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Measuring the lactate gap
ACADEME AND INDUSTRY
to give guidance on areas of potential conflicts of interest. Many academics believe that interactions with industry and the creation of new companies offer potential for great benefit, but the momentum generated is often great and, as the president of University College London wrote on taking up his new position: “we have to resist the commercial cart driving the academic horse”.4 This will need a clear definition of some of the ground rules.
References 1 2 3 4
Spurgeon D. Canadian whistleblower row prompts code of conduct. Nature 1998; 396: 715. Mansour P. More lessons from unfortunate events in Toronto. Lancet 1999; 353: 1888. Schull M. Effect of drug patents in developing countries. BMJ 2000, 321: 833–34. Llewellyn-Smith C. Message from the Provost. UCL Newsletter 1999; April/May: 7–10.
Uses of error: Measuring the lactate gap Combined elevations of anion and osmolar gaps are characteristic of methanol and ethylene glycol poisonings. However, the rapid diagnosis of ethylene glycol poisoning can be a challenge. We describe how an error in laboratory measurement can be used to identify a third gap, the lactate gap, which is highly suggestive of ethylene glycol poisoning and can speed the diagnosis of this potentially lethal condition. A 38-year-old female was transferred unconscious from another hospital to our intensive care unit with a history of multiple drug overdose 24 hours previously. She had received naloxone and flumazenil in the referring hospital with little improvement in her conscious state. Initial biochemical analysis showed mild azotaemia, severe hypocalcaemia and metabolic acidosis with a high anion gap. Although the presentation suggested ethylene glycol poisoning, there was no crystalluria and the osmolar gap was only moderately raised. Nevertheless, urgent haemodialysis was commenced. An empty bottle of antifreeze was subsequently found in the patient’s home, retrospectively supporting the diagnosis. She was discharged from ICU after one week and made a full recovery. Initial plasma lactate measurements on the ICU blood gas analyser (ABL 625, Radiometer, Denmark) had resulted in error messages. Simultaneous analysis of the same sample on another lactate analyser in the main laboratory (Vitros 250, Johnson & Johnson, Rochester, NY) produced a value of 2·3 mmol/L. We looked at the ABL software and found that the “errors” were mainly values suppressed because they exceeded the upper reportable lactate limit (30 mmol/L). The initial measurement was actually 31 mmol/L, such that there was a difference (lactate gap) of approximately 28 mmol/L in comparison with the Vitros device. Glycolate, the principal toxic metabolite of ethylene glycol, can cause artifactual elevation of measured plasma lactate in at least three commonly used blood gas analysers (ABL 625, Chiron Diagnostics and Nova Biomedical) as well as the Beckman Analyser (Beckman LX20, Beckman Coulter) owing to cross-reaction with certain types of lactate oxidase. Analysers using lactate dehydrogenase are unaffected, and some using lactate oxidase (such as the Vitros device) are also free of interference. The “lactate gap” (the difference between lactate concentrations measured on two devices, one of which is prone to interference) might provide a rapid and sensitive method of diagnosing ethylene glycol intoxication. Many hospital laboratories are not set up for immediate measurement of ethylene glycol or its toxic metabolites (glycolate and oxalate), and current indirect methods of diagnosing ethylene glycol poisoning (crystalluria and elevated osmolar gaps) have limitations. We therefore suggest that emergency medicine and critical care doctors determine the response of their blood gas machines to glycolate interference, and see whether discordant machines give them the possibility of calculating the lactate gap. Doctors should look carefully at all error messages generated by lactate measuring devices. Bala Venkatesh, Thomas Morgan, Peter Garrett Royal Brisbane Hospital, University of Queensland, Brisbane, Queensland 4029, Australia
1806
THE LANCET • Vol 358 • November 24, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
to give guidance on areas of potential conflicts of interest. Many academics believe that interactions with industry and the creation of new companies offer potential for great benefit, but the momentum generated is often great and, as the president of University College London wrote on taking up his new position: “we have to resist the commercial cart driving the academic horse”.4 This will need a clear definition of some of the ground rules.
References 1 2 3 4
Spurgeon D. Canadian whistleblower row prompts code of conduct. Nature 1998; 396: 715. Mansour P. More lessons from unfortunate events in Toronto. Lancet 1999; 353: 1888. Schull M. Effect of drug patents in developing countries. BMJ 2000, 321: 833–34. Llewellyn-Smith C. Message from the Provost. UCL Newsletter 1999; April/May: 7–10.
Uses of error: Measuring the lactate gap Combined elevations of anion and osmolar gaps are characteristic of methanol and ethylene glycol poisonings. However, the rapid diagnosis of ethylene glycol poisoning can be a challenge. We describe how an error in laboratory measurement can be used to identify a third gap, the lactate gap, which is highly suggestive of ethylene glycol poisoning and can speed the diagnosis of this potentially lethal condition. A 38-year-old female was transferred unconscious from another hospital to our intensive care unit with a history of multiple drug overdose 24 hours previously. She had received naloxone and flumazenil in the referring hospital with little improvement in her conscious state. Initial biochemical analysis showed mild azotaemia, severe hypocalcaemia and metabolic acidosis with a high anion gap. Although the presentation suggested ethylene glycol poisoning, there was no crystalluria and the osmolar gap was only moderately raised. Nevertheless, urgent haemodialysis was commenced. An empty bottle of antifreeze was subsequently found in the patient’s home, retrospectively supporting the diagnosis. She was discharged from ICU after one week and made a full recovery. Initial plasma lactate measurements on the ICU blood gas analyser (ABL 625, Radiometer, Denmark) had resulted in error messages. Simultaneous analysis of the same sample on another lactate analyser in the main laboratory (Vitros 250, Johnson & Johnson, Rochester, NY) produced a value of 2·3 mmol/L. We looked at the ABL software and found that the “errors” were mainly values suppressed because they exceeded the upper reportable lactate limit (30 mmol/L). The initial measurement was actually 31 mmol/L, such that there was a difference (lactate gap) of approximately 28 mmol/L in comparison with the Vitros device. Glycolate, the principal toxic metabolite of ethylene glycol, can cause artifactual elevation of measured plasma lactate in at least three commonly used blood gas analysers (ABL 625, Chiron Diagnostics and Nova Biomedical) as well as the Beckman Analyser (Beckman LX20, Beckman Coulter) owing to cross-reaction with certain types of lactate oxidase. Analysers using lactate dehydrogenase are unaffected, and some using lactate oxidase (such as the Vitros device) are also free of interference. The “lactate gap” (the difference between lactate concentrations measured on two devices, one of which is prone to interference) might provide a rapid and sensitive method of diagnosing ethylene glycol intoxication. Many hospital laboratories are not set up for immediate measurement of ethylene glycol or its toxic metabolites (glycolate and oxalate), and current indirect methods of diagnosing ethylene glycol poisoning (crystalluria and elevated osmolar gaps) have limitations. We therefore suggest that emergency medicine and critical care doctors determine the response of their blood gas machines to glycolate interference, and see whether discordant machines give them the possibility of calculating the lactate gap. Doctors should look carefully at all error messages generated by lactate measuring devices. Bala Venkatesh, Thomas Morgan, Peter Garrett Royal Brisbane Hospital, University of Queensland, Brisbane, Queensland 4029, Australia
1806
THE LANCET • Vol 358 • November 24, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.