A single syringe of remifentanil and propofol can deliver safe, effective IV anesthesia to patients undergoing ambulatory orthopedic surgery, a recent study has found.

The researchers, from the University of Utah, say their results may be hard for some clinicians to accept, given what they have been told to believe about total IV anesthesia (TIVA). Many anesthesiologists view TIVA with suspicion, wary of the pitfalls involved in proper dosing of anesthetic and the cumbersome use of multiple infusion pumps.

The technique described by the Utah researchers—in which amounts of propofol and remifentanil (Ultiva, Bioniche Pharma) are combined into a single syringe based on the patient’s ideal body weight—streamlines TIVA and minimizes the amount of dose tinkering while remaining hemodynamically stable.

“If you look at the way anesthetics are done in the United States, doing a TIVA is certainly outside the norm,” said Jeff D. Swenson, MD, professor of anesthesiology and director of anesthesia at the University of Utah Orthopaedic Center, in Salt Lake City. Not only are residents here pushed in their training to perform inhalational anesthetics, but the average practitioner hears a drumbeat at meetings that to successfully administer a TIVA anesthetic, one requires a detailed understanding of pharmacokinetics and pharmacodynamics.

But that’s not so, Dr. Swenson said. “What this study shows is that TIVA is a lot easier to do than a lot of people might think. It’s safe and it’s cost-effective and can be done with a basic understanding of safe principles of pharmacokinetics and pharmacodynamics.”

Dr. Swenson and his colleagues studied their single-syringe TIVA technique in 31 patients (ASA status 1-2) undergoing elective orthopedic surgery. Patients ranged in age from 20 to 62 years, and had body mass indices between 21 and 46 kg/m².

The TIVA regimen included an induction dose of propofol (2 mg/kg) and fentanyl (3 mcg/kg) based on each patient’s ideal body weight. Remifentanil was then added to a propofol drip—10 mg/mL at a rate of 100 mcg/kg per minute at a concentration of 20 mcg/mL, resulting in an infusion rate for the opioid of 0.2 mcg/kg per minute.

The protocol called for adjustments to the infusions in three cases:

• Elevated blood pressure: If patients experienced a spike in systolic blood pressure of greater than 20% above their preoperation values, they received 3 mcg/kg of fentanyl. If high systolic pressure persisted, the infusion rate was raised by 10%.
• Movement: Patients who moved during the procedure received a bolus dose (0.1 mL/kg) of the TIVA solution, along with a 10% increase in the infusion rate.
• Hypotension: Patients whose systolic blood pressure fell below 90 mm Hg were given 5 to 10 mg of ephedrine. If the hypotension did not resolve, the rate of infusion was ratcheted back by 10%.

The typical infusion lasted 51 minutes (range, 36-58 minutes); four patients (13%) required a change in the rate of infusion (Table). Time between the end of the infusion and extubation averaged eight minutes (range, six to nine minutes; Figure). Five patients (16%) received intraoperative boluses of fentanyl; seven (20%) required ephedrine.

None of the patients moved, received neuromuscular blockers or required tape over their eyes. All were questioned postoperatively and denied intraoperative awareness. Although the researchers used ideal weight instead of true weight for dosing, Dr. Swenson said that for heavier patients he would recommend adjusting for true weight to ensure adequate anesthesia is achieved.

“The reason remifentanil is so favorable to use is because it has a very, very short half-life and no residual active metabolites,” Dr. Swenson said. “After nine to 10 minutes, there’s virtually no effect of the drug on the brain. It’s a very forgiving drug in that regard. We have safely administered over 8,000 of these anesthetics at our center now, with very positive feedback from patients and surgeons.”

Super Synergy

Remifentanil is extremely potent as an analgesic, allowing clinicians to use a broad range of hypnotics and sedatives during surgery. And it has been shown to act synergistically with propofol.

“Those two drugs when combined provide profound analgesia,” said Ken Johnson, MD, a co-author of the study. “It’s like 2 plus 2 equals 27. For sedation, it’s more like 2 plus 2 equals 5. What sounds like a low-ball dose of propofol and a middle-of-the-road dose of remifentanil in regular-weight people is a borderline overdose. These folks are plenty comfortable. With larger folks, the analgesia is still there, but you may be pushing the edge of where you’d want to be on sedation.”

Peter S. Sebel, MBA, PhD, MD, professor and vice chair of anesthesiology at Emory University School of Medicine in Atlanta, said he is “in favor” of the single-syringe method—with a few caveats. “I’d rather be able to flex my components,” Dr. Sebel said, and he advocates the use of neurophysiologic monitoring. “But it works.”

Dr. Sebel blamed much of the reluctance among U.S. physicians to use TIVA on the lack of FDA-approved computerized infusion devices in this country. “Half the blame appears to belong to the FDA and half the blame belongs to the equipment device makers,” he said.

The Utah team has been using the single-syringe TIVA technique on a wide variety of surgery patients, from laparoscopic cholecystomies to joint replacements. “We’ve done them by the thousands and it just seems to work,” Dr. Johnson said.

However, Dr. Johnson acknowledged that the technique does have drawbacks. By mixing two powerful drugs together and treating them as a single agent, clinicians lose the ability to titrate each to effect. Although some anesthesiologists might balk at that loss of freedom, Dr. Johnson said that for the majority of cases, “it’s overkill.” In addition, the single-syringe combination is an off-label indication for both propofol and remifentanil.

As a result, Dr. Johnson said he and his colleagues hope that the method can undergo the kind of “high-level scrutiny” required to bring a new anesthetic technique to patients. But they stand by the approach. “I use it every day,” Dr. Johnson said. “My commitment to it is based on clinical experience.”