The present study extensively reviewed and summarized the predictors of POP in patients undergoing hip fracture surgery. A total of 34 predictors were available for meta-analysis, of which 15 predictors, namely, male sex, advanced age, ASA scale ≥3, anemia, COPD, coronary heart disease, arrhythmia, congestive heart failure, chronic kidney disease, cerebrovascular accident, time from injury to surgery, delayed surgery > 48 h after admission or injury, lower preoperative hemoglobin and ALB levels, lower partial pressure of oxygen in arterial blood, and higher BUN and alanine aminotransferase levels, were statistically significant.
POP occurs frequently in patients undergoing hip fracture surgery, particularly in older patients. Results of this meta-analysis revealed that the overall prevalence of POP was 4.8%, which was comparable to the previously reported range of 4.1-15.3% in patients with hip fracture [7,8,9, 11]. POP is closely associated with prolonged hospital stay and significantly increased mortality [5,6,7,8]. It is directly associated with patient prognosis. Therefore, identification and medical optimization of high-risk patients associated with these risk factors are increasingly important.
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Advanced age and male sex have long been associated with adverse postoperative morbidities, including POP, in non-cardiac and orthopedic surgeries [20,21,22,23]. Airway inflammation and pneumonia increase with age because of swallowing and immune dysfunctions [24,25,26]. In addition, impaired spirometric lung age, which is correlated with advanced chronological age, is a well-known risk factor for POP [27]. Furthermore, male patients might have more extensive smoking histories, which can modify lung cell biology and impair mucociliary clearance by the increased number of abnormal cilia. In the same context as impaired lung function, the present study found that patients with lower partial pressure of oxygen in arterial blood were more susceptible to POP development.
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In terms of basic demographic data predictors, this meta-analysis also found that ASA scale ≥3 was a significant risk factor for POP following hip fracture surgery, consistent with results of previous studies [28, 29]. Therefore, it is needed to give more attention to monitor elderly male patients, particularly those with current status of smoking, dependent functional status, and higher ASA scale, so that early detection could be achieved and prevention strategies could be implemented to reduce POP incidence.
The presence of medical comorbidities has a significant impact in the development of POP after hip fracture surgery. The present study found that anemia, COPD, coronary heart disease, arrhythmia, congestive heart failure, chronic kidney disease, and cerebrovascular accidents were significant risk factors for POP. In particular, comorbid COPD dramatically increases the risk of POP development in patients undergoing hip fracture surgery. COPD is a common condition in elderly patients with hip fractures, and is associated with increased risk of death and postoperative complications [30, 31]. Patients with COPD are in a state of chronic systemic/vascular inflammation and immune system derangements with upregulated C-reactive protein and increased production of inflammatory cytokines and tissue factors [32,33,34]. Additionally, limited gas exchange and impaired mucociliary clearance of pathogens can predispose patients with COPD to postoperative pulmonary complications [35, 36]. Targeted interventions to reduce the risk of pneumonia are essential in patients with COPD. Potential interventions for COPD include the use of incentive spirometry, elevation of the head of the bed, early ambulation with pain control, and institution of oral hygiene with chlorhexidine [37].
Previous evidence has suggested that anemia is a significant risk factor for postoperative complications, including POP and increased mortality [38, 39]. Consistent with previous studies, the present study showed that patients with comorbid anemia had an increased risk of POP. In the same context, the pooled results showed an increased risk of POP in patients with lower baseline hemoglobin levels. Thus, medical care in the perioperative period, including patient blood management, should be optimized in patients with comorbid anemia to decrease complications, including POP following hip fracture surgery [40].
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Evidence suggests that pneumonia is associated with various medical comorbidities, including coronary heart disease, arrhythmia, congestive heart failure, and chronic kidney disease [41,42,43,44,45,46]. Cerebrovascular accidents are well-known risk factors for dysphagia and pneumonia [8, 47, 48]. Consistent with previous evidence, the pooled results of the present study showed that coronary heart disease, arrhythmia, congestive heart failure, chronic kidney disease, and cerebrovascular accident were significant risk factors for POP following hip fracture surgery. Generally, co-existing medical morbidities are unmodifiable. However, clinicians should have detailed information on coexisting diseases to assess the risk of POP and identify high-risk patients to apply preventive strategies.
Measurement of ALB level can provide an index of severity of protein-energy malnutrition in patients with hip fractures [49]. Preoperative hypoalbuminemia is a well-described risk factor for perioperative morbidity and mortality in patients undergoing orthopedic surgery [50]. In addition, BUN level is frequently elevated in patients with pneumonia because of hydration and increased reabsorption of urea by the kidneys [51, 52]. An elevated BUN/ALB level has also been reported as an independent predictor of mortality and pneumonia severity [51, 53]. Abnormal liver function test results are common in patients with pneumonia. Patients with low ALB or elevated alanine aminotransferase levels show increased mortality and length of stay [54]. Several lines of evidence suggest that the lung liver axis is characterized by a shared and prominent feature of pneumonia with a hepatic acute-phase response [55, 56]. In the same context, the present study found that lower ALB, higher BUN, and higher alanine aminotransferase levels as baseline laboratory predictors were associated with POP development.
Importantly, the present study also found that the time from injury to surgery and delayed surgery for over 48 h after admission or injury were significantly associated with the development of POP. The impact of delays in hip fracture surgery on postoperative complications and mortality has been the object of scientific discussion. Most studies have shown that delays in surgery can lead to worse outcomes, such as mortality, pain, complications, and length of stay [57,58,59,60,61,62]. Therefore, the international clinical practice guidelines recommend early hip surgery within 48 h of admission, if possible [63].
This study has several strengths. This systematic review and meta-analysis is the first to investigate risk factors for POP in patients undergoing hip fracture surgery. In addition, this meta-analysis was based on the most recent studies published within the last 5 years. Nevertheless, this study has several limitations. First, only retrospective studies with low levels of evidence were included. A general limitation of meta-analyses of observational studies is that the result may be a precise, but biased estimate due to inherent biases and confounding in the original studies. We assessed carefully the quality of the component studies and performed sensitivity analyses excluding studies with a high risk of bias. Second, some of our findings showed a significant heterogeneity and require careful interpretation. However, after sensitivity analyses, the heterogeneity was resolved (I2 < 50%) for most results, except for some variables, such as alcohol consumption, ALB level, and the time from injury to surgery. Third, the small sample size might limit the generalizability of the results. Well-designed studies with a large sample and high quality are required in the future.
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