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Cerebral oedema

Clinical, Emergency medicine, General paediatrics, Neurology

Cytotoxic vs vasogenic (resistant to steroids) vs interstitial (obstruction eg meningitis – not steroids, ?osmotic) vs osmotic (CSF, ECF low osmo) vs hypertensive.

In DKA, there is a 25% mortality from cerebral oedema, 34% long term neurodisability. 

Presents with headache, irritability, agitation (which can be difficult when child is unwell with something else).  Then altered consciousness, posturing, focal neurology (check eye movements, pupils).  Classically Cushing’s triad: hypertension, bradycardia, irregular breathing pattern.

Clinical diagnosis really.  CT can show (better than MRI!).

Hypertonic saline (2.7 or 3%, 2.5-5ml/kg over 10-15 mins) or mannitol (20%, 0.5-1g/kg over 15 mins), some people prefer hypertonic saline but whatever is closest to hand!  Frusemide adjunctive.   

Consider Aciclovir if diagnosis unclear (in case herpes encephalitis – CT not great, LP can be non specific).

Brain protection = 30deg head up, midline position. Avoid hypotension. Avoid hypocapnia (intubate and ventilate if in doubt).

Hyponatraemia common – typically due to SIADH but treat any underlying cause, esp hypovolaemia.

Constipation

Common, Gastro, General paediatrics, OPD, Psychology

Consider constipation if:

  • episodes of faecal incontinence (stains or smears in pants, potentially larger accidents),
  • retentive posturing (standing or sitting with their legs straight and stiff or crossed legs, some will sit on their own heel),
  • occasional massive but soft stools that virtually obstruct toilet.

Not just hard painful infrequent stools! Beware also dyschezia, where baby appears to strain at stool but not actually hard/large.

In a population-based prospective birth cohort, where dietary types were extracted from questionnaire, adherence to a ‘Western-like’ dietary pattern was associated with a higher prevalence of constipation up to 48 months [aOR 1.39; 1.02-1.87], which was not mediated by overweight or sedentary behaviour. Adherence to a ‘Health Conscious’ dietary pattern was only associated at short term, with a lower prevalence of constipation at 24 months (aOR; 0.65; 0.44-0.96). This suggests that specific dietary patterns in early childhood could be associated with higher or lower risks for constipation, but these effects are time-dependent. [Maternal & Child Nutrition. 9(4):511-23, 2013 PMID: 22288911]

Straining is not a criteria, in NICE, interestingly, although it is in Rome III criteria!

Red flags:

  • multiple anal fissures,
  • gross abdo distension,
  • tenderness with guarding,
  • abnormal lumbosacral or lower limb findings,
  • failure to thrive
  • ribbon like stools (?anal stenosis)
  • etc

“Do not use dietary interventions alone as first-line treatment for idiopathic constipation” – because no evidence that it helps! But yes, adequate hydration and fibre important (whole grains, fruit/veg, pulses).

NICE recommends Movicol/Laxido (macrogol) as first line, combining with a stimulant (picosulfate, biscodyl, senna) as second line. If macrogol not tolerated, use stimulant +/- softener (lactulose, docusate).

Warn that pain and soiling gets worse before getting better!

Review of adherence and dose important.

Toilet training eg diary, reward system, regular post prandial sitting 5 mins +/- feet on hard surface eg stool.

“Poo should be as soft as toothpaste and should come out like a snake” (Snakes and ladders booklet, Kidney Kids Scotland). Tell your teacher if no toilet paper/soap or broken seat/locks etc.

Soiling

Typically, episodes of soiling (large and small) are due to overflow of liquid stool past a large impacted stool in the rectum.  The child is unable to control, due to the distortion of the rectum.

However, children often try to deny being aware of soiling, despite the obvious smell or discomfort – this is simply a coping method, and normal sensation is usually easy to demonstrate.

The diagnosis is easier in the presence of a large suprapubic mass, or a rectal mass on digital examination.  Some children however soil for attention, without any bowel or rectal disorder.

