Authors?? Response

Abstract

To the Editor: We appreciate the comments by Drs Mamatha P. Reddy and Sridhar P. Reddy regarding noninvasive measurements of methemoglobinemia (MetHb) by pulse oximetry. We concur with their view that the prompt diagnosis and treatment of an acquired dyshemoglobinemia is dependent on a high index of suspicion and an infrastructure that facilitates prompt identification and treatment when necessary. They go further to discuss using a unique newly patented technology in pulse oximetry involving eight wavelengths of light along with signal extraction technology (not available at the time of our toxic occupational event) to earlier identify and prevent potentially toxic events involving methemoglobin and carboxyhemoglobin (COHb). An accurate, easy-to-use, yet noninvasive portable monitoring device capable of rapid turnaround time for onsite or point-of-care methemoglobin determinations would seem highly desirable, especially a device that requires no user calibration. The Rad-57 cm pulse oximeter that they discuss offers the additional advantages that it can be used stationary (like in an intensive care unit) or can be moved from person to person (like in an emergency room setting or workplace). The instrument appears well suited for many field or hospital settings because the pulse oximeter can be handheld, is relatively small in size (17.5 cm × 7.6 cm × 3.6 cm), and only weighs 13 oz.1 The technology available with the Masimo Rad-57 cm pulse oximetry demonstrates considerable capabilities not available in previous pulse oximeters. In 1995, the company introduced Read-Through Motion and Low Perfusion pulse oximetry, known as SET. In 2005, Masimo introduced the Rad-57 cm pulse oximetry device, which provided for the first time noninvasive monitoring of carbon monoxide and methemoglobin in the blood. In older pulse oximeters, hemoglobin oxygen saturation by pulse oximetry did not correlate with COHb levels and consistently overestimated the fractional arterial oxygen saturation in patients with severe carbon monoxide poisoning.2 Comparison of pulse oximetry and arterial blood gas oxygen saturation (measured and calculated values, respectively) in the presence of methemoglobin has displayed significant discrepancies as the methemoglobin levels exceed 9%, whereas oxygen saturation uniformly was lower with pulse oximetry. Because of these findings, Rausch-Madison and Mohsenifar have recommended that when methemoglobin levels exceed 10%, cooximetry be used as a screen for methemoglobinemia and that serial cooximeter measurements are used to guide therapy.3 Haymond and others studied oxygen saturation (SO2) measurements by pulse oximetry, cooximetry, and arterial blood gas analysis, which they observed were often used interchangeably. They found oxygen saturation results from these methods were virtually identical, but in cases of increased dyshemoglobin fractions, including methemoglobinemia, it is crucial to distinguish the specific limitations of these methods. They concluded that SO2 calculated from pH and PO2 in blood gas analyzers should be interpreted with caution as the algorithms used assume normal O2 affinity, normal 2,3-diphosphoglycerate concentrations, and no dyshemoglobins or hemoglobinopathies. They recommended that cooximeter reports should include dyshemoglobin fractions in addition to the oxyhemoglobin fraction. In cases of an increased MetHb fraction, they observed pulse oximeter values trend toward 85%, underestimating the actual oxygen saturation. They also found that hemoglobin M variants may inaccurately yield normal MetHb and increased COHb or sulfhemoglobin (SulfHb) fractions measured by cooximetry.4 Ralston and others also found several potential sources of error in pulse oximetry investigated resulting from electrical interference, dyes, dyshemoglobins, and various other pigments.5 At present, cooximeters are the most frequently used instrument for assessing MetHb, although errors occur when other types of hemoglobin are present such as SulfHb and fetal hemoglobin.6 Cooximeters use spectrophotometric techniques, yet results vary among different instruments as well as when compared with gas chromatography (considered to be the “criterion” standard).7 Gas chromatography is used in a variety of situations for determining the number and concentration of components in a volatile mixture or volatile impurities in a substance. The major disadvantages for clinical use of gas chromatography include the need for specialized equipment, measurements are labor- and time-intensive, and analyses require sophisticated technical expertise. We suggest that blood analysis through cooximetry in the hospital setting is the current standard of analysis for the acute and periodic testing of persons who are exposed, work in contact, or must handle products that potentially could induce acquired methemoglobinemia. Drs. Reddy state that “blood testing for methemoglobin by cooximetry from arterial or venous samples is not readily available in medical clinics or hospitals.”8 A recent study by Hampson and others evaluated the ability of hospitals in the Pacific Northwest to measure COHb levels by surveying the clinical laboratory of every acute care hospital in Washington, Idaho, Montana, and Alaska regarding their ability to measure COHb levels, the method used, and the time required. If they could not measure COHb, they were