Monthly Archives: February 2014

Dose of Oxytocin Is Associated With Higher Epidural Drug Consumption



San Francisco—Women who receive higher doses of oxytocin during labor require greater amounts of epidural analgesics, suggesting augmented labor is more painful, new research indicates.

Although previous studies support a correlation between augmented labor and pain using pain scores, the new study is the first to assess epidural consumption in this situation, said Andrew W. Geller, MD, an obstetric anesthesiologist at Cedars-Sinai Medical Center, in Los Angeles. Dr. Geller presented his team’s findings at the 2013 annual meeting of the American Society of Anesthesiologists (abstract 3140).

That higher oxytocin dosing results in increased pain during labor is important for two reasons, Dr. Geller said. Increasing cases of augmented labor will boost the use of anesthesia services for these women. And the need for more epidural pain medication may be perceived by the patient as a failed epidural, which could negatively affect patient satisfaction—and, as insurers increasingly turn to such ratings to determine payments, ultimately the hospital’s bottom line.

The use of oxytocin for induction or augmentation of labor is increasing, with the overall rate of induction more than doubling between 1990 and 2006, according to recent literature. The investigators aimed to compare administration of oxytocin before delivery as calculated by area under the curve (AUC) with epidural drug consumption, also calculated as AUC.

The retrospective review included 216 charts of first-time laboring women who received oxytocin for labor augmentation in 2008. The total AUC of oxytocin administered before delivery was calculated from the dosage rate and time interval of administration. The researchers also calculated an AUC for epidural medications from bolus and infusion dosing.

For this study, epidural analgesia consisted of a 0.2% ropivacaine infusion without narcotic in addition to boluses of ropivacaine, bupivacaine, lidocaine or chloroprocaine (with or without fentanyl). The researchers converted epidural boluses to ropivacaine-equivalent doses in milligrams by minimal local anesthetic concentration equivalency. To account for differences in the length of epidural use and to obtain an hourly ropivacaine equivalency rate, the epidural AUC was divided by the duration. The researchers compared oxytocin AUC in quartiles of exposure with the hourly ropivacaine-equivalent rate.

Increasing quartile oxytocin AUC was associated with increasing total (infusion and bolus) and bolus ropivacaine use in the augmented patients (P<0.0001). The increase in ropivacaine also was seen when the researchers compared mean hourly ropivacaine dosage with quartile oxytocin AUC (P=0.035).

Joy Hawkins, MD, professor of anesthesia and director of obstetric anesthesia at the University of Colorado School of Medicine, in Aurora, said she was not surprised by the results. “We know that needing higher doses of oxytocin and increased pain in labor are markers for dystocia,” Dr. Hawkins said. “And we know that the need for higher doses of epidural medications—more top-ups—is a marker for dystocia leading to cesarean delivery. So this study goes along with all those associations.”

Interestingly, the rate of cesarean delivery nearly doubled between oxytocin exposure quartile 1 (16%) and quartile 4 (30%), although the interquartile rates were not statistically significant, Dr. Geller said. He hypothesized that dysfunctional labor could be leading to cesarean delivery and therefore higher doses of oxytocin, or that higher doses lead to cesarean delivery. “It’s most likely the former, though,” he said.

Dr. Hawkins noted that higher rates of cesarean delivery would increase the use of anesthesia services.

Dr. Geller said he and his colleagues would like to compare epidural use and pain management requirements of women who do not receive oxytocin before delivery with those of patients who have augmented delivery.




Anesthesia and The Real-Time Mind

AnesthesiologyInterdisciplinary group seeks mechanism of action for inhalation agents


Fallopius of Padua, the 16th-century anatomist and physician, famously complained, “When soporifics are weak, they are useless, and when strong, they kill.” Western medicine has come a long way in the centuries since, but anesthesiologists are only beginning to understand how the drugs of their trade work at the most fundamental level.


“We don’t understand how general anesthetics work in any detail,” said Roderic Eckenhoff, MD, the Austin Lamont Professor of Anesthesiology and Critical Care at the Perelman School of Medicine at the University of Pennsylvania, in Philadelphia. “We don’t know the molecular targets that they need to engage to create their effects.”


To find out, Dr. Eckenhoff is leading a multi-institution team, along with researchers at Thomas Jefferson University, Temple University, Drexel University, Rutgers University, the University of Pittsburgh and Penn, in five connected projects. Each has the dual aim of identifying the precise binding sites where anesthetics interact with proteins in the neuronal membrane, and characterizing those interactions in detail. In addition to anesthesiologists, the group includes electrophysiologists, biophysicists, computational physicists, and structural and molecular biologists, who approach the question of how anesthetics work from different angles.


“If we can use the parable of the blind man and the elephant, we’re sort of each seeing a different bit of this problem,” Dr. Eckenhoff toldAnesthesiology News. “But we’re then able to assemble it back to what’s really happening—what the mechanisms really are.”


Inhaled anesthetics produce a variety of effects: analgesia, immobility and amnesia, along with hypnosis and the alteration of blood pressure. Researchers know that the drugs work by regulating the activity of particular proteins in the neuronal membrane, but not which proteins are involved or how specific drugs interact with them (Figure). The likeliest candidates are voltage-gated ion channels, which control the flow of sodium and potassium ions throughout the neuronal membrane, said Manuel Covarrubias, MD, PhD, an electrophysiologist and professor at Thomas Jefferson University’s Farber Institute for Neurosciences, in Philadelphia.

“The idea is to identify within these particular types of ion channels, which have been implicated in general anesthesia, to identify binding sites that will allow us to find the best fit for the drug, the way a hand fits in a glove,” Dr. Covarrubias said. “To do that, we induce mutations in these ion channels in specific regions that we guess are the binding sites.


“Within those regions, we have identified specific residues that are possible binding sites for anesthetics,” Dr. Covarrubias added. That information is crucial to creating anesthetics that target the binding sites specifically, therefore reducing or eliminating the toxicity of present drugs, such as desflurane and sevoflurane.

In addition to identifying the binding sites, the researchers also are using nuclear magnetic resonance spectroscopy to study the interaction between the anesthetics and the binding sites in real time. To complement and enhance that work, they also are creating computer simulations to model the activity of these systems over time spans as long as a microsecond—“an eon” in terms of brain activity, Dr. Eckenhoff said. Finally, they are using shallow-angle x-ray scattering and neutron spectroscopy to confirm the electrophysiologic observations and the test hypotheses derived from the computer simulations.

The project, Interaction of Inhaled Anesthetics with Macromolecules, is the continuation of a collaboration that began 15 years ago. The researchers recently received $8.6 million in renewed funding for the next five years from the National Institutes of Health.

“We’re trying to get to the very basic level,” Dr. Eckenhoff said. “If you don’t know what the binding site looks like, and what atoms are needed to bind, it’s hard to do anything besides empirically alter the drug. For us to intelligently alter it—to predictably alter it—we really need to understand, at the atomic level, what’s going on.”