The presence or implication of a large rectal mass requires disimpaction – an escalating regimen of a paediatric formulation of macrogol (Laxido or Cosmocol are cheaper than Movicol) as per NICE guideline 99 (doses and licensing may differ from product literature):

  • Child under 1 year: ½-1 sachet daily (non-BNFC recommended dose)
  • Child 1-5 years: 2 sachets on 1st day, then 4 sachets daily for 2 days, then 6 sachets daily for 2 days, then 8 sachets daily (non-BNFC recommended dose)
  • Child 5-12 years: 4 sachets on 1st day, then increased in steps of 2 sachets daily to maximum of 12 sachets daily (non-BNFC recommended dose)
  • If macrogol not tolerated, use stimulant laxative eg picosulfate +/- lactulose

If no progress after 2 weeks add stimulant laxative eg senna, picosulfate, bisacodyl, docusate.

Enemas eg citrate can prevent megarectum where prolonged medical treatment fails.

Polyethylene glycol licensed for distal intestinal obstruction!?

Maintenance

I suggest half disimpaction dose for maintenance.

Preferred treatment is paediatric formulation of macrogol (Laxido or Cosmocol are cheaper than Movicol) as per NICE guideline 99 (doses and licensing may differ from product literature).

  • Child under 1 year: ½–1 sachet daily (non-BNFC recommended dose)
  • Child 1–6 years: 1 sachet daily; adjust dose to produce regular soft stools (maximum 4 sachets daily) (for children under 2, non-BNFC recommended dose)
  • Child 6–12 years: 2 sachets daily; adjust dose to produce regular soft stools (maximum 4 sachets daily)
  • If macrogol not tolerated, use a stimulant laxative eg sodium picosulfate (5mg/5ml, NICE recommended doses):
    • Child 1 month to 4 years: 2.5–10 mg once a day
    • Child/young person 4–18 years: 2.5–20 mg once a day
    • Add lactulose or docusate if stools hard

For babies, Senna and lactulose from age 1/12.

At least 3/12 of maintenance before weaning if disimpaction required initially.

I always highlight that laxative use does not induce dependency, rather, that chronic constipation is unlikely to improve without adequate treatment.

Review regularly – symptoms, toileting, taking medication.

Continue maintenance treatment until regular bowel habit established for at least a few weeks or until toilet trained. Do not stop dose abruptly.

General advice re balanced diet including fruit, vegetables, high-fibre bread/breakfast cereals, baked beans, regular toileting, exercise, sufficient fluid intake (1000-1400ml age 4-8yrs, 1200–2100ml age 9–13yrs).

Involve Health Visitor in pre-school group.

Consider trial of milk exclusion (to rule out cow’s milk protein allergy if intractable (ESPGHAN 2023).   Coeliac disease, hypothyroidism, cystic fibrosis, Hirschsprung’s disease and hypercalcaemia also come into the differential.

Surgery

Rectal biopsy indicated if delayed meconium at birth (ie >48hrs), Downs, enterocolitic episodes.

Anal fissures have high spontaneous healing rate with medical treatment.

Manual evacuation under GA may be required if resistant. No benefit on RCT for anal dilatation. Small RCT found botox as good as internal sphincter myectomy for refractory constipation.

Appendicostomy or caecostomy antegrade colonic enema (where bowel irrigated using catheter) has a role in refractory cases after age 6yrs. QOL, continence improve but appreciable morbidity.

Relapses more common in boys, under age 4, background of psychosocial or behavioural probs, encopresis. 1/3 of post pubertal children continue to have severe problems.  See also parenting and constipation.

Parent information

ERIC website – www.eric.org.uk

[NICE clinical guideline 99 – constipation in children and young people (Published 2010)]

[BMJ 2012]

Chronic fatigue syndrome

General paediatrics, Mental health, Neurology, OPD, Psychology, Rheumatology

NICE update 2021 a bit depressing:

  • Therapy based on physical exercise should NOT be offered “as a cure”, nor should graded exercise programmes (which by definition use fixed increments in exercise) be used!
  • Instead, self management, flexible and tailored
  • CBT should only be offered to manage symptoms, improve functioning and reduce distress.
  • Talks about “energy management” – includes emotional, social, cognitive.
  • “Care and support plan” – physical activity including mobility but also activities of daily living.  Plan periods of rest and activity, and incorporate the need for pre-emptive rest.  Management of relapses and flares.

Main thrust of update is that CFS/ME is a complex, chronic medical condition affecting multiple body systems and its pathophysiology is still being investigated. It affects everyone differently and its impact varies widely – for some people symptoms still allow them to carry out some activities, whereas for others they cause substantial incapacity.  It is a fluctuating condition in which a person’s symptoms can change unpredictably in nature and severity over a day, week or longer.

