Sick day rules for diabetes

Cite this article as:
Tessa Davis. Sick day rules for diabetes, Don't Forget the Bubbles, 2013. Available at:

You receive a phone-call from the mother of a 7-year-old child with diabetes – he’s been unwell all day with temps and coryzal symptoms and he’s off his food.

The BSLs have been creeping up all day and are now 16 mmol/l.She’s not sure what else to do so they are on their way into hospital.

You’re the paeds reg on and it’s down to you to manage this before he gets into DKA. Are you up to the task?

What happens to blood sugar levels when children with diabetes get an intercurrent illness?

The BSLs can be high or low.

With vomiting and diarrhoea, the BSLs may well be low due to reduced intake but also poor absorption from oral intake.

Although it might seem counter-intuitive, BSLs often go high even though the child is unwell and not eating as much as normal (particularly with pyrexial illnesses).  The body’s stress response is to produce more glucose and this is often resistant to insulin.

Where does ketone monitoring come in?

When your patient has high BSLs (>15 mmol/l) and is unwell, the main focus is to keep an eye on the ketone level because the illness could potentially lead to DKA if not managed correctly – blood ketones are preferable to urine ketones as they show up earlier.

If ketones are present and BSL>15 mmol/l, give extra insulin as below and then check again in 2 hours.  Don’t go overboard with checking every five minutes!

How do I manage the unwell diabetic?

There are three key aims of management: prevent dehydration; prevent DKA; and prevent hypoglycaemia.

  • Encourage the patient to drink fluids (carbs if BSL<8 mmol/L and sugar-free if BSL>8 mmol/l) – go for small volumes often.
  • Keep the normal insulin doses going if sugars are high!

How much insulin should I give?

Give extra doses according to the table.  Add up the total number of units per day and then work out the percentage accordingly (i.e. if the patient has 20 units of insulin per day then 10% will be 2 units).  If you are needing to give repeated doses then make sure the consultant is aware.

Blood ketonesBlood ketones 0.6-1.5 mmol/l; Urine: + to ++Blood ketones >1.5 mmol/l; Urine: ++ to +++
BSL<4 mmol/lGive sweet fluids/food/carbohydrate. Repeat BSL in 30 mins. Continue with regular insulin but consider lowering doses. Consider glucagon. Consider hospital admission if BSL remains low.Give sweet fluids/food/carbohydrate. Repeat BSL in 30 mins. Continue with regular insulin but consider lowering doses .Consider glucagon. Consider hospital admission if BSL remains low and ketones not clearing.Give sweet fluids/food/carbohydrate. Repeat BSL in 30 mins. Continue with regular insulin but consider lowering doses. Consider glucagon. Consider hospital admission if BSL remains low.
BSL 4-8 mmol/lRepeat BSL in 2 hours.Give extra glucose/carbohydrate. Continue with regular insulin. Repeat BSL and ketones in 2 hours.Give extra glucose/carbohydrate. Continue with regular insulin and consider 5% extra insulin if ketones do not clear. Repeat BSL hourly and ketones in 2 hours.
BSL 8-15 mmol/lRepeat BSL in 2 hours. Consider 5% extra insulin if BSL remains elevated.Repeat BSL and ketones in 2 hours. Give 5-10% extra insulin if BSL remains elevated.Give 10% extra insulin. Repeat BSL and ketones in 2 hours.
BSL >15 mmol/lGive 5% extra insulin. Repeat BSL and ketones in 2 hours.Give 5-10% extra insulin. Repeat BSL and ketones in 2 hours.Give 10-20% extra insulin. Repeat BSL and ketones hourly.

Table reconstructed from the wonderful book by Ambler and Cameron (see refs).

What if the blood sugar is low?

Use gastrolyte or hydralyte and additional carbs if needed.  Follow the guide in the table.

If you really cannot push oral intake and the BSL is <4 mmol/l then consider glucagon

1 unit of glucagon per year of age (i.e. 7 units for a 7-year-old) – administer just like an insulin injection. Then recheck BSL in 30 mins.


Ambler G, Cameron F. Caring for diabetes in children and adolescents. Blue Star Print Group: 3rd edition. 2010:p 98.

Basic pharmacology

Cite this article as:
Marc Anders. Basic pharmacology, Don't Forget the Bubbles, 2013. Available at:

Routes of administration and systemic absorption of drugs:

Rate of systemic absorption determines onset, intensity and duration of action. Drug solubility and blood flow to the site of absorption are the most important factors:


  • most convenient & economic route of administration
  • complicated by nausea/emesis & irregularities in absorption
  • principle site of absorption is the small intestine
  • GI mucosa and the liver contribute to extraction and metabolism of drugs

Oral/nasal transmucosal:

  • drains to the SVC and/or VIJ and bypasses 1st pass hepatic metabolism


  • highly unpredictable and irritant to rectal mucosa
  • absorption is slow due to the small available surface area
  • distal rectal administration will bypass 1st pass hepatic metabolism
  • proximal rectal administration will not bypass 1st pass hepatic metabolism


  • includes subcutaneous, intramuscular and intravenous routes
  • absorption is more reliable and complete
  • IV administration avoids factors that limit systemic absorption by other routes and is a more comfortable way to administer irritant drugs


  • epidural route is used to provide analgesia and anaesthesia
  • significant systemic absorption may occur through the epidural venous plexus especially with lipid soluble drugs and continuous infusions (e.g. fentanyl)
  • intrathecal or spinal administration rarely causes unwanted systemic effects

Distribution of drugs after systemic absorption:

Highly perfused tissues (heart, lungs, brain, kidneys and liver) receive a disproportionate amount of drug and initially sequester it from the plasma. Once plasma concentration falls following a bolus dose, drug will redistribute back into the plasma.

Following a bolus dose, plasma concentration first falls rapidly during the distribution phase and then more gradually during the elimination phase.

Remember that increasing an infusion of a drug to increase its desired effect should be preceded by a repeat bolus/load otherwise its effect will take ~5 half times!

