Abstract
OBJECTIVE: To enhance the understanding of postoperative pulmonary thromboembolism in neurosurgery and improve the prevention and treatment of postoperative pulmonary embolism in neurosurgery specialties.
Methods: We analyzed the clinical data of 7 patients with pulmonary thromboembolism in neurosurgery in our hospital, and analyzed the various risk factors and treatment measures involved. After diagnosis, all 7 patients were treated with heparin or low-molecular heparin anticoagulation, and later with warfarin anticoagulation, and 2 of them underwent emergency inferior vena cava permanent filter implantation before anticoagulation.
One case died of respiratory and circulatory failure caused by pulmonary embolism on the fourth day after anticoagulation. The remaining 6 cases were discharged with significant clinical improvement after treatment.
Conclusion: There are multiple risk factors for pulmonary thromboembolism after neurosurgery, and CTPA is a rapid and clear method to diagnose pulmonary embolism, and multiple measures should be taken promptly to treat pulmonary embolism after neurosurgery.
Keywords: pulmonary thromboembolism; lower extremity deep vein thrombosis; neurosurgery; surgery; complications.
General information of patients
The cases were 3 male and 4 female; age 43-48 years old in 4 cases and 61-69 years old in 3 cases, mean 53.7 years old. The admission diagnoses were: 2 cases of Cushing’s disease, 1 case of pituitary growth hormone adenoma, 1 case of paraganglioma of the sagittal sinus, 1 case of cervical spinal canal spinal meningioma, 1 case of hypertensive cerebral hemorrhage, and 1 case of acute subdural hematoma.
Underlying disease conditions
Among the patients, there were 6 cases with previous history of hypertension, 3 cases with history of stroke, 2 cases with history of diabetes mellitus, and 1 case with history of hyperlipidemia.
1. Neurosurgery status and timing of pulmonary embolism
Patients with paraganglioma of the sagittal sinus had 2 operations within 1 week due to complications, and the remaining 6 cases had 1 operation. All patients wore gradient compression elastic stockings after surgery. Two cases were in a coma after neurosurgery (preoperative coma), and five cases were conscious. The time of pulmonary embolism was 3-10 days after surgery, with an average of 7.86 days. 3 of the 7 patients with pituitary tumors had not used dehydrating drugs (2 of them had urinary collapse after surgery, and the urine volume fluctuated between 3500-4500 ml for 24 h after taking the drugs); the other 4 patients had been treated with mannitol intravenously before and after surgery.
2. Clinical manifestations of pulmonary embolism
The clinical symptoms of the four awake patients at the time of pulmonary embolism were mainly panic, chest tightness, weakness and pain in the lower limbs, and one awake patient had no subjective symptoms, mainly changes in heart rate, blood pressure and oxygen saturation. The common signs in the seven patients with pulmonary embolism were increased heart rate (all heart rates were above 110 beats per minute at the onset), increased respiration, decreased blood pressure and decreased oxygen saturation (90%-97%).
3. Electrocardiogram performance
The preoperative electrocardiogram of all patients was sinus rhythm and normal electrocardiogram. The electrocardiographic changes at the onset of pulmonary embolism were mainly the manifestations of T-wave hypoplasia, inversion and ST-segment depression in some leads, and pulmonary P-wave in 2 patients. Two patients showed signs of impaired right heart function such as complete or incomplete right bundle branch conduction block.
4. Laboratory tests
Three of the cases (1 meningioma and 2 Cushing’s disease) showed abnormal hypercoagulation of APTT and APTT-R in the preoperative examination, and the rest of the laboratory indexes were normal. The pH of the blood gas analysis at the time of pulmonary embolism ranged from 7.451-7.483, and the partial pressure of oxygen was less than 90 mmHg in all cases, 66.1-89.4 mmHg. The partial pressure of CO2 was 33.8-39 mmHg. 4 of the 7 patients had Fbg>3.88 g/L, which was significantly higher than the upper limit of the reference value (1.8-3.5 g/L), and 3 patients had APTT and APTT and APTT-R hypercoagulation was abnormal in 3 patients at the time of pulmonary embolism (preoperative hypercoagulation in meningioma). Six patients with pulmonary embolism had D-dimer values ranging from 573 μg/L to 1498 μg/L, which was higher than the upper reference value of 420 μg/L, and one patient had normal measurements.
