Blood-soft tissue barrier breach and soft tissue recoil pressure on local anesthetic: two physiological mechanisms for local anesthetic systemic toxicity

Dear Editor,

Local Anesthetics (LA) are safe when limited to the site of therapy, such as tissue infiltration near a nerve or a plexus. However, if a large amount of LA reaches the systemic circulation, supra-therapeutic blood levels can cause Local Anesthetic Systemic Toxicity (LAST). Variables that increase the risk of toxicity include the type and dose of LA, site of injection, patient's age and comorbidities, and muscle mass.¹ The transit of LA into the blood may be due to inadvertent intravascular injection or vascular uptake from local spread.

We hypothesize two physiological mechanisms which may contribute to LAST.

1. Breach of blood-soft tissue barrier due to multiple needle punctures.

2. Regional anesthesia may require multiple needle punctures to confirm proper needle placement. This may breach the blood-soft tissue barrier due to direct microvascular injury leading to opening of low-pressure vessels (capillaries, venules, and veins). The vascular uptake from local spread gets exaggerated following breach in blood-soft tissue barrier.

   Elastic recoil force of soft tissue builds a pressure surrounding the capillaries after injection of the LA (Fig. 1).

   

   Figure 1
   Soft tissue recoil force over the injected LA.
   

Injection of the fluid into soft tissue creates a small pocket of free fluid, the pressure in this isolated pocket of fluid is measured as interstitial fluid pressure. Brace et al.² used the needle technique to detect negative pressure in the tissue space if no fluid was injected. However, positive pressure was detected when fluid was injected. This changes in interstitial fluid pressures were in accordance with Starling's hypothesis. This pressure corresponds to the total tissue pressure, which is the sum of fluid and solid pressure. There is a constant absorption of the fluid from the created pocket of free fluid into the surrounding tissues, indicating that the fluid pressure in the surrounding tissues is more negative than in the pocket of free fluid.² The recoil pressure depends upon volume and site of injection, besides the elastance of tissue near the nerve. Whenever pressure surrounding the capillaries after injection of the LA exceeds the capillary pressure, then it would cause increased convective flux of LA due to increased inward interstitial fluid pressure gradient.

The two mechanisms above might also explain the mechanism of LAST despite negative blood aspiration before drug injection even at submaximal doses. Aydin³ detected unexpected LAST during the Ultrasonography-Guided (USG) peripheral nerve block despite negative blood aspiration before injecting the drug. The exact cause of LAST in this case was not found out. The possible cause behind rapid absorption of LA into the system circulation could have been multiple needle punctures while using peripheral nerve stimulator before USG drug injection. The maneuver of aspirating prior to injection can yield a false negative result in 2% of the population.¹

We would require contrast-enhanced ultrasound LA spread,⁴ ultrasound microbubble behavior and sonoporation study or targeted microbubbles for molecular imaging study to validate our hypothesis.⁵ There is no facility to do contrast enhanced local anesthetic spread in the animal or human models at our centre. Hence, further studies might be required to validate our hypothesis.

References

• ¹
  Wolfe JW, Butterworth JF. Local anesthetic systemic toxicity: update on mechanisms and treatment. Curr Opin Anaesthesiol. 2011;24:561-6.
• ²
  Brace RA, Guyton AC, Taylor AE. Reevaluation of the needle method for measuring interstitial fluid pressure. Am J Physiol. 1975;229:603-7.
• ³
  Aydin G. Unexpected local anesthesia toxicity during the ultrasonography-guided peripheral nerve block. J Clin Anesth. 2018;50:26.
• ⁴
  Sasaki H, Yamauchi M, Ninomiya T, Tatsumi H, Yamakage M. Possible utility of contrast-enhanced ultrasonography for detecting spread of local anesthetic in nerve block. J Anesth. 2017;31:365-73.
• ⁵
  Lee H, Kim H, Han H, et al. Microbubbles used for contrast enhanced ultrasound and theragnosis: a review of principles to applications. Biomed Eng Lett. 2017;7:59-69.

Publication Dates

• Publication in this collection
  30 July 2021
• Date of issue
  Jul-Aug 2021

History

• Received
  26 Feb 2021
• Accepted
  17 Apr 2021