We collected medical data of patients who underwent awake craniotomy at our hospital from June 2018 to July 2019. This manuscript adheres to the applicable CONSORT guidelines. This clinical trial was approved by the Institutional Ethics Committee (approval number: KY2018–232) and registered at http://www.chictr.org.cn/index.aspx (registration number: CHiCTR1800016621).
The inclusion criteria: 1). Patients were 14–70 years of age. No gender preference; 2). Intracranial tumors or epileptic lesions located in the eloquent brain areas and its peripheral areas, wake-up anesthesia was required in craniotomy; 3). American Society of Anesthesiologists (ASA) physical status: Grade I or II; 4). Patients had no aphasia or changes in muscle strength before surgery.
The exclusion criteria: 1). Patients had severe organ diseases and were in decompensation (such as medical severe complications: a. Cardiac functional capacity ≥ class III; b. Respiratory failure; c. Hepatic and renal dysfunction; d. Hematological diseases; e. Uncontrolled hypertension; f. Patients with a history of COPD, pulmonary fibrosis, or long-term heavy smoking before surgery; g. Patients with severe intracranial hypertension, or even had cerebral herniation before surgery); 2). Patients who were extremely fear of surgery and were expected to have difficulty in cooperating during the operation; 3). Patients with conscious or cognitive dysfunction before surgery; 4). Patients who were unable to communicate well before surgery; 5). Patients with morbid obesity (BMI ≥ 40) accompanied by obstructive sleep apnea syndrome; 6). Patients had difficult airways; 7). Patients suffered from glioma along with other tumors outside the nervous system; 8). Pregnant women; 9). Patients involved in other clinical trials in the past three months.
Sixty-five patients were eventually enrolled in this study. They were randomly assigned into the following three groups according to the airway management during anesthesia: Group 1 (n = 22), patients used HFNC device with an oxygen flow rate of 40 L/min (HFNC 40); Group 2 (n = 20), patients used HFNC device with an oxygen flow rate of 60 L/min (HFNC 60); Group 3 (n = 23), patients used nasopharyngeal airway (NPA). Patients were evaluated during the pre-operative visit by the anesthesiologist and the procedure was explained in detail.
In the operating room, the peripheral intravenous catheters were set up, and standard monitors such as electrocardiograph, pulse oximeter, and non-invasive blood pressure measurement devices were connected. Invasive blood pressure was monitored after arterial cannulation with local antiesthetic (LA) infiltration in radial or dorsalis pedis artery. Bispectral index (BIS®) monitoring (A-2000; Aspect Medical Systems, Newton, MA, USA) was connected to titrate the amount of sedatives and hypnotics. Sedative drugs were injected by a pump in the following sequence: 1). A loading dose of 0.6 μg/kg dexmedetomidine was infused within 15 min. Then, dexmedetomidine was maintained at 0.1 μg/kg/h. 2). Remifentanil Target controlled Infusion model (TCI) (Ce) was maintained at 0.5–2.0 ng/ml, which started from 0.5 μg and increased by 0.5 μg every 5–10 min till respiration frequence was at least 12 times/min. When respiration was nearly 12 times/min, TCI increased by 0.25 μg till stabilized. After the scalp nerve was blocked with 20 mL of 0.75% ropivacaine + 10 mL of 2% lidocaine + 1: 200,000 of epinephrine, propofol was infused under TCI (Ce) model at the dose of 1.0–2.0 μg/ml. Specifically, titration target of propofol was to reach BIS: 60–70, and respiration frequency: 10–20 times/min. Propofol TCI was set to 1.0–2.0 μg/mL, which started from 1.0 μg and increased by 0.5 μg every 10–15 min till BIS reached 70. If BIS decreased to 60, TCI concentration increased by 0.25 μg till stabilized. Three ways of oxygen delivery were established. 1). Group I- HFNC 40, high-flow nasal cannula (HFNC) device was used, and oxygen flow rate was set at 40 L/ min, FiO2 60%, airway humidified temperature was set at 34°C; 2). Group II- HFNC 60, high-flow nasal cannula (HFNC) device was used, and oxygen flow rate was set at 60 L/ min; FiO2 60%, airway humidified temperature was set at 34°C; 3). Group III-nasopharyngeal airway (NPA): nasopharynx airway device was used. The end of the nasopharyngeal airway was connected to the threaded tube of anesthesia machine. The oxygen flow rate was set at 6 L/min, FiO2 60% with no humidification.
