Recovery from prolonged deep rocuronium-induced neuromuscular blockade

Abstract

Background

Deep neuromuscular blockade (NMB) may not always be maintained to the end of surgery and the depth of block may be allowed to gradually diminish over time, particularly if reversal of NMB is not routinely performed.

Aim

The current study aimed to assess recovery from deep rocuronium-induced NMB with sugammadex compared with placebo, provide data regarding the extent of residual blockade after deep rocuronium-induced NMB (placebo group), and to determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group).

Materials and methods

This was a randomized, placebo-controlled, safety-assessor-blinded study in adult patients of American Society of Anesthesiologists Class I to III. Patients with clinically relevant kidney or liver insufficiency were excluded. Anesthesia was administered as routinely practiced at each study site. Rocuronium 0.6 mg/kg was administered for intubation, with maintenance doses of 0.1–0.2 mg/kg as needed. After the last rocuronium dose, at deep NMB (target depth 1–2 post-tetanic counts), patients received a single dose of sugammadex 4.0 mg/kg or placebo as randomized. The primary endpoint was time from sugammadex or placebo administration to recovery of the train-of-four (TOF) ratio to 0.9. Safety was assessed through monitoring of adverse events, vital signs and physical examination. Patients were also assessed for evidence of residual or recurrence of NMB. With this design, the study will provide data regarding the extent of residual blockade under these conditions (placebo group), and determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group).

Results

Recovery to a TOF ratio of ≥ 0.9 with sugammadex was significantly faster (~ 40 times) than spontaneous recovery: geometric mean (95 % confidence interval) times were 2.2 (1.9–2.5) and 89.8 (80.1–100.7) min, respectively (p < 0.0001, N = 134); maximum spontaneous recovery was 289.8 min. Safety was comparable between groups, with no recurrence of blockade.

Conclusions

This study confirms a prolonged residual blockade in patients who did not receive sugammadex, with median time to recovery > 1.5 h in the placebo group and one patient taking 4.8 h to achieve a safe level of neuromuscular function recovery following deep NMB. In contrast, sugammadex provided complete and reliable recovery of neuromuscular function (median time to recovery of 2.0 min). Thus, deep NMB with rocuronium until the end of the operation may be possible in combination with sugammadex reversal.

Zusammenfassung

Ziel der Arbeit

In der vorgestellten multizentrischen Studie sollte die Wirksamkeit und Sicherheit von Sugammadex für die Umkehrung von Rocuronium-induzierter, tiefer, neuromuskulärer Blockade untersucht werden und gleichzeitig die Frage geklärt werden, wie lange ohne Sugammadexgabe eine klinisch relevante Menge Rocuronium wirkt.

Materialien und Methoden

In dieser randomisierten und Sicherheits-Assessor-verblindeten Studie wurden Operationen unter tiefer Relaxation unter repetitiver Gabe von Rocuronium (Standard-intubationsdosis: 0,6 mg/kg; Erhaltungsdosis: 0,1–0,2 mg/kg) bis zur Naht durchgeführt. Am Operationsende erhielten Patienten entweder Sugammadex 4,0 mg/kg (n = 70) oder Plazebo (n = 70).

Ergebnisse

Die Muskelerholung zu einem Train-of-four von ≥ 0.9 war in der Sugammadexgruppe etwa 40-mal schneller als in der Plazebogrupe (2,2 min im geometrischen Mittel gegenüber 89,8 min; p < 0,0001; n = 134). Die spontane Erholung in der Plazebogruppe hatte zudem eine größere Streuung (80,1–100,7 min; Sugammadexgruppe: 1,9–2,5 min). Bei einem Patienten in der Plazebogruppe dauerte es sogar 4,8 h bis die Muskelfunktion wieder hergestellt war. Die Sicherheitsparameter waren in beiden Gruppen vergleichbar ohne Wiederauftreten von Blockaden.

Diskussion

Ohne Gabe von Sugammadex zeigte sich, dass noch über lange Zeit klinisch signifikante Restmengen Rocuronium vorhanden waren und die Erholungszeit wegen interindividueller Variabilität schwierig zu prognostizieren war. Im Gegensatz dazu bot eine Einmalgabe von Sugammadex 4,0 mg/kg eine schnelle, berechenbare und zuverlässige Erholung.