption and leading to increased anemia. This could explain why the higher inflammatory rate resulting from the combination of anemia and PU is more fatal than either alone.
Dementia. Persons with advanced dementia tend to be bedridden, often accompanied by severe spasticity in areas of flexion and malnutrition, increasing the risk for PUs. In a retrospective study of data from the Minimum Data Set14 involving nursing home patients with advanced dementia, 71% of patients died within the first 6 months of admission. Mitchell et al6 conducted an 18-month, multicenter, prospective study among 323 nursing home residents with advanced dementia, which the authors found to be a terminal disease with a mortality rate of 24.7% in the first 6 months and a median survival time of 1.3 years. These results were equal to the mortality rates in metastatic breast cancer and Stage IV congestive heart failure. An interesting but not recognized as significant finding was that 38.7% of patients with advanced dementia developed a PU within 18 months before death.
The natural course of dementia presents with eating and swallowing difficulties, episodes of fever, increased risk of infections, and increased agitation. In an experimental study by Khan and Alkon,15 cognitive impairment in dementia was found to correlate with inflammatory activity in the central nervous system, is most likely systemic, and hypothetically occurs in the periphery of the organ systems and tissues, such as signal transduction impairment in skin fibroblasts. Potential associated mechanisms between dementia and PUs involve autonomic system dysfunction appearing in dementia that can lead to increased susceptibility to PUs; a review16 found blood pressure dysregulation, heart rate variability, and vasoconstriction of microcirculation in soft tissue organs correlate with dementia and PU. All these factors increase the tendency toward PUs in patients suffering from advanced dementia and reduce survival.
PD. In persons with PD, at least 2 mechanisms are associated with decreased survival when combined with PUs. According to a literature review,17 1 mechanism is the characteristic rigidity associated with PD that leads to immobility. A community-based, prospective study18 showed PD has a cognitive impairment etiology commonly allied with dementia. Thus, PD and advanced dementia are both associated with the development of PUs and concurrently the combination of these 3 condition can decrease survival time.
Nutrition. In a retrospective cohort study,19 specific nutritional factors such as low BMI were found to highlight the effect of malnutrition through insufficient food intake and unintentional weight loss known to be associated with PUs. Due to progressive chronic conditions from the combined effect of impaired motor, sensory, immune, and hormonal systems, patients may experience eating and swallowing problems, and as a result, lose weight and subcutaneous tissue and lean body mass (a condition known as sarcopenia), which affects mobility and can lead to the development of a PU. In a randomized, controlled study20 of long-term care patients with low BMI hospitalized for >3 weeks, reduced tissue thickness and mechanical loading caused ischemic effects, predisposing patients to increased morbidity that resulted in skin impairment, onset of PUs, and decreased survival. In a review of the role of nutrition in the treatment and prevention of PUs, Thomas21 noted that although malnutrition has been found to be associated with the development of PUs, no consistent evidence supports use of nutritional supplements to decrease PU risk.
PVS. PVS was found to be associated with risk for PU development, but the HR indicates it is a protective rather than a risk factor for survival (HR = 0.51, P = 0.09). A retrospective study22 of 51 patients with PVS and PUs in 4 nursing homes showed increased survival time with PVS and PUs. This might be explained by the fact the patient with PVS is not active as well as by etiology results reflecting anoxic, ischemic, or traumatic brain damage that occurred in the past.
The implications of knowing the survival time for patients with PUs in various care settings are both clinical and ethical. On a clinical level, identifying intrinsic factors that contribute to decreased survival in patients with a PU should facilitate early detection, prevention, and intervention. For example, understanding low oral intake leads to low BMI and low BMI decreases the survival time of patients with PUs can motivate health care providers to take steps to improve oral feeding (or even introduce tube feeding), potentially preventing the development of malnutrition and decreasing PU risk. On a broader level, recognizing contributing intrinsic factors for PU development allows clinicians to develop a comprehensive view of the patient, enabling accurate medical decisions and improved clinical planning. Appreciating the patient’s comorbidities as related to nutritional status, Hg level, and mental status can help determine whether surgical options or more conservative measures are recommended. An additional benefit relates to the ability of the family members to realistically prepare for transience and to make the necessary adjustments to the prognosis for decreased survival. It is important to understand PUs combined with advanced dementia, PD, anemia of chronic disease, and low BMI is significant for accelerated mortality and leads to shortened survival time. In focusing on the combination of comorbidities and PU, multiple ethical dilemmas are presented to clinicians who are helping patients and families navigate the end-of-life questions and ultimately survival time.
The immediate study was to focus on prevention of PU, particularly in advanced dementia patients and other associated medical conditions. Families and medical staff emphasis requires research and instruction in techniques for prognosis, quality of life, and related dilemmas.
The recall bias concerns typical of retrospective studies are not relevant in this case because the data were collected from charts rather than patient memory. The data were collected by medical research staff and primarily from patients with a severe PU (grade III and IV). In addition, it is important to distinguish the medical setting when referring to PU treatment, management, and survival time. The results of this study may not apply to patients with PUs in community, acute, or other long-term care settings.
A retrospective chart review of patients in a skilled nursing department found decreased survival and increased mortality when PUs were present on admission along with comorbidities compared to PUs alone — specifically, the numbers of PUs in the presence of advanced dementia. Although this finding is not evident in previous literature, it is not particularly surprising; previous studies already have demonstrated that PUs alone in patients with advanced dementia decrease survival and increase mortality rates. The results of this and other studies infer that PUs appear to be a final pathway of an intrinsic pathological process that accelerates deterioration, leading to lower survival and higher mortality rates both via intrinsic and extrinsic mechanisms.
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Potential Conflicts of Interest: none disclosed
Dr. Jaul is Director, Department of Geriatric Skilled Nursing; and Dr. Rosenzweig is a Clinical Researcher, Center for Brain Sciences, Herzog Hospital, Hebrew University, Jerusalem, Israel. Please address correspondence to: Efraim Jaul, MD, MPH, Director, Department of Geriatric Skilled Nursing, Herzog Memorial Hospital, PO Box 3900, Jerusalem 91035, Israel; email: firstname.lastname@example.org or email@example.com.