Often it profoundly affects different aspects of the lives of both people with ME/CFS and their families/carers including social life, emotional wellbeing and education.

Another big theme is prejudice, disbelief and stigma experienced by patients.

US IOM expert panel have rejected the name “chronic fatigue syndrome”, as patients hate it!  Myalgic encephalitis (ME) also rejected on basis of insufficient evidence that this is the pathological process.  They suggest “Systemic exertion intolerance”, which is probably even more rubbish, in my opinion.

Diagnostic criteria: all of the following 3 [BMJ 2015; 350]

  1. Substantial reduction/impairment in pre-illness levels of activity, that persists for more than six months [NICE 2007 says 3/12 for children], and accompanied by fatigue (often profound, new or definite onset, not the result of ongoing excessive exertion and not substantially alleviated by rest)

  2. Worsening of symptoms after any type of exertion (including cognitive and emotional stress) – “post-exertional malaise“

  3. Unrefreshing sleep, and/or sleep disturbance.

In addition, should have at least one of:

  • Cognitive impairment

  • Orthostatic intolerance.

Doesn’t mention chronic pain?! NICE says reconsider diagnosis in absence of cognitive difficulties or chronic pain.

Causes

Evidence (reproducible) implicating certain infections as a trigger. Co-existing mood disorder in substantial proportion of patients, sometimes sleep-wake disorder – likely to perpetuate/exacerbate.

Brain imaging has identified alternations suggesting that it is a brain problem.

Investigations

[NICE 2007]

  • Urinalysis
  • FBC, LFTs
  • TFTs
  • Coeliac disease screening
  • CK
  • ESR/CRP
  • Glucose
  • Ferritin

NOT microbiology unless indicated: borrelia, HIV, Hepatitis viruses, EBV, CMV, toxoplasmosis

Management

Exercise

Cochrane review of graded exercise therapy – may benefit sleep, physical function, self-perceived general health, and no evidence that it worsens outcomes. Curiously, no evidence for loss of aerobic fitness! Perhaps graded exercise tackles a hyper-reactive CNS response to exercise-related physiological signals. Note that fear of physical activity becomes conditioned when it commonly exacerbates symptoms.

Warn that exercise programmes can make things worse rather than better. Exercise should only be done as part of supervised programme, with physiotherapist – don’t just tell them to go the gym more! Start below baseline activity level.

Other

Relaxation techniques recommended by NICE.

CBT – should only be offered to manage symptoms, improve functioning and reduce distress.  Again, not a “cure”. Analysis of both CBT and graded exercise suggests that benefit comes from reducing inactivity.

Sleep hygiene important.  Include rest periods in plan but avoid day time naps, especially since sleep doesn’t usually help anyway!

Many people find exclusion diets useful, esp bowel symptoms, not recommended but involve dietician if attempted anyway.

Equipment to maintain independence can improve quality of life and should be part of overall management.

Beware boom-bust! Many patients over do it when they have a period of relative wellness. Flares and relapses are to be expected.  Trigger? New medical problem? Adjust plan as necessary.

Pain and orthostatic intolerance are big issues for some people.

Severe CFS can increase risk of pressure ulcers, DVT, vitamin D deficiency and contractures.

Prognosis

Important to be honest at time of diagnosis.  More optimistic in young people.  Most adults improve, some are able to return to usual activities but others experience long term symptoms or relapse.

PACE trial aimed for less than full restoration of health as “recovery”, future trials should use clinically relevant improvement and patient self-perception.

[bmj 2015;350:h2087]

[NICE 2021] 

2010 Scottish Good Practice statement needs update.

National Review of asthma deaths

Common, General paediatrics, Respiratory

2014 Report (adults and kids) finds that routine asthma care, management of previous and final attacks is generally poor, but particularly for children cf adults.

Almost half did not seek medical help before death. 10% deaths within 1 month of discharge from hospital for asthma. Many being treated for mild/mod asthma, but review suggested prob poorly controlled severe asthma. Widespread over reliance on reliever inhalers and underuse of preventers. Overall 39% had used more than 12 blue inhalers in the year before death. 80% of deaths did not get 12 preventer inhalers in the previous year. Nearly half had not had an asthma review in previous year.