Repeated large doses and/or prolonged infusions will saturate inactive tissues which will then act as reservoirs and prolong the duration of action of drugs.

Pharmacokinetic variables:

Volume of distribution (Vd):

  • apparent volume a drug is injected into (calculated from dose and initial plasma concentration before any clearance)
  • determinant of elimination half time (t½β)
  • depicts the distribution characteristics of a drug in the body
  • used to determine loading doses
  • mainly influenced by physicochemical characteristics of the drug


  • hepatic microsomal enzymes are responsible for most drug metabolism
  • hepatic extraction may be perfusion dependent (affected by hepatic blood flow) or capacity dependent (affected by ionisation and protein binding)
  • lungs (eg. catecholamines), kidneys (e.g. morphine) and the GIT have considerable drug metabolising ability
  • plasma cholinesterase and non-specific esterases are important in drugs containing ester bonds (e.g. esmolol, succinylcholine)
  • Hoffman elimination is spontaneous non-enzymatic breakdown (e.g. cisatracurium)

Clearance (Cl):

  • volume of plasma cleared of drug per unit time
  • determinant of elimination half time (t½β)
  • metabolism, excretion and non-organ clearance (e.g. ester hydrolysis) all contribute to clearance
  • may be 1st order (proportional to plasma concentration) or zero-order (constant amount of drug cleared independent of plasma concentration)


Half times:

  • time necessary for the plasma concentration of a drug to decrease by 50% (t½β ~ Vd/Cl)
  • can be during distribution ( t½α) or elimination (t½β)
  • plasma concentration does not always correlate with the clinical effect of the drug
  • elimination half time determines the dosing interval to achieve steady state (~5 half times)
  • context sensitive half time (CSHT) is the time necessary for the plasma drug concentration to decrease by 50% after ceasing a continuous infusion of a specific duration (context = duration of infusion)

Effect site equilibration time (ESET):

  • delay between IV administration and onset of clinical effect reflects the delay in delivery of the drug to its site of action and subsequent dynamic response
  • mainly determined by physicochemical properties of the drug
  • important in determining dosing intervals when titrating to effect

Physicochemical properties of drugs:


  • most drugs are present as both ionized and non-ionized molecules
  • the proportion is determined by the pK of the drug and the pH of the surrounding fluid
  • only the non-ionised drug is free to diffuse across membranes, be metabolized or be excreted

Protein binding:

  • a variable amount of drug may be bound to various plasma proteins which affects distribution
  • clinically significant protein binding is >90%
  • acidic and neutral drugs generally bind to albumin and alkaline drugs generally bind to alpha1-acid glycoprotein
  • only unbound drug is free cross membranes, be metabolised or excreted

Molecular size:

  • small molecules diffuse much more readily than large ones

Lipid solubility:

  • ability to physically diffuse through cell membranes (does not necessarily correlate with rapid onset of action)


  • mixtures often contain either inactive isomers or isomers that have different and/or adverse clinical effects (racemic and non-enantiopure preparations can be considered mixtures of different drugs)

Individual variability in dynamic response:

  • the response (therapeutic and adverse effects) to many drugs varies widely among patients
  • there is up to a five-fold range of plasma concentrations required to achieve the same pharmacologic effect in different individual patients
  • there is up to a two-fold range of plasma concentrations required to achieve the same pharmacologic effect in the same patient using the same dosing regime
  • absorption and bioavailability as well as variations in cardiac, renal and hepatic function contribute to inter- and intra-individual variability.
  • enzyme activity (e.g. induction/inhibition) and genetic factors (e.g. fast/slow acetylators) also play a role


Effects of age and disease:

Renal disease will affect drugs excreted by the kidneys to an extent proportional to the degree to which the drug depends on renal excretion.

Hepatic disease alters plasma protein levels (decreased binding), increases Vd (ascites), reduces metabolism and may alter bioavailability (decreased 1st pass metabolism and/or porto-caval collaterals).

Neonates and infants:

  • proportionally more water, larger intravascular volume and larger highly perfused organs
  • immature blood-brain barrier makes them more sensitive to drugs acting in the CNS
  • immature and inefficient hepatic metabolising capacity and lower plasma protein levels
  • GFR < 10% of adult values will affect clearance

 All Marc’s PICU cardiology FOAM can be found on PICU Doctor and can be downloaded as a handy app for free on iPhone or AndroidA list of contributors can be seen here.


Heart transplantation

Heart transplantation

Cite this article as:
Marc Anders. Heart transplantation, Don't Forget the Bubbles, 2013. Available at:

Indication: life expectancy <2 years and/or unacceptable quality of life, end stage CHD, DCM, HCM (see cardiomyopathy)

Risk profile:

PVR (low risk: PVR ≤4 WU or TPG ≤10 mmHg, medium risk: PVR 5-9 WU or TPG 10-20 mmHg)

High risk/contraindicated: PVR >9 WU or TPG ≥15 mmHg. In high risk patients: trial with pulmonary vasodilator in cardiac cath (NO, prostacyclin).

Donor: Size mismatch up to 4:1, good systolic function (EF >50%), serology for EBV, CMV, HIV, HTLV, hepatitis, syphilis, toxoplasmosis


Recipient (MDT decision): metastatic incurable neoplasm, severe sepsis, fixed PHT (consider heart-lung transplantation).

Donor: AIDS, HTLV infection or hepatitis B antigen positive.

Preoperative preparation:

ECG, CXR, FBE, clotting, UECs, BNP, LFTs, ABO, HLA, CMV, EBV, HSV, HIV, VZV, measles, hepatitis serology, ECHO, cardiac cath (PVR, TPG), angio CT, MRI, V/Q scan.


Previously biatrial, now commonly bicaval technique.

