Rare, Fatal Pulmonary Fat Embolism after Acupuncture Therapy: A Case Report and Literature Review

Background: In the clinic, death from nontraumatic pulmonary fat embolism associated with minor soft tissue contusion, surgery, cancer chemotherapy, hematologic disorders and so on has been reported. Patients often present with atypical manifestations and rapid deterioration, making diagnosis and treatment dicult. However, there are no reported cases of death from pulmonary fat embolism after acupuncture therapy. This case aims to emphasize that awareness of nontraumatic pulmonary fat embolism as a complication of acupuncture therapy needs to be improved. In addition, it suggests that in such cases, autopsy should be used to identify the source of fat emboli. Case presentation: The patient, a 72-year-old woman, experienced symptoms of dizziness and fatigue after silver-needle acupuncture therapy. She experienced a signicant drop in blood pressure and died 2 hours later despite treatment and resuscitation. A systematic autopsy and histopathology examination (H&E and Sudan (cid:0) staining) were performed. More than 30 pinholes were observed on the surface of the lower back. Focal hemorrhages were seen surrounding the pinholes in the subcutaneous fatty tissue. Microscopically, numerous fat emboli were observed in the interstitial pulmonary artery and a large number of alveolar wall capillaries, in addition to the vessels of the heart, liver, spleen and thyroid gland. The lungs showed congestion and edema. However, the cause of death was identied as pulmonary fat embolism. Conclusion: This article suggests that high vigilance for risk factors and the complication of pulmonary fat embolism following silver-needle acupuncture therapy should be exercised. In postmortem examinations, examining the peripheral arterial system and the venous system draining from noninjured sites for the formation of fat emboli is helpful to differentiate posttraumatic and nontraumatic pulmonary fat embolism.


Background
Fat embolism is the partial, subtotal, or total blockage of vessels in multiple organs, such as the lungs and brain, due to the presence of lipid droplets [1]. It is most frequently observed following severe trauma, particularly long bone fractures and contusions in soft tissue rich in adipose tissue. Nontraumatic pulmonary fat embolism associated with minor soft tissue contusion [2,3], surgery, cancer chemotherapy, hematologic disorders and so on has also been reported [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Intrinsic or extrinsic stimuli evokes a biological response, known as stress [19]; stress can be induced by trauma, blood loss, hypoxia, pain, heat and cold, fear, infection, surgery, and anesthesia. It should be noted that pulmonary fat embolism caused by stress is sometimes associated with mild tissue damage, but some stress-related factors, such as strong external stimuli and mental stimulation, are essential. Additionally, subclinical conditions, such as obesity, multiple organ adipose hyperplasia and other conditions, may be risk factors for nontraumatic fat embolism [3].

Medical history
The patient, a 72-year-old woman, received silver-needle acupuncture therapy lasting for 2 hours for back pain. The silver needles used for acupuncture were 1.1 mm in diameter. Immediately after the therapy session, the patient showed symptoms of dizziness and fatigue. The symptoms gradually worsened, and she developed an altered mental status, a pale complexion, and pale lips. The physical examination showed the following: T: 36.8℃, R: 20 t/min, P: 124 t/min, and BP: 159/131 mmHg. The bilateral pupils were equal in size and round, and she had light re ex sensitivity, clear respiratory sounds in both lungs and a regular heart rhythm. Her lower back region was swollen, and multiple pinholes oozing blood were observed. The preliminary diagnosis was heart disease and heart failure. Then, 1.5 hours later, the patient's blood pressure dropped to 53/35 mmHg, and she died 2 hours later after treatment and resuscitation. The cause of death was heart disease, heart failure, and respiratory arrest. She had a history of hypertension for more than 20 years; however, any additional medical history was unknown.

