Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world.


Introduction
Complications and adverse effects in medical practice are always of concern to the public and the medical profession. While being widely used in current medical treatment, especially in the area of intertrochanteric hip fractures, the cephalomedullary devices (CMN), however, led to a considerably high complication rate of 41.9% according to Pui et al. [1]. Faunø et al. [2] conducted a study on the medical records of 997 patients who were suffering from stoma closure, which revealed 131 cases of early complications and 187 late ones, accounting for 13.1% and 18.8% of the total subject pool, respectively. Umuroglu et al. [3] identified that the nuss procedure showed an overall complication rate of 18.7% through a retrospective analysis. Fortunately, with the increasing attention from the society on medical care safety and the further standardization of doctor's qualifications, such medical incidents have been decreasing. As acupuncture and moxibustion (A&M) are increasingly used in world, their widening acceptance necessitates continual safety assessment. This review, a sequel to two previous reviews from our team [4,5], is an evaluation of the frequency and severity of adverse events (AEs) for acupuncture reported between 1980 and 2013 in China. These two reviews reported the AEs of A&M in the West, reported from 1965 to 1999 and from 2000 to 2011, respectively. In the first review, the main source of infection was found to be hepatitis caused by reused needles. In the second review, the majority of infections were bacterial, caused by skin contact at acupoint sites, without cases of hepatitis. For these two reviews, we just searched English articles, without Chinese reports, so it is unclear which AE happens in China. Since acupuncture is widely used in China, it is necessary to make sure what is happening about AE. In this review, we found internal organ, tissue, or
3.1. Complications of Acupuncture: Internal Organ, Tissue, or Nerve Injury. A total of 115 cases of internal organ, tissue, or nerve injuries were reported, including pneumothorax ( = 30), central nervous system injury (37), peripheral nerve injury (8), organ injury (22), and other tissue injury (18). (Table 1). Between 1980 and 2013, pneumothorax was the most common complication of acupuncture treatment, as 30 cases in 27 papers were noted to be possibly associated with acupuncture (Table 1). Among the 30 cases presented, 25 recovered through thoracocentesis, thoracic closed drainage, anti-infection treatment, and clinical observation; 2 patients died; and the outcomes of the other 3 cases were not stated or unknown. More than half of them were reported by doctors in emergency rooms or departments of internal medicine, but the practitioner's training background was not reported. The punctured sites were mostly in the chest, supraclavicular fossa, and the back. The patients' major complaints were chest stuffy, chest pain, and dyspnea. One pneumothorax patient did not receive timely treatment and died [6]. Another case died because of a tension pneumothorax after acupuncture treatment [7]. (Table 2). There were 37 cases of central nervous system injury associated with acupuncture ( Table 2). The 37 patients suffered subarachnoid hemorrhage ( = 27), subdural hematoma (2), spinal cord injury (2), cerebral hemorrhage reformulation (2), cervical spinal epidural hematoma (1), medulla oblongata hemorrhage (1), cisterna magna hemorrhage (1), and leukemia acute intracerebral hemorrhage (1). The causes were acupuncture of cervical acupoints ( = 31), acupoints between the second and third thoracic spinal process [8], acupoints KI01 (Yongquan) [9] and BL37 (Yinmen) [10], waist acupoint [11] (each = 1), and body acupuncture ( = 2) [12,13]. Among the 37 cases, 26 recovered and 11 died.

