Caution with interpreting laboratory results after lipid rescue therapy
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American Journal of Emergency Medicine
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Caution with interpreting laboratory results after lipid rescue therapy
Abstract
Intravenous lipid rescue therapy (LRT) may be implemented to attenuate drug toxicity. Little is known about LRT interference with laboratory tests in overdose settings. A 54-year-old man with a history of depression consumed unknown amounts of diphenhydramine, amitriptyline, and acetaminophen (APAP). Initial workup showed aspartate aminotransferase of 138 U/L, APAP of 177 ug/mL, and a QRS interval of 136 milliseconds. N-acetylcysteine, sodium bicarbon- ate, and 20% intravenous LRT were initiated. Laboratory test results drawn less than 6 hours later showed an APAP level of 44 ug/mL and an undetectable AST (Siemens Vista 1500 analyzer, lower limit of detec- tion: alanine aminotransferase, 6 U/L; AST, 3 U/L). N-acetylcysteine and LRT infusions were stopped. Eight hours later, serum AST was measured at 488 U/L and increased over the next 2 days to a peak of 1600 U/L before recovery. Given a gradually rising course of AST following APAP ingestion, a single undetectable measurement is highly unlikely and probably erroneous. For this Siemens analyzer, serum lipid concentrations greater than 400 mg/dL cause interference with the AST measurement. Because lipid levels greater than 400 mg/ dL with other similar analyzers are known to falsely decrease the AST, it is possible that extreme lipemia caused this laboratory result; a triglyceride level of 3648 mg/dL has been reported after LRT infusion. This conclusion is limited by the lack of repeat measurement of Liver enzymes or measurement of serum lipid levels. Lipid rescue therapy may cause lipemia that interferes with the assay for liver enzymes. Suspected abnormal laboratory values should be repeated, or other techniques can be used to remove lipemic interference.
The effectiveness of intravenous lipid rescue therapy (LRT) in treating systemic toxicity from local anesthetics is well known, but because other appropriate indications are not well established, LRT may be used to attenuate effects from a wide range of other toxins in unstable overdose patients. Little is known about interference by the lipemia induced by the use of LRT with laboratory tests in overdose settings, and lipid levels after LRT are not well described. We (Georgia Poison Center) recently treated a patient for a multidrug overdose with LRT and discovered what appears to be Laboratory interference with the aspartate aminotransferase (AST) result. This erroneous result led to a change in clinical management, which likely con- tributed to the patients’ development of hepatotoxicity from an acetaminophen (APAP) overdose.
A 54-year-old man with a history of depression had been found after consuming an unknown amount of diphenhydramine, amitrip- tyline, and APAP. The patient had unstable vital signs and signs of cardiotoxicity on his electrocardiogram. Pertinent initial laboratory tests results were AST of 138 U/L, APAP of 177 ug/mL, and a QRS interval of 136 milliseconds (compared with a previously normal
baseline QRS duration). N-acetylcysteine (NAC), hypertonic sodium bicarbonate boluses, and 20% intravenous LRT (100-mL loading dose, infusion of 0.25 mL/kg per minute) were initiated upon our advice. Laboratory test results drawn less than 6 hours later showed an APAP level of 44 ug/mL and an undetectable AST (Siemens Vista 1500 analyzer, lower limit of detection: AST, 3 U/L). As a result, NAC and LRT infusions were stopped by the primary team without discussion with the Poison Control Center. Eight hours later, serum AST was measured at 488 U/L and increased over the next 2 days to a peak of 1600 U/L before recovery.
Many analyzers use spectrophotometric measurement of NADH to calculate rate of appearance (or disappearance) to indirectly measure analyte concentration. Unusually high serum lipemia in some patients will interfere with the colorimetric analysis as large droplets of fat scatter light and decrease transmittance through the sample. Intralipid is a fat emulsion containing soybean oil, egg yolk phospholipid, and glycerin, with particles ranging from 200 to 600 nm in size. Intralipid is also used to spike samples to test for interference-but does not exactly mimic the characteristics of the chylomicrons and triglycerides found in natural lipemia [1].
For this Siemens analyzer, serum lipid concentration greater than 400 mg/dL can cause a 12% bias with the AST measurement (personal communication with Siemens). Interference causing an undetectable measurement is not reported by the manufacturer. In a study with intralipid spiked samples, Ji and Meng [2] tested a Roche instrument and found many more interferences than reported by the manufacturer and at a lower level, including negative interference with AST. In another similar study, unde- tectable AST (and many other analytes) were reported by Grunbaum et al [3] using Beckman-Coulter DXC800 and DXI and Roche Modular-P analyzers.
In our patient, given the AST trend, a single undetectable measurement was probably erroneous. N-acetylcysteine has not been reported to interfere with this assay; however, a triglyceride level of 3648 mg/dL has been reported after LRT [4], well above the 400 mg/dL limit for this assay. The erroneous AST led to premature discontinuation of NAC therapy, possibly contributing to development of hepatotoxicity. This case demonstrates that acting upon erroneous laboratory values can have adverse effects on patient care. This conclusion is limited by the fact that there was no repeat measurement of liver enzymes and no measurement of serum lipid levels. In addition, we cannot exclude the possibility that the blood sample was drawn from the line infusing LRT.
We advise that clinicians repeat suspected abnormal laboratory values before acting upon them and, when erroneous laboratory values are suspected, obtain the limits for interferent levels of the assay by contacting laboratory or pathology personnel. Be aware of the potential of extreme lipemia, particularly after intravenous LRT
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therapy, to alter assays that use spectrophotometric analysis. Techniques such as dilution and centrifugation can be used with varying success in removing the lipemic interference.
Mohan Punja MD Georgia Poison Center, Atlanta, GA 30303, USA Emergency Medicine, Emory University, Atlanta, GA, USA
Stewart G. Neill MD
Department of Pathology, Emory University, Atlanta, GA 30322, USA
Stella Wong DO Georgia Poison Center, Atlanta, GA 30303, USA Emergency Medicine, Emory University, Atlanta, GA, USA
E-mail addresses: [email protected]; [email protected];
http://dx.doi.org/10.1016/j.ajem.2013.05.009
References
- Kroll MH. Evaluating interference caused by lipemia. Clin Chem 2004;50(11): 1968-9.
- Ji JZ, Meng QH. Evaluation of the interference of hemoglobin, bilirubin, and lipids on Roche Cobas 6000 assays. Clin Chim Acta 2011;412(17-18):1550-3.
- Grunbaum AM, Gilfix BM, Gosselin S, Blank DW. Analytical interferences resulting from Intravenous lipid emulsion. Clin Toxicol 2012;50(9):812-7.
- Levine M, Skolnik A, Levitan R, Pizon AF. Assessing the prevalence of pancreatitis following resuscitative use of intravenous lipid emulsion [abstract]. Clin Toxicol 2012;50:574-720.