then asked whether samples were sent elsewhere, the location of the referral laboratory, and time required to obtain a result. In the four states surveyed in 2003 to 2004, only 44% of acute care hospitals have the capability to measure COHb, whereas the remaining 56% send blood samples to other laboratories.4 In contrast to these findings, all but one of our 10 Northern Ohio community-based acute care and referral center hospitals involved in the Bowling Green State University Respiratory Technology Program have immediate onsite availability of at least one cooximeter for measuring MetHb and COHb. One of our affiliate teaching institutions (Fairview Hospital, Cleveland, OH) indicated a purchase intention for a Rad-57 cm pulse oximeter to be used as a “screening” device in their emergency services department (Frank Sandusky, Manager of Respiratory Care Services, Fairview Hospital, Cleveland, OH, personal communication, July 11, 2006). We have not been able to document similar availability in workplaces in affiliate hospital service areas known to be at risk for causing methemoglobinemia. In our case series review, five steam press operators were repeatedly exposed at a rubber processing plant (through manual handling) to an adhesive containing dinitrobenzene. Methemoglobin levels in the steam press workers were obtained and processed at our community hospital emergency room by using an IL 282 Cooximeter ranged from 3.8% to 41.2%.9 The subsequent investigation following the exposure incident uncovered that p-DNB had formed during the manufacture of one of the proprietary substances used as a base chemical in the adhesive. This p-DNB-contaminated chemical was then introduced into the adhesive during its formulation. The National Institute of Occupational Safety and Health recommended that plant workers use butyl rubber gloves to avoid skin contact with the dried adhesive and that plant management institute periodic follow up medical monitoring of all workers exposed to the adhesive.10 We suggest that mandatory recommendations specifically include either periodic blood cooximetry determinations or specific Masimo Rad-57 cm pulse oximetry for methemoglobin tracking. Drs. Reddy describe the new Masimo pulse oximetry technology as “cheap noninvasive way to screen for methemoglobin as well as carboxyhemoglobin in the workplace.”8 The Rad-57 cm pulse oximeter has a relatively modest retail price of $4995 and requires minimal technical skills, yet the device until now has been marketed by Masimo to the medical community where “hospitals and EMS providers are now using this device” as well as “being used mainly in ERs and by the RT world” (D. Hunt, Masimo Sales Consultant, written communication, July 06, 2006). Masimo has indicated plans to target nonhospital workplace use of the technology in the near future. Before extending the use of cooximetry, another population that could benefit from early screening and detection of acquired methemoglobinemia by a noninvasive screening device is infants younger than 4 months of age who are fed formula diluted with water from rural domestic wells. These particular infants are especially at risk for developing acute acquired methemoglobinemia from nitrate exposure.11 Several factors may contribute to this phenomenon. Because the pH of the upper gastrointestinal tract typically is higher in infants than in older children and adults, conversion of ingested nitrate to nitrite is enhanced. Premature or newborn infants may also be more susceptible because of their higher levels of fetal hemoglobin (HbF).12 Normal HbF fractions at birth are approximately 65% to 80% of total hemoglobin. During the next few months after birth, hemoglobin F production declines and production of hemoglobin A predominates. By the age of 4 months, normal HbF fractions are approximately 10% of total hemoglobin.13 Infant concentrations of nicotinamide–adenine dinucleotide-dependent methemoglobin reductase (an enzyme responsible for reduction of methemoglobin back to normal hemoglobin) provides only half the reductase activity present in adults,14 thus resulting in increased methemoglobin that place newborns and young infants fed formula diluted with nitrate-contaminated well water at higher risk for toxicity.15 It seems certain that continued advancement will occur in the measurement of dyshemoglobinemias such as methemoglobinemia that can pose life-threatening toxicities. At this time, Masimo is awaiting U.S. Food and Drug Administration (FDA) 510(k) clearance for its new bedside Radical-7 pulse oximeter, which will allow continuous noninvasive measurements of COHb, MetHb, O2 saturation, pulse rate, and perfusion index. The Rad-57 cm pulse oximeter is the newest FDA-approved advancement in screening devices offering several advantages over older pulse oximetry technology. Additional data in the higher ranges of MetHb and COHb in higher ranges would be helpful in assessing the accuracy of the device as referenced by Drs Reddy.15,16 This device is likely to be clinically useful in several settings, including occupational and environmental sites where rapid, simple, noninvasive assessments of MetHb, COHb, and oxyhemoglobin are warranted. Anthony J. Linz, DO, MPH Firelands Regional Medical Center Sandusky, Ohio Ohio University College of Osteopathic Medicine Athens, Ohio L. Fleming Fallon, MD, DrPH Bowling Green State University Bowling Green, Ohio