Total intravenous anesthesia (TIVA) presents an alternative to inhalational anesthesia. Common practice is to administer propofol and remifentanil in separate syringe pumps. An alternative is to combine propofol and remifentanil and administer them in a single syringe.1
This approach has been in use for >25 years at our institution but combining these drugs in 1 syringe is an “off-label” use. The aim of this study was to evaluate the efficacy of a single-syringe propofol-remifentanil TIVA to maintain adequate hypnosis as determined by a processed electroencephalogram (pEEG) in an outpatient orthopedic surgical population. We hypothesized that a pEEG index would be within the target range for adequate hypnosis for approximately 70% of the duration of maintenance of anesthesia in each patient.
METHODS
This single-center observational study was approved by the University of Utah’s Institutional Review Board (IRB; protocol number 00128764). Written informed consent was obtained from eligible patients undergoing procedures at the University of Utah Orthopedic Center from June 2021 to January 2023. Before patient enrollment, the study was registered at clinicaltrials.gov (NCT04987580, principal investigator: K. Johnson, date of registration: July 22, 2021).
Nonpregnant patients aged 18 years or older undergoing elective orthopedic procedures receiving only single-syringe propofol-remifentanil TIVA were recruited. Exclusion criteria included patients who received a peripheral nerve block before surgery and those undergoing surgical procedures in the prone position. Patients were instrumented with a pEEG and standard American Society of Anesthesiologists monitors.
The primary measure was the percentage of time during maintenance of anesthesia that the Patient State Index (PSi, Masimo SedLine) was between 25 and 50, the manufacturer-recommended range for hypnosis. The duration of maintenance of anesthesia was defined as time from procedure start to procedure end. The infusion consisted of propofol 10 mg/mL combined with remifentanil 20 µg/mL; the syringe pump was programmed to deliver propofol in mcg/kg/min. A horizontal syringe pump was used. Remifentanil separates from propofol in vertical syringe pump configuration.2 Secondary measures included propofol infusion rates, administration of vasoactive agents, hypotension defined as mean arterial pressure <65 mm Hg >15 minutes,3 intraoperative awareness, postoperative nausea and vomiting, and postoperative delirium. Delirium was assessed using the nursing delirium screening scale. A score ≥2 was considered positive for delirium.4,5
The primary measure was calculated by dividing the duration of the maintenance phase of anesthesia with a PSi between 25 and 50 by the total duration of the maintenance phase of anesthesia for each patient. As this was bounded at 0 to 100, data were reported as medians, interquartile rangel (IQR), and minimum to maximum range. The percentages of time the PSi was below 25 or above 50 were reported in similar fashion. Analysis performed using GraphPad Prism 9 software (Dotmatics).
The sample size, estimated in nQuery 9.2, was based on prior work using bispectral index (BIS, Medtronics) to maintain a target index of 40 to 60 during a TIVA.6 The mean and standard deviation percentage of time during maintenance with BIS values in this range was 61% ± 25%. Based on this prior work, a sample size of 89 would provide a 95% confidence interval range from 59.3% to 79.3% when the sample percentage was 70% (confidence interval width =0.2). The confidence interval was calculated using the Clopper-Pearson Exact Method.
RESULTS
Patient demographics, surgical procedure, and frequency of vasoactive agent used are presented in the Table. The median and IQR duration of maintenance of anesthesia was 76 (53–103) minutes and ranged from 11 to 285 minutes.
| Patient demographics | ||
|---|---|---|
| Male/female (%) | 51/58 (47/54) | |
| Age in y (min–max) | 39 (18–74) | |
| Height in cm (min–max) | 173 (150–198) | |
| Weight in kg (min–max) | 82 (47–134) | |
| Body mass index (min–max) | 27 (16–55) | |
| ASA PS I/II/III (%) | 43/49/17 (39/45/16) | |
| Airway technique | ||
| Endotracheal tube/laryngeal mask airway (%) | 45/64 (41/59) | |
| Surgical procedure | N (%) | |
| Hand | Carpal/metacarpal/phalangeal | 15 (14) |
| Wrist | 9 (8) | |
| Upper extremity | Elbow and biceps | 5 (5) |
| Shoulder and clavicle | 22 (20) | |
| Foot/ankle | Phalangeal/metatarsal | 7 (7) |
| Ankle | 6 (6) | |
| Lower extremity | Knee | 30 (28) |
| Hip | 15 (14) | |
| Vasoactive agent use | Number of patients | |
| No vasoactive agents | 64 | |
| Single dose of vasoactive agents per hour | 17 | |
| Two to four doses of vasoactive agents per hour | 19 | |
| Five or more doses of vasoactive agents per hour | 9 | |
Figure A presents the percentage of time during maintenance of anesthesia that the PSi was between, below, and above a range of 25 to 50. Of the 109 patients, 84 had PSi values between 25 and 50 for ≥70% of the duration of maintenance of anesthesia. The median (IQR) for the percentage of PSi values within 25 to 50 was 96% (64%–99%) for all patients. The median (IQR) for the percentage of PSi values <25 was 0.4% (0%–15%), and >50 was 0.2% (0%–3%) for all patients. Figure B presents the percentage of time in a mean arterial pressure (MAP) range of 65 to 100 mm Hg during the maintenance of anesthesia. Fifteen (14%) patients experienced as mean arterial pressure <65 mm Hg for longer than 15 minutes. Figure C presents a scatterplot of duration of propofol infusion rates. Median (IQR) TIVA infusion rates were 90 (80–100) mcg/kg/min.
Forty-six (43%) patients required a vasoactive agent (Table). There was no intraoperative awareness. Ten patients (8%) had mild postoperative nausea and vomiting (PONV), and 6 patients (6%) exhibited postoperative delirium with no persistent delirium 1 day later.
DISCUSSION
Results confirmed our hypothesis; single-syringe TIVA achieved a pEEG index within the recommended range for adequate hypnosis for 70% of the duration of maintenance of anesthesia and provided adequate sedation and autonomic nervous system control. Our results are consistent with previous work published by Gross et al6 using BIS monitoring and target-controlled propofol and remifentanil infusions. The duration of time below the recommended range for hypnosis was substantial, suggesting anesthesia providers may administer excessive anesthesia because of unfamiliarity or distrust with pEEG index or fear of awareness with recall.
Twenty-five percent of the infusion rates were between 110 and 150 µg/kg/min. Increased infusion rates may have been due to prior substance use, younger patients who require more anesthetic, and use of different weight scalars (eg, total versus ideal body weight) when programming infusion pumps. Twenty-five percent of the infusion rates were between 50 and 80 µg/kg/min. Decreased infusion rates may have been due to diminished anesthetic requirements in frail patients and reduced stimuli in selected procedures.
The frequency of vasoactive agent usage during maintenance of anesthesia was comparable to other anesthetic techniques. Recent studies exploring vasoactive use in lower extremity joint replacement surgery found up to 59% of patients received multiple doses of vasoactive agents.7,8 In our study, 43% required intraoperative vasoactive agents.
Further work is warranted to confirm this finding, explore whether this technique is generalizable to other types of surgical procedures, and to further validate this approach using a standardized protocol to minimize variability in its administration among anesthesia providers.