Anaesthetic toxicity-what you need to know in 2017

Symposium organised by the American Society of Anesthesiologists (ASA)

Sunday 4 June, 16h00-17h30, Room 3

The first talk in this three-part session in Sunday’s Euroanaesthesia program, on neurotoxicity of local anaesthetics, will be given by Andrew Rosenberg, Professor and Dorothy Reaves Spatz, MD Chair, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York University (NYU) Langone Medical Center, NY, USA.

“In properly trained hands, peripheral nerve blocks (both single injection and continuous catheter techniques) and spinal anaesthetics are safe and effective with relatively rare complication rates,” explains Prof Rosenberg. “When complications do occur there can be many possible causes. One consideration is local anaesthetic (LA) neurotoxicity, for which relevant evidence will be addressed in this talk.”

Despite safe use of LAs in patients for many years, in vitro data demonstrate that in certain concentrations, LAs are directly neurotoxic. Conditions such as cauda equina syndrome and transient neurologic syndrome (TNS) also implicate LAs as neurotoxic. For example, lidocaine is associated with significantly higher rates of TNS than other local anaesthetics. However, while chloroprocaine was considered significantly neurotoxic in vivo it was ultimately determined that the antioxidant sodium bisulfite was the real culprit.

Analysis of LAs neurotoxicity in vitro indicates that both 7-day old and adult rat dorsal root ganglia are equally susceptible to LA toxicity.  Other scenarios in which LAs may exhibit neurotoxicity include use of spinal catheters, which may result in maldistribution and lack of dilution of LAs creating an environment more conducive for LA neurotoxicity. “These same factors call for a risk-benefit analysis for use or modification of dose of LAs in cases of severe spinal stenosis,” says Prof Rosenberg. “Despite evidence that LAs may cause neurotoxicity under specific circumstances, LAs when used properly are very safe.”

The second part of this session will be a presentation on “neurodevelopmental toxicity of general anaesthetics in infants and children,” given by  Sulpicio G. Soriano, BCH Endowed Chair in Pediatric Neuroanesthesia and Professor of Anesthesia, Harvard Medical School, Boston, MA, USA.

Abnormal development of neural cells and networks leading to neurocognitive impairments after general anaesthesia have been unequivocally demonstrated in laboratory animal models. The possibility of anaesthesia-induced developmental neurotoxicity during an uneventful anaesthetic in neonates or infants has led to serious questions about the safety of paediatric anaesthesia. Although the direct translation of these preclinical findings in humans is still unknown, these reports have fuelled a cautionary statement by the SmartTots collaborative and a recent US FDA Drug Safety Communication on the use of anaesthetic and sedative drugs in patients aged three years and under.

“Retrospective clinical studies have positively linked exposure to general anaesthesia with an increased chance of developing learning deficits, but these have recently been defused by prospective investigations,” explains Professor Soriano. “Therefore, the applicability of animal data to clinical anaesthesia practice remains uncertain. The irrefutable findings in the neuroscience literature should prompt clinicians to acknowledge this issue and recognise that these empirical findings may be more complicated and subtle. The focus of my review is to examine the evidence for the effects of commonly used anaesthetics on neuronal structure and neurocognitive function in laboratory models and evaluate its relevance to clinical care in paediatric patients.”

The final part of the session will be on systemic toxicity of local anaesthetics, given by Brenda A. Gentz, Banner University Medical Center and Associate Professor of Anesthesia, University of Arizona, AZ, USA.

She says: “The United States is currently experiencing an opioid epidemic.  The reasons for this are multifactorial, but include campaigns touting the alleged under treatment of pain, liberalisation of laws governing the prescribing of opioids for treatment of chronic non-cancer pain and aggressive marketing by the pharmaceutical companies that saw a quadrupling of opioid sales over the last decade.”

A concerted effort is taking place to limit opioid requirements both in the operating room and during the recovery period.  As a result, there is a renewed interest in regional anaesthesia as an analgesic adjunct.  However, regional anaesthesia with either peripheral nerve stimulation (PNS) or ultrasound still carries a risk of local anaesthetic systemic toxicity (LAST).  The overall frequency of LAST after ultrasound-guided regional anaesthesia is 0.42 – 1.9/1000 and remains remarkably similar to that reported using PNS guidance.

Dr Gentz says: “This clinical review will focus on the pharmacology, patient factors and technical issues that will increase the likelihood of LAST.  The signs and symptoms of local anaesthetic toxicity with possible sequence of events, prevention, detection, interventions and treatments will be discussed.  The updated ASRA* checklist for managing local anaesthetic system toxicity will be reviewed.  Controversies surrounding LAST treatment will be identified.”

*ASRA= The American Society for Regional Anaesthesia and Pain Medicine