Materials and methods
delirium, bleeding, obese, overdose, restless, Pain, bipolar disorder, pain, NRS pain, Delirium, psychological illness, abdominal or thoracic aortic aneurysm, renal dysfunction, NRS
DISEASE, OBESE, COMPLICATIONS, BLEEDING
Ethical approval for this study (Ethical Committee CRB4180011) was provided by the Ethical Committee of Aichi Medical University Hospitals, Nagakute, Japan (Chairperson Prof. Masayuki Hanyuda) on 18 October 2018. The current study was registered according to WHO and ICMJE standards under the registration number Japan controlled jRCTs041190013. In addition, written informed consent was obtained from all participants. With our misunderstanding of the procedure of jRCT registration, difference of the registration between our IRB and jRCT on the WEB (in detail in Patients of either sex aged 60 years or older who were scheduled for endovascular repair of abdominal or thoracic aortic aneurysm under general anesthesia at our hospital were eligible. The reason why we chose aged 60 years or older was not to decrease the incidence of delirium, Exclusion criteria were: (1) patients who required emergency surgery; (2) patients with severe complications, including cardiac, renal (including dialysis), blood, lung, liver, or life-threatening disease; (3) patients with serious complications arising from psychological illness (including bipolar disorder, suicide intent). Severe renal dysfunction was defined as estimated glomerular filtration rate (eGFR) less than 30 ml•minPatients were assigned randomly to one of two groups to receive intra-operative magnesium (magnesium sulphate; Otsuka Pharmaceutical, Japan) (magnesium group) or 0.9% saline solution (control group). A computer-generated randomization program “Research randomizer” from on the Web was used and randomization was 1:1 ratio. The independent anesthesiologist who was not involved in anesthesia management and outcome evaluation provided a pharmacist with sealed envelopes which included patient identification, group allocation and body weight, and the attending pharmacist prepared the colorless coded solutions in transparent syringes. The codes were kept confidential by the independent anesthesiologist until completion of the study. The pharmacist prepared the magnesium-solution syringes by mixing magnesium sulphate with 0.9% saline according to the actual body weight or ideal body weight. To avoid overdose of magnesium administration to obese patients, we applied ideal body weight (body mass index: 22) when the actual body weight was greater than the ideal one. We used magnesium sulphate solution containing 123 mg of magnesium per 1 ml. For each patient, a total dose of magnesium sulphate of 60 mg•kgNo patient received premedication. On arrival at the operating room, standard monitoring of pulse oximetry (SpOAnesthesia was induced with propofol 0.5 to 2 mg•kgAll the EVAR surgeries were performed with radiological imaging in a hybrid operating room attended by not only vascular surgeons but also radiologists who were specialists in this field, thus ensuring that all patients obtained sufficient cerebral blood perfusion during surgery. For anticoagulation, routinely 3,000 units of intravenous unfractionated heparin were administered during surgery, and the administered heparin was titrated to maintain 150 to 200 seconds of activated coagulation time. In our EVAR surgeries there was no use of additional oral anticoagulation drugs before and after surgery. However, if the patients used oral anticoagulation drugs before surgery for any reason, the drugs were stopped before surgery and restarted 24 h after surgery. As for a radiological contrast, the minimum volume of a radiological contrast was administered to perform surgical procedure by vascular surgeons and radiologists.The infusion of magnesium or saline was terminated when the operator started to close the wound. We set the upper limit of the total infusion period to 4 h for 60 mg•kgWe recorded total doses of fentanyl, remifentanil and magnesium sulphate, duration of anesthesia, duration of operation, amount of bleeding, amount of crystalloid fluid infusion (contains Mg 1 mmol•lAll patients were extubated at the operating room and were moved to the ICU. And, as soon as the patients arrived at the ICU, the ICU nurses examined vital signs and evaluated RASS, NRS and CAM-ICU. Discharge criteria from the ICU were stable vital signs, free of major complications that require intensive care. Delirium was defined as CAM-ICU positive. RASS score (0, alert and calm; +1, restless; +2, agitated; +3, very agitated; +4, combative; −1, drowsy; −2, light sedation; −3, moderate sedation; −4, deep sedation; −5, unrousable1) was assessed in the ICU by a blinded observer, an attending ICU nurse. Pain scores were assessed using an NRS pain score as rated by the patient, where 0 represents no pain and 10 is the worst imaginable pain. Blinded nurses in the ICU assessed and recorded CAM-ICU, RASS and NRS at the postoperative ICU admission (time 0 h) and 1 h, 6 h and 24 h after the admission of ICU. If the patient was discharged from the ICU within 24 h, the nurse recorded those values of sedative level at the time of ICU discharge. Usage of acetaminophen and dexmedetomidine, and the length of stay in ICU, were also recorded.Primary outcome of this study was postoperative RASS score at the postoperative ICU admission. Secondary outcomes were incidence of delirium defined using CAM-ICU, pain according to NRS, use of analgesic drugs, which were during ICU stay and length of ICU stay. Therefore, attending surgeons, attending anesthesiologists, attending operative staff, attending ICU staff, and outcome evaluators could never know which group to which the patient belonged.