Prognosis of Postoperative Pulmonary Embolism in High Altitude

Background: Pulmonary embolism (PE) is a common cause of death and serious disability, with risks that extend beyond the acute phase. Despite advances in diagnosis and treatment, high mortality rates remain a persistent problem. Aim: The current study aimed to investigate PE prognosis and its determinants among native highlanders in Taif City, Saudi Arabia. Methods: This is a retrospective study where data was collected from the medical records of native high-altitude PE patients in Taif, Saudi Arabia, from 2017 to 2022. Results: The study included 154 native high-altitude PE patients with a mean age of 54±19 years. Most were females and nonsmokers (51.3% (n=79) and 89% (n=137), respectively). Of them, 28.6% (n=44) had undergone a previous surgery, and 61.4% (n=27) of these surgeries were within 1-3 weeks before hospital admission. The majority of patients had sub-massive PE (59.1% (n=91)), followed by non-massive PE (24% (n=37)) and massive PE (16.9% (n=26)). After management, 98 (63.6%) patients were improved, and 56 (36.4%) patients were not improved at the time of data collection. In terms of improvement after PE, patients who had undergone a previous surgery were less than those who had not, with no significant difference (56.8% (n=25) and 66.4% (n=73), respectively, p=0.266). All patients with heart rates (HRs) less than 70 bpm improved after PE compared to those with higher HRs (p=0.003). The thrombus location had no statistically significant association with patient outcomes (p=0.058). Conclusion: This study provides valuable insights into patient outcomes at high altitudes after PE and the prognostic factors influencing these outcomes. It was identified that a low HR was associated with positive outcomes.


Introduction
A pulmonary embolism (PE) arises when a blood clot originating from another location obstructs the blood flow within the pulmonary artery or its branches.In deep vein thrombosis (DVT), the formation of a blood clot, known as a thrombus, within the deep veins typically occurs in the lower extremities.PE typically results from a thrombus fragment entering the pulmonary circulation, but it can also occur due to the embolization of air, fat, or tumor cells.Venous thromboembolism (VTE) describes a combination of PE and DVT [1].PE and VTE rank as the third most common causes of cardiovascular mortality [2].The disease has an incidence of 0.5-1 cases per 1,000 [3].In Saudi Arabia, the incidence rate of PE is estimated to be 5.5% [4].
Major adverse outcomes associated with untreated PE include recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, and death [5].Hence, early management is crucial to prevent complications or death.Medical treatment involves anticoagulants to prevent new clots from forming.Thrombolytic drugs may be reserved for life-threatening conditions to dissolve clots due to various side effects.In resistant cases, surgical management may be necessary for a catheter to remove clots or a filter to prevent clot passage from the inferior vena cava to the lungs [6].
As a result, early diagnosis is crucial since acute PE can be fatal if not detected and treated promptly.The diagnostic approach of PE includes clinical and risk assessment, pretest probability assessment, D-dimer testing, and certain imaging such as chest radiograph, computed tomography (CT) scan, and magnetic resonance imaging (MRI) [5].
Nearly 25% of VTE cases are attributed to recent surgical procedures.Over the past 25 years, evidence-based guidelines worldwide have recommended active strategies to prevent VTE in patients who are at risk and undergoing surgery [7].Major general surgery, including liver, gastric, pancreatic, orthopedic, thoracic, or bowel surgery, leads to a higher risk of developing PE, with a percentage of 0.8%-1.7%[8].
Furthermore, the risk of developing postoperative PE is estimated to be highest within the first five weeks after surgery and varies depending on the type of surgical procedure.International guidelines currently advocate for prophylactic anticoagulation treatment for a duration of up to five weeks following surgery [7].
There are several major risk factors for thromboembolic events, such as recent immobilization, surgery, cardiovascular diseases, recent trauma, older age, prior VTE, malignancy, and indwelling venous catheters.The moderate risk factors include the use of estrogen or hormone replacement therapy, smoking, obesity, pregnancy, and family history of VTE [2].
On the other hand, it was observed that exposure to high altitudes can increase the chance of blood clots during air travel, mountain climbing, or sports [9].Moreover, Shlim et al. [10] and Dickinson et al. [11] reported that PE is common among climbers.
Although there are scattered case reports and current knowledge of altitude and pulmonary disease, there is no clear association between altitude and the risk of PE or its prognosis.Therefore, our study aims to investigate the prognosis of PE and determine the risk factors that impacted the patients' outcomes in native highlanders in Taif City.By focusing on this specific population, we aim to contribute to the existing body of knowledge and provide insights into the prognosis of PE in individuals residing at high altitudes.Through our study, we hope to identify the risk factors that influence the outcomes of PE in native highlanders, thereby improving our understanding of this condition and facilitating targeted interventions for better patient care.

