A study evaluating the effect of anesthesia on post-surgical inflammation

The objective of the study was to identify drugs that can modulate the liberation of coagulating substances inside organisms, preventing hemorrhage and thrombosis.

By Karina Toledo

Agência FAPESP – A study performed at the Universidade Estadual Paulista (UNESP) investigated the effects of the two most commonly used inhalational anesthetics—isoflurane and sevoflurane—on the inflammatory reaction that occurs in organisms following surgery.

The investigation was performed on rats submitted to a procedure involving the removal of one kidney. It revealed that isoflurane caused the release of higher levels of one of the inflammatory substances evaluated.

“When we undergo surgery, our body understands that it has undergone trauma, and it releases what we call inflammatory cytokines, which help to prevent hemorrhaging,” explained Norma Sueli Pinheiro Módolo, coordinator of the FAPESP-financed study.

According to Módolo, this reaction is expected but cannot be exaggerated because of the risk of thrombosis. “We are trying to discover an anesthetic that can modulate the inflammatory response. The response cannot be completely inhibited because the patient would suffer from hemorrhaging. However, the response should also not be overly exacerbated by the drug. This is mostly important in higher-risk patients, such as those with heart disease,” she said.

To compare the effects of the two substances, 16 animals were divided into two groups. Half received isoflurane, and the other half received sevoflurane. Blood samples were collected from the tail at four different time points: before the anesthetics were administered (M0); one hour after anesthesia (M1); 30 minutes after surgery (M3); and 24 hours after surgery (M4).

“We measured five different inflammatory cytokines: tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukins 12, 6 and 10. With the exception of interleukin 10, which has an anti-inflammatory effect, the others are all pro-inflammatory,” stated Módolo.

The test results showed that the drugs caused significant changes only in the release of TNF-α, which primarily occurred in the group that received isoflurane.

TNF-α is the first cytokine released after a lesion occurs, and it has the mission of activating what is called an inflammatory cascade in the organism. “In a situation of trauma or infection, it induces fever, activates coagulation, causes systemic vasodilation and can lead to hypoglycemia,” explained Módolo.

In the isoflurane group, the concentration of TNF-α in the blood increased from 0 nanograms per milliliter (ng/ml) at M1 to 10.54 ng/ml at M3, or soon after surgery. In the samples taken the following day, the concentration had fallen to 4.55 ng/ml.

In the sevoflurane group, TNF-α increased from 0 ng/ml at M1 to 4.43 ng/ml at M3. The following day, the concentration had fallen to 1.76 ng/ml. “We could see that the anesthetic changed the inflammatory response, but not in an exaggerated way. The levels were already nearing normal the next day,” evaluated Módolo.

The researcher emphasizes, however, that the study was performed on healthy animals. “I imagine that a healthy patient undergoing relatively simple surgery would not have problems with either of the anesthetics. However, in obese people, who already have more inflammatory substances in their systems, or in heart patients, patients with pulmonary disease or newborns, these anesthetics could cause a more exacerbated inflammatory response,” she said.

The team plans to move forward with this same line of investigation, first evaluating the effect of the drugs on rats with health problems and then evaluating the effects in humans. “We also want to investigate the actions of other anesthetics, including intravenous ones,” said Módolo.

As a result of the study, Diego Freitas Tavares was awarded a scholarship for an undergraduate research project by FAPESP.