ACS is a complication of a fracture or other trauma that occurs within a closed fascial compartment [1,2]. Postprocedural reperfusion-induced edema is the pathophysiological process causing ACS, which may lead to elevated compartment pressure and tissue necrosis [6]. A delayed diagnosis may result in irreversible nerve and muscle damage, amputation, or even death [5]. Blisters are the consequences of the increasing pressure in the compartment, which commonly occur in the leg and forearm impacted by ACS [3, 4]. Blisters have impacted 2.9% of hospitalized patients and are often caused by high-energy orthopedic injuries to areas of the body where skin adheres tightly to bone and subcutaneous fat is limited [12]. Clinicians may face various problems caused by blisters, such as delayed surgery time and an increased risk of infection [13]. Due to the high incidence and poor prognosis of blisters, it is essential to investigate its predictors and apply preventative measures. Although ongoing research has focused on the development of blisters [14], limited attention has been paid to the predictors of blister formation in ACS patients. To our knowledge, this is the first study to investigate the risk factors for blisters in patients with ACS.
In the present study, we found that the rate of blisters (45 of 206) was 21.8%. Several predictors were identified to be associated with blisters by using univariate analysis, including seasonal factors, referral, a history of alcohol, the level of TC, and higher MLR and PLR. According to logistic regression analysis, patients admitted in the winter or spring, patients with a referral history, and patients with a higher PLR were relevant predictors of blisters. ROC curve analysis revealed that 138.17 was the cut-off value for PLR for predicting the formation of the blister. Furthermore, the combination of seasonal factors, PLR, and referral had the highest diagnostic accuracy.
Our study reported an increased occurrence of blisters among patients with referrals. We also discovered that, compared with patients who first came to our hospital, those who experienced referral had a 4.235-fold increase in the risk of blisters. Not only did the referral increase the waiting time before hospitalization, but it also reflected that the patients had undergone repeated moves, multiple imaging and physical examinations. Before being admitted to our hospital, a number of patients in our research were referred multiple times to several other hospitals for the same imaging and physical tests. Throughout this procedure, there would inevitably be frequent patient transfers, repetitive motions of the fractured region, prolonged waiting times, and repeated evaluations at various medical facilities. These undoubtedly delayed early interventions, such as the use of dehydrant or ice to relieve soft tissue swelling, resulting in worsened soft tissue injury and edema. Previous research has demonstrated that the soft tissue damage caused by ACS is usually enough to cause soft tissue edema and inflammation, which in turn leads to dermal hypoxia and much more soft tissue damage [17]. This extra soft tissue damage may result in skin blistering and, in some circumstances, cutaneous and even muscular necrosis [18]. The above results were consistent with our study. Furthermore, Nelson et al. recommend early fracture reduction and stabilization to decrease the incidence of fracture blisters [19]. Frank et al. believed that the initial stage of fracture-related soft tissue damage therapy was immobilizing the broken limb as quickly as possible, ideally on the site of the accident, to avoid additional soft tissue injury [20]. The perspectives of the researchers, as mentioned above, were consistent with the findings of this research, reflecting that the occurrence of blisters in ACS patients was closely related to repeated referrals. Therefore, enhancing the capability of primary care hospitals, early temporary external fixation, and prompt information exchange between different referral hospitals are crucial measures to reduce blistering in ACS patients.
In our study, the level of PLR was much higher in BG than in CG. There was no previous research investigating the connection between PLR and blisters, but we can get valuable information from the perspective of trauma severity. Maria et al. suggested that ACS caused by fractures was related to the degree of energy release suffered at the moment of injury, with more energy release resulting in more severe soft tissue damage that may in turn worsen ACS [21]. In the meantime, some researchers believe that the degree of soft-tissue damage after fractures is directly associated with the occurrence of blisters [22]. Therefore, the blisters that develop in ACS patients were treated as a particular kind of fracture blister and were thought to indicate the severity of the trauma. The platelet-to-lymphocyte ratio (PLR) is becoming recognized as an indicator of systemic inflammatory response in fractures, malignant tumors, and polytrauma. [23-26] The previous study has shown that significant trauma often leads to increased platelet (PLT) activation and activity, initiating the coagulation cascade and immunological reactions [27]. Wang et al. [23] found that postoperative PLR seems to be a valuable biomarker that correlates strongly with the severity of surgery-related trauma in patients with bicondylar TPFs. The findings of the research mentioned above demonstrated that PLR is an indicator of the severity of the injury, and the severity of trauma is correlated with the emergence of blisters, demonstrating the relationship between blisters and PLR. Our findings indicated that PLR was a predictor of blisters in ACS patients, which was consistent with the above findings. In clinical work, with the prediction of PLR, there can be a reliable basis for forecasting the occurrence of blisters and implementing appropriate countermeasures for patients with ACS. Furthermore, we investigated the role of MLR, a valuable indicator of inflammation, in blister diagnosis. In univariate analysis, MLR was shown to be associated with blisters. However, it was not an independent risk factor based on logistic regression analysis.
