We appreciate the interest for our randomized controlled trial of our esteemed readers. Pupillometry enables a safe reduction of intraoperative opioid consumption in cardiac anesthesia, resulting in hemodynamic stability and less postoperative pain, but without influencing the primary endpoint of extubation time. We refer to the eMethods section (1), and are pleased to discuss this relevant limitation in more detail here as well. Specifically, the study was stopped early based on the study results at an a priori planned 50% interim analysis (n = 64/128 randomized participants, of 200 patients to be screened), which were evaluated very positively at the DAC 2019 and 2020; this early study termination was CONSORT-compliant, with feedback to the local ethics committee due to the ethically justified concerns about withholding these advantages of a drastic opioid reduction from further patients. Thus, randomization and preoperative exclusion resulted in unequal group sizes and distribution (eFigure 1) (1).
Despite a legitimate criticism that early termination of the study could underestimate the effects of treatment, positive secondary effects emerged (p ≤ 0.005, O’Brien-Fleming correction), which need to be investigated more closely (, see Limitations). Rather the primary endpoint of extubation time—admittedly vulnerable to confounders, than the population, is affected by the multimorbidity of the aged cardiac surgery population (68.5 ± 10 years, Euroscore II up to 34%, 32% diabetes mellitus, 17.5% chronic renal failure; , Table 1), with a high risk of postoperative complications in both groups (71.4% ≤ 8 hours, 19.6% 8–12 hours, 8.9% > 12 hours), therefore no statistical difference between groups was to be expected.
In fact, a retrospective matched case-control study showed a shortened extubation time for opioid-free cardiac anesthesia (2). Despite the mentioned limitations, our exploratory results showed for the first time that the vulnerable cardiac surgery population benefits from pupillometry-based nociception monitoring, for example through the improved hemodynamic stability, with a safe opioid reduction, which is now supported by a study (n = 50) with even lower opioid quantities (3); thus, we provide important impulses for future studies with endpoints that should be better operationalized.
On behalf of the authors
Priv.-Doz. Dr. med. Christine H. Meyer-Frießem
BG-Universitätsklinikum Bergmannsheil gGmbH
Klinik für Anästhesie, Intensiv- und Schmerzmedizin
Conflict of interest statement
The authors of the contributions declare that no conflict of interest exists.
|1.||Bartholmes F, Malewicz NM, Ebel M, Zahn PK, Meyer-Frießem CH: Pupillometric monitoring of nociception in cardiac anesthesia—a randomized controlled study. Dtsch Arztebl Int 2020; 117: 833–40 VOLLTEXT|
|2.||Guinot, PG, Spitz A, Berthoud V, et al.: Effect of opioid-free anaesthesia on post-operative period in cardiac surgery: a retrospective matched case-control study. BMC Anesthesiol 2019; 19: 136 CrossRef MEDLINE PubMed Central|
|3.||Berthoud, Vivien, Nguyen M, Appriou A, et al.: Pupillometry pain index decreases intraoperative sufentanyl administration in cardiac surgery: a prospective randomized study. Sci Rep 2020; 10: 21056 CrossRef MEDLINE PubMed Central|