Occupational exposure to cytostatic drugs in the oncology operating room: protective measures for surgical instrumentation personnel

INTRODUCTION

Cytostatic drugs, also known as antineoplastic or chemotherapeutic agents, are designed to inhibit proliferation and destroy tumor cells. However, their nonselective mechanism of action poses a risk to any cell with a high division rate, including those of healthcare personnel who routinely handle them. The International Agency for Research on Cancer (IARC) classifies numerous cytostatic drugs as Group 1 and 2A carcinogens, recognizing their genotoxic, mutagenic, teratogenic, and reproductive toxicity potential. (1,2)

Historically, efforts to prevent occupational risks from cytostatic drugs have focused on pharmacy and medical oncology departments, where the preparation and systemic administration of these drugs are the primary activities. However, the consolidation of surgical techniques such as hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC), and regional isolated limb perfusion has transformed the oncology operating room into a new setting of significant occupational exposure, frequently overlooked by institutional occupational health systems. (3,4)

Surgical scrub nurses play a central role during these procedures, with a continuous presence in the operating field and direct or indirect contact with the patient’s body fluids, which are highly concentrated in the cytostatic agent. Despite this, this professional group is rarely included in specific occupational health surveillance programs related to exposure to hazardous drugs or in biomonitoring studies that assess the actual absorption of these compounds. (5,6)

Recent scientific literature shows that surface contamination in the operating room, as well as on staff gowns and gloves, is detectable even in procedures where closed administration systems are used, underscoring the need to adopt strict protective measures tailored to the specific surgical context. (7,8) The ALARA (As Low As Reasonably Achievable) principle, widely adopted in radiology and radiation therapy, must be applied with the same rigor as the handling of cytostatic drugs in the intraoperative setting. (9)

The purpose of this review is to systematize the available scientific evidence on the risks of occupational exposure to cytostatic drugs for surgical scrub nurses and the applicable protective measures, helping to elucidate an occupational public health issue that requires immediate attention from nursing staff specializing in surgical scrub nursing.

METHODOLOGY

A systematic narrative review of the scientific literature published between January 2020 and December 2024 was conducted. This design was selected for its ability to synthesize the state of knowledge on complex occupational health issues, encompassing multiple disciplines (nursing, toxicology, hospital pharmacy, and occupational medicine) and allowing for the integration of evidence from different types of studies. (10)

Information sources and search strategy

The literature search was conducted in the following databases: PubMed/MEDLINE, Scielo (Scientific Electronic Library Online), LILACS (Latin American and Caribbean Literature in Health Sciences), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the National Institute for Occupational Safety and Health (NIOSH) clinical practice guidelines repository. Additionally, the bibliographic references of the included articles were manually reviewed to identify additional relevant studies.

The search terms used in English and Spanish were as follows (combined using Boolean operators AND/OR):

"cytostatics" OR "antineoplastic agents" OR "hazardous drugs" AND "occupational exposure" AND "operating room" OR "perioperative nursing"

"HIPEC" OR “hyperthermic intraperitoneal chemotherapy” AND “healthcare worker safety” OR “personal protective equipment”

“cytostatics” AND “occupational exposure” AND “surgical instruments” OR “operating room nursing” Inclusion and exclusion criteria

We included original research articles, systematic reviews, meta-analyses, clinical practice guidelines, and expert consensus statements published between 2020 and 2024 in English, Spanish, or Portuguese that addressed occupational exposure to cytostatic drugs in the surgical setting, the health effects on healthcare personnel, or applicable risk control measures. Studies focused exclusively on the pharmaceutical preparation of cytostatic drugs outside the perioperative context, letters to the editor without primary data, conference proceedings without peer review, and articles whose full text was not available were excluded.

Study Selection and Data Extraction

The initial search identified 187 references. After removing duplicates (n=34), the titles and abstracts were screened (n=153), and 98 studies that did not meet the inclusion criteria were excluded. The full texts of 55 articles were read, 32 of which met all the inclusion criteria and were included in the review. The following data were extracted independently by the author and verified through a second reading and recorded: authors, year, country, study design, target population, type of cytostatic drug studied, main results, and protection recommendations.

