麻豆传媒

The tubing and other bendable equipment used in cardiopulmonary bypass (CPB) exposed young children to phthalates at levels that may be clinically significant, preliminary research found.

At one hospital, pediatric patients who received blood products during cardiac surgery had immediate post-procedural increases in serum levels of DEHP (from a median of about 3 µM preoperative to about 5 µM, P<0.0001) and MEHP (~0 µM to ~7 µM, P<0.0001), bringing total phthalates up as well (about 4 µM to about 13 µM, P<0.0001).

The youngest children tended to have greater phthalate spikes, as post-surgical phthalate levels correlated with more blood products used, longer bypass times, and methylprednisolone usage, reported Devon Guerrelli, MS, of Children's National Hospital in Washington, at the American Academy of Pediatrics (AAP) virtual meeting.

Although phthalate levels returned to baseline by post-surgery day 1, the children who had larger phthalate spikes were more likely to experience junctional ectopic tachycardia and hypotension in the 24 hours after surgery. What's more, glucose levels shot up with greater MEHP concentration in particular, and the two patients who suffered cardiac arrests both had MEHP levels that were 20-25 times greater than the acceptable limit.

MEHP is the more toxic metabolite of DEHP, the most common phthalate plasticizer used in flexible polyvinylchoride (PVC) medical equipment (e.g., tracheal tube, tubing, plastic packaging of red blood cells or RBC). DEHP, not chemically bound to PVC, can leach into blood, and it and its metabolites have been linked with endocrine, reproductive, renal, neurologic, hepatic, and cardiac toxicity in prior studies.

Without RBC use, pediatric CPB was not associated with post-surgical increases in phthalate levels. Guerrelli noted that during storage, DEHP leaches into blood products and can be metabolized to MEHP within the bag.

The problem with methylprednisolone may be its boosting of pancreatic lipase activity, which is responsible for converting DEHP into MEHP, Guerrelli said.

"Overall, our results indicate steps should be taken to minimize exposure to DEHP during cardiac surgery," she said. Her suggestions included:

• Using DEHP-free products
• Stopping preoperative methylprednisolone administration
• Decreasing volume of blood products used
• Choosing fresh blood products

DEHP-free alternatives on the market contain plasticizers that are thought to be less cardiotoxic and leach out more slowly.

AAP session co-moderator Juan Villafane, MD, of University of Cincinnati, said the study justifies raising a "red flag" that patients may be harmed when DEHP products are used during CPB procedures. Alternative equipment could be used to avoid costly complications, he suggested.

Guerrelli said that cost is the reason why hospitals haven't made the switch to totally DEHP-free products -- some components can go up to four times higher in price.

Guerrelli's group conducted the study using routine plasma samples from 53 children undergoing heart surgery. Sampling had occurred preoperatively, immediately after surgery when the child went to the cardiac ICU, then a day later in the cardiac ICU.

Clinical data were gathered from the institution's electronic health records.

The study was limited by the small sample and the single-center nature. Investigators are continuing to probe the effect of phthalates in CPB with data from another 50 patients, Guerrelli said.

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