INTRODUCTION

Pressure ulcers (PU) can occur in any area of the body that is subjected to pressure. Pain, length of intensive care unit (ICU) stay, diabetes, time of MAP <60-70 mmHg, length of mechanical ventilation (MV), haemodialysis or CRRT, vasopressor support, sedation, decreased consciousness level, hypoalbuminemia, anemia, malnutrition, obesity, dehydration, smoking, advanced age, excessive humidity are known risk factors for PU (1,2).

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in China in December 2019 and became a pandemic in a short period of time (3). In Coronavirus disease-2019 (COVID-19) cases, pneumonia caused by the SARS-CoV-2 may be decompensated due to hypoxemia respiratory failure compatible with acute respiratory distress syndrome (ARDS) (4). In patients with ARDS, the need for the prone position (PP) is increasing gradually as it allows gathering dorsal lung regions, increased end expiratory lung volume, and reduced alveolar shunt (4,5). It has been known for many years that in patients with moderate and severe ARDS, PP for 12 hours or longer together with lung protective ventilation improves the PaO₂/FiO₂ ratio and leads to lower mortality (6,7). However, prone positioning has been associated with higher rates of PU (6). It is clear that PU will be an important health and cost factor for all countries, despite the positive effect of PP on survival during the pandemic.

In this study, the risk factors for the development of PU in patients with ARDS who were admitted to the ICU of the study hospital during the COVID-19 pandemic were evaluated in terms of treatment and results.

METHODS

Ethical Considerations

In the study, the patients who developed PU due to PP between patients who were admitted to the COVID-19 ICU between March 1, 2021 and May 31, 2021 were analyzed retrospectively with the approval of University of University of Health Sciences Turkey, Prof. Dr. Cemil Tascioglu City Hospital Local Ethics Committee (date: 24.05.2021, protocol number: 213) and was conducted in accordance with the Helsinki Declaration.

Study Design and Patient Selection

Written informed consent was obtained from the patients for their anonymized information to be published in this article. Patients over the age of 18 who stayed in ICU for more than 48 hours were included in the study, and those under the age of 18 were excluded from the study.

Patients were divided into two groups (group I= developing PU, and group II= did not develop PU). Demographic data, duration of the ICU stay, time in PP, comorbid conditions, days with PU, duration with MV, albumin (Alb) level (reference range 3.5-5.2 g/dL), the hemoglobin (Hb) level (reference range 12-16 g/L), and C-reactive protein (CRP) (mg/L, reference range 0-5 mg/L) level were analyzed. The approach to PU and wound infection were examined.

Definitions

PU risk scale: Braden scale is the most widely employed risk assessment tool. It is considered the gold standard PU risk assessment scales (8).

Statistical Analysis

All the statistical analyses were performed in the 1.15.3 program [R Core Team (2017) R Faundation for Statistical Computing, Vienna, Austria]. Minimum, maximum, mean, standard deviation, median, first quartile, third quartile, frequency, and percentage were used in reporting study data. The conformity of the quantitative data to the normal distribution was evaluated with the Shapiro-Wilk test and graphical examinations. Independent groups t-test was used for the evaluation of the normally distributed variables between two groups. The Mann-Whitney U test was used for the evaluation of the non-normally distributed variables between two groups. Chi-square test was used for comparison of qualitative data and the Pearson correlation test was used to evaluate the association between certain variables. Significance was assessed at p<0.05 level.

RESULTS

A total of 105 patients with moderate to severe COVID-19 ARDS were admitted to the COVID-19 ICU during the three-month period. All of the patients were under invasive MV support and they received enteral and parenteral nutrition and sedoanalgesia. PU developed in 20 patients in the follow-ups performed using the Braden PU risk assessment scale. In group I (n=20), the mean age was 58.45±13.35 and 11 were men (55%) while 9 patients were women (45%). In group II (n=85) the mean age was 62.58±15.31, 43 patients were female and 42 patients were male.

The incidence of PU (number of PU developing in the ICU/total number of days of hospitalization in the ICU x100) was 19%. It was found that the day of PU development was 6/days following the hospitalization, the durations of hospitalized in the ICU was 15.05/days, and the mean duration of MV was 12.15/days.

In group I, the duration of ICU hospitalization was 13.5/day, and the mean duration of MV was 11.5/day. In group II, the duration of ICU hospitalization was 6/day, and the mean duration of MV was 0 (0, 16) day.

It was determined that the duration of ICU stay and MV of group I cases were longer than the durations of group II cases (p=0.009, p=0.002, respectively).

The duration of uninterrupted prone positioning was 23.55±4.38 hours among the study patients. The patients were positioned prone for an average of 5.75 times (2-12) and at least 16 hours during the care unit stay. In group II, it was under 12 hours.