Postoperative management:

  • Keep intubated, ventilated, sedated for 24 hrs, (longer with open chest)
  • Inotropes: dobutamine or isoprenaline, milrinone plus adrenaline (despite denervation the donor heart responds well to exogenous inotropes), SNP for increased SVR. Consider potential combination of milrinone and adrenaline 0.05 mcg/kg/min
  • Haemodynamics: age donor/recipient adjusted. Early recovery systolic function. Diastolic function longer impaired (milrinone)
  • Respiratory: normoxaemia, normocapnea, may consider NO for RV afterload reduction
  • Fluid restriction: 1ml/kg/hr
  • Haemostasis

Antibiotic prophylaxis until drains removed. PJP prophylaxis. Ganciclovir if donor CMV positive/recipient negative.


Methylprednisolone 15-20 mg/kg/dose BD for 2 days

Thymoglobulin 1.5 mg/kg/dose OD for 5 days or basiliximab

Consider IVIG 0.4 g/kg/dose OD for 5 days

Calci-neurininhibitor: cyclosporine or tacrolimus (0.05 mg/kg/dose BD) adjusted to level

Mycophenolate mofetil (MMF) 30 mg/kg/dose BD or azathioprine 3 mg/kg/dose OD adjusted to level

Specific problems:

  • Early graft failure: dominant left heart failure requiring mechanical support: retransplantation
  • Right heart failure (especially in setting of preoperatively increased PVR/TPG): iNO, milrinone, dobutamine or adrenaline. Consider mechanical support
  • Low CO: keep paralysed; don’t wean inotropes <24 hrs; pacing (infant 140 bpm, adolescent 100 bpm); consider mechanical assist
  • Acute rejection (rare in the first 7-10 days): LV dysfunction, arrhythmia. Diagnosis: biopsy shows lymphocytic infiltrates. Therapy: methylprednisolone high dose

Longterm morbidity & mortality:

Renal failure, cardiac allograft disease (CAD), lymphoma, neoplasia, PTLD (post transplant lymphoproliferative disease) usually EBV related.

Therapy: temporarily decrease immunosuppression, rituximab


1y: 90%, 5y: 80%, 10y: 70%


[1] Paediatric Heart Transplant Society:

[2] Curr Cardiol Rev. 2011 May;7(2):72-84: Chinnock et al: Heart transplantation for congenital heart disease in the first year of life

[3] Eur J Cardiothorac Surg. 2012 Jun 24. Seddio et al: Is heart transplantation for complex congenital heart disease a good option? A 25-year single centre experience

[4] Curr Treat Options Cardiovasc Med. 2011 Oct;13(5):425-43: Gazit et al: Perioperative management of the pediatric cardiac transplantation patient

[5] Lancet. 2006 Jul 1;368(9529):53-69: Webber et al: Heart and lung transplantation in children

All Marc’s PICU cardiology FOAM can be found on PICU Doctor and can be downloaded as a handy app for free on iPhone or AndroidA list of contributors can be seen here.


Cite this article as:
Marc Anders. Arrhythmias, Don't Forget the Bubbles, 2013. Available at:
  • Prevalence of postoperative arrhythmia: 15-48%
  • At risk: young age, low body weight, long CPB time, complex surgery, presence of residual defects
  • Prevalence of postoperative arrhythmia is up to 50%
  • Haemodynamic impairment in >50%
  • Aggressive treatment in >50% required
  • Most common is sinus bradycardia with/without junctional escape; then premature complexes; then supraventricular tachycardia; then AV block; then JET
  • Mechanisms: re-entry: on/off, inducible, overdriveable, cardiovertable; automatic/ectopic: warm up, not inducible, not overdriveable, not cardiovertable

Prevention and unspecific treatment:

Strict maintenance of normothermia, avoid triggering drugs, avoid volume overload, avoid acidosis, Mg++ >1.0, Ca++ >1.0, K+ 4.5-5 mmol/L


Sinus bradycardia causes: increased vagal tone, elevated ICP, drugs (digoxin, β-blocker, amiodarone, dexmedetomidine), respiratory (hypoxia), metabolic (hypoglycaemia, hyper/hypocalcaemia, hypomagnesiaemia), post-surgical (Fontan circulation, Mustard/Senning)

Sinus bradycardia treatment: correction of underlying cause, atropine 0.02 mg/kg, isoprenaline 0.1-2 mcg/kg/min infusion, pacing (AAI, DDD, DDI)

AV block causes: congenital, increased vagal tone, drugs, respiratory, metabolic, post-surgical (VSD, AVSD, ccTGA, TGA, Fontan circulation)

AV block treatment: correction of underlying cause, pacing (VVI, DDD, DDI)


Sinus tachycardia causes: central (pain, awake, fever, seizure), cardiovascular (hypovolaemia, LCOS, pulmonary hypertension), respiratory (hypoxia, hypercarbia), heart failure

Sinus tachycardia treatment: correction of underlying cause, sedation, fluid bolus, general prevention and treatment

Intraatrial reentry tachycardia (IART ≈ atypical atrial flutter) causes: post-surgical (Fontan circulation, Mustard/Senning, ccTGA, TOF, Ebstein's anomaly, VSD, ASD, TGA)

Intraatrial reentry tachycardia treatment: adenosine (100 mcg/kg IV, increasing up to 300 mcg/kg); overdrive pacing if rate low enough; cardioversion (1 J/kg); amiodarone (loading 25 mcg/kg/hr for 4 hours followed by 5-15 mcg/kg/min infusion for rate control or digoxin (20 mcg/kg IV in infants, 30-40 mcg/kg in children). Titrate for effect. AV reciprocating tachycardia (WPW if preexcitation on baseline ECG).