Study design
A retrospective study was conducted among native high-altitude PE patients in Taif, Saudi Arabia, to investigate the prognosis of PE and factors impacting patient outcomes.The study aimed to explore the relationships between various clinical parameters and prognosis.

Data collection
Data was collected from the medical records of PE patients during the period from 2017 to 2022.The collected variables included demographic information (age and sex), medical history (pregnancy status and chronic diseases), laboratory values (D-dimer, international normalized ratio (INR), red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, platelet count, blood pH, and cardiac biomarker), clinical measures (blood pressure, systolic blood pressure (SBP), O2 saturation, CO2, and heart rate (HR)), medical conditions (history of deep venous thrombosis (DVT) or PE, cardiac problems, hemodynamic stability, past medical disease, previous surgery, and smoking status), imaging data (location of thrombus), and length of stay (LOS).Moreover, PE types among patients were classified into massive, sub-massive, and non-massive PE.Patient improvement was defined based on the medical records, and patient factors potentially affecting the improvement were investigated.

Statistical methods
Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 21 (IBM SPSS Statistics, Armonk, NY).Categorical data was described using numbers and percentages, while numerical data was presented using mean and standard deviation (SD) measures, median (interquartile range (IQR)), and range.A normality test was performed for continuous variables.According to the normality test, it was found that the age variable was not normally distributed.
The Monte Carlo test was utilized to explore the relationship between qualitative variables.Since assumptions for Pearson's chi-square test were violated, the Monte Carlo test was a more appropriate choice.Binary logistic regression was employed to assess the odds between dependent and independent variables, with age as a potential predictor.
A p-value of 0.05 or less was considered statistically significant for all analyses.All statistical tests were two-tailed, ensuring a comprehensive examination of the data.

Ethical considerations
Approval was obtained from the institutional review board of Taif University before conducting any studyrelated procedures (approval number: HAP-02-T-067).Data was collected anonymously, and data confidentiality was maintained during and after study conduction.

Risk factors associated with patients' outcomes
By assessing the risk factors impacting patients' outcome in terms of improvement after PE, patients' demographics and medical history has no impact on the improvement of patients with PE (Table 3).Concerning the clinical characteristics of patients and their relation to patients' outcomes (Table 4), the patients' HR showed a statistically significant correlation with patients' outcomes.Having an HR of less than 71.1 bpm had a significant impact on improving patients' prognosis (p=0.003).No other factors showed any significant association with the patients' outcomes (Table 4).

Correlation between patients' outcomes and age
By applying binary logistic regression, the age had no statistically significant relation with the patients' outcomes in terms of improvement after PE (Table 5).p-values less than 0.05 are considered statistically significant.

