Volatile Organic Compound Exposure in Neonates Undergoing Cardiac Surgery: Yet Another Risk Factor for Impaired Neurobehavioral Development?
Viviane Nasr, Susan Nicolson, Lindsey Loveland Baptist, James DiNardo
Every once in a while, as I scan the medical literature for articles that are “PAAD worthy”, I come across one that just scares the bejesus out of me (and I’m not Irish or Catholic). Today’s article by Gaylor et al.1 is one of those articles and is so scary that it is, to my mind “a break the glass” emergency. I asked the PAAD’s cardiac group (and the neuro development/neuro apoptosis reader/writers) to review this as quickly as possible.
If this article doesn’t scare you as well, I don’t know what will. After reading it, let me know what you think and I will post in a Friday reader response. Myron Yaster MD
Original article
Gaynor JW, Graham EM, Bhandari D, Fenchel M, Bradman A, Klepczynski B, Collier H, Ittenbach RF, Reese CM, Blount BC. Perioperative exposure to volatile organic compounds in neonates undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2023 Aug 7:S0022-5223(23)00658-X. doi: 10.1016/j.jtcvs.2023.07.049. Epub ahead of print. PMID: 37558202.
Patients with congenital heart disease (CHD), especially neonates and infants, are at risk of perioperative brain injury following cardiac surgery. Studies have identified prematurity, medical complexity, and duration of cardiopulmonary bypass (CPB) as risk factors for short and long-term impaired neurobehavioral development.2,3 In addition, prenatal exposure to volatile organic compounds (VOC) has been associated with poor postnatal growth and impaired neurodevelopment.4,5 VOCs are organic substances that evaporate at room temperature and can be inhaled. The risk of exposure to VOCs in neonates undergoing cardiac surgery has been not quantified. Exposure to plastics, adhesives and other medical equipment can lead to exogenous exposure to VOCs such as formaldehyde, benzene, toluene, ethyl benzene, cyanide, xylene, and styrene.
This exploratory observational study was designed to investigate the incidence and magnitude of exposure to VOCs in neonates with CHD undergoing cardiac surgery. This convenience sample included neonates residing in the cardiac ICU postoperatively. Ten full term neonates (9 male and 1 female) with hypoplastic left heart syndrome or transposition of the great arteries, scheduled to undergo surgical procedures with CPB at age 44 weeks post conception or younger were studied. The number and type of medical devices the patients were exposed to was collected daily. These included endotracheal tubes, ventilator tubing, intravenous tubings, stopcocks, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) circuits, feeding tubes, and preservatives in medications. Quantification of daily urinary levels of 20 metabolites of 16 VOCs was conducted using ultrahigh performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. This was compared to saline control samples.
All subjects received periods of mechanical ventilation, CPB was used in 9 and ECMO in 4. The median number of urine samples collected per subject was 28 (range, 10-53). The median number of samples analyzed per subject was 15 (range, 10-22). The median number of metabolites detected in each sample was 14 (range 3-15). The median number of medical devices for each subject each day was 44 (range, 2-101). The number of devices was directly related to the severity of the patient’s clinical status and the number typically decreased after 3 weeks.
It is sobering that exposure to VOCs is pervasive throughout the hospitalization in neonates undergoing cardiac surgery. Metabolites of multiple VOCs were identified in daily spot urine samples of every subject for every day sampled. The VOCs toluene, benzyl alcohol, ethylene oxide, vinyl chloride, acrylonitrile, and acrolein detected by their metabolites in this study are all potentially significantly toxic. These chemicals are used in the manufacture of plastics and pesticides, as preservatives in medications, and as sterilization agents. Consequently, they are ubiquitous in the environment of critically ill children. Virtually everything the neonates are exposed to during hospitalization may be as source of VOCs including cribs, mattresses, the additives to extend shelf-life of medications, and a wide array medical equipment. Furthermore, exposure in neonates and infants is likely greater then in adults due to larger volume of air contaminated with VOC per unit body mass.
Obviously, we cannot definitively associate perioperative VOC exposure to impaired neurobehavioral outcomes, and it is highly unlikely that such a link could ever be definitively established. Nonetheless, this study suggests that efforts should be directed toward minimizing VOC exposure with either better air filtration or modification of the manufacture of medical equipment. Whether either of these goals can ever be accomplished is unknown particularly given the fact that the economic impact would likely be enormous.
From Myron: Although the exposure to VOCs may be greatest in patients undergoing bypass, virtually every hospitalized patient is, to varying degrees, also exposed. Should this study be repeated in hospitalized infants, children, and adolescents? Can any of the products that release the highest levels of VOCs be eliminated? Are some more dangerous than others? I have no idea but this is really scary. Let me know your thoughts and I will post in a Friday reader response.
References:
1. Gaynor JW, Graham EM, Bhandari D, Fenchel M, Bradman A, Klepczynski B, Collier H, Ittenbach RF, Reese CM, Blount BC: Perioperative exposure to volatile organic compounds in neonates undergoing cardiac surgery. J Thorac Cardiovasc Surg 2023
2. Butler SC, Sadhwani A, Stopp C, Singer J, Wypij D, Dunbar-Masterson C, Ware J, Newburger JW: Neurodevelopmental assessment of infants with congenital heart disease in the early postoperative period. Congenit Heart Dis 2019; 14: 236-245
3. Wypij D, Newburger JW, Rappaport LA, duPlessis AJ, Jonas RA, Wernovsky G, Lin M, Bellinger DC: The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg 2003; 126: 1397-403
4. Chang M, Lee D, Park H, Ha M, Hong YC, Kim Y, Kim BN, Kim Y, Lim YH, Ha EH: Prenatal TVOCs exposure negatively influences postnatal neurobehavioral development. Sci Total Environ 2018; 618: 977-981
5. Everett AD, Buckley JP, Ellis G, Yang J, Graham D, Griffiths M, Bembea M, Graham EM: Association of Neurodevelopmental Outcomes With Environmental Exposure to Cyclohexanone During Neonatal Congenital Cardiac Operations: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open 2020; 3: e204070