Appropriate sevoflurane concentration to stabilize autonomic activity during intubation with rocuronium in infants: a randomized controlled trial

BACKGROUND: In infants, sevoflurane is commonly used for induction of anesthesia, following which a muscle relaxant is administered to facilitate tracheal intubation. When rocuronium is used as the muscle relaxant, intubation may be performed before reaching an adequate depth of anesthesia because of its rapid onset. The purpose of this study was to investigate the optimal sevoflurane concentration that would minimize the impact of intubation on hemodynamics and autonomic nervous system (ANS) activity in infants. METHODS: Sixty-one infants aged 1–6 months, undergoing cleft lip repair, were enrolled. Patients were randomly assigned to three end-tidal sevoflurane concentration (E’(Sevo)) groups, 3%, 4% and 5%. Anesthesia was induced with 5% sevoflurane with 100% oxygen, and rocuronium (0.6 mg/kg) was administered. The concentration of sevoflurane was adjusted to the predetermined concentration in each group. Mechanical pressure control ventilation via a face mask was commenced. Five minutes after E’(Sevo) became stable at the predetermined concentration, tracheal intubation was performed. Immediately after tracheal intubation, ventilation was restarted at the same ventilator settings and continued for 150 seconds. Heart rate (HR) and mean arterial pressure (MAP) were measured 5 times in the 150 seconds after intubation. Normalized units (nu) of high frequency (HF: 0.04-0.15 Hz) and the ratio of low frequency (LF: 0.15-0.4 Hz) to HF components (LF/HF) of HR variability were calculated by MemCalc/Tonam2C™. Normalized units of HF (HFnu) and LF/HF reflect cardiac parasympathetic and sympathetic activity, respectively. RESULTS: After intubation, HR increased slightly in all groups and MAP increased by 9.2% in the E’(Sevo)-3% group. LF/HF increased (p < 0.01) and HFnu decreased (p < 0.01) in all groups 30 seconds after intubation. HFnu was lower (p < 0.001) and LF/HF was higher (p = 0.007) in the E’(Sevo)-3% group than in E’(Sevo)-5% group. ANS responses to intubation were reduced in a dose-dependent manner. CONCLUSIONS: Sympathomimetic and parasympatholytic responses to intubation in the E’(Sevo)-3% group were much greater than those in the E’(Sevo)-5% group. During tracheal intubation in infants, 4% or 5% sevoflurane is appropriate for prevention of sympathetic hyperactivation and maintenance of ANS balance as compared to 3% sevoflurane, when a muscle relaxant is co-administered. TRIAL REGISTRATION: The study was registered at UMIN-CTR (UMIN000009933).