In this research, seasonal factors were found to be an independent risk factor for the development of blisters in patients with ACS, with a higher incidence in the winter and spring. Shijiazhuang and Baoding are located in the north of China, where the average temperature in winter and spring could reach -3.0°C to 7.0°C. Seasonal changes are essentially changes in temperature, which might have an influence on fracture-related disorders. In previous studies, several researchers discovered a link between fracture and temperature. Cecilie et al. believed that cold ambient temperatures can increase the incidence of forearm and hip fractures, as well as post-hip fracture mortality [28]. Moreover, Kinga et al. found that the changes in fracture incidence throughout the observation time are related to the season (warmer versus colder) and the increase of mean temperature during the observation period [29]. This could be due to the cold weather requiring thicker and additional clothing, resulting in repeated movements due to the inconvenience of exposing the affected limb during the emergency examination. In addition to this, cold weather may have a negative impact on the patient's exposure to the external environment at the time of injury and during ambulance transport. Hypothermia could have a detrimental impact on trauma patients' metabolic and coagulation systems. Thermostasis may be maintained with simple interventions starting in the prehospital setting, such as passive external warming (covering the patient, away from the cold surroundings), active external warming (hot packs, reflective blankets), and core warming (warmed IV fluids) [30]. Despite the above approach, studies have also reported that 85% of the patients had a finger temperature below the comfort zone in the ambulance, and 44% felt the ambient temperature to be chilly. There was a significant decrease in finger temperature between the first indoor test and the one performed in the ambulance. In prehospital care, exposure to the winter cold was common. Sick and injured patients respond rapidly to exposure to the cold by experiencing a decrease in finger temperature and pain from the cold. As a result, maintaining the patient at a comfortable temperature was critical. Further research is required to increase knowledge that may be used to improve prehospital care for patients who probably already suffer from cold weather [31]. The correlation between blisters and seasonal factors in this study's ACS patients requires that patients be kept warm at the time of injury and throughout transfer in the future. According to the current research findings, the evaluation of whether or not a patient had been exposed to cold offered some assistance in predicting the occurrence of blisters in ACS patients. This prediction provided a solid basis for our perioperative care and surgical planning, therefore preventing the waste of medical resources and the occurrence of unnecessary surgery and perioperative complications about blisters.
We also identified an indicator that acted as a protective factor against blisters. According to logistic regression analysis, patients with a drinking history performed a protective function in preventing blister development.Previous researchers have established a correlation between alcohol consumption and bone mineral density [32-34]. Patients with a history of alcohol consumption tended to have higher bone mineral density. Lower bone density was more likely to result in the development of comminuted fractures [34], which in turn caused significant soft tissue injury. As mentioned above, severe soft tissue injury was positively correlated with the appearance of blisters, which may explain the protective role of a drinking history in delaying the development of blisters.
Even though this is the first study to investigate the risk factors for blister development in patients with ACS, some limitations should be noted. First, because this was a retrospective analysis, several possible factors that may be related to blisters, such as surgical history, were only partly available. Second, owing to the small number of ACS patients, we did not perform a subgroup analysis based on the location of blisters, such as lower leg blisters or upper limb blisters. Third, similar to any other multivariate study, we could not incorporate all confounding variables, and residual confounding remains a concern.
In conclusion, univariate analyses indicated that seasonal factors, referral, MLR, PLR, and TC were associated with blisters, and logistic regression demonstrated that patients who developed ACS in the winter or spring, patients with referral, and patients with a higher PLR were independent predictors of blisters. We determined that 138.17 was the cut-off value of PLR to predict the blister. A drinking history was also discovered to be a significant protective factor for developing blisters. Our results offered a personalized risk assessment for blister formation in patients with ACS, enabling prompt and targeted interventions.