Nurses administer antineoplastic (chemotherapeutic) drugs to patients to treat many types of cancers. The use of these drugs has expanded beyond oncology to several other specialties, including dermatology, neurology, and rheumatology, as well as to the operating room setting.1, 2 The International Agency for Research on Cancer lists about a dozen antineoplastic drugs as known human carcinogens and another dozen as probable human carcinogens.3 The reproductive toxicity of antineoplastic drugs has long been recognized, based on evidence from studies of patients treated with these drugs.4 Yet over the past 20 years, only a few studies have explored associations between occupational exposures to antineoplastic drugs and reproductive outcomes.5 One recent review concluded that health care workers with long-term, low-level occupational exposure to such drugs "seem to have an increased risk of adverse reproductive outcomes."6
Recommendations for the safe handling of antineoplastic and other hazardous drugs have been in place since the 1980s and have been updated by numerous government and professional organizations ever since.7-11 In 2004, for example, the National Institute for Occupational Safety and Health (NIOSH) described the adverse health effects of occupational exposure to antineoplastic and other hazardous drugs, and made recommendations for workers on how to safely handle these drugs.8 Many occupational safety groups have sought to increase awareness and training regarding the hazards of such exposure; improve workplace controls, including engineering controls such as biological safety cabinets and administrative controls such as work practices and policies; and encourage the provision and use of personal protective equipment (PPE) when handling these drugs.7, 10-12
All occupational health authorities in the United States and Canada-as well as numerous professional nursing, oncology, and pharmacology societies-recommend that, at minimum, health care workers should wear double chemotherapy or latex gloves (two pairs of gloves, one worn over the other) and a nonabsorbent gown when administering antineoplastic and other hazardous drugs to patients. But whether these basic recommendations are consistently followed by nurses remains unknown.
Study purpose. The purpose of this study was to assess glove and gown use among nonpregnant female nurses who had administered antineoplastic drugs within the past month and among pregnant nurses who had administered such drugs during the first 20 weeks of pregnancy.
METHODS
Recruitment. The Nurses' Health Study 3 (NHS3; http://www.nurseshealthstudy.org) is an entirely web-based study of U.S. and Canadian nurses and nursing students born on or after January 1, 1965. Open recruitment started in 2010 and is ongoing. RNs, LPNs, LVNs, and nursing students are eligible to participate. Historically the cohort included only female nurses; in 2015 eligibility was extended to male nurses.13 Our analysis involves only data collected on female nurses, since male nurses were only recently enrolled. The NHS3 participants complete online questionnaires at enrollment and approximately every six months thereafter.
Survey instruments. The baseline NHS3 questionnaire, administered to all participants, contained a module specific to antineoplastic drugs. This included the following questions: whether the nurse had ever administered antineoplastic drugs (possible responses: yes, no), number of years' experience the nurse had in administering antineoplastic drugs, number of times the nurse had administered such drugs during an average week in the past month, how often in the past month latex or chemotherapy gloves were worn when administering such drugs (always, sometimes, never), and how often in the past month a water-resistant gown or outer garment with closed front and tight cuffs was worn when administering these drugs (always, sometimes, never). (For this study we looked only at glove and gown use, because gloves and gowns are considered the minimum necessary PPE for workers administering antineoplastic drugs.) Additional questions on the mode of antineoplastic drug administration were added partway through the study (and thus weren't available to all participants). These questions asked whether the nurse had administered such drugs via infusion (yes, no), whether the nurse had administered such drugs via oral pills (yes, no), and whether the nurse "typically" handled crushed pills (yes, no).
Pregnant nurses completed an additional questionnaire that asked whether, during the first 20 weeks of pregnancy, the nurse had administered antineoplastic drugs to patients (yes, no); how often during those 20 weeks latex or chemotherapy gloves were worn (always, sometimes, never); and how often during those 20 weeks a water-resistant gown or outer garment with closed front and tight cuffs was worn (always, sometimes, never). On the two-year follow-up questionnaire, nurses were asked to report their current primary job (nonnursing, student, ED, operating room, ICU, oncology, other inpatient, nursing education or administration, outpatient or community, school, home health, other hospital, nursing outside hospital, homemaker, retired, not currently employed, or other).
