Tag Archives: laboratory

Salicylate poisoning and pseudohyperchloraemia

Severe salicylate poisoning can cause metabolic acidosis from an accumulation of salicylic acid, lactic acid, and ketone bodies. A high anion gap acidosis is therefore the typical metabolic abnormality seen. A case series illustrates salicylate poisoning presenting with a normal gap (hyperchloraemic) acidosis – one patient had a chloride of 111 mmol/l and the other 123 mmol/l. This can occur when some analysers falsely read an elevated chloride in the presence of high concentrations of salicylate.

Severe salicylate poisoning is classically associated with an anion gap metabolic acidosis. However, high serum salicylate levels can cause false increase of laboratory chloride results on some analyzers. We present 2 cases of life-threatening salicylate poisoning with an apparently normal anion gap caused by an important laboratory interference. These cases highlight that the diagnosis of severe salicylism must be considered in all patients presenting with metabolic acidosis, even in the absence of an increased anion gap.

Falsely Normal Anion Gap in Severe Salicylate Poisoning Caused by Laboratory Interference
Ann Emerg Med. 2011 Sep;58(3):280-1

What do I do with a high sensitivity troponin?

Newer high-sensitivity troponin tests can be positive in patients who would have negative tests with the ‘traditional’ assay, which can result in confusion about what to do with the patient, particularly those patients without an obvious cardiac presentation. A recent study1 shows that the majority of patients that fall into this group had non-cardiac discharge diagnoses.

Background: High sensitivity troponin T (hsTnT) detects lower levels of troponin T with greater precision than the 4th generation (cTnT) assay. However, the clinical implications of this are uncertain.

Objectives: Primary: Describe the proportion of patients who test ‘positive’ with hsTnT but negative with cTnT. Secondary: Determine proportion in each group with an adverse event (representation, AMI or died) within 90 days of the index test.

Method: 161 patients samples were tested with cTnT and hsTNT assays. McNemar’s test was used to compare paired samples. Electronic medical records were reviewed, with discharge diagnosis and 90 day outcomes determined blind to hsTnT results. Patients were then classified as ‘TnT negative’ (hsTnT was <0.014 mcg/mL), 'new positive' (hsTnT was ≥0.014 mcg/mL and cTnT <0.03 mcg/mL) and 'TnT positive' (cTNT was ≥0.03 mcg/mL)
Results: Positive results more than doubled with the hsTnT assay (50% vs 22%, P < 0.001). 81 patients were ‘TnT negative’, 44 were ‘new positive’ and 36 ‘cTnT positive’. The discharge diagnosis for ‘new positives’ was AMI in 4 (9%), other cardiac in 13 (30%) and non-cardiac in 27 (61%). At 90 days adverse events occurred in 30%, 54% and 50% of the groups respectively. There were no late cases of AMI or cardiovascular death in ‘new positive’ patients.

Conclusion: Many patients with diagnoses other than AMI will have hsTNT above the reference level. Indiscriminate testing with hsTnT might lead to more patients requiring serial troponin testing and/or invasive further tests, which will have process and resource implications for EDs and health services.

An accompanying editorial2 highlights that:

Elevations are seen in pathological conditions, including structural heart disease, renal impairment and pulmonary embolism, but might also be seen in extreme exertion, such as marathon runners. It is now clear that when using a highly sensitive assay, circulating levels of troponin will be detected in many normal people.

The editorial makes the interesting observation that the duration of rise may help elucidate the cause; ischaemic elevation of troponin falls rapidly, since the rise might be due to the release of small amounts of troponin that exist free within the cytoplasm, in contrast to the more persistent elevation seen with myocardial necrosis. The editorialist provides the following caution:

Overall, our practice for ordering troponin will need to be urgently reviewed. Single troponin values will continue to be of little to no use in defining disease states in the ED. Identifying a chronic versus an acute elevation will only be revealed by serial troponin testing. The time interval between testing is currently contentious.

High sensitivity troponins are referred to in the newly published 2011 Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the Management of Acute Coronary Syndromes (full text link below)3:


  • All patients with a suspected ACS should undergo troponin testing on arrival at ED to ‘rule in’ ACS within the differential diagnosis
  • For a patient with a positive troponin result or a change in troponin levels over time, neither ACS nor other significant pathology (e.g. pulmonary embolus, aortic dissection, and sepsis) can be excluded. These patients are at higher risk of subsequent events. A positive result should be considered within the entire clinical context (history, examination, ECG findings and other investigations). Further investigations directed at all plausible clinical diagnoses should be considered and, if ACS is thought to be the likely cause, these patients may require cardiology assessment.
  • All patients with a negative result should undergo repeat testing 3–4 hours later.
  • The testing interval to ‘rule out’ MI may be reduced to 3 hours, provided that one sample is taken at least 6 hours after symptom onset:
  • Patients with a negative result at 3 hours after presentation and at least 6 hours after the onset of pain should be considered for early assessment by non-invasive anatomic or functional testing, as determined by local availability.
  • For patients presenting more than 6 hours after pain onset, a single high sensitivity troponin assay is sufficient to rule out myocardial infarction in the absence of ongoing chest pain.

High sensitivity troponin assays have an increased sensitivity for the detection of “myonecrosis”, but a reduced specificity for the diagnosis of “MI”. A positive result (≥99th centile for reference population OR where there is a change of ≥50% above an initial baseline level) should be interpreted in the context of the entire clinical presentation and does not necessarily represent an indication for coronary angiography. The management MI secondary to other conditions (e.g. anaemia, thyrotoxicosis, and sepsis) should be primarily directed at those conditions.
The finding of troponin concentrations that remain stable over time suggests that the presence of troponin is due to chronic disease. Acute exacerbations of chronic disease that result in elevated troponin levels can mimic an MI release pattern.

