 |
|
 |
|
 |
 |
|
 |
 |
 |
 |
 |
 |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PEDIATRICS Vol. 104 No. 5 November 1999, pp. 1095-1100
, and
From the * Department of Occupational and Environmental Health,
College of Public Health, University of Oklahoma Health Sciences
Center; and the Department of Pediatrics, Children's Hospital of
Oklahoma, Oklahoma City, Oklahoma.
 |
ABSTRACT |
|---|
Top
Abstract
Methods
Results
Discussion
Conclusion
References
|
|---|
Objective. This study was an assessment of potential exposures of medical personnel to nitrogen oxides during simulated and actual inhaled nitric oxide treatment of newborn and pediatric patients.
Design. Breathing zone exposures to nitric oxide (NO) and nitrogen dioxide (NO2) were monitored using data-logging personal dosimeters during simulated and actual administration of NO gas to patients in an intensive care setting.
Sample. A total of 28 bedside nurses and 18 respiratory therapists were monitored during 6 different patient treatments.
Analysis. The highest measured concentrations of NO and NO2 in the personal breathing zones of the nurses and respiratory therapists were peak readings (<1 minute in duration) of 6.7 parts per million (ppm) NO and 3.1 ppm NO2. Exposures averaged throughout 15 minutes and throughout the work shift were below the limit of detection (0.8-ppm NO and 0.5-ppm NO2).
Conclusion. Detectable exposures to NO and NO2 were brief, infrequent, and well below Occupational Safety and Health Administration permissible exposure limits or any other exposure guideline, eg, American Conference of Governmental Hygienists Threshold Limit Values. Key words: occupational exposure.
Since 1991, inhaled nitric oxide (I-NO), a selective
pulmonary vasodilator, has been used in clinical trials in the
treatment of persistent pulmonary hypertension of the
newborn.1 Concentrations up to 80 ppm have been
administered to newborns.2 Individual patients are
reported to have received I-NO therapy for periods as long as 23 days.1
Nitric oxide (NO) is a colorless gas that is chemically and
toxicologically distinct from the familiar anesthetic gas nitrous oxide. Like many other medical agents, NO poses a potential
occupational hazard under certain conditions of exposure. The primary
observed toxic effect of NO is formation of
methemoglobin.3 Methemoglobin is formed when NO, which has
an affinity for hemoglobin nearly 1 000 000 times that of oxygen,
combines with the heme centers of the blood and prevents oxygen from
being transported to the tissues of the body.3 It has been
reported that among patients receiving NO therapy, the fraction of
hemoglobin converted to methemoglobin typically does not exceed
5%.4 In a multicenter study,2
methemoglobinemia, defined as >7% methemoglobin, was seen in 13 of 37 patients administered NO at the 80-ppm level, but was not seen in the
groups of 41 and 36 patients administered 5-ppm NO and 20-ppm NO,
respectively. A second potential hazard of NO is its conversion, in the
presence of oxygen, to nitrogen dioxide (NO2), a
brownish gas that is a potent pulmonary irritant.3 Because
NO always exists in equilibrium with NO2 in air,
mixed NO and NO2 are often referred to
collectively as nitrogen oxides or NOx. The
conversion of NO to NO2 can be quite
slow5-7: in a 20-ppm mixture of NO in air, only ~1- to
3-ppm NO2 would be generated in 10 minutes.
