Hyperbaric oxygen therapy in China

Indications refer to the scope and standards for the suitable use of HBOT. A few countries other than China have developed their own standards for HBOT. In the United States, in 1989, the Undersea and Hyperbaric Medical Society (UHMS) formulated indications for HBOT use that include 13 diseases [5]. In 2014, the number of indications increased to 17 (Table 1). In 2004, the European Committee for Hyperbaric Medicine (ECHM) divided their recommended indications into 4 categories: 8 highly recommended indications, 10 recommended indications, 9 controversial indications,and 13 other indications that include 40 other diseases [6]. Compared to the United States and Europe, the number of hyperbaric oxygen indications approved in China is relatively high. The indications of HBOT were initially released in China in 1982. With the practice and recognition of HBOT, the CMA revised the recommended indications in 2004 [4] to include 12 emergency indications and 48 non-emergency indications.

Emergency indications are diseases where HBOT should be administered as soon as possible. The following are emergency indications: (1) acute carbon monoxide poisoning and other harmful gas poisoning; (2) gas gangrene, tetanus and other anaerobic bacteria infections; (3) decompression sickness; (4) air embolism syndrome; (5) after cardiopulmonary resuscitation (CPR) due to a variety of risks for acute brain dysfunction; (6) aid in the treatment of shock; (7) brain edema; (8) pulmonary edema (except cardiac pulmonary edema); (9) crush syndrome; (10) limb (finger, toe) and the blood supply after skin transplantation; (11) drug and chemical poisoning;(12) acute ischemia anoxic encephalopathy.

Additionally, the following non-emergency indications are approved for use: (1) carbon monoxide poisoning or other toxic encephalopathy; (2) sudden deafness; (3) ischemic cerebrovascular disease (cerebral arteriosclerosis, transient ischemic attack, cerebral thrombosis, cerebral infarction); (4) craniocerebral injury (concussion, cerebral contusion of intracranial hematoma removal surgery, brain stem injury); (5) cerebral hemorrhage recovery; (6) poor healing fractures; (7) central serous retinal inflammation; (8) vegetative state; (9) plateau adaptation insufficiency syndrome; (10) peripheral nerve injury; (11) intracranial benign tumor surgery; (12) periodontal disease; (13) viral encephalitis; (14) facial paralysis; (15) osteomyelitis; (16) aseptic osteonecrosis; (17) cerebral palsy; (18) fetal developmental delays; (19) diabetes and diabetic foot; (20) coronary atherosclerotic heart disease (angina and myocardial infarction); (21) rapidity arrhythmia (atrial fibrillation, premature beat, tachycardia); (22) myocarditis; (23) peripheral vascular disease, vasculitis, e.g., Raynaud’s, deep vein thrombosis, etc.; (24) vertigo; (25) chronic skin ulcer (arterial blood supply obstacles, venous congestion, bedsore); (26) spinal cord injury; (27) peptic ulcer; (28) ulcerative colitis; (29) infectious hepatitis (use the special chamber of infectious disease); (30) burns; (31) frostbite; (32) plastic surgery; (33) skin grafting; (34) sports injuries; (35) radioactive damage (bone and soft tissue, cystitis, etc.); (36) malignant tumors (with radiotherapy or chemotherapy); (37) otic nerve injury; (38) fatigue syndrome; (39) angioneurotic headache; (40) pustular; (41)psoriasis; (42) pityriasisrosea; (43) multiple sclerosis; (44) acute Guillain-Barre syndrome; (45) recurrent oral ulcer; (46) paralytic ileus; (47) bronchial asthma; and (48) acute respiratory distress syndrome.

The current HBOT indications and contraindications were released at the 22nd academic meeting held in Qingdao in 2013 and approved on the 1st of November 2013. The new indications include diseases that were directly or indirectly caused by hypoxia and/or ischemia or a series of conditions that are related to hypoxia and/or ischemia in the evolution of the disease process. In comparison to the 2004 edition, the new indications broaden the use of HBOT.

Contraindications refer to the diseases or predicaments where the use of HBOT is inappropriate, possibly leading to adverse consequences, including body injury and even death. The CMA published the contraindications of hyperbaric oxygen treatment in 2004, which includes 4 absolute contraindications and 10 relative contraindications.