Atrial ectopic tachycardia (AET ≈ chaotic atrial tachycardia): difficult to control pharmacologically –

  • β -blocker: esmolol (bolus up to 500 mcg/kg IV followed by 100-1000 mcg/kg/min infusion) or propranolol (bolus 10-100 mcg/kg slowly IV)
  • Digoxin, procainamide, flecainide (3-6 mg/kg/day), sotalol (2-6 mg/kd/day), amiodarone
  • Overdrive-pacing if rate low enough
  • Catheter ablation
  • Consider sedation if compromised cardiac output

Atrial fibrillation causes: preexcitation syndromes, post-surgical (ASD, Fontan circulation, AS)

Atrial fibrillation treatment: amiodarone, overdrive pacing, cardioversion (1 J/kg). Consider anticoagulation if persistent >48 hrs

Junctional ectopic tachycardia (JET) (180-250 bpm) causes: congenital, post-surgical (ASD, VSD, AVSD, TOF, Fontan circulation)

Junctional ectopic tachycardia (JET)  treatment: decrease adrenergic drugs if feasible, electrolyte correction (Mg++and K+), sedation and paralysis, overdrive pacing, amiodarone, surface cooling to 35°C to slow heart rate (and allow AV sequential pacing)

Premature ventricular contraction (PVC): < 1/min acceptable, otherwise – treatment of underlying cause. Beta-blocker if clinically indicated.

Ventricular tachycardia causes: respiratory, metabolic (inborn errors of metabolism), drugs (Class I, Class III, digitalis toxicity), anatomical (myocarditis), post-surgical, idiopathic.

Ventricular tachycardia treatment: in anunstable patient – immediate cardioversion (1-4 J/kg) and CPR; correction of underlying cause; amiodarone (loading over 20 mins at 5 mg/kg IV) or procainamide (loading over 30 mins: 10 mg/kg IV), catheter ablation, ICD .

Torsade de pointes (polymorph VT) causes: TCA intoxication, long QT Syndrome, dyselectrolytaemia, see also VT

Torsade de pointes treatment: MgSO4 (0.2 mmol/kg), consider beta-blocker or pacing if recurrent.

Ventricular fibrillation: immediate DC and CPR – resuscitation.


[1] Critical Heart Disease in Infants and Children; 2nd ed, Nichols et al: Arrhythmia

[2] Am J Emerg Med. 2008 Mar;26(3):348-58: O'Connor et al: The pediatric electrocardiogram part II: Dysrhythmias

[3] Anaesth Intensive Care. 2009 Sep;37(5):705-19: Skippen et al: Diagnosis of postoperative arrhythmias following paediatric cardiac surgery

[4] Nat Clin Pract Cardiovasc Med. 2008 Aug;5(8):469-76. Snyder: Postoperative ventricular tachycardia in patients with congenital heart disease: diagnosis and management

[5] Pacing Clin Electrophysiol. 2008 Feb;31 Suppl 1:S2-6: Roos-Hesselink et al: Significance of postoperative arrhythmias in congenital heart disease

[6] Circulation. 2007 Jun 26;115(25):3224-34: Walsh: Interventional electrophysiology in patients with congenital heart disease

[7] Circulation. 2007 Jan 30;115(4):534-45: Walsh et al: Arrhythmias in adult patients with congenital heart disease

[8] Z Kardiol. 2004 May;93(5):371-80: Haas et al: Postoperative junctional ectopic tachycardia (JET)

[9] Circ Arrhythm Electrophysiol. 2010 Apr 1;3(2):134-40: Chang et al: Amiodarone versus procainamide for the acute treatment of recurrent supraventricular tachycardia in pediatric patients

[10] Pediatr Emerg Care. 2007 Mar;23(3):176-85; Manole MD: Emergency department management of the pediatric patient with supraventricular tachycardia

All Marc's PICU cardiology FOAM can be found on PICU Doctor and can be downloaded as a handy app for free on iPhone or AndroidA list of contributors can be seen here.

Microscopic haematuria

Cite this article as:
Ben Lawton. Microscopic haematuria, Don't Forget the Bubbles, 2013. Available at:

A previously well 3-year-old girl presented to your ED with a history of fever. You have confidently diagnosed otitis media and are just about to discharge the child when the nurse mentions a urine was requested at triage and has come back positive for blood.

The nurse asks you what it means if the girl has blood in her urine….

The Bottom Line

  • With a urine dipstick that is positive for blood, the first thing to do is establish whether the finding is real (by microscopy).
  • Remember to look for UTI, hypertension, proteinuria and concerning family history
  • In the absence of red flags on history and examination, no investigations beyond microscopy are required until the microscopic haematuria has proved to be persistent.

What does this finding represent?

Microscopic haematuria is a common finding in the setting of febrile illness. It can be caused by many benign phenomena including adenovirus, ibuprofen, antibiotics including penicillin and indeed by fever itself.

There is always a concern that haematuria represents significant underlying renal pathology but in this circumstance, the risk is extremely small.

What further assessment should you perform and what are you looking for?

Clinical examination and urine microscopy are sufficient at this stage. The following table outlines the major things you should be looking for. There are more sensitive and specific ways of searching for all these findings but in this context, underlying renal disease is pretty unlikely so clinical assessment alone is good enough for now.

The key things to remember are to check for hypertension, proteinuria, UTI and a family history of renal failure.

FindingSuggestive of
Failure to thrivechronic disease process
WTU for proteinglomerulonephritis
WTU for leucs/nitriteUTI
FH renal failureany hereditary nephropathy
FH deafnessAlport syndrome
FH renal stonesfamilial hypercalciuria
Hx infection (2 weeks ago)post strep GN
Hx infection (1-2 days ago)TBMN/IgA nephropathy
bruises/bleedingbleeding diathesis
loin massesWilm’s tumour
oedemanephrotic syndrome

If this is all normal the only investigation required at this stage is urine microscopy and culture to confirm and quantify the presence of blood and determine if the cells are dysmorphic (suggesting a glomerular source of bleeding), This is also the definitive test for a UTI.

Any positive findings from the list above should prompt more sensitive/specific investigation.


So the history, exam and urine microscopy was normal, can I forget about the haematuria?

No, although significant renal disease is unlikely the child should be referred back to their GP for a repeat urinalysis in 2-4 weeks when they are well. If the haematuria has resolved at that time then no further action is required. Persistent haematuria will require further investigation.