However, because the rate of NO2 formation is
proportional to the oxygen concentration and to the square of the NO
concentration, NO2 is formed more rapidly in
oxygen enriched atmospheres, such as those found in a patient
ventilation circuit, or at higher concentrations of NO. It may take <1
minute for 1-ppm NO2 to be generated from a
20-ppm mixture of NO in 95% oxygen at 100% relative humidity.7 Effects of human exposure to various levels of
NO2 have been reported; these include increased
flow resistance of the airway after 10-minute exposure at 0.7 to 2 ppm,8 mild irritation of the eyes, nose, and upper
respiratory tract at 10 to 20 ppm,9 respiratory irritation
and chest pain after 60-minute exposure at 25 ppm,8 and
pulmonary edema and death after 60-minute exposure at 100 ppm.8
In 1971, the Occupational Safety and Health Administration (OSHA)
established legal permissible exposure limits for NO and NO2.10 The OSHA limit for NO is a
concentration of 25 ppm averaged throughout an 8-hour work shift. This
limit is believed to offer adequate protection against the risk of
methemoglobinemia.9 Based on NO2's
acute irritant properties, OSHA has established a ceiling limit of 5 ppm for NO2, which is not to be exceeded at any
time during the work shift.10 The National Institute for
Occupational Safety and Health recommends that the average NO2 exposure throughout any 15-minute period not
exceed 1 ppm.9
Because the use of I-NO for the treatment of pulmonary hypertension is
a pioneering effort, the potential exposure of health care workers to
this agent and its byproducts during the therapeutic use of NO has not
previously been investigated. Young and Dyar4 reported
that NO concentrations detected during intermittent sampling of air in
a NO treatment room did not exceed 1 ppm; however, grab samples of this
type cannot be assumed to be representative of personal exposure. The
primary objective of this study was to make a preliminary assessment of
potential exposures of medical personnel, such as the respiratory
therapist and the bedside nurse, to nitrogen oxides during simulated
and actual NO treatment of newborn and pediatric patients at
Children's Hospital of Oklahoma.
This study was approved by the Institutional Review Board of the
University of Oklahoma Health Sciences Center.
NO Delivery System
The system used during this study for administration of NO
consisted of a prototype Ohmeda (Ohmeda PPD, Liberty Corner, NJ) INOvent Delivery System and either a conventional ventilator or a high frequency oscillatory ventilator. The INOvent delivery system
used 400- or 800-ppm NO (INOmax, INO Therapeutics, Inc, Clinton,
NJ) in nitrogen from a cylinder as its NO source. This concentrated NO
was injected into the ventilator breathing circuit between the
ventilator and the humidifier chamber at a controlled flow rate that is
synchronized with ventilator flow to deliver a constant concentration
of up to 80 ppm to the patient. The INOvent continuously monitors the
concentrations of NO, NO2, and
O2 in the inspiratory limb immediately proximal
to the endotracheal tube. The expiratory limb was vented to the room.
It should be noted that during earlier clinical trials of the INOvent,
the expiratory gas was vacuum scavenged to prevent release into the room air10; however, under revised operating instructions from Ohmeda,11 this practice had been discontinued before the inception of the present study.
The INOvent also included a manual NO delivery system that drew oxygen
from the hospital oxygen system and delivered a constant NO
concentration of 10 ppm (400-ppm cylinder source concentration) and 20 ppm (800-ppm cylinder source concentration) to the manual resuscitator
bag.
Air Monitoring Instruments and Procedures
Air monitoring was performed using Toxi Ultra data-logging
dosimeters (Biosystems, Inc, Middletown, CT) that were configured for
the detection of either NO or NO2 by means of a
chemical-specific electrochemical cell sensor.12 These
dosimeters were continuous monitors that electronically recorded the
highest NO or NO2 concentrations occurring during
each 1-minute time interval. After each monitoring session, the
collected data were downloaded to a computer for analysis.