1. Clinical diagnosis and outcomes for Troponin T ‘positive’ patients assessed by a high sensitivity compared with a 4th generation assay
Emerg Med Australas. 2011 Aug;23(4):490-501
2. Troponin: A risk-defining biomarker for emergency department physicians
Emerg Med Australas. 2011 Aug;23(4):391-4
3. 2011 Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the Management of Acute Coronary Syndromes
Heart, Lung and Circulation 2011 Aug;28(8):487-502 Free Full Text

Venous gas in COPD exacerbation

Prolific emergency medicine researcher Anne-Maree Kelly and colleague Dr Lim from Tan Tock Seng Hospital in Singapore have published a systematic review of articles assessing the utility of peripheral venous blood gases (pVBG) in exacerbations of COPD1. Their conclusion:
Available evidence suggests that there is good agreement for pH and HCO3 values between arterial and pVBG results in patients with COPD, but not for pO2 or pCO2. Widespread clinical use is limited because of the lack of validation studies on clinical outcomes
pVBG may however be useful as a screening test for significant arterial hypercarbia; Kelly et al. previously reported2 a cutoff value of 45 mmHg (5.9 kPa).
1. A meta-analysis on the utility of peripheral venous blood gas analyses in exacerbations of chronic obstructive pulmonary disease in the emergency department
Eur J Emerg Med. 2010 Oct;17(5):246-8
2. Kelly AM, Kerr D, Middleton P. Validation of venous pCO2 to screen for arterial hypercarbia in patients with chronic obstructive airways disease.
J Emerg Med 2005; 28:377–379

Complex acid-base problems

Working out the expected compensatory response to an acid base disturbance often reveals a second acid-base problem that was otherwise hidden. I regularly use Winter’s formula when I see a metabolic acidosis, but I have trouble remembering the others, so here they are, from Harwood-Nuss’ Clinical Practice of Emergency Medicine (apologies if you ‘think’ in kilopascals):
Formulas Describing Expected Compensatory Response to Primary Acid–Base Disturbances
Simple Metabolic Acidosis

  • Predicted decreased PCO2 mm Hg = 1.2 × Δ(HCO3-) mEq/L
  • Predicted PCO2 mm Hg = 1.5(HCO3-) mEq/L + 8 ± 2
  • Anticipated PCO2 approximates last two digits of arterial pH

Simple Metabolic Alkalosis

  • Predicated increased Δ PCO2 mm Hg = 0.67 × Δ(HCO3-) mEq/L

Simple Acute Respiratory Acidosis

  • Predicted decreased ΔpH units = 0.8 × Δ PCO2 mm Hg
  • Predicted increased Δ(HCO3-) mEq/L = 0.1 × Δ PCO2 mm Hg

Simple Chronic Respiratory Acidosis

  • Predicted decreased ΔpH units = 0.3 × Δ PCO2 mm Hg
  • Predicted increased Δ(HCO3-) mEq/L = 0.35 × Δ PCO2 mm Hg

Simple Acute Respiratory Alkalosis

  • Predicted increased ΔpH units = 0.8 × Δ PCO2 mm Hg
  • Predicted decreased Δ(HCO3-) mEq/L = 0.2 × Δ PCO2 mm Hg

Simple Chronic Respiratory Alkalosis

  • Predicted increased ΔpH units = 0.17 × Δ PCO2 mm Hg
  • Predicted decreased Δ(HCO3-) mEq/L = 0.5 × Δ PCO2 mm Hg

Bloodtest Not Pertinent (BNP)

Despite a lack of evidence that it’s useful, many emergency departments have introduced BNP testing. Some smart Australians decided to properly evaluate its benefit the best way possible – with a randomised controlled trial on 612 patients with acute severe dyspnoea. Guess what? Clinician knowledge of BNP values in patients who presented with shortness of breath to the emergency department did not reduce the probability of hospital admission or alter management or length of hospital stay. The study findings do not support indiscriminate BNP testing in all dyspnoea patients, but do not rule out a possible role in patients with milder dyspnoea.
B-type natriuretic peptide testing, clinical outcomes, and health services use in emergency department patients with dyspnea: a randomized trial
Ann Intern Med. 2009 Mar 17;150(6):365-71

Take bloods before giving Lipid Rescue

Intralipid therapy is recommended for local anaesthetic toxicity and in some overdoses. After large doses of Intralipid, the results of blood tests may be difficult to analyse, delayed, or spuriously abnormal. If possible, all blood tests should be taken before the administration of Intralipid. While laboratories will readily identify significant lipaemia, communication about the presence of Intralipid is important. In one case, the inability to obtain a haemoglobin result led to delay in the identification of haemorrhage which was the cause of deterioration initially thought to be local anaesthetic toxicity.
Possible side effects of Intralipid rescue therapy
Anaesthesia 2010;65(2):210-11

Can venous blood gases replace arterial gases?

A comprehensive summary of the literature presented by Professor Anne-Maree Kelly in June 2009 at 4ème SYMPOSIUM INTERNATIONAL BLOOD GASES AND CRITICAL CARE TESTING in France can be viewed on her presentation slides at the link below.
She summarises:

  • pH – Close enough agreement for clinical purposes in DKA, isolated metabolic disease; more work needed in shock, mixed disease
  • Bicarbonate – Close enough agreement for clinical purposes in most cases; more work needed in shock, mixed disease, calculated vs measured gap
  • pCO2 – NOT enough agreement for clinical purposes; potential as a screening test
  • Potassium – Insufficient agreement between serum and BG values for clinical purposes
  • Base excess – Insufficient data

Can venous blood gas analysis replace arterial in emergency and critical care?