5. Pre-operative and post-operative ultrasound examination
None of the patients had preoperative ultrasonography of both lower extremities, and 3 elderly patients with routine cardiac ultrasonography suggested reduced cardiac left ventricular relaxation function. After pulmonary embolism, 5 patients underwent ultrasound examination of bilateral lower extremities, among which 2 cases were bilateral lower extremity venous thrombosis or bilateral intermuscular venous thrombosis, and 3 cases were right lower extremity deep and superficial venous thrombosis.
In 6 cases, pulmonary embolism was diagnosed by CTPA, and in 1 case, deep vein thrombosis and pulmonary embolism in the lower extremities were diagnosed by the patient’s refusal of CTPA examination, combined with clinical manifestations, D-dimer, blood gas analysis and ultrasound examination of bilateral lower extremities. 5 of the 6 cases had pulmonary embolism of multiple lobes and segments of lungs bilaterally, accompanied by thickening of pleura bilaterally, and 1 case had pulmonary embolism of multiple segments of upper and lower lobes on the left side.
Treatment methods and results
1.Treatment method
Two cases underwent emergency inferior vena cava permanent filter implantation, and then anticoagulation was performed in all cases. and other coagulation functions, control APTT between 50S-70S, APTT-R at 1.5-2.5, add warfarin 3mg, qd after 2 days; after overlapping 3-5 days, according to INR (International Normalized Ratio) value, adjust the dose of warfarin to maintain INR between 1.8-2.5, discontinue heparin sodium after reaching the standard, maintain anticoagulation with warfarin, and test coagulation function regularly; ( (2) 0.6ml with Kesse, subcutaneously, q12h, with warfarin 2.25mg added the next day, after overlapping 3-5 days, warfarin to maintain anticoagulation; (3) 4100U of Speedy Bilin, subcutaneously, q12h; with warfarin 3mg added the next day, qd, after overlapping 3-5 days, warfarin to maintain anticoagulation, and regular testing of INR.
2. Results
One 68-year-old patient with hypertensive cerebral hemorrhage died of respiratory and circulatory failure caused by pulmonary embolism on the 4th day after anticoagulation therapy in 7 treated patients. The remaining 6 cases showed significant improvement in clinical symptoms, 5 cases had D-dimer in the normal range on reexamination, and 1 patient was automatically discharged with D-dimer of 556 μg/L, which was also significantly lower than before anticoagulation therapy. Repeat CTPA showed significant improvement in pulmonary artery embolism.
3, Discussion
Pulmonary thromboembolism, a clinical and pathophysiological syndrome in which thrombus from the venous system or the right heart occludes the pulmonary artery or its branches causing pulmonary circulation and respiratory dysfunction. In turn, the source of thromboemboli is predominantly the deep veins of the lower extremities. In the United States, the annual incidence of pulmonary embolism is about 630,000 to 700,000 cases. In the United States and Europe, approximately 100,000 to 300,000 patients die from PE each year. the specificity of the disease in neurosurgical patients determines that neurosurgical patients are an extremely high-risk group for acute pulmonary embolism. A large prospective study abroad found that the incidence of acute pulmonary embolism after neurosurgery is 25%, the mortality rate is 9~50%, and acute pulmonary embolism accounts for 3% of the causes of death after neurosurgery. Similar epidemiological data are not available in China, but strengthening the prevention and management of perioperative acute pulmonary embolism in neurosurgery, reducing the incidence of pulmonary embolism, and improving surgical outcomes should be of utmost concern to every neurosurgeon.