There was no significant difference between the groups in terms of Alb, Hb and CRP values (p>0.05) (Table 1).

While there was no comorbid condition in 5 patients in group I (25%), hypertension + diabetes mellitus (HT+DM) (25%) in 5 patients, DM in 4 patients (20%), HT in 3 patients (15%) were observed. In group II patients, there was no comorbid condition in 13 patients (15.29%); however, DM+HT in 13 patients (15.29%), DM in 22 patients (25.88%), HT in 20 patients (23.52%), asthma bronsiale (5.8%) in 5 patients, and COPD (5.8%) in 5 patients were observed.

While 2° and necrotic PU occurred in 7 patients in group I, the main areas were forehead and nose in all patients. Klebsiella was observed in the trachea culture of 3 patients with PU, Carbapenem resistant Klebsiella + Enterococcus was observed in one patient, Klebsiella + Candida was observed in blood culture of one patient. One patient had Candida.

Forehead (80%), thorax and anterior abdomen (40%), nose (25%), knee (25%) were the most common areas of PU development (Table 2), (Figures 1, 2). The approach to PS in patients was the application of wet dressing (stage I-II, Figure 3).

DISCUSSION

During the COVID-19 pandemic, a disproportionate level of prone ventilation was required to improve prognosis in patients with respiratory distress compared to the general intensive care population. However, making patients prone leads to important complications such as PU (8-10).

Metaanalyses of randomized controlled trials showed that survival increased when patients with severe ARDS (PaO₂/FIO₂ <150mm Hg) were treated with lower tidal volume (≤8 mL/kg), higher PEEP (10-13 cm H₂O), and longer PP duration (>0-12 hours/session) (11). Intubated patients may stay in PP for up to 12-16 hours (12). In COVID-19 ICU, few complications were observed when the PP duration of 8±5 hours in the first 24 hours was continued for an average of 10±5 days, and the conscious use of PP was emphasized (13). It has been suggested that hypoxemia, microvascular injury, and thrombosis may increase the risk of PU in COVID-19 pneumonia. Hypoxemia results in a decrease in peripheral perfusion, including skin perfusion, and this leads to the developments of ischemic skin lesions. Anatomopathological analyses of purpuric skin lesions also showed the presence of pauci-inflammatory thrombogenic vasculopathies (14). In the present study, the uninterrupted duration in the PP was 24 hours/session (16-32). Although all patients were placed in the left and right PP every 6 hours, PU developed. These patients required continued prone positioning to improve respiratory mechanics and oxygenation due to increased hypoxemia.

As the PP needs to be maintained for 10 to 12 hours to become effective, prolonged pressure may cause potential ischemic lesions at pressure points on the face. These facial ulcers most often occur around bony structures, including the forehead, cheekbones, and chin (2,4).

The face was shown as the most affected area (69%) in patients who developed PU due to the PPn. The most common stage II ulcer was observed (9). In our study, the forehead (80%) and thorax and anterior abdomen (40%) were the most common areas of PU in our patients. Stage II ulcers were detected in 35% of the cases.

Five potential causes have been identified that may have contributed to the increase in pressure-related tissue damage in COVID-19 patients. Physiological changes were associated with COVID-19 due to increased use of medical devices needed to support therapy (nasal cannulas, oxygen masks, high-flow oxygen devices, chest drains, tracheostomy tubes, endotracheal tubes, bi-level positive airway pressure or continuous positive air tract pressure masks, malnutrition, reduced mobility, and labor difficulties (15).

In addition to long-term invasive MV and immobility required for PP, friction/shear, use of vasopressors such as norepinephrine, advanced age, anemia, low risk scale score, fecal and urinary incontinence, dehydrated skin, and the presence of chronic diseases are additional risk factors (8,13,16,17). MV longer than 72 hours has been associated with a 23-fold higher risk of developing PU (6). Long-term invasive MV was applied to all of the patients [group I, 12.15 (6-23)/day; group II, 12.09 (2-108)/day]. However, PU developed in 20 patients (19%). Maintaining PP for more than 16 hours was the common point of the patients in the present study and this requires us to consider the long-term PP as a possible risk factor over MV in the development of PU in this patient group. In group II, it was under 12 hours.

In a prospective multicentre randomized controlled study including patients with severe ARDS by Girard et al. (18) prone positioning was associated with higher PU than supine position, while invasive MV, number of hospital stay, age >60 years, female gender, a body mass index of >28.4 kg/m², and a simplified acute physiology score II of >46 at inclusion were shown as covariates independently associated with the development of PU. It was emphasized that these patients would need active protection.