So what proportion of kids with microscopic haematuria actually have significant renal disease?

A large study where urinalysis was performed in asymptomatic school children to evaluate its suitability as a screening tool for occult renal disease found the following:

  • Children screened – 7 million
  • Abnormal UA – 1044
  • Isolated haematuria – 719 (of 1044)
  • Biopsy performed (indications for biopsy = severe proteinuria, hypertension, abnormal renal function of a family history of renal disease) – 52
  • Thin glomerular basement membrane nephropathy (benign condition) on biopsy – 33
  • Other defined pathology on biopsy – 16

In other words of 719 children with isolated haematuria, 16 went on to have proven renal disease that warranted further management.

This was a population of well children and you can imagine that in a population of febrile kids, with the benign reasons for having haematuria outlined above, the proportion of kids with significant renal disease as a cause of their microscopic haematuria would be even smaller.


Does a positive dipstick mean there is definitely blood in the urine?

No, false positives on a dipstick can result from haemoglobinuria (e.g secondary to haemolysis) or myoglobinuria. It is also worth remembering that blood in the urine may originate from the vagina or rectum and some causes (e.g. anal fissure) may not be immediately evident on exam). Several things have been reported to cause a red tinge to the urine that may be mistaken for blood.

The following can all cause the appearance of gross haematuria but they should not cause a dipstick to read positive:

  • Drugs – chloroquine, ibuprofen, iron, sorbitol, nitrofurantoin, phenazopyridine, phenolphthalein
    Foods – beets, blackberries, food colouring metabolites
    Other – bile pigments, homogentisic acid, melanin, methemoglobin, porphyrin, tyrosine, urates

Microscopy should be able to confirm that the blood is for real.



McTaggart S. Childhood Urinary Conditions. Aust Fam Phys 2005; 34:937-41.

Park YH, Choi JY, Chung HS, et al. Hematuria and proteinuria in a mass school urine screening test. Pediatr Nephrol 2005; 20:1126–1130.

Quigley R. Evaluation of hematuria and proteinuria: how should a pediatrician proceed? Current Opinion in Pediatrics 2008, 20:140–144.

Rees L, et al. Oxford Specialist Handbooks in Paediatrics: Paediatric Nephrology, Oxford University Press. 2007. p18-19.

Febrile neutropenia

Cite this article as:
Henry Goldstein. Febrile neutropenia, Don't Forget the Bubbles, 2013. Available at:

You’re working as the paeds reg overnight at a regional centre when ED phones you about an incoming patient – Josef, 8 – who’s in a delayed intensification cycle of his treatment for ALL and has a fever of 38.6oC. Josef’s last chemotherapy was last week, and an FBC done 2 days ago showed WCC 4.0×109/L with an absolute neutrophil count 0.9×109/L.


Bottom Line

  • Fever in the setting of neutropaenia may be the only herald of a severe, potentially life-threatening infection.
  • Febrile neutropenia is an oncologic emergency.
  • A thorough history and physical examination are essential in cases of febrile neutropaenia.
  • Find and follow your local protocol and discuss it with a senior early.
  • Isolate the child to reduce the chances of further infection.


Why is fever in an oncology patient dangerous?

Febrile neutropaenia may be the only feature of a life-threatening infection, a major cause of morbidity and mortality in paediatric oncology patients. A 2005 study of over 12000 children established a mortality rate as high as 3%. Around 1 in 5 children will have microbiologic evidence of infection during induction chemotherapy, and this number jumps to ~40% if the fever returns upon ceasing antibiotic therapy.


You move Josef to a resus bay with isolation (and cytotoxic) procedures in place. He is febrile to 38.6oC, mildly tachycardic but normotensive. You do not identify an immediate threat to life after considering shock, overwhelming sepsis, respiratory compromise.  You take a thorough history and examine Josef.


What is the criteria for febrile neutropenia?

Fever is any temperature >38.5°C, or >38.0°C for one hour.

Neutropenia is an absolute neutrophil count  <0.5×109/L, or <1×109/L with a predicted decline to less than 0.5×109/L within 48 hours.

What are the specific features of the history?

What is the child’s oncology diagnosis and where in the treatment course are they? Different chemotherapeutic agents have relatively stronger myeloablative effects, leading to more fulminant and predictable neutropenia. As chemo agents vary with diagnosis and cycle, it’s important to clarify which medications have been given and the number of many days since last chemotherapy.

Compliant with antifungal & pneumocystis prophylaxis? Think about PCP pneumonia in any oncology child presenting with work of breathing.

What kind of central venous access +/- last accessed? Central venous access is a double-edged sword – an essential access for chemo that allows a reduction in the number of peripheral venipuncture, but also the most common source of bacterial infection in chemo kids.

Sick contacts? Remember, just because your patient has an oncology diagnosis doesn’t mean they don’t catch other age-appropriate illnesses, like gastroenteritis, upper respiratory infections and the like. Of course, they’re often more severe, but it’s important to look!


Specific features on examination?

Examine for signs of dehydration, sepsis and anaemia.

Examine the central line site. A good time to look is when the line is being accessed for cultures. Check the age of the dressing and note any erythema or cracks in the line.

Look at the skin all over.

Examine as for a fever without source.

Have a good look in the mouth – mucositis is common and a possible entry site.

Likewise, the perianal area is susceptible to skin breakdown, with or without perianal abscesses.

Take particular note of any areas of erythema.


Why is skin erythema of particular importance?

It’s worth considering the pathophysiology of erythema; local inflammatory mediators (IL-1, IL-6, TNFa) signal neutrophils to marginate, roll and undergo diapedesis to the area of action. But in the absence of a full neutrophil response, any localized erythema will likely be reduced, and pus not formed in the usual volume.

Thus, the smallest area of erythema should be considered as a possible source for infection, especially around central access sites or surgical wounds.


Which investigations are indicated?

FBC (are they actually neutropaenic?)

