Study Design
Ethics statement
This randomized, non-blinded clinical trial was approved from the Human Research Ethics Committee of Shenzhen People’s hospital, China (No. LL-KT-2018304) on 27/02/2018, and was performed in accordance with the principles of the Declaration of Helsinki. This study was conducted in strict accordance with the requirements of ClinicalTrials.gov (ID: NCT04111783). Registered 01/10/2019, https://clinicaltrials.gov/. The main technical approach in this study, DPUA, was applied to the Chinese national invention patent (No. 202110758366.5).
Study Setting and Population
Participants
Samples were collected from 60 patients who underwent emergency surgery under general anesthesia at Shenzhen People’s hospital from September 1, 2020, to December 31, 2020. Written informed consent was obtained from all participants.
The inclusion criteria were as follows:
1) age between 18 and 70 years;
2) emergency intubation and general anesthesia;
3) surgery within 24 hours of admission;
4) estimated operation time <4 hours;
5) American Society of Anesthesiologists (ASA) classification I to III.
If the patient had the following conditions, they were excluded:
1) patients who could not be evaluated by ultrasound (the part of the skin that the ultrasound probe must touch was covered with bandages, crusts, or open wounds).
2) participation in other clinical trials within three months before being enrolled in this study;
3) patients with organic heart diseases or heart surgery;
4) organ transplantation patients;
5) obstetric surgery patients;
6) patients who underwent emergency treatment, such as cardiopulmonary resuscitation;
7) the condition did not allow ultrasound scanning;
8) inability or unwillingness to cooperate with this research for any reason.
Study Protocol
Randomization and Intervention
Sixty patients were assigned to experience or ultrasound groups using a random number table (Fig.1).
The patients in the experience group were laid down and rested without any operation or infusion within 5 min after the indwelling needle was placed. After a period of five min, the anesthesiologist infused different rehydration fluids based on their medical history, clinical manifestations, ECG monitoring, and experience. The type and amount of fluid administered to the patient's body over a 30-min period were recorded. The optional liquids were crystalline liquid (lactated Ringer’s injection) and colloidal liquid (hydroxyethyl starch 130/0.4 sodium chloride injection, Wanwen). If emergency blood transfusion is considered, the anesthesiologist must document the situation in detail. After fluid supplement adjustment was completed, anesthesia induction was initiated.
Patients in the ultrasound group were instructed to lie on the left side or in the supine position without fluid infusion. The anesthesiologist scanned three slices sequentially within five min. First, the apical four-chamber view was used to evaluate the left and right heart ratios, blood flow direction, valve morphology, and function of the patients using two-dimensional, M-mode, Doppler, and other methods. This step excluded patients with previously unknown structural heart disease, such as segmental wall motion abnormalities, right heart function, pericardial effusion, or severe valvular regurgitation. The second step was the parasternal long-axis view, which was used to determine the presence of pericardial effusion. The M-mode was used to measure the left ventricular ejection fraction (LVEF); additionally, LVEF scores are shown in Table 1. Finally, the subxiphoid inferior vena cava section was scanned, the maximum inner diameter of the inferior was measured, and a calculation was performed to check whether the collapse rate of the inferior vena cava during inspiration exceeded 50%. The calculation formula was: the collapse rate of the inferior vena cava = ((maximum inner diameter of inferior vena cava) – (minimum inner diameter of inferior vena cava)) / (maximum inner diameter of inferior vena cava) × 100%. The subxiphoid vena cava scores were recorded (Table 1). After the ultrasound operation was completed, these two integrals were combined to obtain the total integral. Table 1 showed the final scores of the corresponding fluid management plans. If the total score was 6 points, the superior anesthesiologist was asked to decide on the fluid replacement plan, judge the necessity of blood transfusion, and analyze the risks of surgery and anesthesia. After the fluid replacement plan was obtained based on the total score, the required fluid volume was calculated and recorded according to the patient’s weight; additionally, the corresponding fluid type and volume were injected within 30 min. If the patient experienced any adverse reactions related to the infusion during the rehydration process, the infusion was stopped immediately and recorded in detail.
