Read on to go from bread-and-butter pediatric blood work to answer the question – what’s up with troponin, lactate, d-dimer, and BNP in kids?
Someone with a cough and fever may simply have a viral illness, or he may have pneumonia. Our obligation is to evaluate for the pneumonia. It’s ok if we “miss” the diagnosis of a cold. It could be bad if we don’t recognize the pneumonia.
Depending on the disease and the particular patient, we have a threshold for testing, and the threshold for treating. Every presentation – and every patient for that matter – has a complicated interplay between what we are expected to diagnose, how much we suspect that particular serious diagnosis, and where testing and treating come into play.
Easy to do right? They are but a click away…
Often a good history and physical exam will help you to calibrate your investigational thresholds. This is especially true in children – the majority of pediatric ambulatory visits do not require blood work to make a decision about acute care. If your patient is ill, then by all means; otherwise, consider digging a bit deeper into the history, get collateral information, and make good use of your general observation skills.
First, a brief word about basic labs.
If you don’t have a trusted online reference available during your shift, make sure you have something like a Harriett Lane Handbook accessible to you. Don’t rely on your hospital’s lab slip or electronic medical record to save you, unless you are sure that they use age-specific pediatric reference ranges to flag abnormal values. Believe it or not, in this 21st century of ours, some shops still use adult reference ranges when reporting laboratory values on children.
Potassium: tends to run a bit higher in infants, because for the first year of life, your kidneys are inefficient in excreting potassium.
BUN and creatinine: lower in children due to less muscle mass, and therefore less turnover (and usually lack of other chronic disease)
Glucose: tends to run lower, as children are hypermetabolic and need regular feeding (!)
Alkaline phosphatase: is always high in normal, growing children, due to bone turn over (also fond in liver, placenta, kidneys)
Ammonia: high in infancy, due to immature liver, trends down to normal levels by toddlerhood
ESR and CRP: low in healthy children, as chronic inflamation from comorbidities is not present; both increase steadily with age
Thyroid function tests: all are markedly high in childhood, not as a sign of disease, but a marker of their increased metabolic activity
Reliably elevated in myocarditis, and may help to distinguish this from pericarditis (in addition to echocardiography)
Other causes of elevated troponin in children include: strenuous activity, status epilepticus, toxins, sepsis, myocardial infarction (in children with congenital anomalies). Less common causes of troponemia are: Kawasaki disease, pediatric stroke, or neuromuscular disease.
In adults, we typically think of a BNP < 100 pg/mL as not consistent with symptoms caused by volume overload.
Luckily, we have data in children with congenital heart disease as well. Although each company's assay reports slightly different cut-offs, in general healthy pediatric values match healthy adult values.
One exception is in the first week of life, when it is high even in healthy newborns, due to the recent transition from fetal to newborn circulation.
Use of BNP in children has been studied in both clinic and ED settings. Cohen et al. in Pediatrics used BNP to differentiate acute heart failure from respiratory disease in infants admitted for respiratory distress. They compared infants with known CHF, lung disease, and matched them with controls.
Later, Maher et al. used BNP in the emergency department to differentiate heart failure from respiratory causes in infants and children with heart failure and those with no past medical history.
The bottom line is:
To cut to the chase: d-dimer for use as a rule-out for pulmonary embolism has not been studied in children.
The only data we have in using d-dimer in children is to prognosticate in established cases. It is only helpful to track therapy for children who have chronic clots.
This is where our adult approach can get us into trouble. Basically, think of the d-dimer in children like it doesn’t even exist. It’s not helpful in our setting for our indications. An adult may have an idiopathic PE – in fact, up to a third of adults with PE have no known risk factor, which makes decision tools and risk stratification important in this population.
There is at least one identifiable risk factor in up to 98% of children with pulmonary embolism. The majority have at least two risk factors.
If you’re suspecting deep venous thrombosis, perform ultrasonography, and skip the d-dimer.
If you’re worried about PE, go directly to imaging. In stable patients, you may elect to use MR angiography or VQ scan, but most of us will go right to CT angiography. Radiation is always a concern, but if you need to know, get the test.
This is yet another reminder that your threshold is going to be different in children when you think about PE – they should have a reason for it. After you have excluded other causes of their symptoms, if they have risk factors, and you are still concerned, then do the test you feel you need to keep this child safe.
A sick child with sepsis syndrome?
The short answer – yes.
In the adult literature, we know that a lactate level above 4 mmol/L in patients with severe sepsis was associated with the need for critical care. This has been studied in children as well, and an elevated lactate in children – typically above 4 – was a predictor of prolonged ICU course and mortality in septic patients.
And it’s all about perfusion and providing oxygen to the tissues. Lactate and other laboratory testing is not a substitute for clinical assessment – it should be used as an extension of your assessment. There are two main reasons for an elevated lactate: the stress state and the shock state.
The stress state is due to hypermetabolism and an increase in glycolysis, as an example, in early sepsis. The shock state is due to tissue hypoxia, seen in septic shock. The confusion and frustration with lactate is that we often test the wrong people for it.
We could use it to track treatment, and see if we can clear the lactate; decreased lactate levels are associated with a better outcome in adults. Serial clinical assessments are even more useful to gauge your success with treatment.
We should use lactate to detect occult shock. Children compensate so well for shock, that subtle tissue hypoxia may not be detected until later. It may inform your decision for level of care, intensive care versus some other lower level.
Have you every been in this situation:
There are times when a lactate is ordered – maybe by protocol or maybe accidentally – or maybe in retrospect, the patient didn’t need it. Here is a quick mnemonic to remember the reasons for an elevated lactate: LACTATES
L – liver – any liver disease affects how lactate is metabolized by the Cori cycle
A – albuterol (or for our international friends, salbutamol), beta-agonists like albuterol, increase lactate production via cyclic amp
C – “can’t breathe” – respiratory distress and increased work of breathing shifts the ratio of aerobic and anerobic repiration
T – toxins – all kinds of wonder drugs and recreational drugs do it – look up your patient’s list if you’re suspicious
A – alcohol, not an infrequent offender
T – thiamine deficiency – think of this in your cachectic or malnourished patients
E – epinephrine – a by-product of the cori cycle, how lactate is metabolized. Difficult to interpret lactates when a patient is on an epinephrine drip.
S – seizure or shock – most commonly septic, but can be any type: cardiogenic, bstructive, hypovolemic, distributive.
Bottom line: high serum lactate levels have been associated with morbidity and mortality in children with sepsis and trauma, the two best-studied populations.
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This post and podcast are dedicated to Daniel Cabrera, MD for his vision and his leadership in thinking 'outside the box'.
Troponin | BNP | D-Dimer | Lactate
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