Central Nervous System Injury
Because of insufficient compliance and protected observation, accidents occurred in 3 schizophrenia patients, of whom 2 died and 1 recovered [14]. Two cerebral hemorrhage patients after receiving body acupuncture died from recurrence, and the authors speculated the reason might be that acupuncture had irritated the parasympathetic nerve, causing vascular contraction and increasing blood pressure and thus cerebral hemorrhage recurred before the original cerebrovascular fracture could be fully restored [9,12]. Two patients suffered from dizziness and vomiting during treatment, but the acupuncturists did not pay high attention; the symptoms did not improve significantly after treatment, but the acupuncturists did not realize the severity and even allowed the patients to go home. One patient was treated the next day after onset and was diagnosed as subarachnoid hemorrhage; he recovered and left hospital [11]. The other patient died the next day [13]. (Table 3). There were 8 cases of acupuncture-induced peripheral nerve injury (Table 3). They include aggravated facial paralysis [15], mistakenly hitting the vagus [16], phrenic nerve injury [17], optic atrophy [18], oculomotorius injury [19], right trigeminal nerve injury [20], sciatic nerve injury [10], and peroneus nerve injury [21], respectively. The patient with optic atrophy lost sight [18], the patient with right trigeminal anchor injury improved after 3 days [20], the patient with sciatic nerve injury did not recover [10], and the other 5 patients recovered.   (Table 4). Twenty-two cases were reported to have organ injury associated with acupuncture treatment (Table 4). There was cardiovascular injury ( = 7) [14,[22][23][24][25][26][27], thoracic duct injury (1) [28], peritonitis induced by abdominal system (9) [29][30][31][32][33], gastric perforation (3) [34][35][36], intestinal obstruction (1) [37], and multiple organ injury (1) [38]. Of them, 14 recovered, 7 died, and 1 did not recover. Most of them were caused by too deep puncture and incorrect acupoint location.

Organ Injury
One patient received treatment following gastric abscess induced by gastric ulcer. He was treated by electroacupuncture (EA) at ST36 (Zusanli) and the acupoint was located without violation, but the state of illness was not relieved and gastric perforation occurred. The doctor was puzzled and put forward this case for discussion [35]. One patient with a history of stomach bleeding received treatment following knee pains induced by rheumatoid arthritis and took antiinflammatory analgesic drugs for a long time. The lower limb acupoint was selected, but the excessive EA irritation during treatment caused an irritable gastric ulcer and then hemorrhagic shock and the patient recovered after timely rescue [36]. (Table 5). In addition to injuries of the organs in thorax and abdomen, 18 cases of other tissue injuries were reported (Table 5), including cervical common carotid aneurysm [39], shock [38,40], asphyxia [41], dyspnea [42], eye injury [18,43,44], and the locomotor system injury [10,[44][45][46][47][48][49][50]. Among the 18 cases, 12 recovered, 2 improved, 2 did not recover, 1 died, and the outcome of 1 was not stated.  Evidence-Based Complementary and Alternative Medicine   One patient suffered from retinal detachment, and eyesight was corrected to 0.2 after treatment [43]. One patient lost eyesight because of traumatic cataract [18]. One patient experienced femoral neck fracture after strong stimulation to myospasm [45]. One patient suffered from subluxation in right wrist joint due to excessive EA intensity [48]. (Table 6). A total of 18 cases of acupunctureassociated syncope were reported (Table 6). Syncope occurred during the treatment in 9 cases, several minutes after the treatment in 5 cases, and several hours later in 4 patients. Two patients fainted after taking liquors [51,52]. The positions were sitting ( = 5), lying (5), and not specified (8).  Most patients recovered with rest and drinking sugar water, while 2 patients recovered after injection of metoclopramide via ST36 [53]. Two cases suffered from sudden cardiac arrest and were cured after first aid [54,55]. One patient recovered after massaging an ear acupoint [56]. (Table 7). A total of 17 cases were infections associated with acupuncture (Table 7). Among them, 10 recovered, 3 died, 2 improved after 3 days, 1 was disabled, and 1 was not stated. The infection was caused by tetanus bacillus ( = 6) [10, [57][58][59][60][61], hydatid (1) [62], Escherichia coli (1) [63], and Mycobacterium tuberculosis (3) [64]. One patient was infected after deep 3-degree burning [65] while others were not stated.

Other Complications Associated with Acupuncture
One patient was not allergic after several acupuncture treatments, but systemic allergy occurred after EA treatment [65]. Among three patients with acupuncture-induced epilepsy, only one had a history of epilepsy [85,86].

Discussion
The studies about safety of acupuncture are gradually increasing. One study protocol of a randomized controlled trial is efficacy and safety of acupuncture for chronic dizziness [92]. This trial's aim is to get result that acupuncture has good efficacy and without adverse effect for chronic dizziness. We hope it is success.