The study was approved by the institutional review boards of Brigham and Women's Hospital and NIOSH. Completion of the web-based questionnaires implied informed consent.
Data analyses. We used SAS statistical software, version 9.4 (Cary, NC) to conduct all analyses. Enrollment in the NHS3 is ongoing; these analyses were based on data that were available on October 15, 2017, for all questionnaires.
RESULTS
Sample. From the 44,612 nurses who completed the baseline questionnaires, we excluded the 535 male nurses, 3,656 female nurses who did not provide data regarding their history of working with antineoplastic drugs, and one nurse who was over the age of 55 years, leaving 40,420 female nurses who contributed data to the analyses. A total of 39,124 nurses contributed data when they were not pregnant, and 4,269 did so when they were pregnant. (Because some nurses became pregnant after completing the baseline questionnaire, they were in both the nonpregnant and pregnant study groups.) Some respondents answered questions for more than one pregnancy; we included responses associated with only the first pregnancy occurring during the study. See Figure 1 for more details.
Findings. The 39,124 nonpregnant nurses had a mean age of 33.7 years (SD, 7.26). Thirty-six percent (14,171) of these nurses reported administering antineoplastic drugs at some point during their career, and 27% (3,845) of the 14,140 who reported whether they had administered such drugs recently (within the past month) reported doing so. Of these 3,845 nurses, 24% (924) had administered such drugs more than three times per week. Drug administration status-whether or not nurses had administered antineoplastic drugs-did not vary notably by age among either nonpregnant or pregnant nurses.
The 4,269 pregnant nurses had a mean age of 29.5 years (SD, 4.05). Among these, 7% (315) had administered antineoplastic drugs during the first 20 weeks of pregnancy. Information on how chemotherapy was administered (via pills or infusion) was not available on the pregnancy questionnaire.
Use of gloves and gowns when administering antineoplastic drugs varied by pregnancy status (see Table 1). Among nurses who had recently administered antineoplastic drugs, a higher percentage of pregnant nurses (86%) than nonpregnant nurses (80%) reported that they always wore gloves when doing so. Similarly, a higher percentage of pregnant nurses (52%) than nonpregnant nurses (41%) reported that they always wore a gown. This indicates that 14% of pregnant nurses didn't always wear gloves, and nearly half (48%) didn't always wear gowns, when administering antineoplastic drugs during the first 20 weeks of pregnancy. Twelve percent of nonpregnant nurses and 9% of pregnant nurses reported never wearing gloves when administering antineoplastic drugs, and 42% of nonpregnant nurses and 38% of pregnant nurses reported never using a gown. (Note that percentages are based on all reported data, including "missing" values.) Gown and glove use did not vary notably by age among either nonpregnant nurses or pregnant nurses.
Information on the mode of antineoplastic medication administration was added to the baseline questionnaire partway through the study period. These data were available for a subset of nonpregnant nurses. Because the pregnancy questionnaire didn't ask about mode of administration, no data were available for pregnant nurses.
Among the 1,492 nonpregnant nurses who administered chemotherapy recently and who provided data on the mode of administration, 46% reported administering pills only, 12% reported infusion only, and 43% reported both. Always wearing gloves was most common among nurses who reported administering the drugs by infusion only (89%) and via both infusion and pills (89%), and less common among nurses who reported administering only intact pills (66%) or crushed pills (54%). The percentage of nonpregnant nurses who reported not wearing gloves varied by type of administration: 32% of those who administered antineoplastic drugs only as crushed pills never wore gloves, compared with 5% of those who administered such drugs only via infusion. While gown use was less common than gloves, in general, a similar pattern was found. Gown use was most common among nurses who administered antineoplastic drugs by infusion only (56%) or via both infusion and pills (57%) and was rare among nurses who administered only pills. (See Table 2.)
In the two-year follow-up questionnaire, we asked respondents to report their current primary job. Of the 7,257 pregnant and nonpregnant nurses who answered this question and had provided data regarding their history of working with antineoplastic drugs, 11% (786) reported working in oncology.