The limits of detection for the Toxi Ultra dosimeters were determined
using a Dasibi 5008 Programmable Multi-Gas Calibrator (Dasibi
Environmental Corporation, Glendale, CA) and EPA Protocol Standards
(Scott Specialty Gases, Plumsteadville, PA) to generate NO and
NO2 test atmospheres in the 0.3- to 1.2-ppm
range. The limit of detection was ~0.8 ppm for the NO dosimeters and
~0.5 ppm for the NO2 dosimeter. These limits
were distinguishable from the normal baseline fluctuations of the
dosimeter readings in the absence of NOx. The
dosimeters recorded and displayed gas concentrations to a precision of
0.1 ppm. Dosimeters were calibrated monthly using certified gas
standards to verify the accuracy and stability of instrument response
in the 5- to 50-ppm range for NO and the 1- to 10-ppm range for
NO2. Dosimeter response to the gas standards was
reproducible to within 8% between monthly calibrations, and was linear
to within 10%. In addition to the monthly calibrations, calibration
checks of the dosimeters were performed before and after data
collection on each day that monitoring was conducted. A calibration
check consisted of checking the dosimeter response to a zero gas
(certified NO-free and NO2-free air or nitrogen) and to a certified 5-ppm or 10-ppm gas standard.
Cross-sensitivity of the dosimeters was checked by applying each of the
certified NO gas standards to the NO2 dosimeters
and applying the certified NO2 gas standards to
the NO dosimeters. The NO dosimeter response was <20% of the applied
NO2 concentrations, and the
NO2 dosimeter response was <10% of the applied
NO concentrations.
Monitoring was conducted during simulated administration of the
treatment gas and during actual administration to the patient. Informed
consent was obtained from all health care workers who participated in
the monitoring. No work practices or treatment protocols were altered
for the purposes of this study. Decisions regarding patient treatment
were totally independent of this study. During simulated and patient
administration, personal monitoring was performed on the respiratory
therapist and the bedside nurse with the dosimeters being worn in the
breathing zone of each individual. To ensure that observed exposures
were collected in the breathing zone, 1 NO dosimeter and 1 NO2 dosimeter were mounted in a canvas bib worn
around the neck of the respiratory therapist and the bedside nurse.
This bib placed the dosimeter sensors ~4 to 6 inches from the
individual's chin and 3 inches from each other.
Simulations
Simulated administration runs consisted of setting up the
INOvent delivery system, administering the NO treatment to an
artificial lung for 5 minutes, and disassembling the INOvent delivery
system. The set-up and disassembly of the NO delivery system was
performed by the respiratory therapist, and simulated administration,
including manual bagging, was performed by either the respiratory
therapist or the bedside nurse. The 2 types of ventilators used for the simulations were the Sechrist IV-100B constant pressure ventilator (Sechrist Industries, Inc, Anaheim, CA) and the SensorMedics 3100A oscillatory ventilator (SensorMedics, Yorba Linda, CA). Two simulations were conducted on the Sechrist, whereas 6 were conducted on the oscillator. Only NO monitoring was conducted during the 2 Sechrist runs.
In addition to personal monitoring, area monitoring was also conducted
during the simulation runs. During use of the oscillatory ventilator,
dosimeters were positioned below the front control panel of the
INOvent, at the back of the INOvent below the purge line (this outlet
is intentionally designed to vent excess NO away from the breathing
zone of operator), and/or at either of 2 outlets on the oscillator
circuit's expiratory limb. Both outlets vented directly to the room
air. The locations of area measurements performed during use of the
Sechrist differed slightly from the area measurements taken for the
oscillator because of the difference in ventilator setup and design.
Dosimeters were located at the exhalation port of the ventilator and at
the patient radiant warmer bed. These locations represented the
areas that carried the highest potential for measuring NO and
NO2 leakage into the room. The simulated
administration runs were ~30 to 45 minutes in duration.
Staff Monitoring During Patient Treatment
Six patients received NO therapy during the study period: 3 patients in the neonatal intensive care unit (NICU) and 3 patients in
the pediatric intensive care unit (PICU). Patient treatment involved
around-the-clock administration of NO. Typically, the therapy gas was
initially delivered to the neonatal or pediatric patient at a
concentration of 20 ppm. If patient response was satisfactory, after
several days the concentration would gradually be reduced to wean the
patient off the vasodilator. Personal monitoring of the caregivers for
NO and NO2 exposure was conducted continuously from the initiation of patient treatment until the treatment was discontinued for that patient. Only the bedside nurse and respiratory therapist were monitored because these individuals were primarily responsible for administering the NO treatment to the patient.