After a rehydration time of 30 min after the selection of the plan, the two groups would use sodium lactate Ringer’s injection or hydroxyethyl starch 130/0.4 sodium chloride injection according to the anesthesiologist until the end of the operation. Finally, after the patient left the operating room, the anesthesiologist recorded the type of fluid replacement and total fluid volume from entry to exit.
The process of anesthesia induction and maintenance in two groups were the same. The drugs were injected intravenously in the order and dose of lidocaine 1 mg/kg, sulfentanyl 0.4 μg/kg, cis-atracurium 0.20 mg/kg, and propofol 2 mg/kg. The blood pressure, heart rate (HR), and oxygen saturation were recorded during the induction of anesthesia (T1). Intravenous general anesthesia was used with dexmedetomidine 0.5 μg/kg/h, remifentanil 0.15 μg/kg/min, and propofol 6 mg/kg/h. Anesthesiologists used vasoactive drugs according to patients' condition to maintain the average arterial pressure above 65 mmHg or the systolic pressure fluctuation within ±20% of the baseline level. If the patient had hypotension, priority was given to a single use of ephedrine (6 mg), and the ephedrine was capped at 30 mg. Internal jugular vein puncture, catheterization or norepinephrine administration were performed if necessary.
The blood pressure, HR, and oxygen saturation were recorded immediately after the beginning of the operation (T2) and immediately after the end of the operation (T3). At the end of the operation, a second blood gas analysis was performed. After the patient waked up, an assessment of whether the patient had reached the extubation index was conducted, and the patient was observed for at least 15 min after the tracheal tube was removed. After reaching the standard for leaving the room, the patient was moved to the ward.
Follow-up
After the completion of the operation, the patient was observed and the data regarding the patient survival, complications, and hospitalization days were recorded. A telephonic follow-up interview was conducted 30 days after the operation enquiring about the patient’s survival after surgery and the health status score. The 30-day postoperative health status score was used to assess the postoperative health. The scores ranged from 0 to 100 points (zero points for extremely unhealthy individuals and 100 points for extremely healthy individuals). The patients would score by themselves. If some patients could not understand the researcher’s statement, the family members were asked to explain the researcher’s intentions, and the family members could relay the patient’s score.
Endpoints
This study was conducted in accordance with the Consolidated Reporting Test Standard (CONSORT) guidelines[22]. The results were evaluated by team members who were not directly involved in the operation. The main outcome indicator of this study was the stability of the circulatory blood pressure of the two groups of patients, which was mainly reflected in the comparison of the mean arterial pressure (MAP) at different times between the two groups of patients at different times, including comparisons between groups and comparisons within groups. The different moments referred to immediate entry (T0), induction of anesthesia (T1), beginning of surgery (T2), and end of surgery (T3). The secondary outcome indicators of the study were the use of vasoactive drugs in the two groups: comparison of HR and blood oxygen saturation (SpO2) at T0 to T3 and blood gas analysis indicators at T0 and T3, including pH, hemoglobin (Hb), Red blood cell specific volume (HCT), lactic acid value (Lac), number of days in hospital, postoperative complication rate, mortality within 30 days after surgery, and the 30-day postoperative health score.
Statistical Analysis
A database of medical records of patients who underwent emergency general anesthesia was established; additionally, SPSS software (version 25.0) was used for statistical analysis and processing. According to the results of the pre-experiment and literature search[23], the power for the primary endpoint map change was calculated based on a two-sided t-test with a significance level of 5%, and the calculated sample size was 25 cases in each group. Assuming that the loss to follow-up rate was 20%, 30 patients were included in each group at the time of enrolment. The measurement data are expressed as mean ± standard deviation (±S). For the comparison of data between groups at the same time point, the mean comparison t-test of two samples was selected to compare and analyze the data of the ultrasound group and the experience group at the same time. For the comparison of data within the group at different times, a repeated measurement design variance analysis was selected. The counting data selection row × list chi-square test was used to compare the composition ratios. A rank data selected Wilcoxon rank-sum test was used to compare two independent samples. According to the standard α=0.05, a P value<0.05 was observed to be statistically significant.