These ulcers are painful and significantly reduce a person’s quality of life. Management of ulcers is expensive and negatively impacts the success of cost-effective, efficient care delivery (10). In our patient group, all ulcers were treated with dressings. The use of dressings such as hydrocolloids, clear film and silicone has been beneficial in reducing facial skin deterioration. The use of multi-layered silicone foam dressings as tissue protectors on the forehead and chin. Similarly, chin dressing has been shown to reduce the stress exposure of soft tissues and strain energy densities by 78% and 92%, respectively (19).

Pain, hypotension, hyperthermia, decreased consciousness level, hypoalbuminemia, low Hb levels, malnutrition, dehydration, smoking, advanced age, excessive humidity are other known risk factors (16,20,21).

Comorbidities such as asthma, COPD, diabetes, and obesity cause patients to become bedridden and live a sedentary life for longer, which increases their risk of developing PU (15). While DM and HT was the most common comorbid conditions in our patients, 25% of the patients who developed PU had no comorbidities. However, the Hb levels of these patients were lower than those in the other group (9.82 g/L vs. 11.15 g/L). Similarly, Alb levels of the patients in group I was low (26.3 g/dL vs. 29.05 g/dL) and CRP, one of the acute phase reactants, was high (109.8 mg/L vs. 80.19 mg/L).

It has been emphasized that the risk of PU increases when the duration of hospital stay in the ICU is extended (22). However, in the present study, there was no difference between the groups in the number of the days of hospital stay [group I, 15.05 (6-26)/day; group II, 15.67 (2-114)/day]. All of these patients generally required long-term high-level intensive care due to COVID-19-related ARDS. Prolonged stay in the PP, low Alb and Hb levels were the factors distinguishing patients with PU from other patients. Insufficient oxygen delivery to the tissues leads to ischemia and this may cause the development of PU (23). Anemia should be treated in these patients.

A pressure of 60-70 mmHg against the skin is sufficient to develop a pressure sore within one to six hours. Decreased blood flow due to decreased capillary blood pressure may cause ischemia, hypoxia, and necrosis in tissues (20). With a set of equipment and devices required for the treatment of COVID-19 (antiembolic stockings, nasogastric tubes, endotracheal tube and mask, central venous catheters, CRRT therapy catheters) which may cause an increased risk of tissue damage, it is obvious that this results in increased facial PS (6). In the Montgomery et al. (24) study, in patients diagnosed with COVID-19; age, male gender, risk of mortality, severity of illness, and long hospital stay were found to be risk factors. The effects of PP were not studied in this study.

When a patient is in the PP, it is recommended to position the patient in the swimmer position, reposition him/her every 2 hours, and keep the skin clean. When the patient is positioned supine, the evaluation of pressure points and early mobilization should be encouraged (12).

Study Limitations

There are some limitations to the present study. First, this study was done in a single centre with a limited number of patients. The duration of uninterrupted prone positioning was 24 hours (16-32) among the study patients. The patients were positioned prone for an average of 5.75 times (2-12) and at least 16 hours during the care unit stay. Statistical analysis of PP time and other risk factors associated with PU is difficult in this study. Because the number of cases is limited to 20. A larger number of patients are necessary for a more accurate analysis, the exclusion of observational biases and a deeper analysis of the risk factors most related to PU.

CONCLUSION

Particular attention should be paid to patient groups with a Braden score ≤13. PU are a preventable condition. The measures to be taken to prevent these wounds are easier and less costly. It is essential that risk factors relevant to clinical practice be identified. Although the risk factors that play a role in the development of PU such as anemia, hypoalbuminemia, long-term MV and prolonged ICU stay are known, situations that require prolonged prone positioning, such as in COVID-19 related ARDS patients, are independent risk factors for the development of PU.

In order to prevent PU in these patients, it is important to observe early symptoms and make appropriate interventions, and to change positions frequently.

Ethics

Ethics Committee Approval: In the study, the patients who developed PU due to PP between patients who were admitted to the COVID-19 ICU between March 1, 2021 and May 31, 2021 were analyzed retrospectively with the approval of University of University of Health Sciences Turkey, Prof. Dr. Cemil Tascioglu City Hospital Local Ethics Committee (date: 24.05.2021, protocol number: 213) and was conducted in accordance with the Helsinki Declaration.

Informed Consent: Written informed consent was obtained from the patients for their anonymized information to be published in this article.

Peer-review: Externally and internally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: E.A.T., H.K., S.M., F.G., H.S., N.K., N.T., Concept: E.A.T., H.K., H.S., N.T., Design: E.A.T., H.K., S.M., F.G., H.S., N.K., N.T., Data Collection or Processing: H.K., S.M., H.S., N.K., Analysis or Interpretation: E.A.T., F.G., N.K., Literature Search: S.M., F.G., H.S., N.K., N.T., Writing: E.A.T., N.T.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.