Ethical approval for the present study (approval number: 2632) was given by the Ethical Committee of the Institutional Review Board of the Kanazawa University School of Medicine, Kanazawa, Japan on November 3, 2017. The present retrospective observational cohort study was conducted at Kanazawa University Hospital between November 2016 and March 2018. As the present study involved a retrospective analysis of in-patient charts and anesthetic report data from a concurrently recorded computerized database, the Ethics Committee of the Kanazawa University Hospital waived the need for informed consent. We will instead release information regarding the present study to the public on an opt-out basis.
Incision criteria
Admitted into the present study were patients undergoing cardiac surgery procedures, such as coronary artery bypass grafting (CABG), heart valve surgeries, and cooperations on the aorta through a primary full median sternotomy. We included patients with an American Society of Anesthesiologists physical status (ASA-PS) of under 3.
Exclusion criteria
We did not include patients with any of the following characteristics: an ASA-PS of 4 or 5, a Glasgow Coma Scale score <15, history of or current dialysis, and severe liver damage (Child-Pugh grade of B or C). We also excluded patients with use of a preoperative opioid, a central nervous depressant (phenothiazine or barbiturate), a narcotic antagonist analgesic (buprenorphine or pentazocine), a monoamine oxidase inhibitor, a tricyclic antidepressant, or an antihistamine agent. Furthermore, patients who underwent emergency surgery or surgery without a median sternotomy were excluded.
Anesthesia Procedure
Anesthesia was induced with midazolam and fentanyl over a 60 s period. After rocuronium was administered for muscle relaxation, tracheal intubation was performed. Anesthesia was then maintained with fentanyl and/or remifentanil, sevoflurane and/or propofol infusion. Five-lead ECG, pulse oximetry, invasive arterial and pulmonary artery pressure and bispectral index values through IntelliVue MX8OOTM (Royal Philips, Amsterdam, Netherlands) were also monitored. The volume of fluids, the number of transfusions, and the doses of vasopressors administered during the operation were calculated from medical records. Immediately after the operation, all patients were moved to the ICU. They were then extubated after demonstrating functional recovery and hemodynamic and respiratory stability, as determined by their respective attending physicians.
In the present study, patients were divided into two groups based on the pain management each received. One group (group S) received a single administration of fentanyl (25 mg boluses and 30 min lockout time) and an administration of acetaminophen (l5 mg kg-1 and 6 hour lockout time), and the other (group C) underwent a continuous administration of fentanyl (25 mg hour-1 with 35 mg boluses and a 30 min lockout time) and an administration of acetaminophen (l5 mg kg-1 and 6 hour lockout time) (Table S1, Additional file 1).
As our primary outcome metric, we used the Intensive Care Delirium Screening Checklist (ICDSC) scores 12 hours after extubation. Secondary outcomes included the following: total doses of dexmedetomidine and propofol; time to extubation; a total post-surgical dose of fentanyl; total time of continuous administration of fentanyl; total doses of acetaminophen; NRS scores 8 hours after extubation; oxygenation (PaO2/FiO2 (P/F) ratio) after extubation; an incidence of postoperative nausea and vomiting (PONV) and constipation; postoperative hepatic (aspartate aminotransferase (AST), alanine aminotransferase (ALT)) and renal (serum creatinine) functioning; and a total length of ICU stay.
Nurses evaluated the ICDSC and numerical rating scale (NRS) scores in the ICU. PONV was defined as the occurrence of at least one episode of nausea or vomiting within the first 24 hours after extubation, where vomiting was defined as the expulsion of gastric content. Constipation was defined as a failure of the bowel to open for three consecutive days [17]. Nurses in the ICU monitored patient symptoms and collected these data. The AST, ALT, serum creatinine, the P/F ratio, and the total length of ICU stay were collected from the electronic chart of each subject.
Statistical analyses
Continuous data are described as means ± standard deviations. Categorical variables are presented as numbers and percentages. The Student’s t-test for continuous variables and the chi-square or Fisher's exact test for categorical variables were used to compare the baseline of the two groups. The ICDSC scores (0, 12, 24, and 36 hours after extubation), as well as the NRS scores (0, 8, 16, and 24 hours after extubation) across time points, were compared between the two groups using a repeated-measures analysis of variance. p-Values <0.05 were considered statistically significant. The Statistical Package for the Social Sciences (Version 23, IBM Inc., Armonk, NY, USA) was used for all analyses.