The survey of 250 Anesthesiology departments that we have presented here indicates that a profound portion of anesthesia providers in China have limited knowledge about the usage LE for LAST resuscitation, as well as the poor managements during LAST, especially in non-academic hospitals. Better understanding of the LAST resuscitation and the usage of LE should be improved in countries such as China, where the LA usage is increasing.
LA Usage and Preference
As nerve stimulator and ultrasound guided techniques have become available in China, the use of regional anesthesia has become increasingly popular especially for the growing aging population. Hence, the usage of LA is growing. Moreover, the development of safer drugs and increased awareness of LAST have greatly improved the safety of LA administration. Because of its lower cardiac toxicity, longer effective duration and effective sensory-motor segregation during labor, ropivacaine is the most preferred long-acting LA for regional anesthesia according to our survey, which is consistent as in other countries (10). In addition to restricted maximum dose (11), LA test-dosing is an extremely important part of safe anesthesia delivery and aim to alert the provider to accidental insertion of the epidural catheter into subarachnoid space or blood vessels (12, 13). However, 10 out of 250 hospitals do not practice test-dosing in the surveyed hospitals. This poor practice is more epidemic in non-academic hospitals than academic hospitals. Unlike the western countries, some hospitals in China used bupivacaine for test-dosing, which needs to be approved as safe for testing. All these factors underscore the need to standardize LA usage across all hospitals in China, as well as in other countries.
LAST and Epinephrine Resuscitation
LAST is a severe complication of clinical LA used and can lead to CA in serious situations (3, 4). Epinephrine is the preferred drug for cardiac resuscitation and is recommended to treat LAST induced CA. However, the safe and effective dosage that should be used in these situations is still a subject for debate (14). In a rabbit model of bupivacaine-induced CA resuscitated with LE, high-dose of epinephrine (100 μg/kg) was associated with a significant increase in coronary perfusion pressure but was subsequently associated with declining hemodynamic variables (15). Furthermore, epinephrine overdose might cause severe pneumorrhagia, oedema and acidosis, which argues against using traditional doses for resuscitation, particularly in anesthetized patients (16). ASRA has recommended that the epinephrine dosage used to treat LAST should be decreased to 1 μg/kg (7). In our survey, the most common dose that Chinese anesthesiologists used was 1mg (with weight about 70 kg), which is the common dose in general cardiopulmonary resuscitation (not LAST induced CA) and ten times more than the recommended dose for LAST (7).
LE for LAST Resuscitation
In addition to epinephrine, LE is also considered as an effective treatment for LAST resuscitation (6). The optimal timing for epinephrine administration is also immediately after the bolus of LE, which produces better outcomes of successful cardiopulmonary resuscitation (17). In 1998, Weinberg et al (18). reported the usage of LE for resuscitation during bupivacaine-induced cardiac toxicity in dogs. In 2006, Rosenblatt and collegues (4) successfully used LE to save one patient with bupivacaine-induced cardiac stroke. So far, LE has been established as an effective assistant for resuscitation and accepted worldwide and recommended by the American Heart Association guideline for LAST (19). However, the knowledge of this delivery method is still sparsely known by Chinese anesthesiologists, especially in the non-academic hospitals, as revealed in our survey. More academic hospitals have established precise procedures for the LE resuscitation during LAST, while fewer non-academic hospitals. What's more, fewer non-academic hospitals have developed precise delivery methods in their procedures. Emphasis should be made to establish or refine continuing medical education programs and increase the awareness and use of modern treatment techniques, including LE resuscitation.
Different Types of LE for LAST Resuscitation
At the very beginning, LAST resuscitation with LE ignored the types of the LE preparations (20). Nowadays, studies revealed that different types of LE may have different effects on LAST resuscitation, especially for reversing LA induced cardiotoxicity (21). LLE may be superior to MLLE as it was associated with fewer asystole recurrences after resuscitation and lower myocardial bupivacaine concentrations (22), hence the patients awaked and arrhythmia disappeared quickly (23). However, results have also indicated that MLLE has higher affinity than LLE for LA extraction from human serum (24). Also, another in vivo experiment indicated that MLLE and LLE have no difference in its effects on blood pressure and cardiac index for ropivacaine-induced LAST in swine (25). These arguments all calls to determine the appropriate LE preparation for LAST resuscitation. In particular, different LA has different outcome based on their characteristics. In vitro experiments revealed that long-acting LAs have a high affinity for LE, and the extraction capability of LLE for these LAs is 2.5 times higher than MLLE (26). Bupivacaine was more effectively extracted than ropivacaine by lipid agents, with a 40% and 20% reduction in initial concentration, respectively (27). And the magnitude of LE mediated reversal of vasodilatation appears to be correlated with the lipid solubility of the LA (28). In our survey, MLLE is the most common type of storage. Unfortunately, the survey did not determine the cause.
As LE bolus combined with basic life support benefits LAST resuscitation, LE availability in operation room determines the speed of the onset of recovery. In our survey, LE is available for LAST resuscitation within 10 min in most surveyed hospitals, both academic and non-academic, which allows for the most optimal treatment timing (17). However, an alarming number of hospitals, academic and non-academic hospitals viewed LAST as a rare event and did not store LE for LAST. The LE availability was even worse in a recent survey in the orthopaedic anesthesia group of academic hospitals (29). This situation greatly impacts the safety of the LA delivery in the clinic.
Center Nerve System (CNS) Toxicity and LE Treatment
CNS toxicity and cardiotoxicity are two major signs of LAST. A seizure is a common sign of CNS toxicity during LA administration and might be aggravated without treatment (1). LE is sufficient to treat LA induced CNS toxicity, in addition to cardiotoxicity (30), hence it is the recommended course of treatment when seizure occurs (18). The academic hospitals in our survey were 1.6 times more likely to choose LE for LA-induced seizure than non-academic hospitals. However, the proportion of all the responders is still low in both types of hospitals, and signals the needs to modernize and standardize treatment protocols for LAST induced seizure. Moreover, nearly 30% of the responders, both academic and non-academic hospitals, thought that propofol can be used for LAST resuscitation, even though its LE component is just 10%. It should be noted that propofol can be used for sedation to control seizure, but large doses are required for LAST resuscitation, which can only worsen the hemodynamic stability and cardiac function of the patients.
The limitations of our survey are as followed. First, the survey was conducted by an academic hospital and questionnaires were designed based on the researchers' attitude and knowledge of LAST and LE resuscitation. Hence there could be bias against non-academic hospitals, which might have not been revealed in the survey. Second, there is no guideline for LE resuscitation in China, and providers in academic hospitals are more likely to be exposed to updated treatment procedures through continued medical education while providers in non-academic hospitals are less likely to participate in conferences or training classes. This factor may lead to bias against non-academic hospitals in their understanding of LE use for resuscitation. Third, although the understanding of LE for LAST resuscitation has been validated by many clinics across the world, the misunderstanding between medical providers and patients might impact the usage of LE for LAST resuscitation when it's not recommended by the expertise consensus in China. In spite of this, we're glad that some doctors and medical providers turn to us for LE resuscitation details when they encountered LAST, by days after the survey conducted. In this way, the survey has its practical meaning to spread the idea of LE resuscitation for LAST.
In conclusion, the survey of the 250 hospitals, including academic and non-academic hospitals, revealed the poor practice procedures for regional anesthesia and LE use for LAST resuscitation in China. This alarming situation calls for improvements in education especially in non-academic hospitals.