Participation in this study was solicited from each bedside nurse and
respiratory therapist assigned to the care of a patient on NO. The
participation rate was 100%. A total of 28 nurses (1 male, 27 female)
and 18 respiratory therapists (7 male, 11 female) were monitored during
patient treatment. Many individuals were monitored multiple times in
the course of 1 or more patient treatments. Caregivers were monitored
for their entire workshifts, which were usually 8 hours for the
respiratory therapist and 12 hours for the bedside nurse. During the
sixth patient treatment, the nurses worked either 4-, 8-, or 12-hour
shifts. Caregivers who found prolonged wearing of the dosimeters
uncomfortable were allowed to remove the dosimeters when they were
outside the patient treatment area.
The NO and NO2 data collected in this study
consisted of 3 types of measurements: the peak exposure, the short-term
exposure level (STEL; 15-minute average), and the 8-hour
time-weighted average (TWA). A peak measurement was classified as the
highest NO or NO2 reading detected by the
dosimeter in any 1-minute period. The STEL was the concentration of NO
or NO2 averaged throughout a 15-minute period.
The 8-hour TWA was calculated by dividing the cumulated NO and
NO2 exposures for the entire sampling period by 8 hours. This calculation method allows direct comparison between the
OSHA 8-hour TWA permissible exposure limit and the average exposure throughout a work shift of duration different from 8 hours,
such as the 12-hour shifts worked by the NICU and PICU nurses.
Results of Simulation Runs
As stated above, the 8 simulation runs included 2 runs with the
Sechrist IV-100B ventilator and 6 runs with the Sensor Medics 3100A
oscillator. The simulation data included results of both personal and
area sampling with the dosimeters. The average duration of a simulation
run was 30 minutes. The highest peak, STEL, and 8-hour TWA measured for
the respiratory therapist and the bedside nurse during simulation
runs with the Sechrist were less than the limit of detection for NO.
The area measurement results indicated that NO was not detectable at
the patient bed. At the exhalation port of the ventilator, however, the
highest NO readings were a peak of 13.0 ppm and a STEL of 9.0 ppm.
Measurements were collected for the respiratory therapist during all 6 runs of the oscillator; however, because of scheduling constraints,
monitoring was performed for the bedside nurse only during the first 2 runs of the oscillator. Both NO and NO2 were monitored during the oscillator runs. The highest exposure readings for
the respiratory therapist were peaks of 1.4-ppm NO occurring during
disassembly of the NO delivery system, and 0.7-ppm
NO2 occurring during set-up of the delivery
system. The STEL and 8-hour TWA for the respiratory therapist did not
exceed the limits of detection for both NO and
NO2. All NO and NO2 results
for the bedside nurse were below the limits of detection. The highest measured NO and NO2 readings at either outlet on
the expiratory limb of the oscillator circuit were peaks of 4.7 and 0.8 ppm, respectively, at the dump valve outlet. The STEL and 8-hour TWA at
both outlets were below the limit of detection. The highest NO readings
at the back of the INOvent were a peak of 14.9 ppm and a STEL of 2.0, whereas the highest NO2 readings in this location were 0.8 ppm for the peak and below the limit of detection for the STEL
and 8-hour TWA. Results recorded at the front of the INOvent
included a maximum NO peak of 1.5 ppm, but all other measurements from
this area were below the limits of detection.
It should be noted that when the INOvent was purged during initial
setup, the sensor of the delivery system measured
NO2 concentrations of up to 20 ppm at the point
where the NO gas is introduced into the patient ventilator circuit.
These elevated concentrations did not seem to have an effect on the
personal or area measurements taken by the NO2
dosimeters.