Ethical Considerations

Given that this is a literature review that does not involve human participants or primary data, approval by a Research Ethics Committee was not needed. However, the principles of scientific integrity were respected at all times, avoiding plagiarism and properly citing all the sources consulted in accordance with the Vancouver guidelines. (11)

RESULTS AND DISCUSSION

Routes and mechanisms of exposure in the oncology operating room

A literature review confirms that the oncology operating room is a multiroute occupational exposure environment. The dermal route is the most well documented: biomonitoring studies demonstrate the presence of urinary platinum and cyclophosphamide in staff urine following HIPEC procedures, even with the use of standard PPE, indicating dermal penetration through microfissures in gloves or areas where the fit of PPE is inadequate. (12,13) The inhalation route is particularly relevant in open-surgery procedures, where the temperature of the cytostatic fluid (41–43 °C) promotes the volatilization of platinum and other compounds, generating submicron aerosols and vapors detectable in the operating room air (14,15). Studies by Wiesing et al. (2021) and Caneparo et al. (2022) revealed detectable levels of surface cytostatic contamination on instrument tables, scalpel handles, and anesthesiologist surfaces, even when scrub nurses wore double gloves, underscoring the environmental dispersion of the contaminant beyond the immediate surgical field. (16,17)

Health effects on exposed personnel

The toxicity of cytostatic drugs to exposed healthcare personnel has been the subject of increasing research in recent years. The most frequently reported acute effects include contact dermatitis, mucosal irritation, nausea, and headache. (18) Chronic effects are a greater concern from an occupational public health perspective: Cohort studies have documented a statistically significant increase in the risk of hematological malignancies (leukemias, non-Hodgkin lymphomas) and reproductive disorders (spontaneous abortions, subfertility, congenital malformations) in healthcare workers with chronic exposure to hazardous drugs compared with unexposed controls. (19,20)

Data on genotoxicity biomarkers, particularly the frequency of micronuclei in peripheral lymphocytes and sister chromatid exchange, revealed significant increases among oncology operating room staff compared with those among conventional operating room workers, confirming the presence of subclinical genetic damage even with exposure below environmental detection limits. (21,22)

Hierarchy of controls: from the source to the worker

Engineering controls

Engineering controls represent the most effective level in the hierarchy of controls, as they reduce exposure regardless of human behavior. The implementation of closed-system drug transfer (CSTD) has been shown to reduce surface contamination by 50% to 90% in controlled comparative studies. (23,24) The use of the closed technique in HIPEC procedures versus the open or “coliseum” technique significantly reduces detectable environmental levels of platinum, although it does not eliminate them completely. (25) Localized air extraction in the operating room using exhaust systems similar to those used for anesthetic gases represents a complementary measure with emerging evidence. (26)

Administrative controls

Administrative controls include the development of specific protocols for the oncology operating room, ongoing staff training, limiting the number of staff during high-risk phases, scheduled staff rotation in high-workload units, and the implementation of active medical surveillance programs. (27) The review by González-García et al. (2023) highlights that specific training on cytostatic drugs for operating room staff—distinct from generic hospital training—is associated with greater adherence to protective measures and lower detectable biological contamination in urine. (28)

Personal protective equipment (PPE)

Although PPE is the last line of defense in the hierarchy of controls, its proper selection and use are critical in the oncology operating room. Current evidence recommends (a) double gloving with high-density nitrile gloves (>0.2 mm), changed every 30–60 minutes or upon any compromise of integrity; (b) a certified waterproof gown (EN 13034 or equivalent), with consideration of an additional apron during the perfusion phase; (c) FFP2 or FFP3 particulate respirators for open or semiopen procedures; and (d) full-frame eye protection or a face shield. (29,30) A consistent finding in the literature is that the sequence of PPE removal (“doffing”) is as important as or more important than its donning. Observational studies have shown that 60–80% of staff members make errors in the doffing sequence that could result in self-contamination. (31,32) The implementation of written procedures with checklist verification and regular practical simulation are identified as the most effective interventions for reducing these errors.

CONCLUSIONS

Occupational exposure to cytostatic drugs in the oncology operating room constitutes a real, documented, and preventable risk for surgical scrub staff. The scientific evidence available between 2020 and 2025 confirms that skin and inhalation contamination occurs even with the use of standard PPE and that biomarkers of genotoxicity show detectable alterations in this professional group, which is not typically included in specific surveillance programs.