Discussion
This study shed light on the risk factors that impacted PE prognosis in terms of improvement after PE.Decreased HR has a significant impact on improving the prognosis in all patients.
In the current study, most of the native high-altitude PE patients had an improvement after having PE (63.6%, n=98).Few cases were reported of PE among patients at high altitudes [10,11].To the best of our knowledge, no prior studies investigated patient outcomes after PE among patients at high altitudes and the prognostic factors associated with these outcomes.
Regarding the impact of low HR, in accordance with our findings, Jaureguízar et al. [12] conducted a study on the association between HR and PE.They found that low HR was associated with low mortality and a borderline significant correlation between increased HR and in-hospital death.However, in our study, slightly higher HR had a positive prognosis, which is in contrast to several previous findings [13].This could be because the blockage causes pulmonary damage and reduces the oxygen amount in the blood.As a result, a slightly increased heart rate compensates for the blockage, resulting in a better prognosis.
In terms of thrombi location, García-Sanz et al. [14] and Cha et al. [15] reported that patients with subsegmental PE had a higher survival rate.However, our study concluded that the thrombus location had no significant correlation with PE patients' outcomes.
Regarding age as a predictor of PE prognosis, Cefalo et al. [16] and Spirk et al. [17] reported higher mortality rates among massive PE patients aged 65 years or older.However, in the current study, age was not found to affect PE prognosis.This could be explained by the small percentage of massive PE in our study.
Additionally, Secemsky et al. [18] and Meneveau et al. [19] found that massive PE patients had greater mortality rates compared with sub-massive PE patients.Rehman et al. [20] reported that thrombolysis is associated with improved outcomes for sub-massive PE, with no significant effect on mortality or major bleeding.Several studies estimated that the 90-day mortality rates were 58.3% in patients with massive PE versus 15.1% in those with sub-massive PE and 2% in patients with low-risk PE [21].Our study found no significant results with PE patients' outcomes.In our study, a low percentage of the included patients had massive PE, which could justify our findings.
Furthermore, Quezada et al. [22] and Keller et al. [23] reported that systolic blood pressure < 100 mmHg causes an adverse outcome among acute PE patients.However, our results concluded no significant results with PE patients' outcomes.This could be explained by the small percentage of SBP < 90 mmHg in our study from all included PE patients (16.9%, n=26).Moreover, according to Keller et al. [23], systolic and diastolic BPs are excellent prognosis predictors of patients with acute PE.SBP of 120 mmHg or less and diastolic blood pressure (DBP) of 65 mmHg or less at admission are connected with elevated risk of in-hospital death.
Dentali et al. [24] and Smith et al. [25] reported a significant reduction in PE incidence during anticoagulant prophylaxis, reduced mortality in patients with acute PE, and decreased recurrence.
PE is a serious and common complication of several surgery types, especially general surgery [8].In addition, PE development could be highest within the first five weeks after surgery [7].In the present study, about one-third of the patients underwent a previous surgery within 1-6 weeks.However, neither undergoing surgery nor surgery time significantly affected the outcome among patients.On the contrary, a prior study found that patients who had recent surgery had higher 30-day mortality [25].Due to the retrospective nature of the study design and the small number of patients it included, the validity of our findings is limited.Future prospective study involving a larger sample size is required to verify our findings.

Conclusions
This study provides insights into the outcomes of PE at high altitudes and the factors influencing these outcomes after PE.Moreover, the study contributes to the understanding of risk factors associated with PE prognosis in terms of patient improvement.Based on the severity of the PE, the study did not find any appreciable variations in patient outcomes.Low HR was found to have a beneficial effect on PE improvement.Therefore, attention should be given to the impact of PE patients' HR on their recovery.

TABLE 2 : Frequency and percentage of clinical characteristics during hospital stay
%: percentage, n: number, PE: pulmonary embolism, DVT: deep vein thrombosis, HR: heart rate, SBP: systolic blood pressure, ABG: arterial blood gas, SpO2: saturation of peripheral oxygen, RBC: red blood cell, WBC: white blood cell, LOS: length of stay, ICU: intensive care unit

TABLE 3 : Relationship between baseline characteristics and patients' outcomes
*Chi-square, **Monte Carlo Data has been represented as n and %.p-values less than 0.05 are considered statistically significant.