Autopsy And Histopathology Findings
An autopsy was performed the next day. The corpse was 168 cm long, and the patient was obese (Fig. 1A). The abdominal wall was 5 cm thick, with fatty hyperplasia of the omentum and mesentery (Fig. 1B). Systematic congestion was observed. The heart weighed 545 g, with epicardial subepicardial adipose tissue hyperplasia (Fig. 1C) and right ventricular wall adipose tissue in ltration. The right atrium and ventricle were over lled. There were more than 30 pinholes in the lower back, focal hemorrhages in the subcutaneous fatty tissue surrounding the pinholes and massive hemorrhage in the deep musculature (Fig. 1D-F). No spinal cord injury was found on autopsy. The anterior descending wall of the left coronary artery was notably thickened, with atherosclerotic plaque formation. Level II luminal stenosis was observed, and the lumen was unobstructed. There were no abnormalities in the left circum ex branch of coronary artery or the right coronary artery. Both lungs weighed 1055 g, with substantial congestion and edema. Microscopically, the arterial and interstitial capillaries of the alveolar walls in both lungs near the hilus pulmonis and the marginal tissue were embolized, with smooth-margin vacuoles of varying sizes ( Fig. 2A, 2B) that were positive by Sudan staining (Fig. 2C, 2D). The fat emboli were visible in all parts of both lungs under 10 × magni cation, with antler-like con gurations. Furthermore, similar vacuoles were also observed in the interstitial vessels of the liver, heart, spleen and thyroid (Fig. 3). No other fatal diseases were found, except for diffuse hepatocellular fatty degeneration.

Discussion
Cause of death and mechanism of pulmonary fat embolism It was clear that the patient died from pulmonary fat embolism according to the diagnostic criteria of pulmonary fat embolism, with samples evaluated at 100 × magni cation [1]. There were fat emboli with antler-like con gurations that were clearly visible and abundant in all regions of the lungs. There was no sample without fat emboli, indicating degree embolism (massive fat embolism) [1]. The author believes that the speci c cause and mechanism of fat embolism warrant attention in this patient. There were more than 30 pinholes in her lower back, and we calculated that the silver needle used for acupuncture was 1.1 mm in diameter; thus, the total area of damaged fat tissue was approximately 0.2851 cm 2 . However, fat components in some blood vessels of various organs besides the lungs, such as the liver, heart, spleen and thyroid gland, indicated that there was a substantial amount of circulating fat. Hence, it is believed that the cause of death in this case was severe nontraumatic pulmonary fat embolism, which was made on the basis of the pathology ndings, including obesity, multiorgan adipose tissue hyperplasia and stress triggered by silver-needle acupuncture. The mechanism of nontraumatic pulmonary fat embolism is a neuroendocrine effect that leads to an increase in catecholamine secretion, which releases a large amount of peripheral fat into the blood, resulting in an unstable lipid emulsi cation state, chylomicron agglutination and nally blockage of the interstitial vessels in the lungs [20][21][22].

Prevention of pulmonary fat embolism as a complication
The adipose tissue damage caused by silver-needle acupuncture was not a risk factor for pulmonary fat embolism. In practice, acupuncture is part of the healing system of traditional Chinese medicine (TCM) and is widely used in many countries throughout the world for pain relief in the neck, shoulders and lower back [23,24]. Silver-needle acupuncture, as a kind of complementary and alternative medicine (CAM), is a unique branch of acupuncture [25,26] and has not previously been associated with pulmonary fat embolism. In the clinic, death from fat embolism is not uncommon, as it is a complication of minor trauma, surgery, or other treatments, and thus should be given adequate attention. However, in the event of pulmonary fat embolism, patients present with atypical manifestations (Table 1), making diagnosis and treatment di cult. For example, in this case, the patient developed dizziness immediately after silver-needle acupuncture treatment and heart failure 2 hours later, without a series of manifestations associated with pulmonary fat embolism, such as dyspnea, chest pain and hemoptysis. It should be noted that the patient had signs of respiratory insu ciency, cerebral dysfunction, and skin ecchymosis [20,21,27]. Evidently, ageing, obesity, underlying diseases, mental status and irritation due to treatment protocols may be risk factors for stress-induced pulmonary fat embolism, so the choice of treatment must be in strict accordance with the indications and contraindications, and the patient should be closely observed for any related clinical manifestations to reduce the occurrence of complications and adverse events [23]. This case suggests that when the patient's condition suddenly deteriorates or respiratory insu ciency develops after physiotherapy to relieve pain, such as acupuncture, the possibility of pulmonary fat embolism should be considered, and a prompt diagnosis and treatment should be provided.