DISCUSSION
In this cross-sectional study, we found that 36% of nonpregnant nurses reported having administered antineoplastic drugs during their career, including 27% who reported doing so recently (within the past month). Among pregnant nurses, 7% reported having administered antineoplastic drugs during the first 20 weeks of pregnancy.
Nurses reported using PPE with varying frequency. Among all nurses who had recently administered antineoplastic drugs, 20% of nonpregnant and 14% of pregnant nurses did not always wear gloves when doing so; and 59% of nonpregnant and 48% of pregnant nurses did not always wear gowns. In general, glove use was markedly lower among those who administered antineoplastic drugs in pill form compared with those who administered drugs via infusion. Overall, the use of gloves and gowns was higher among pregnant than nonpregnant nurses.
Yet despite longstanding and widespread recommendations regarding the safe handling of antineoplastic and other hazardous drugs, health care workers continue to be at risk-and even to put themselves at risk. Of particular concern to us was the number of nurses in our study population who reported not wearing protective gloves and gowns, which are considered the minimum protective equipment when administering antineoplastic drugs.10 (Indeed, although the NHS3 questionnaire asks about the use of latex and chemotherapy gloves, the current standard calls for wearing two pairs of chemotherapy gloves, one on top of the other.14)
Although pregnant nurses in our study were more likely than nonpregnant nurses to report using gloves and gowns when administering antineoplastic drugs, about one in 10 did not always wear gloves and one in two did not always wear a gown when doing so during the first 20 weeks of pregnancy-a time during which the fetus is highly susceptible to exposure. The proportions of nonpregnant nurses who weren't using gloves (one in five) or gowns (one in two) is also of concern, given that most nurses were of reproductive age and could have become pregnant. The higher prevalence of glove and gown use among pregnant nurses suggests that, in general, nurses are either less aware or less concerned about the potential harm these drugs might pose to their own health. Yet in addition to being reproductive toxicants, many antineoplastic drugs are known or probable carcinogens.
These data underscore the need for continued education and training to ensure that both employers and nurses-pregnant and nonpregnant-are fully aware of such hazards and of precautionary measures. As an added precaution, many organizations (including the Oncology Nursing Society, among others) have proposed offering employees who are actively trying to conceive, pregnant, or breastfeeding alternative work assignments that would allow them to avoid handling antineoplastic drugs.15 This could be one reason why the percentage of pregnant women administering antineoplastic drugs during the first 20 weeks of pregnancy (7%) was substantially lower than that of nonpregnant women administering such drugs within the past month (27%).
As noted earlier, safe handling guidelines recommend that both double chemotherapy gloves and water-resistant gowns be worn when handling and administering antineoplastic drugs; this applies not only to liquid but also to solid forms (pills or capsules), especially when these are crushed or otherwise manipulated.14, 16 Yet in our study, among nonpregnant nurses, use of gloves and gowns varied considerably by mode of administration, with such use markedly lower among those administering antineoplastic drugs via pills only. Moreover, nurses who handled intact pills were more likely to report always wearing gloves (66%) than those who handled crushed pills (54%). Our results show less compliance with recommended glove and gown use than a national study of 2,069 health care workers (98% were nurses) by Boiano and colleagues, in which 85% of nurses reported always wearing at least one pair of chemotherapy gloves and 58% reported always wearing a nonabsorbent gown when handling antineoplastic drugs.17 In a 2012 study of oncology nurses by Polovich and Clark, compliance was similar to what we found in this study, although the use of double gloves was much lower.18
Because nursing personnel have had to rely on gloves and gowns for their sole source of protection, the U.S. Pharmacopeia's "USP General Chapter <800>: Hazardous Drugs-Handling in Healthcare Settings" states that closed-system drug-transfer devices must be used as adjuncts for antineoplastic drug administration "when the dosage form allows."11 And the Occupational Safety and Health Administration recommends that workers who handle such drugs receive information and training on hazards and means to control exposure at the time of initial assignment and annually thereafter.9
Occupational exposure to antineoplastic and other hazardous drugs can be complex. It can occur not only through direct handling and administration, but also as a result of contamination in areas where drugs are prepared and administered.19-21 Numerous studies in the United States and several other countries show that workplace contamination with antineoplastic drugs is still occurring.22-30 In one study among hospital workers, Hon and colleagues found that 20% of provided dermal wipe samples had detectable amounts of one antineoplastic drug-and the highest levels were found among workers who did not directly handle or administer the drug, pointing to workplace contamination.19
