Temporal Analgesic Heterogeneity Behind the Apparent Non-Inferiority of Infraspinatus-Teres Minor Interfascial Block [Letter]

Dear editor

We read with great interest the randomized non-inferiority trial by Yin et al comparing ultrasound-guided infraspinatus-teres minor interfascial block (ITMB)) with interscalene brachial plexus block (ISB) after arthroscopic shoulder surgery.1 The authors reported non-inferior 24-hour oxycodone consumption with ITMB, together with substantially lower rates of hemidiaphragmatic paralysis and dyspnea. These findings are clinically relevant. However, two aspects warrant consideration when interpreting ITMB as an analgesically non-inferior alternative to ISB.

First, the cumulative 24-hour opioid endpoint may conceal important time-dependent differences between the two techniques. The mean difference in 24-hour oxycodone consumption was only 0.34 mg (95% confidence interval [CI], −1.42 to 2.11), meeting the prespecified non-inferiority criterion.1 However, this small cumulative difference resulted from opposing effects across postoperative periods. During 0–12 hours, oxycodone consumption was 3.9 mg lower with ISB than ITMB, whereas during 12–24 hours, consumption was 3.8 mg lower with ITMB.1 Pain scores showed a similar reversal: ISB provided better analgesia at 1 and 6 hours, whereas ITMB was favored at 24 hours.1 The significant group-by-time interactions reported by the authors further support the presence of heterogeneous temporal effects.

The authors appropriately recognize that these countervailing effects reciprocally offset one another in the cumulative 24-hour endpoint.1 Our concern is therefore not the validity of the prespecified non-inferiority analysis, but the clinical meaning assigned to it. A 24-hour cumulative opioid endpoint establishes non-inferiority for total rescue opioid exposure over that interval; it does not establish non-inferiority at clinically important individual time points. ITMB may therefore be better characterized as providing a distinct temporal analgesic profile rather than uniformly non-inferior analgesia. Time-specific treatment effects or repeated-measures estimands could complement cumulative opioid consumption in future comparative trials.

Second, the magnitude of the respiratory-sparing advantage of ITMB should be interpreted in relation to the local-anesthetic volume used for the ISB comparator. Both groups received 25 mL of 0.375% ropivacaine.1 The authors acknowledged that this relatively high volume may facilitate cephalad spread toward the phrenic nerve. Hemidiaphragmatic paralysis occurred in 2.6% of patients receiving ITMB versus 90.2% receiving ISB.1 However, phrenic nerve involvement after ISB is strongly influenced by injection volume. A systematic review and meta-analysis found that low-volume approaches reduce hemidiaphragmatic paralysis,2 and a randomized trial demonstrated a reduction from 80% with 20 mL to 19% with 10 mL of ropivacaine using an extrafascial ISB, although lower volume was associated with shorter analgesic duration.3,4

Thus, the study supports a phrenic-sparing effect of ITMB, but the magnitude of this advantage may partly depend on the relatively high-volume ISB comparator. The use of an identical volume is reasonable for controlling drug exposure when comparing analgesic efficacy; however, it does not eliminate volume-related differences in the respiratory safety of the two techniques. This distinction is clinically relevant when extrapolating the findings to contemporary low-volume ISB practice.

In summary, this study provides valuable evidence that ITMB can achieve similar cumulative 24-hour opioid consumption while reducing phrenic nerve-related adverse effects. Nevertheless, the opposing early and late analgesic effects and the volume-dependent respiratory effects of ISB complicate a simple interpretation of ITMB as a directly interchangeable, non-inferior replacement for ISB. Future studies comparing ITMB with contemporary low-volume ISB and incorporating prespecified time-specific analgesic outcomes may better define the clinical role of this technique.

Disclosure

The authors report no conflicts of interest in this communication.