In addition to the common risk factors such as advanced age, surgery, hemostatic drugs and prolonged bed rest, neurosurgical patients also face the application of hormones, dehydrating drugs, severe underlying diseases, malignant tumors, possible limb paralysis after surgery, and obesity and hypercoagulability of blood in patients with Cushing’s disease. All 7 patients in this group were over 40 years old, all had onset about 1 week after neurosurgery (mean 7.86 days), the patients had a mean surgical time of 3.5 hours at that time, and 4 patients had applied different doses of mannitol for dehydration after surgery, and the other 2 patients with pituitary tumors had a postoperative dysuria. It is interesting to note that 6 of the 7 patients had hypertension (3 of them had a previous history of stroke and 2 of diabetes); the only patient with meningioma without underlying disease had 2 operations of >5 hours within 1 week and had postoperative paralysis of the right limb, while ultrasound showed that the site of the lower limb thrombosis was both on the side of the paralyzed limb and that this patient had muscle strength of grade 4 at the time of discharge. Therefore, analysis of the data of this group of patients can give us the following hints: (1) we must pay attention to the underlying diseases of patients before neurosurgery, on the one hand, we must raise the vigilance to prevent pulmonary embolism, on the other hand, we must control the underlying diseases well before surgery and improve the auxiliary examinations. Unfortunately, none of the six patients with underlying diseases had preoperative lower extremity venous ultrasound data, which affected the preoperative judgment of high-risk factors, and there was no reliable data for medical research comparison, which should be paid great attention. (2) Common high-risk factors related to pulmonary embolism, such as advanced age, long operation time and bed rest, will not be further elaborated, but it should be emphasized that patients with pituitary tumors, especially those with Cushing’s disease, should be focused on prevention. The pituitary gland is harassed by surgery or due to partial resection of the posterior pituitary gland often leads to urinary collapse and is prone to impaired water and electrolyte balance, which will further promote the development of pulmonary embolism. (3) Post-operative neurosurgical patients have a negative balance of in and out due to the application of dehydrating drugs such as mannitol, tachypnea and albumin. The blood will be further concentrated, leading to the formation of venous thrombosis in the lower extremities, which in turn “triggers” the dislodgement of the thrombus.
The Guidelines for the Prevention of Major Orthopedic Venous Thromboembolism in China, using the time of surgery, patient age, and the presence of risk factors as indicators, classify patients into four levels of risk for PTE: low risk, moderate risk, high risk, and very high risk.
There are no clear guidelines or definitive conclusions regarding the risk stratification of DVT/PTE in patients after neurosurgery. The contribution of each risk factor to the development of DVT/PTE in patients after neurosurgery (i.e., the relative risk) is also unclear at this time. Therefore, there is a need for more large clinical randomized controlled trials to regress these risk factors, so as to guide physicians to stratify the risk of DVT/PTE in patients after neurosurgery and to take individualized prevention and treatment measures for different patients.
The clinical presentation regarding pulmonary embolism is basically similar and will not be the focus of this article. Based on the medical data of this group of patients, we believe that special attention should be paid to the diagnosis of the detected condition. Only when the diagnosis is clear can the treatment be tailored to the disease and prevent delays. The main diagnostic tests often involved in the clinic and in the literature are D-Dimer, ECG, CTPA, nuclear ventilation-perfusion lung scan (V/Q imaging), ultrasound and pulmonary arteriography. Elevated levels of transcatheter D-Dimer can indicate the possibility of DVT formation, but many literatures believe that D-dimer cannot determine the presence or absence of PTE, and in addition, diseases such as infections and tumors can also lead to elevated D-Dimer. Therefore, it has been suggested that its specificity for diagnosing DVT is low and can only be used as an initial screening test for low- and intermediate-risk patients. And routine screening for D-Dimer is not recommended in high-risk patients because its diagnostic sensitivity is also low in high-risk patients. Our data showed that six of the seven patients with suspected pulmonary embolism had higher than normal reference values at the time of presentation, and all of the patients reviewed showed a significant decrease in D-dimer and five were within the reference range after later anticoagulation therapy. The patients’ clinical symptoms, lower extremity ultrasound and CTPA results all showed a significant effect of anticoagulation data, which basically complemented each other. The ECG at onset has its specific aspects, but compared to pulmonary angiography, cardiac ultrasound and V/Q imaging, CTPA and CTV are more concise, rapid and reliable for the diagnosis of pulmonary embolism. Six cases in our group were clearly confirmed by CTPA imaging.