Exposure to active drug and drug metabolites can also occur through handling patient waste, and it's recommended that nurses and other facility staff take precautions when changing bed linens, washing patients, and disposing of bodily waste (including blood, feces, urine, and vomit).8, 12, 20 In the study by Polovich and Clark, nurses' glove use was lower when handling patient waste than when preparing or administering antineoplastic drugs.18 Contaminated work clothes can be another source of exposure to antineoplastic drugs. In the study by Boiano and colleagues, 12% of health care workers who administered antineoplastic drugs reported taking home clothing that had come into contact with these drugs, and another 11% didn't know whether they had or not.17 And drug spills, which are not uncommon and can be yet another source of exposure, appear to be underreported. A study by He and colleagues found that just 20% of oncology nurses reported a recent spill.31
In our study, no information was available regarding why some nurses did not use the recommended minimal PPE (gloves and gowns). But previous studies indicate that several factors may influence nurses' adherence to safe handling recommendations. In a study by Silver and colleagues of 1,094 hospital nurses who administer antineoplastic drugs, factors associated with more PPE use included the perception that adequate PPE was available, familiarity with safe handling guidance documents, training in safe handling, and working in a hospital that had procedures for safe handling.32 Silver and colleagues also found that giving nurses enough time to don and doff PPE before moving on to other nursing functions could reduce the potential for contamination.
In the study by Boiano and colleagues, respondents had collectively administered over 90 antineoplastic drugs in the week prior to taking the survey.17 The most common reason given for not wearing gloves during such administration was "skin exposure was minimal," followed by "not provided by employer" and "not part of our protocol." Those who didn't wear gowns offered an additional reason: "no one else who does this work uses them." And Polovich and Clark found that many oncology nurses, despite having been trained in safe handling, had misconceptions about exposure; for example, 15% of respondents indicated believing that "[c]hemotherapy cannot be absorbed from contaminated surfaces."18 In that study, the most common reported barriers to PPE use were the perceptions that PPE was uncomfortable, that PPE interfered with job duties; and that their coworkers did not use PPE. Having fewer patients per day to whom one administered chemotherapy was associated with greater use of PPE. Similarly, He and colleagues found that higher workloads were associated with both reduced PPE use and more drug spills.31
It's worth noting that, in our study, only 11% of the nurses who reported at baseline having administered antineoplastic drugs during their career, and who also reported their current primary job on the two-year follow-up questionnaire, were working in oncology two years later. This suggests either that some nurses had changed specialties or that a majority of respondents who administered such drugs were doing so outside of oncology settings. It's also of interest that of the 786 oncology nurses in the two-year follow-up questionnaire, 17% (133) held more than one job. If some nurses were administering antineoplastic drugs during a part-time or temporary job, or at a job outside an oncology setting, they might have been less likely to receive adequate training on safe handling practices. These results indicate a need for expanded training of health care personnel working outside oncology settings.
Limitations. First, we did not collect information on the use of double versus single gloves, engineering controls, training on safe handling practices, and reasons or barriers for not following safe handling recommendations. Second, we had no information on the nursing specialties of respondents; that said, antineoplastic drugs are widely used outside oncology settings. We expect that the study population included nurses from various specialties, and the extent of training in safe handling practices may vary across specialties. Third, we had no information on facility type or size, which might also affect the training provided and the procedures in place with regard to safe handling of antineoplastic drugs.
CONCLUSION
This is one of the first studies to explore antineoplastic drug administration and the use of PPE among pregnant as well as nonpregnant female nurses. Given the increasing use of such drugs in health care and the potential adverse effects of chronic occupational exposure, we recommend that administrators and nursing educators continue to raise awareness among health care employers and workers about these matters. We further urge employers to provide improved training, adequate PPE, and adequate time for workers to handle these drugs safely.
REFERENCES