Challenges to implement minimum effective volume in regional anesthesia.

The incidence of providing regional anesthesia either as a sole anesthetic or combined with general anesthesia for surgical procedures has increased significantly in the past few decades.[1] Ensuring patient safety and providing quality regional blockade are the key components of a good nerve block. The success is also related to the total volume of local anesthetics administered for any given nerve block.[2] Nerve stimulator has been used to achieve better quality of nerve blockade with relatively less volume of anesthetics.[3] With significant increase in the utilization of ultrasonography for regional anesthesia, anesthesiologists are now not only able to visualize the desired anatomical structures easily but also substantially reduce the volume of local anesthetics, required to achieve the same quality of nerve blockade.[456]

Nerve blocks that are performed in close proximity of either major vascular structures or nerve tissues may adversely affect the physiological functions warranting usage of lesser drug volume. One such example is the interscalene block (ISB), which invariably compromises breathing by causing partial or complete phrenic nerve palsy.[7] Avoidance of phrenic blockade is vital in geriatricpatients, especially those with compromised pulmonary status. Many approaches have been proposed to minimize the phrenic nerve blockade such as using less drug volume,[8] different approaches such as periplexus[9] or intrafascial[10] or multisite injections, or completely avoiding ISB and choosing alternative blocks for shoulder surgery.[11] Among these methods, minimum effective volume (MEV) technique is widely used to minimize complications associated with nerve blockade with varying responses.[8] ED50, ED90, and ED95 are used by the investigators to calculate MEV for local anesthetics.[121314]

In this issue, Mittal et al. attempted to determine the MEV90 for 0.5% ropivacaine for ISB to avoid untoward complications/side effects.[15] Determining MEV is paramount in clinical practice, as it balances toxicity and safety. Furthermore, miscalculation of the MEV may lead to misleading information and serious consequences in the future larger sized clinical trials.[16]

Methods to Determine MEV

Various “up-down methods” such as “3 + 3,” accelerated titration, biased coin, k-in-a-row, group up-and-down, cumulative group up-and-down, nonparametric optimal, and dose selection based on isotonic regression have been described to determine MEV or maximum tolerated dose (MTD) in other clinical scenarios. Among these, isotonic regression method has shown superior performance but is more challenging to implement in clinical practice, as it selects desirable drug volume based on the isotonic estimate of toxicity probability which is undesirable for regional anesthesia. In most of the clinical scenarios, researchers choose biased coin design as it is easy to apply, and most importantly, it is very flexible. To choose MEV or MTD, by biased coin method, researchers used only outcome data of the recently used patient/subject. It has a disadvantage of having low efficiency compared with other up and down methods mainly due to not including the data from previously treated individuals. This imposes challenges for the readers in interpreting outcomes from the studies based on coin biased method.[161718]

Mittal et al. highlighted the rationale for choosing MEV primarily to avoid phrenic nerve palsy by assessing the diaphragmatic function with ultrasound.[15] They choose most commonly used up-down method in spite of its limitations. Even though there are a few limitations in their study design, their observations on MEV90 for ropivacaine are promising. MEV (8.64 mL) reported by Mittal et al. is much lower in similar clinical settings[15]; however, Falco et al. estimated lower MEV (4.29 mL) in their study when they used bupivacaine with epinephrine.[13] The authors concluded that there was no significant change in the onset and duration of the blockade with one-third of the usual volume required to perform the ISB.[15] Studies have shown challenges in measuring MEV accurately for ISB in spite of using unique method for up down by Narayana. Narayana rule estimates volume based on the cluster dose around the effective dose. Choi et al. had to end their observational study for ISB prematurely, due to no influence of decreasing well-defined complications, such as phrenic nerve palsy in spite of reducing block drug volume as per Narayana rule.[19]

To conclude, the study by Mittal et al. contributes to the limited evidence of determining MEV in ISB.[15] Authors addressed one of the unique challenges in regional anesthetic technique; however, it still raised many questions whether one can perform block with minimum drug volume to prevent complications, but without comprising quality of blockade. Based on the literature, it is always challenging to estimate MEV for any local anesthetics as it is primarily determined by up-down method used, technique used to perform block (single versus multiple sites), and the endpoints decided by the investigators mostly for the duration of blockade. Unfortunately, there is no one single safest way to estimate MEV; however, by combining ultrasound along with nerve simulator technique, there is a possibility to administer the desired volume of local anesthetics with minimal or no untoward complications related to nerve blockade.