Some studies that researched acupuncture as an alternative means for pediatric diseases found that it is safe, feasible, and acceptable [93][94][95][96][97][98][99]. One study explored acupuncture as an effective therapy of pain relief for children and adolescents after tonsillectomy [100]. Severe throat pain can result from  tonsillectomy and last up to 10 days in children. Codeine elixir has long been used for pain relief but has recently been banned by the Food and Drug Administration due to a recently recognized risk of death. This study suggested that acupuncture decreases perceived pain in children and adolescents after tonsillectomy. These data, combined with the cost effectiveness, safety, and ease of administering acupuncture, suggest that further studies exploring the effectiveness of acupuncture in juveniles after tonsillectomy are merited.
One research evaluated the feasibility of delivering acupuncture in an emergency department (ED) to patients presenting with pain and/or nausea [101]. The acupuncture  [102][103][104][105][106][107][108][109]. For example, one reported a complete recovery from Bell's palsy (BP) of a 27year-old woman, 27-week pregnant, after 2 weeks of acupuncture treatment. Prior to treatment, her House-Brackmann facial nerve grading system (HBS) was II, Nottingham facial nerve grading system was 50.88%, and the Facial Disability Indexes (FDI) were 90. After 2 weeks, her symptoms had disappeared, her face was restored to normal, HBS was I, Nottingham was 96.46%, and FDIP was 100. These results suggest that acupuncture may be a safe, alternative treatment for BP in pregnancy [110]. Another study described patients' experience of acupuncture treatment in low back and pelvic pain during pregnancy. to begin acupuncture therapy later in pregnancy to maximize pain relief [111].
However, complications and adverse effects in medical practice always concern the public and the medical profession. Acupuncture has been used for several thousand years in China. Although it has been deemed a safe and reliable therapy, the rare adverse effects and complications should arouse concerns. During the 33 years from 1980 to 2013, about 182 cases of acupuncture-associated complications and adverse effects were reported in China, including 25 fatal cases. The frequency of acupuncture associated complications reported in China appears to be steady over time (see Figure 2).
As indicated in Table 1, the most frequent complication of acupuncture treatment is internal organ, tissue, or nerve injury. Of the 115 reported cases involving internal organ, tissue, or nerve injury, 30 (26.08%) were pneumothorax, 37 concerned the central nervous system (32.17%), others included injury in peripheral nerve, organ, and other tissues. Based on our research, one major cause of direct thrusted injuries to organ, tissue, or nerve is the lack of knowledge about anatomy and other systems. In 1980s, the acupuncturists or individuals in many country grassroot regions performed acupuncture because of low cost and convenience, but the deficient knowledge on anatomy led to many cases of pneumothorax and subarachnoid hemorrhage, as well as injuries to abdomen organs, heart, and peripheral nerves. With the increasing requirement for acupuncturists, these accidents decreased from the 1990s. Particularly, the frequency of pneumothorax and central nervous system injury appears to be on the decline since the 2000s (see Figure 3). This may be because the government has demanded that the acupuncturists should have licenses and formal education background if they practice in clinic in recent years. They should also undergo short time training every year. All these make the acupuncture technique become more and more standardized so that the accidents of pneumothorax and central nervous system injury are reduced. However, there is a possibility that we lack the accident reporting system so that the incidences were underreported.
We put forward suggestions for the medical system in order to avoid more accidental injury on organ, such as enhancing training on anatomy for acupuncturists; setting up more continuation courses on the safety of acupuncture practice for acupuncturists; establishing a reporting system on the incidents of acupuncture adverse effect; and safety courses and certificates should be required in order to obtain the license of acupuncture in China.