Differential diagnosis of fat embolism source
This was a very interesting case of pulmonary fat embolism that was suspected to be due to stress. In fatal posttraumatic pulmonary fat embolism caused by subcutaneous soft tissue contusion, there are no uniform criteria regarding the area of the damage or the extent of the injury.
Moreover, in fatal pulmonary fat embolism cases, the soft tissue contusion area generally affects 30-35% of the body surface [27,28]. Some studies have also shown that fat compression in different body regions can range from 20 cm 2 to 21-70 cm 2 [2]. In this case, based on the isolated puncture injuries on the skin, the nature of the adipose tissue injury was wounds formed by needle pricks and peripheral bleeding due to ruptured vessels and blood in ltration, not soft tissue contusions. In addition, the degree (about 0.2851 cm 2 by 30 pinholes) of adipose tissue damage in this case was very low and far from the degree of adipose tissue damage noted in previous reports.
Those performing postmortem autopsy and histopathology examinations of patients who died of suspected of pulmonary fat embolism should take into account whether there was a history of trauma, and the degree of adipose tissue damage should be assessed. Signi cantly minor adipose tissue injury in the presence of trauma is an indication of death from nontraumatic pulmonary fat embolism. Examinations of sites for fat emboli should include each major organ [3] as well as the peripheral arterial system and the venous system draining from noninjured sites to identify the possible source of the fat embolus. It has been reported that biochemical testing of the deceased's cardiac blood should be performed, with attention to abnormal changes in VLDL, cholesterol, TG, FFA, and CRP [3]. Lipid analysis of fat emboli, if necessary, may also be performed, which may suggest a possible mechanism of pulmonary fat embolism formation [4]. Moreover, attention should be paid to individual factors and subclinical conditions, such as obesity, multiple organ adipose hyperplasia and other condition, that may be risk factors for nontraumatic fat embolism [3].
There are some limitations in this report, including the availability of clinical examination results for the patient before and after silver-needle acupuncture; this prevented us from knowing the full extent of the patient's underlying diseases and collecting fresh tissue from additional organs for Sudan III staining. We report a case of nontraumatic pulmonary fat embolism resulting in death following acupuncture, which has not been reported previously. Despite this case, acupuncture therapy is not considered to be a dangerous; however, the major risk factors for nontraumatic pulmonary fat embolism need to be emphasized in relation to similar treatments.

Conclusions
The patient developed dizziness immediately after treatment with silver-needle acupuncture and died 2 hours later, without a series of manifestations indicative of pulmonary fat embolism. In the early stage of nontraumatic pulmonary fat embolism, clinical symptoms were atypical, and deterioration was rapid. Consequently, it is suggested that when a patient's condition suddenly deteriorates or respiratory insu ciency develops after physiotherapy, the possibility of pulmonary fat embolism should be considered, and a differential diagnosis should be provided.
In the presence of risk factors, such as obesity and multiorgan adipose tissue hyperplasia, stress caused by silver-needle acupuncture can lead to fatal pulmonary fat embolism.
In forensic pathology practice, it is essential to identify the fat emboli source by autopsy and histology examination when the case involves fat embolism. This article does not contain any studies with human participants or animals. Ethics approval is not applicable. Informed consent was given by the family of the deceased.

Consent for publication
All authors approve the submission of this paper.
Availability of data and materials