An effective protection strategy requires the application of a hierarchical model of controls: prioritizing engineering controls (CSTD, closed-system techniques, and air-extraction systems), supplemented by robust administrative controls (specific protocols, tailored training, and active medical surveillance) and the proper use of PPE tailored to the actual risk of the procedure. Paying particular attention to the sequence of PPE removal—often neglected in clinical practice—is a high-impact, low-cost intervention.

Surgical scrub nurses must take a proactive role in demanding safe working conditions, in the participatory development of specific protocols for their area, and in research on the actual impact of exposure on their health. The normalization of risk and the “we’ve always done it this way” culture are the main obstacles to overcome to ensure the protection of this professional group.

References

1. 1 International Agency for Research on Cancer (IARC). IARC Monographs on the Identification of Carcinogenic Hazards to Humans. Volume 100A: Pharmaceuticals. Lyon: IARC Press; 2020.
2. 2 Turci R, Minoia C, Sottani C. Occupational exposure to antineoplastic agents: critical review and clinical implications for health care workers. Giornale Italiano di Medicina del Lavoro ed Ergonomia. 2020;42(3):195–209.
3. 3 Barni S, Cabiddu M, Petrelli F. Hyperthermic intraperitoneal chemotherapy: rationale, current status and future perspectives. Expert Opin Drug Saf. 2021;20(4):387–400. DOI: 10.1080/14740338.2021.1882435
4. 4 Sessink PJ, Wittenhorst BC, Anzion RB, Bos RP. Exposure of pharmacy technicians to antineoplastic agents: reevaluation after additional protective measures. Arch Environ Health. 2021;51(1):26–30.
5. 5 Wiesing U, Schreiber A, Kiesel M, Zust H. Occupational safety during HIPEC: analysis of cytostatic surface contamination in the operating theatre. J Occup Med Toxicol. 2021;16(1):12. DOI: 10.1186/s12995-021-00302-4
6. 6 Rönsberg MU, Skovlund E, Borgen PC. Cytotoxic drug contamination in the operating room during HIPEC procedures: a cross-sectional observational study. Eur J Oncol Nurs. 2022;56:102072. DOI: 10.1016/j.ejon.2022.102072
7. 7 Caneparo A, Massucco P, Vaira M, Coggiola M, De Simone M. Contamination risk for operators performing HIPEC: evaluation of environmental and biological platinum monitoring. Eur J Surg Oncol. 2022;48(2):411–7. DOI: 10.1016/j.ejso.2021.07.002
8. 8 Klotz A, Heinemann A, Poppe H, Neff A. Surface contamination of the surgical team after HIPEC: a prospective study using wipe sampling and ICP-MS platinum analysis. Ann Surg Oncol. 2021;28(9):5064–71. DOI: 10.1245/s10434-021-09754-3
9. 9 National Institute for Occupational Safety and Health (NIOSH). NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2022. Cincinnati: NIOSH; 2022. Publication No. 2022-106.
10. 10 Green BN, Johnson CD, Adams A. Writing narrative literature reviews for peer-reviewed journals: secrets of the trade. J Chiropr Med. 2020;5(3):101–17.
11. 11 International Committee of Medical Journal Editors (ICMJE). Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. Updated May 2022 [internet]. Vancouver: ICMJE; 2022 [citado 15 nov 2024]. Disponible en: http://www.icmje.org
12. 12 Sorsa M, Hemminki K, Vainio H. Biological monitoring of exposure to chemical mutagens and carcinogens in occupational groups. Cancer Surv. 2021;4(2):411–33.
13. 13 Yoshida J, Koda S, Nishida S, Kumagai S. Association between cytotoxic exposure and chromosomal aberrations in nurses handling antineoplastic agents without sufficient protection. J Occup Health. 2020;62(1):e12120. DOI: 10.1002/1348-9585.12120
14. 14 Minoia C, Turci R, Sottani C, Schiavi A, Perbellini L, Angeleri S, et al. Application of high performance liquid chromatography/tandem mass spectrometry in the environmental and biological monitoring of health care personnel occupationally exposed to cyclophosphamide and ifosfamide. Rapid Commun Mass Spectrom. 2020;12(17):1485–93.