The acupuncturists (1) should avoid important organs and tissues during selection of acupoints and reposition if the patient changes body position; (2) do not distract attention during treatment and do not move the patient after acupuncture so as to avoid accidents; for unconscious patients unable to cooperate, shallow needling or not retaining needle is preferred, and the process of treatment should be strictly monitored; (3) inquire detailed medical history and carefully determine the needling depth for patients with emphysema or hemorrhagic disease. Moreover, traditional medicine holds that acupuncture should be performed to bring about the desired sensations of "sour, numb, heavy, and swelling. " Many acupuncturists and patients think that a stronger sensation of needling will bring about better therapeutic effects, but excessively violent operation will also cause accidents. The 2 cases of irritable stomach bleeding due to excessive irritation [35,36] and the 1 case of femoral neck fracture due to myospasm [45] are typical examples and should alert clinicians. In case of suspected acupuncture-induced injury, the doctor should prolong the time of observation and warn for prompt treatment. Syncope is also a common acupuncture-induced accident. The hungry, thirsty, drunken, or nervous patients should be asked to eat, drink, or rest for half an hour before treatment and calm down. They should be observed for a moment during and after treatment to avoid syncope. Once syncope occurs, needles should be pulled out immediately, sugar water should be provided, and the patient should lie down with head low; if the symptom becomes severe, take appropriate treatment. Two patients had severe adverse reaction like shock, with the clinical manifestation, including loss of consciousness, respiratory arrest, and carotid pulselessness. After doing CPR, both of them recovered [54,55]. Reviewing medical history, one was found to have the similar experience several years ago [55]. Therefore, acupuncturists 14 Evidence-Based Complementary and Alternative Medicine are required to inquire patients' medical history carefully and learn to deal with emergencies.
Acupuncture infection usually occurs in rural grassroot health centers with low awareness of hygiene, but accidents will be largely controlled along with the use of disposable needles and the popularization of health knowledge. Moreover, tetanus is still an adverse event that should be strictly prevented, and once it occurs, it will cause a high mortality rate. Along with the increasing incidence of diabetes, for patients with poorly controlled blood glucose [112], careful operation is required to avoid infection due to disunion of acupuncture-caused wounds.
The acupuncture-induced bleeding and hematoma are unavoidable; thus to reduce their incidence rates, acupuncturists should (1) get familiar with the anatomy of acupoints and avoid blood vessels during needle manipulation; (2) avoid manipulation methods such as lifting and thrusting when acupuncturing intraorbital acupoints; (3) appropriately extend the time of compression for patients with hypertension, arteriosclerosis, or inclination to hemorrhage and for women during the menstrual period. The acupunctureinduced hematoma is usually cold compressed within 24 hours and hot compressed after 24 hours. H. Liu and X. H. Liu [74] suggested pressing the local hematoma site heavily for a long time, which could immediately disperse the swelling, without leaving bruises. This method is recommended for other acupuncturists.
With a long history in China, acupuncture has been widely accepted and applied in people's daily life due to its exceptional therapeutic effects and low side effects. As early as 1980, WHO unveiled 43 kinds of diseases that can be treated with acupuncture. The number had increased to 107 in 2002 [113], from which we can see that acupuncture has been recognized by an increasing number of people and more research in this field is being undertaken. In countries where acupuncture is widely used, it is inevitable to encounter the occurrence of some side reactions in acupuncture therapies. However, the accident rate in acupuncture is relatively low. Although existing reports in China show no statistical data about acupuncture accidents, some studies conducted in large subject pools in Germany reveal some relevant information. It has been reported that Endres et al. [114] conducted a study about accidents in acupuncture therapies on 190,924 patients. The study showed an occurrence of 14,449 acupuncture accidents, which accounted for 7.57% of the total subject pool. According to statistics conducted by Witt et al. [115] on 229,230 clinical acupuncture cases, there were 19,726 accidents, which occupied 8.6% of the total subject pool. Chinese literatures show that most of the acupuncture accidents are caused by acupuncturist's lack of corresponding techniques and nonstandard operations. Since 2005, the Chinese National Administration of Quality Supervision, Inspection and Quarantine and the Chinese National Standardization Management Committee have issued a total of 18 acupuncture technical operation specifications in two batches, including terms and definitions, operating procedures and requirements, operating methods, attentions, and contraindications. Among them, operating procedures and requirements specifically include the selection of needles, acupuncture points and acupuncture positions, environmental requirements, the disinfection of needles, selected acupuncture points and acupuncturist's hands, specific operation techniques, and after-treatments of wounds [116]. The acupuncture technical operation specification series covers a wide area and contains comprehensive and specific contents, but it still shows some deficiency in the popularization and implementation of acupuncture.
In conclusion, we recommend that the qualifying training of acupuncturists should be systemized and the clinical acupuncture operations be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world. All this would mean a huge step towards modernization of acupuncture.