Blood culture (central lines/PICC)

Urea & electrolytes, consider calcium, magnesium, phosphate (dehydration, renal dysfunction, tumor lysis syndrome)

Liver function tests (liver dysfunction secondary to chemotherapy agents)

Urinalysis (clean catch)

CXR if increased work of breathing, poor SpO2

Nasopharyngeal aspirate if rhinorrhoea (make sure the PLT >50×109/L beforehand)

Consider coagulation profile

Focused investigations as per history and examination

Stool sample if diarrhoea, with C. difficile toxin if on recent antibiotics


IV access is gained, via Josef’s tunneled central line, by an experienced staff member. Bloods are sent for FBC, culture and UEG, LFT, Ca/Mg/PO4, coags.


What is the management?

Most hospitals have well-established protocols for the treatment of febrile neutropenia. Be aware of where to find yours and the choice of anti-infective agents.

Start antibiotic treatment promptly; it may be life-saving. This is not a time to faff about waiting for the results of investigations as antibiotics are the treatment irrespective of any preliminary results.

Some protocols advise anti-fungal treatment in addition to antibiotics. These protocols will vary between centres and over time with changing resistance patterns.

Remember to discuss your patient with the oncologist on call; these kids will usually need admission and, on occasion, transfer to the tertiary oncology centre.

Antibiotics are the mainstay of treatment in febrile neutropaenia. Miadema and her Dutch colleagues are presently undertaking a Cochrane Review of intravenous vs oral empiric treatment of febrile neutropaenia.

The Therapeutic Guidelines currently recommends:

Piperacillin+tazobactam 100+12.5mg/kg (Max 4+0.5g) IV q8h

or cefipime 50mg/kg (Max 2g) IV q8h

or ceftazidime 50mg/kg (Max 2g) IV q8h

If you have a suspicion of MRSA, central line infection or haemodynamically unstable, add vancomycin. Gentamicin or amikacin may be indicated.

Treat dehydration with the appropriate fluids and if the child is nauseated or vomiting, antiemetics.



Basu, K et al. Length of stay and mortality associated with febrile neutropenia among children with cancer. J Clin Oncol. 2005 Nov 1;23(31):7958-66.

RCH Melbourne CPG – Febrile Neutropenia 

Management of Fever in the Paediatric Oncology Patient v3.0 17102012 Febrile Neutropenia Protocol QPHON QCCC

Miadema et al. [Protocol] Empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients. Cochrane Library.

Lehrnbecher, T. Guideline for the Management of Fever and Neutropenia in Children With Cancer and/or Undergoing Haematopoetic Stem-Cell Transplantation. JCO Dec 10, 2012, vol. 30, no 35 4427-4438

Afzal, S. et al. Risk Factors for Infection-Related Outcomes During Induction Therapy for Childhood Acute Lymphoblastic Leukemia, The Pediatric Infectious Disease Journal • Volume 28, Number 12, December 2009 pp 1064-68

Therapeutic Guidelines : Antibiotic. Severe Sepsis: empirical therapy (no obvious source of infection): febrile neutropenic patients. Therapeutic Guidelines Group. Revised June 2010. (etg40 July 2013) 


ITP – Idiopathic Thrombocytopenic Purpura

Cite this article as:
Tessa Davis. ITP – Idiopathic Thrombocytopenic Purpura, Don't Forget the Bubbles, 2013. Available at:

A 4-year-old girl presents with bruising over her legs, trunk and face.  Mum has noticed them appear over the last week.  She has been completely well with no other symptoms.  There is no history of trauma.  After an anxious 1 hour wait, the bloods are back-Hb 113, WCC 7.3, Plt 8 x 109/L.


Bottom Line

  • Uncomplicated idiopathic thrombocytopenic purpura (ITP) is new-onset bruising and bleeding with a platelet count <100 x 109/L in the absence of other symptoms
  • It generally resolves itself in 80% by six months
  • 5% will have a recurrence
  • Only treat if there is active bleeding, not just because of a low platelet count
  • Advise parents to avoid NSAIDS and lookout for signs of bleeding
  • Follow up regularly for the first six weeks or until platelet count stabilises


What is it and how did she get it?

Idiopathic thrombocytopenic purpura (ITP) is a reduction in platelet count in the absence of any other cause (<100 × 109/L).  Whilst normal platelets last eight to ten days, in ITP there are autoantibodies that destroy them in the first few hours. It has a peak incidence of two to five years of age (chronic ITP peaks in adolescence).  There is often a recent history (one to six weeks) of a viral illness or immunisation.

What are the commons symptoms and signs?

The most common sign is petechiae (1-5 mm red or purple non-blanching spots) on the skin or mucosa – these indicate capillary haemorrhages.  Some mucocutaneous bleeding is often seen, but it is rare for this to be severe (<5%).

Other symptoms of autoimmune disorders should NOT be present in ITP – e.g. no weight loss, rashes, alopecia, joint swelling. The examination should be normal with no hepatosplenomegaly or lymphadenopathy.

How is it diagnosed?

It is diagnosed by having a low platelet count with a normal haemoglobin (unlike in leukaemia, TTP, HUS and DIC). If there is a history of previous bleeding then consider other diagnoses. Bone marrow aspirate is only recommended if there is persistent bleeding in spite of a platelet count >20 × 109/L.


What treatment should we use?

The answer is simple: treat the patient not the platelet count.  Assess if the patient has haematuria, melaena, menorrhagia, epistaxis, mucosal bleeding or tonsillar purpura/petechiae.

Although there is variation between specialists, they will all be more concerned with the signs of wet purpura or haematuria rather than just the petechiae on the skin.


Prednisolone 1-2mg/kg OD for at least three weeks then taper


Methylprednisolone 30mg/kg/day for three days, then 20mg/kg /day for four days


IVIG (intravenous immunoglobulin)

Consider where there is significant bleeding (0.8-1g/kg) – can rapidly raise the platelet count Effects takes place in one to five days and lasts for two to four weeks



Only give platelets if there is an intracranial hameorrhage (ICG) or significant bleeding.  Can be effective after IVIG administration and this can prolong platelet survival (otherwise transfused platelets are quickly destroyed)


When to admit?