Results of Monitoring During Patient Treatment
Conditions during the 6 patient treatment episodes, including the
location and duration of treatment, the type of ventilator, and the
number of bedside nurses and respiratory therapists monitored, are
presented in Table 1. The duration of NO
administration ranged from 10 hours to 5 days. The summary of the
highest measured peak, STEL, and 8-hour TWA exposures for the bedside
nurse and the therapist during each patient treatment are presented in
Table 2.
TABLE 1 TABLE 2
METHODS
Top
Abstract
Methods
Results
Discussion
Conclusion
References
RESULTS
Top
Abstract
Methods
Results
Discussion
Conclusion
References
Summary of Patient Treatments
Highest NO2 and NO2 Exposure Readings During
Patient Treatments
In >900 hours of monitoring during 6 patient treatments, the NO and NO2 8-hour TWA exposures and the NO STEL exposures never exceeded the dosimeters' limit of detection. The STEL for NO2 exceeded the limit of detection only twice. The highest peak exposures measured for the bedside nurses were 6.7-ppm NO and 1.5-ppm NO2. Peak NO readings of 6.1 and 3.4 ppm were recorded when the dosimeters were worn by certain respiratory therapists on their smoking breaks. Smoking would increase the potential exposures to NO and NO2 because of the presence of NO and NO2 in cigarette smoke. The highest peak NO2 reading was 3.1 ppm for a respiratory therapist. It could not be determined what activity the respiratory therapist was performing at the time of this peak reading; however, the simultaneous NO reading was not elevated greater than background. Overall throughout the patient treatments, the dosimeter measurements did not reveal simultaneous elevation of NO and NO2 concentrations greater than the level of detection.
A plot of NO and NO2 readings during a representative work shift for an NICU nurse is presented in Fig 1.
|
The distribution of minute peak readings of NO and NO2 concentration is summarized in Table 3. During the patient treatments and the simulations, a total of 54 269 minute readings were collected for NO2, and 55 245 minute readings were collected for NO. Peaks greater than the limit of detection occurred in <1% of the minute readings.
|
| |
DISCUSSION |
|---|
|
Top
Abstract
Methods
Results
Discussion
Conclusion
References
|
|---|
In >900 hours of monitoring during patient treatment with NO, as well as 8 simulated setup and disassembly runs with the NO delivery system, personal exposure readings greater than the limit of detection of the NO or NO2 dosimeters were found to be infrequent, of short duration, and well below regulatory exposure limits.
Peak exposures of the bedside nurses and the respiratory therapists were similar in magnitude. Respiratory therapists seemed to experience detectable exposures to NO2 somewhat more frequently than the bedside nurses. This difference in exposure probably results from the respiratory therapist's activities in the operation of the NO delivery system: setup and disassembly of the INOvent, changing of NO cylinders, calibration of the INOvent gas monitor, and adjustment of the treatment gas concentration.
Manual bagging of the patient by the bedside nurse or respiratory therapist did not seem to result in detectable personal exposure. Additionally, on 1 occasion during the fifth patient treatment, the NO flow to the manual bagging system was inadvertently left on for ~91/2 hours after the patient was put on a new ventilator. No effect on personal exposure levels was detected during this incident.
Although elevated NO levels were emitted from the ventilator circuit and delivery system during simulations, personal measurements taken during patient administration did not show NO exposures of similar magnitude. A couple of factors probably account for the lower personal exposures: 1) the treatment gas released to the room was rapidly diluted by mixing with room air. Elevated concentrations occurred only in the immediate vicinity of the release point. 2) The caregivers rarely worked in close proximity to release points.
Because NO2 is gradually formed from NO in the treatment gas, it would be expected that if NO2 were detected NO would also be present. The fact that the dosimeters tended not to detect simultaneously elevated NO and NO2 readings during personal monitoring suggests that areas of elevated NO/NO2 concentration were extremely localized, such that the sensors on both dosimeters were not uniformly exposed.
