EFFETTI DELL’AMINOFILLINA SUL RITORNO DELLA COSCIENZA, TEMPO DI BURST SUPPRESSION E CONCENTRAZIONE STIMATA DI PROPOFOL DURANTE L'ANESTESIA TOTALE ENDOVENOSA CON INFUSIONE CONTROLLATA A TARGET: UNO STUDIO OSSERVAZIONALE SU 54 PAZIENTI

Aminophylline reverses the effects of propofol, and shortens the recovery time from general anesthesia by increasing the neuronal excitability. However, the aminophylline effects during total intravenous anesthesia (TIVA) with target-controlled infusion (TCI) have not been described yet. We compared: (a) the timing from (i) the end of propofol infusion until the return of eye-opening (REO) and the timing from (ii) the end of propofol infusion until the return of responsiveness (RoR) with or without an aminophylline bolus (4 mg kg-1) administered at the end of surgery, and (b) the timing from (iii) the start to the end of a Burst Suppression (BSupp) episode with or without an aminophylline bolus (4 mg kg-1) administered at BSupp emergence. Bispectral Index (BIS) values and the propofol effect-site concentration (CeP) delivered with TIVA-TCI at the 3 time points were also considered. This prospective observational study was approved by the Ethical Committee of Treviso Regional Hospital, Italy (N. 681/CE Marca), and registered with ClinicalTrials.gov (NCT06098196 for the RoR protocol and NCT06134037 for the BSupp protocol). All procedures in the study were in accordance with the ethical standards of our institutional and/or national research committees, as well as the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. We recruited 54 female patients scheduled for breast surgery with propofol (Eleveld PK/PD model) and remifentanil (Eleveld PK/PD model) TIVA-TCI. The patient assignment to deliver an aminophylline bolus was by chance, independently of patient scheduling, based on alternation between aminophylline users within the framework of a daily rotation 6-hour shift of the anesthesiologists involved in the study. The student-t test was used to compare continuous variables between the aminophylline and not-aminophylline groups. Categorical data were compared using a χ2 test. Statistical significance was set at p-values <0.05. Multivariate linear regression evaluating the demographic and treatment-effects on significant variables was also performed. 24 patients were enrolled for the RoR protocol. There were not statistically significant differences among demographic variables, CePs and BIS at Loss of Responsiveness (LoR) and at maintenance of anesthesia (MA), timing of anesthesia and total propofol dosage among the groups. Patients who received aminophylline bolus had lower timing for REO (8 [IQR 4-10] min vs 11 [IQR 10-13] min, p<0.05) and RoR (9 [IQR 6-10] min vs 11 [IQR 10-13] min, p<0.05). CeP REO (1.99 [1.84-2.66] μg ml-1 vs 1.50 [1.29-1.71] μg ml-1, p=0.001) and RoR (1.65 [1.52-2.25] μg ml-1 vs 1.40 [1.19-1.60] μg ml-1, p<0.05) in patients who received aminophylline were significantly higher. 30 patients were enrolled for the BSupp protocol. There were not statistically significant differences among demographic variables, CePs and BIS at LOR and at BSupp arousal, timing of anesthesia and total propofol dosage among the groups. Patients who received aminophylline bolus at BSupp detection, have significantly lower total timing of BSupp (116 [97.5-171.0] min vs 220 [193.5-267.0] min, p<0.01) and higher total % of Suppression Timing (32 [28-45]% vs 23 [20-26]%). Time from decreasing CeP to the time of ending of BSupp episode was significantly lower in patients treated with aminophylline (116 [97-168.5] min vs 158 [139-207.5] min, p < 0.05). Our results confirm the aminophylline effects in neuronal excitability during general anesthesia being useful not only in shortening awakening timing, but also in shortening BSupp episodes and decreasing anesthetic susceptibility, suggesting a potential neuroprotective role for cognitive disorders development.