Absolute contraindications are those where HBOT is prohibited if the patient is accompanied with following: (1) untreated pneumothorax, untreated pneumomediastinum; (2) pulmonary bulla; (3) active hemorrhage and hemorrhagic disease; or (4) the formation of tuberculous cavity and hemoptysis.

Relative contraindications refer to the conditions where the use of HBOT in patients is cautioned and may possibly lead to side effects that increase discomfort or complications. Thus, HBOT should be used with caution if a patient has one of the following conditions: (1) severe upper respiratory tract infection; (2) severe emphysema; (3) bronchiectasis disease; (4) sinus infection; (5) aII degree atrioventricular block; (6) high blood pressure (>160/100 mmHg); (7) bradycardia (<50 times/min); (8) untreated malignant tumor; (9) retinal detachment; and (10) the early stage of pregnancy (3 months).

In 2013, new contraindications for HBOT were released by CMA. The new contraindications include absolute contraindications and relative contraindications. The only absolute contraindication is tension pneumothorax without treatment. The relative contraindications are as follows: (1) intraventricular external drainage; (2) fracture of the skull base with cerebrospinal fluid leakage; (3) birth weight < 2000 g in premature and low birth weight infants; (4) serious infection of the upper respiratory tract; (5) high blood pressure (SBP > 180 mmHg, DBP > 110 mmHg); and (6) patients with chronic obstructive pulmonary disease with CO₂ retention. Compared to the previous contraindications, the current contraindications are less strict. For example, regarding blood pressure, the 2004 standard is > 160/100 mmHg, but the new standard is > 180/110 mmHg. Still, adverse effects can occur even when following stricter HBOT contraindications.

A lot of clinical research on HBOT has been published recently. Within the last ten years (2004–2013), 9 randomized controlled trials (RCTs) have been published. The patients used in those studies had a variety of disorders, including neurologic, otolaryngologic, stomatologic, dermatologic, and urologic disorders. The cohorts for those trials ranged in size from 24 to 236. The Jadad – Bechara scale is often used to assess the quality of a clinical trial study. The Jadad scale (Table 2), which was developed by Columbia doctor, Alejandro Jadad – Bechara, is sometimes referred to as the Jadad score or the Oxford scoring system and is the most widely used rating scale for clinical trial research [7]. According to the Jadad scale, a score between 1 and 3 indicates a low quality study, where as a score between 4 and 7 indicates a high quality study [8]. The 9 RCTs found within the last ten years are summarized and graded for their quality in Table 3 [9-15].

The HBO RCTs in China were generally of low quality (scores ranged from 1–2). Thus, the curative effect of HBOT cannot be determined from these studies. For a more rigorous test of the curative effects of HBOT, future experiments should sea stricter research design that includes a randomized, double blind, and multicenter approach, as well as a large sample.

Although the therapeutic effect of HBOT has been confirmed in the clinic, the mechanism is not fully understood. The principle strategy of HBOT is to increase the oxygen content of the blood, improve blood oxygen partial pressure, improveblood oxygen dispersion and increase the tissue oxygen “effective diffusion distance” while constricting blood vessels and promoting the establishment of collateral circulation. HBOT can affect many physiological processes. In different disease states, HBOT is associated with decreased apoptotic cell death, reduced inflammation, a balance of oxygen free radicals, and the activation of stem cells and other mechanisms. I will mainly describe the next four mechanisms, and most of the related diseases are mainly involved in nervous system.

HBO pretreatment can have a protective effect that alleviates the secondary damage after some stimulation; this is known as hyperbaric oxygen preconditioning (HBO-PC). In a clinical trial of forty-nine elective on-pump or off-pump coronary artery bypass graft surgery patients, Li Y found that HBO-PC improved the outcome of patients undergoing on-pump coronary artery bypass graft surgery. The on-pump group had a reduced length of stay in the intensive care unit and a decreased use of inotropic drugs [34]. Although the mechanism of precondition is not fully understood, animal research suggests that HBOT may mitigate surgery-induced cognitive impairment [35] and reduce ischemia-reperfusion (IR) injury of the rat brain [36]. HBO-PC can reduce the number of apoptotic cells and promote nerve functional recovery [37,38]. The protection mechanism may involve reduction of systemic and hippocampal proinflammatory cytokines, reduction of COX-2 (an inflammatory medium) [39], suppression of caspase-3 activity [35], or up regulation of HSP32 expression (Heat Shock Protein 32, a protein that inhibits normal cell death) [40].