Admit if there is significant bleeding: epistaxis>1 hour; haematemesis; haemoptysis, intracranial haemorrhage, melaena.  Or if there is an unclear diagnosis or problematic social circumstances.

When will it go away?

Most ITP self resolves.  80% will have resolved by six months (with or without treatment).  5% of ITP patients will have a recurrence. Although it seems counterintuitive, the lower the platelet count at the beginning, the better.  Uncomplicated ITP normally has a platelet count of <20 × 109/L. Chronic ITP does not resolve within six months and accounts for 10% of ITP.

Could it be anything else?

Confirmation is based on excluding other differentials such as acute leukaemia, aplastic anaemia, HUS.  A full blood count and film us usually adequate to make the diagnosis.

What do you need to inform the parents to look out for?

While the platelets are low, the patient is at risk of bleeding.  ICH is a serious but rare (1%) side effect.  Parents should watch out for any signs of ICH, urinary bleeding, GI bleeding, excessive mucosal bleeding and menorrhagia (in older patients).

They should avoid NSAIDs while the platelet count is low.

Older children should avoid contact sports.  This is completely impractical for young children so is not helpful advice – will only stress out the parents!

When to follow up?

Patients should be reviewed within two weeks of initial presentation and have a repeat FBC. Aim for weekly GP follow up initially and then PRN until resolution.

Paediatric outpatient review at six weeks three months and six months. Refer to haematology if unclear diagnosis, unresolved after six months or a haematological malignancy is suggested by the blood count.


Selected references

Pediatric EM Morsels – Wet purpura and ITP

UMEM Educational Pearls – ITP

Royal Children’s Hospital, Melbourne – Guidelines for ITP

Princess Margaret Hospital for Children – ITP Guideline

BMJ BestPractice – ITP

Grainger JD, Rees, JL, Reeves M, Bolton-Maggs PHB.  Changing trends in the UK management of childhood ITP. Arch. Dis. Child. 2012;97:8-11.[/toggle]


Cite this article as:
Henry Goldstein. Pertussis, Don't Forget the Bubbles, 2013. Available at:

Winston, a 4-month-old boy, presents to your emergency department after his mother noticed, during his last feed, that he appeared to stop breathing for around 15 seconds and turned blue.

He restarted breathing spontaneously. Further history reveals a two-day history of feeding difficulties, cough, irritability, and rhinorrhoea. He has also had a low-grade temperature (37.8 0C). There has been no diarrhoea and a few vomits, but only after coughing. He has no rashes. His oral intake has been reduced to about half normal, for the last 24 hours.


Bottom Line

  • Have a low threshold for suspicion in any child with a prolonged cough, especially those incompletely immunized
  • Pertussis has a non-typical presentation in infants
  • In clinically or laboratory diagnosed pertussis, antibiotics do not reduce the severity or frequency of coughing paroxysms.
  • Antibiotics do render the child noninfectious
  • Due to the high risk of morbidity and mortality in infants less than six months of age who are incompletely immunized, contact prophylaxis is recommended for families who have an infant less than six months of age


Further Assessment

Birth History

Winston was born at term weighing 3700g. Apgars were 91, 95 after an SVD without any risk factors for sepsis. His well neonate check and six week GP reviews were unremarkable. He is exclusively breastfed. He is up to date with his immunizations.

Family History

Of note, Winston’s 11-year-old brother has had two weeks of rhinorrhoea and cough but is clinically well.


You see a slightly tachypnoeic, thriving 4/12 male. Chest clear. Mildly dehydrated. Irritable. Normotensive fontanelle. No rashes. No focal findings on the chest. Unremarkable cardiovascular and abdominal examinations. ENT; TMs are mild erythematous bilateral without effusion, tonsils are also mildly erythematous, not overly enlarged.


What is the most concerning feature of this history?

Apnoea – apnea is a particularly concerning feature in infants.


What are your differentials and most likely diagnosis – why?

Whooping cough, caused by Bordetella pertussis, a gram-negative coccobacillus whose only reservoir is humans. It’s transmitted by respiratory secretions, particularly in the first few weeks after exposure.

Clinically, pertussis classically progresses in three stages.

  • Firstly, the catharrhal phase which consists of one to two weeks of nonspecific symptoms.
  • This is followed by the paroxysmal phase, in which the characteristic ‘whoop’ sound at the end of a coughing paroxysm may be heard (infants and older children are less likely to have typical whooping cough).
  • Finally comes the convalescent phase in which the coughing paroxysms become less frequent and less severe.

Notably, infants may manifest pertussis infection only as feeding difficulties, cough or apnoeas. Also, immunized children may manifest a more attenuated illness that doesn’t demonstrate the classic three phases of illness.


How is it diagnosed?

Laboratory diagnosis is by nasal swab or nasopharyngeal aspirate showing PCR positive for Bordetella pertussis.

Additionally, when considering which children to swab, there was a distinct paucity of evidence. There were several comparisons of PCR vs culture, but no firm criteria about who should score an NPA or flocked swab in the first place.

The US CDC recommends: “Early diagnosis and treatment might limit disease spread. When pertussis is strongly suspected, attempts to identify and provide prophylaxis to close contacts should proceed without waiting for laboratory confirmation. When suspicion of pertussis is low, the investigation can be delayed until there is laboratory confirmation of the diagnosis. However, prophylaxis of infants and their household contacts should not be delayed because pertussis can be severe and life-threatening to young infants.”

Ditte & colleagues’ excellent (but quite technical) 2004 article investigated a sample size of 3096 patients, swabbed for suspected pertussis.

PCR was superior for detection in patients aged 6 months – 3 years and was highly sensitive for the diagnosis of pertussis.

Also of note, pertussis serology may be of use to confirm diagnosis around the time a patient enters the catarrhal phase, but will unlikely change management as discussed above.


Who is at most risk?

