Effect of continuous infusion of dexmedetomidine on blood loss in orthognathic surgery: a retrospective study

The study is registered at Chinese Clinical Trial Registry (ChiCTR1800018794). Ethical approval (SH9H-2019-T244-2) was obtained from the Shanghai Ninth People’s Hospital Research Ethics Committee. We conducted a retrospective cohort study on patients who underwent orthognathic surgeries between March 2017 and August 2018. Institutional review board approval was obtained before the initiation of this study. Patients with a complete medical history and surgical records were included if they were over 18 years of age and underwent elective orthognathic surgery. Patients were excluded from the analysis if they had a history of any of the following: allergies to intraoperative-related drugs, heart-related diseases (New York Heart Association class III or higher), severe pulmonary disease (asthma, chronic obstructive pulmonary disease), or severe liver and kidney dysfunction. Each controlled hypotension strategy is different, and there is currently no unified standard strategy for controlled hypotension. Indications for dexmedetomidine include tracheal intubation and sedation during mechanical ventilation for patients undergoing general anaesthesia, and the administration of dexmedetomidine depends on the judgement of senior anaesthesiologists. Patients treated with continuous dexmedetomidine were allocated to the dexmedetomidine group, while patients treated without continuous dexmedetomidine were allocated to the control group.

Upon arrival in the operating room, HR, BP, and oxygen saturation were monitored by electrocardiography, non-invasive BP monitoring, and pulse oximetry, respectively, before an intravenous cannula was inserted. Induction of anaesthesia was similar in every patient, comprising the intravenous administration of 2 mg midazolam, 2–4 µg/kg fentanyl, 1.5–2.5 mg propofol, and 0.15–0.2 mg/kg cisatracurium. Patients underwent endotracheal intubation, invasive BP monitoring, and deep-vein catheterisation during anaesthesia induction. According to the requirements of the surgeon, most patients underwent acute normovolemic hemodilution (ANH) after anaesthesia and before the beginning of the main steps of surgery [12]. Patients in the dexmedetomidine group were administered a 0.5–1 µg/kg loading dose of dexmedetomidine, and 200–400 mL autologous blood was rapidly extracted before incision. Crystalloid fluids were simultaneously infused into patients to supplement the circulating blood volume, dilute the blood, and reduce the loss of visible blood components during surgery. The extracted autologous blood was transfused back to patients before the end of the operation. This has been reported to be an efficacious, safe, and protective method to reduce the concentration of circulating erythrocytes with minimal effects on clotting factors and platelets [13, 14].

At the beginning of the operation, controlled hypotension was initiated, and vital signs were closely monitored. Each patient received 4–8 mg/kg/h propofol and 6–18 µg/kg/h remifentanil intravenously and 2–3% sevoflurane via inhalation. To ensure intraoperative sedation and prevent intraoperative awareness, the bispectral index (BIS) of all patients was controlled at the same level of 10–30. All patients were maintained under deep anaesthesia. Patients were administered 0.1 mg fentanyl before incision and later again, if necessary. Patients in the dexmedetomidine group received continuous dexmedetomidine at 0.2–0.5 µg/kg/h. Narcotic drugs and analgesics, including dexmedetomidine, were initially infused 10 min before incision. Mean arterial BP was controlled between 50–60 mmHg. If mean arterial BP was too high, 5 mg urapidil or 5–10 mg esmolol was used. If mean arterial BP was < 50 mmHg, 6 mg ephedrine was used. If a patient was bradycardic during the operation, the infusion of dexmedetomidine was discontinued, and the patient was excluded from the study. Patients were administered 0.5 g tranexamic acid after incision. Intraoperative fluid management was individualised based on the actual condition of the patients, and it was affected by physiological requirements, fasting supplementation, intraoperative loss, and other factors. Rehydration rate changed from fast to slow, and 15 − 20 ml/kg crystal or colloid fluids were administered intravenously in the first hour. During the operation, colloid fluids or blood products would be administered after communicating with a superior anaesthesiologist and surgeon based on the actual condition of the patients. Allogeneic blood transfusion was performed if necessary, at the discretion of the surgeon and anaesthesiologist. Several clinical measures were used to indicate allogeneic blood transfusion, and these included haemoglobin level < 70 g/L, haematocrit < 30%, and blood loss > 15% of estimated blood volume [15]. In addition, the anaesthesiologist and surgeon communicated and arrived at a consensus before allogeneic transfusion was performed. Administration of all narcotic drugs and analgesics, including dexmedetomidine, was discontinued 15 to 30 min before the end of the operation. When the operation was close to completion, the patients’ BP would be increased to the normal level.

The volume of blood loss was measured by the circulating nurses and recorded in medical history data by anaesthesiologists. The method of measuring blood loss was applied as follows: the total volume of liquid in the suction canister, plus the added weight of wet medical gauze and cloth surgical linen, minus the volume of saline used for irrigation during the procedure.

Study data were obtained from intraoperative records and the electronic medical record. The primary outcome was intraoperative blood loss. The secondary outcomes were postoperative haemoglobin level (patients who received allogeneic blood transfusions were excluded); intraoperative HR and BP (both measured at four points: T1, at incision; T2, 30 min after incision; T3, 60 min after incision; T4, 120 min after incision); dosage of fentanyl, remifentanil, urapidil, and esmolol; operation time; and incidence of allogeneic blood transfusion.

A standard operating procedure (SOP) was established to train relevant researchers, research assistants, and statistical analysts. The researchers completed case report forms according to the SOP. Two researchers independently entered the data, and the research assistant checked and generated data query forms (DQFs). If the research data were lost in the electronic database, the researchers went to the medical history room to retrieve the paper medical history data for verification. Problems in DQFs would be modified and resolved after discussion. Most of the problems could be solved using information from the electronic database or paper medical history records. Some problems (such as missing key data) were considered to be at risk of causing bias after discussion, and we would exclude the patients associated with these problems. Once the modification was complete, data was locked and passed to the statistical analyst.

Propensity score matching (PSM) was introduced to reduce bias due to confounding factors, which might affect surgical decision-making in patients with maxillofacial deformities. Confounding factors included age, height, weight, sex, preoperative haemoglobin level, prothrombin time, activated partial thromboplastin time, ANH, preoperative HR and BP, BIS, and volume of crystalloid and colloid fluids. Patients who underwent orthognathic surgeries were matched at a 1:1 ratio with a calliper width equal to 0.02, resulting in the same number of patients in both groups. The t-test was used for parametric scale variables. Scale variables were tested for normality with the Kolmogorov–Smirnov test. The Chi-square exact test was used for nominal variables. Statistical analyses were performed using SPSS version 25 for Windows (IBM, Armonk, NY). Differences between the two groups were expressed as difference in means, standard deviation (SD), mean difference (MD), or odds ratio (OR) with 95% confidence intervals (CI). Statistical significance was defined as a p-value < 0.05.