In general, personal exposure levels could be affected by changes in the NO treatment protocol and delivery method, and by the characteristics of the treatment room. Increased concentration of NO in treatment gas and increased patient ventilation rate (or the simultaneous NO treatment of multiple patients in 1 room) would tend to increase potential exposures. Also, increased residence time of NO in contact with oxygen in the ventilator circuit could lead to more NO2 formation. Providing adequate ventilation in the NO treatment room and ensuring free circulation of air around the release points can control exposures. If necessary, treatment gas vented from the NO delivery system and/or the ventilator circuit could be scavenged by suction or by passing it through a chemical sorbent trap for NOx gas.
| |
CONCLUSIONS |
|---|
|
Top
Abstract
Methods
Results
Discussion
Conclusion
References
|
|---|
The results of personal monitoring of the bedside nurse and the respiratory therapist for NO and NO2 exposures related to the use of NO treatment in a neonatal and pediatric intensive care setting indicated no overexposure to NO or NO2 during this study. Exposure of the caregivers to detectable levels of NO and NO2 in room air was brief, infrequent, and well below established limits. Therefore, clinical and subclinical effects related to NO and NO2 exposure, such as methemoglobinemia and respiratory irritation, are not expected during the use of the INOvent delivery system as described in this study. Although NO levels as high as 15 ppm and NO2 levels as high as 20 ppm were briefly emitted to the ambient environment during simulated setup and disassembly of the INOvent delivery system, these releases did not seem to elevate personal exposure levels.
It should be noted that this study was conducted with a single INOvent delivery system operating in the patient room. The results of this study should not be extrapolated to locations where multiple NO delivery systems are in use in the same room, or where the room is not ventilated at standard rates for NICUs.
| |
ACKNOWLEDGMENTS |
|---|
This research was supported by Ohmeda PPD Corporation.
We wish to thank Christopher Brown, Abraham Cherian, Michael McCoy, and Scott Sears for their assistance in data collection; Kent Stafford and Tracy Henderson of the State of Oklahoma Department of Environment Quality for their assistance in use of the Dasibi calibrator; and the Children's Hospital of Oklahoma NICU and PICU staff for their cooperation and participation in this study.
| |
FOOTNOTES |
|---|
Received for publication Jan 19, 1999; accepted Apr 6, 1999.
Reprint requests to (M.L.P.) College of Public Health, PO Box 26901, Oklahoma City, OK 73190. E-mail: margaret-phillips{at}uokhsc.edu
| |
ABBREVIATIONS |
|---|
I-NO, inhaled nitric oxide; NO, nitric oxide; NO2, nitrogen dioxide; OSHA, Occupational Safety and Health Administration; NICU, neonatal intensive care unit; PICU, pediatric intensive care unit; STEL. short-term exposure level; TWA, time-weighted average.
| |
REFERENCES |
|---|
|
Top
Abstract
Methods
Results
Discussion
Conclusion
References
|
|---|
This article has been cited by other articles:
 |
|
 |
|
  M. A. Qureshi, N. J. Shah, C. W. Hemmen, M. C. Thill, and J. A. Kruse Exposure of Intensive Care Unit Nurses to Nitric Oxide and Nitrogen Dioxide During Therapeutic Use of Inhaled Nitric Oxide in Adults With Acute Respiratory Distress Syndrome Am. J. Crit. Care., March 1, 2003; 12(2): 147 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Dukelow, S. Weicker, T. A. Karachi, H. M. Razavi, D. G. McCormack, M. G. Joseph, and S. Mehta Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia Chest, December 1, 2002; 122(6): 2127 - 2136. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
||
|
||
Home | My Pediatrics | Journal Information | Current Issue | Past Issues | Subscriptions & Services | Contact Us Click here for faster international access © 1999 American Academy of Pediatrics. All rights reserved. |
||
|
||