Infants under six months have the highest mortality from pertussis; the mortality rate is estimated at around 1%, with 80% of these deaths occurring in infants under 2 months. Comorbid apnoea, pneumonia, and seizures may complicate pertussis infection. Less commonly, a leukocytosis >50,000×109/L or encephalopathy potentially caused by pertussis toxin may occur and is associated with a poor prognosis.



Let’s have a look at the evidence around antibiotic management of whooping cough as well as the indications for prophylaxis. This Cochrane review (assessed as up to date in Jan 2011) is the basis for a number of current guidelines.

Altunaiji SM, Kukuruzovic RH, Curtis NC, Massie J. Antibiotics for whooping cough (pertussis). Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004404. DOI: 10.1002/14651858.CD004404.pub3.

The review looks at 13 RCTs regarding the efficacy of antibiotics for treatment & prophylaxis of pertussis. Eleven trials looked at treatment and had the following objectives:


Do antibiotics achieve microbiological eradication of B. pertussis?

  • Multiple studies showed a number of agents successfully eradicating b. pertussis, including erythromycin, oxytetracycline.
  • Azithromycin and clarithromycin as macrolides equivalent to erythromycin has been shown effective at eradicating B. Pertussis.
  • A number of head to head studies showed no superior agent. However, a 1997 study showed roxithromycin was two to four-fold less effective at B. pertussis eradication vs erythromycin.

Do antibiotics improve the clinical illness of whooping cough?

  • No difference in mortality.
  • With regard to clinical cure/ remission; erythromycin ethyl succinate (EES) vs erythromycin estolate. Patients judged they were equivocal re: frequency of cough, and that erythromycin estolate was slightly superior to EES, regarding clinical cure / remission.
  • Erythromycin & azithromycin had no relapses after proven negative culture post-treatment.

What is the appropriate dose and duration of therapy?

  • There was no benefit for a prolonged course of antibiotics vs a standard course.

What are the side effects profile of antibiotics used to treat whooping cough?

  • Regarding side effects, azithromycin 3/7 was superior to erythromycin ethyl succinate 14/7 and clarithromycin 7/7 was superior to erythromycin estolate 14/7
  • Compliance was best for azithromycin vs erythromycin estolate and clarithromycin vs EES

Additionally, Honien et al (1999) describe seven cases of infantile hypertrophic pyloric stenosis in a cohort of 200 neonates treated with erythromycin; a significantly increased risk or IHPS in this population.



Two trials (401 patients in total) reviewed prophylaxis:

Do antibiotics achieve microbiological eradication of B. pertussis?

As for treatment, above.

Do antibiotics prevent the clinical illness of whooping cough?

  • slightly less” but not statistically significant frequency of whooping cough, paroxysms in household contacts of the prophylaxis arm.
  • slightly lower” but not statistically significantly lowered attack rate in prophylaxis groups.

The appropriate dose and duration of therapy?

As for treatment, above.

The side effects profile of antibiotics used for prophylaxis of whooping cough?

  • Placebo was better than erythromycin estolate for compliance and side effect profile.

Of note, erythromycin estolate is not available in Australia.

The reviewers commented on the marked heterogeneity of studies with regard to the outcome measures and definitions. They note that treatment renders patients noninfectious but does not alter the clinical course. Consequently, they make the following recommendations.

The best regimens for microbiological clearance, with fewer side effects, are:

  • three days of azithromycin (10 mg/kg as a single dose);
  • five days of azithromycin (10 mg/kg on the first day of treatment and 5 mg/kg once daily on the second day to fifth days of treatment); or
  • seven days of clarithromycin (7.5 mg/kg/dose twice daily).

Seven days of trimethoprim/sulphamethoxazole (20 mg trimethoprim with 100 mg sulphamethoxazole per dose, twice daily, for children under six months of age; double this dose for older children) appears to be effective in eradicating B. pertussis from the nasopharynx and may serve as an alternative antibiotic treatment for patients who can not tolerate a macrolide.

Additionally, in Australia, a pertussis booster vaccine is recommended for close household contacts of newborns; this advice is part of a neonatal discharge check within the hospital.


Antibiotics for prophylaxis against whooping cough – summary

There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts. Prophylaxis with antibiotics was significantly associated with side effects and did not significantly improve clinical symptoms, whoop, paroxysmal cough, number of cases who develop culture-positive B. pertussis or paroxysmal cough for more than two weeks in contacts older than six months of age. Due to the high risk of morbidity and mortality in infants less than six months of age who are incompletely immunized, contact prophylaxis is recommended for families who have an infant less than six months of age. The recommended antibiotics and dosages for contact prophylaxis are the same as those recommended in the treatment of whooping cough.

Additionally, the American CDC guidelines written in 2006 were reviewed more recently and not rewritten. They were published prior to the 2007 Cochrane Review.



Altunaiji SM, Kukuruzovic RH, Curtis NC, Massie J. Antibiotics for whooping cough (pertussis). Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004404. DOI: 10.1002/14651858.CD004404.pub3.

Chan MH et al. The California Pertussis Epidemic 2010: A Review of 986 Pediatric Case Reports From San Diego County J Ped Infect Dis (2012) 1 (1): 47-54 doi:10.1093/jpids/pis007 Accessed 24/06/2013.

Ditte MD, Dohn B, Madsen J, Jensen JS, Comparison of culture and PCR for detection of Bordetella pertussis and Bordetella parapertussis under routine laboratory conditions. J Med Microbiol August 2004 vol. 53 no. 8 749-754.

Faulkner A, Skoff T, Martin S, Cassiday P, Lucia Tondella M, Liang J, Ejigiri OG, Surveillance Manual, 5th Edition, 2011 Pertussis: Chapter 10-1. 8 July 2011. Accessed 09/07/2013.

Snyder, J & Fisher, Pertussis in Childhood. Pediatrics in Review Vol. 33 No. 9 September 1, 2012 pp. 412 -421 (doi: 10.1542/pir.33-9-412).