When BIS value was maintained at 60–70 and the respiratory rate was maintained at 12–20 times/min by titration of propofol and remifentanil, induction of anesthesia was considered as completed. A urinary catheter was inserted. The head of the patient was fixed with a Mayfield head clamp. The body was adjusted to a comfortable position; with the head slightly elevated in order to avoid jugular venous flow compression. Such position prevents airway occlusion when the patient was asleep. The patient was asleep during the processes of scalp incision, bone flap removal, and dura suspending. Before bone flap removal, mannitol was administrated at the dose of 1.0 g/kg for 20 min. The intracranial pressure was assessed by the surgeons five seconds after removing the bone flap using Brain Relaxation Score (BRS). Specifically, by palpating and feeling the tension of the dura mater, BRS was subjectively scored by the surgeons from 1 to 10, with 10 was the most satisfied intracranial pressure control. After the dura suspending was done, propofol infusion was stopped, and the patient was allowed to wake up spontaneously. If the patient could not be awoken in 10 min after stopping propofol infusion, dexmedetomidine infusion would be decreased or stopped. After the BIS value was maintained above 90, cortical functional mapping was achieved using NIM-ECLIPSE® System (Medtronic Xomed Inc., Jacksonville, FL, USA) with a monopolar probe, delivering stimuli with a single 1 ms pulse with a 60 Hz frequency during surgical tumor resection. Upon the requirement of surgeons, the deep sedation was induced again by the titration of propofol, dexmedetomidine, and remifentanil. BIS value at 60–70 and the respiratory rate at 12–20 times/min could be considered as the completion of re-induction of anesthesia.
The baseline characteristics including age, gender, body mass index (BMI) and ASA physical status was collected. The following intraoperative data were collected: 1). Blood gas analysis at 6 different time points (before induction of anesthesia; 15 min after induction of anesthesia, 15 min after the adjustment of comfortable body position, dura suspension was completed, functional mapping was being performed, 15 min after re-induction of anesthesia). 2). Vital signs (heart rate, blood pressure, SpO2, and respiratory rate were measured every 5 min). 3). Depth of sedation/anesthesia (BIS value and OAA/S score). 4). Brain Relaxation Score, which was assessed every 15 min. 5). The time that patients took to wake up spontaneously. 6). The total time that patients were awake. 7). Total dose of each sedative drug. 8). Total anesthesia time. 9). Gastric antral volume before and after surgery. 10). Incidence of adverse events. The gastric antral volume was evaluated by measuring the cross-sectional area (CSA) of the antrum using the ultrasound . The head to sacral (CC) and anteroposterior (AP) diameter of the antrum was measured. The CSA was calculated by the formula CSA = AP x CC x π/4.
Information of the following adverse events was collected. 1). The incidence of respiratory tract obstruction, which was defined as no airflow, apnea, or snoring due to partial airway obstrction. 2). Airway injury, which was defined as blood or bloody secretion found on the tube of NPA or in the patients’ mouth. 3). Increased intracranial pressure that required instant treatment.
The sample size was calculated using PASS11 software. By ANOVA, took SPO2 as major parameter, that is, gave SPO2 as 100, 95, and 97 for HFNC 40, HFNC 60 and NPA, respectively, and a was 0.05. Sample number was from 5 to 40 with 5 as interval, and standard deviations were 2, 4, and 5. Statistical power and sample size were then calculated. When sample number was 20 and SD was 5, 0.8 of the statistical power was obtained; if SD was 2, 1 statistical power was obtained. Therefore, 20 was chosen as the sample size of each group.
The categorical variables were expressed as the frequency (%), and the Chi-square test was used for comparison. The measurable variables were expressed as mean ± SD, representation or median (interquartile range). Differences between groups were compared using One-way ANOVA when normal distribution was achieved, followed by Student-Newman-Keuls (SNK) test. If the normal distribution was not achieved, the Kruskal-Wallis test was used. Comparison within group, that is, before and after operation, was performed by Paired Student t test. All tests were two-tailed and statistical significance was accepted at P < 0.05. All statistical analysis was performed with SAS 9.2.