After the diagnosis of pulmonary embolism was confirmed, the treatment method was not clearly supported by the current international treatment guidelines for immediate thrombolysis because all of the patients in this group had pulmonary embolism recently after surgery. There are also very few relevant reports in China. The overall outcome of the patients in this group was good, with only one death (this elderly patient had been in a coma before and after surgery, was continuously bedridden, and had a serious underlying disease in the past). This outcome is attributed to the attention given to this disease by the neurosurgeons, and also to the experience and advantages of the multi-departmental collaboration in the treatment of the disease developed over the years at Peking Union Medical College Hospital. During treatment, plain heparin anticoagulation and low-molecular heparin anticoagulation were adopted according to each patient’s condition, and APTT data were closely monitored during the application of heparin therapy to ensure the anticoagulation effect and avoid the risk of bleeding. Recent reports also suggest that there is a good positive correlation and linear relationship between heparin concentration and APTT, and that heparin concentration testing can be replaced by monitoring of APTT. All patients were anticoagulated with oral warfarin at a later stage, and two of them with heavy lower limb venous thrombosis had permanent filters placed in the inferior vena cava before anticoagulation.
The above discussed the risk factors, diagnosis and treatment of patients with pulmonary embolism, we should pay more attention to the issue of preventive measures. Therefore post-neurosurgical patients should be out of bed as early as possible. In addition, the main preventive measures for DVT/PTE include (1) mechanical prophylaxis, including intermittent pneumatic compression (IPC), compression stockings and inferior vena cava filters; (2) pharmacological prophylaxis, including low-dose heparin subcutaneous injection, low-molecular heparin and warfarin. Numerous literature emphasizes the role of compression stockings in prophylaxis, but in fact the effect of compression stockings alone in preventing DVT/PTE is not exact, and a recent large multicenter RCT study found no significant difference in the incidence of DVT/PTE in the compression stockings group compared with the control group. All 7 patients in this group used compression gradient stockings postoperatively, but they did not prevent the occurrence of pulmonary embolism at all. Although the role of compression stockings cannot be fundamentally denied, it should be realized that they are not the “savior” of pulmonary embolism, and their effectiveness in preventing DVT is weak. Intermittent sequential pneumatic pumps have been shown to be effective in preventing DVT formation in neurosurgical patients after surgery. One study found that the use of IPC reduced the incidence of DVT to 2.3% and the incidence of PTE to 1.8% in neurosurgical patients after surgery. Another large meta-analysis even showed that continuous use of IPC after surgery was as effective as drug anticoagulation in preventing DVT. At the same time, IPC has fewer side effects and therefore can be the first choice for DVT/PTE prophylaxis after neurosurgery. There are no definitive conclusions regarding the evaluation of the efficacy and safety of pharmacologic anticoagulation in DVT/PTE prophylaxis in patients after neurosurgery. Further strong statistical evidence is needed to validate this. Currently, low-dose plain heparin or low-molecular heparin anticoagulation is routinely recommended to prevent DVT/PTE after all major orthopedic surgery and vascular surgery patients with a propensity for hypercoagulation. A meta-analysis confirmed that the use of warfarin or low-molecular heparin after surgery reduced the incidence of DVT/PTE by 60% to 80%. A recent foreign meta-analysis covering 7779 patients showed that pharmacologic anticoagulation did not increase the risk of intracranial hemorrhage in patients. The incidence of intracranial hemorrhage was higher with low-dose plain heparin anticoagulation starting 24 hours after surgery than with mechanical prophylaxis, but there was no significant difference between the two; moreover, the meta-analysis found that preoperative heparin anticoagulation was significantly better than postoperative anticoagulation for DVT prevention. For neurosurgery, however, the risk of bleeding associated with pharmacologic anticoagulation may lead to catastrophic complications such as intracranial hemorrhage. Neurosurgeons are also cautious on this issue, and no consensus has been formed. It is also one of the topics that need to be addressed and standardized.
In conclusion, for neurosurgical perioperative patients, especially postoperative patients, an overall analysis of their various risk factors for pulmonary embolism should be performed preoperatively, a preliminary assessment of the patient should be made, an overall perioperative prevention and treatment plan should be formulated in response to the results of the assessment, and the awareness and vigilance of neurosurgical medical staff against pulmonary embolism complications should be improved. It is important to both prevent and improve the level of diagnosis and treatment, and to actively and appropriately treat patients with pulmonary embolism in a comprehensive manner.