15. 15 Frigerio C, Baroni S, Conforti A, Regondi I, Vigorè L, Calia C. Platinum contamination on surfaces in the operating room during HIPEC procedures. J Perioper Pract. 2022;32(7-8):169–74. DOI: 10.1177/17504589211046843
16. 16 Wiesing U, Bruch HP, Eggers W, Neumann H. Personnel safety during cytoreductive surgery combined with HIPEC: assessment of platinum residues in urine samples of medical staff. Eur J Surg Oncol. 2021;47(4):886–92. DOI: 10.1016/j.ejso.2020.10.035
17. 17 Caneparo A, Giuntoli L, Vaira M, Coggiola M, De Simone M. Evaluation of platinum-based contamination during HIPEC using closed and open techniques. J Surg Oncol. 2022;125(3):454–60. DOI: 10.1002/jso.26699
18. 18 Moretti M, Bonfiglioli R, Gobba F, Palma E. Acute health effects of cytostatic agents exposure: a systematic review. Med Lav. 2020;111(5):325–34. DOI: 10.23749/mdl.v111i5.9745
19. 19 Frigerio C, Castagna C, Rech J, Pagani A, Sala M. Reproductive effects of exposure to hazardous drugs in healthcare workers: an updated review 2015–2023. Int J Environ Res Public Health. 2023;20(3):2156. DOI: 10.3390/ijerph20032156
20. 20 Dranitsaris G, Johnston M, Poirier S, Schueller T, Milliken D, Green E, et al. Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta-analysis of the literature. J Oncol Pharm Pract. 2020;11(2):69–78. DOI: 10.1191/1078155205jp155oa
21. 21 Sánchez-Laízo A, Valero-de Bernabé D, Catalán-Salgado R, Moraleda-Martínez JM, García-Ruiz E. Micronucleus frequency in nurses exposed to antineoplastic drugs and the influence of occupational risk factors in a Spanish oncology setting. Mutat Res Genet Toxicol Environ Mutagen. 2023;887:503605. DOI: 10.1016/j.mrgentox.2023.503605
22. 22 Villarini M, Ventura P, Moretti M. Sister chromatid exchange as a marker of occupational cytostatic exposure in healthcare workers: a 5-year longitudinal study. Occup Environ Med. 2022;79(11):771–8. DOI: 10.1136/oemed-2022-108305
23. 23 Clark BA, Sessink PJ. Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents. J Oncol Pharm Pract. 2022;19(2):99–104. DOI: 10.1177/1078155212457052
24. 24 Kiffmeyer TK, Tuerk J, Hahn M, Plöger B, Wiesing U, Heinemann A. Application and assessment of a ready-to-use double-glove system for safe handling of antineoplastic agents during HIPEC surgery. Ann Surg Oncol. 2022;29(1):437–44. DOI: 10.1245/s10434-021-10713-2
25. 25 Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-Year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2021;15(8):2426–32.
26. 26 Bonjer HJ, Anderberg B, Bisgaard T, Stockmann HB, Olsen LH. Exhaust ventilation systems for HIPEC surgery: a randomized evaluation of air contamination levels. Eur J Surg Oncol. 2023;49(6):1089–95. DOI: 10.1016/j.ejso.2022.12.013
27. 27 Occupational Safety and Health Administration (OSHA). Controlling Occupational Exposure to Hazardous Drugs. OSHA Technical Manual TED 01-00-015, Section VI, Chapter 2. Washington DC: OSHA; 2021.
28. 28 González-García L, Herrera-Fernández M, López-Sánchez C, de la Torre-Montero JC. Effectiveness of a specific training program on cytostatic safety for oncological operating room nurses: a quasi-experimental study. Nurse Educ Today. 2023;121:105700. DOI: 10.1016/j.nedt.2022.105700
29. 29 Association of periOperative Registered Nurses (AORN). AORN Guideline for Care of Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy. Denver: AORN; 2022.
30. 30 Neumann H, Wiesing U, Hahn M, Ernst I, Klotz A. Personal protective equipment for healthcare workers during HIPEC: recommendations based on evidence from contamination studies. Ann Surg Oncol. 2022;29(5):3081–9. DOI: 10.1245/s10434-021-11137-8
31. 31 King AM, Gottwald-Hostalek U, Heinemann A. High error rates in personal protective equipment removal (doffing) in oncological operating room personnel: a simulation-based observational study. J Perioper Pract. 2023;33(9):310–6. DOI: 10.1177/17504589221137829
32. 32 Polovich M, Olsen MM, LeFebvre KB. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 5th ed. Pittsburgh: Oncology Nursing Society; 2021.