Poor follow up of previous severe attacks (but only about 20% had been in A&E in the previous year).

Delays in primary and secondary care in about a 1/3 of final attacks.

In 93% children and young people, one or more avoidable factors relating to patients, their families and their environment: eg exposed to smoke or smoked,  allergy,
Poor recognition of risk of adverse outcome from asthma.

Recommendations

Any patient prescribed more than 12 relievers in a year should have urgent review. Follow up should be made after every ED attendance for asthma. Every hospital discharge should have hospital outpatient follow up.

Should have personal asthma action plan (PAAP).

Better education on when to use asthma medication, recognise poor control, how/when to seek emergency advice.

For parents/patients

Triple A online test!

See GP within 48hrs of discharge.

Associations with depression and anxiety. Obesity mentioned.

Hereditary angioedema

General paediatrics, Immunology

=C1 esterase inhibitor deficiency.  Acquired angioedema seen, esp ACE inhibitor associated acquired AE, more common in blacks and transplant patients.

Sense of smell is impaired in HAE, correlates with complement levels!

Angioedema is bradykinin mediated, hence why different from urticaria and not responsive to antihistamines, steroids etc.

Prothrombin fragment F1 and 2 plus D-dimer levels have diagnostic value in acute attacks.

Consensus algorithm in 2010 (more recent American viewpoints).

Clinical

Recurrent circumscribed, non-pruritic, non-pitting oedema. Not usually painful unless a pressure area. Can affect virtually anywhere but typically extremities.   Upper respiratory tract involvement eg tongue, pharynx and larynx accounts for the reported 15–33% mortality. Abdominal pain with vomiting are dominant symptoms in approximately 25% (intestinal wall and mesenteric oedema).

Urticaria is not a feature of C1 INH deficiency. However, prodromal “serpiginous” erythema has been reported in up to 25% of patients which may be mistaken for urticaria or even cellulitis.

Classically, oedema develops gradually over several hours, continues to progress slowly for 12–36 hr, and then subsides after 2–5 days. Sudden onset abdo pain without visible oedema can occur, with or without diarrhoea.

Attacks can be once a year in some, weekly in others.  Triggers are trauma including dental work, surgery; infection; emotional stress; drugs eg OCP, ACE inhibitors (which can cause oedema without HAE, of course).  Can present under 1yr of age.  Laryngeal attacks tend to come later in life (rarely under age 3).  Gets worse with puberty.

Good dental hygiene important in prevention!

Diagnosis

Testing under age 1 unreliable so always repeat.  Baseline C4 is low in 98% of cases so good screening test – if normal during attack then review diagnosis!  No need for CH50.

Low C1 inhibitor suggests type 1 HAE.  Acquired is possible in people over 40 without family history, C1q low in these cases.

If normal C1 inhibitor but strong clinical suspicion, do C1 inhibitor functional assay to look for type 2 HAE.  If still normal, repeat testing during attack.

Type 3 HAE has normal C1 inhibitor and function – mainly women.  Due to Factor XII gene mutations and others.

Genetic testing (SERPING1) may be useful where these tests not conclusive.

Acute attacks

Human pdC1-INH (Berniert, Cinryze else Conestat-alpha which comes from transgenic rabbits) is recommended for all attacks (for adults and children). Not licensed for acquired? Beware rabbit allergy!?

  • “Wait and see” is only an option for attacks not involving the face, neck, or abdomen and intestine.
  • Attenuated androgens no longer available – stanozolol (up to 16 mg/day) or danazol (up to 1 g/day) given early (may shorten its duration).
  • Tranexamic acid weak – needs to be taken immediately – most don’t bother now
  • Upper airway esp voice alteration and dysphagia – give C1 INH promptly. How easily can family find veins?? Else family bring to emergency department! Dose depends on weight and seriousness of reaction. In a life-threatening situation we recommend 1000–1500 U. In other situations 500–1000 U is often sufficient. Administering C1 INH concentrate shortens the duration of attacks by about a third and also halves the time to the beginning of the relief of symptoms.
  • For acute attacks of abdominal oedema, pain relief should be given at an appropriate level. Non-steroidal anti-inflammatory drugs are useful.
  • If the attack is severe, C1 INH concentrate should be infused at the same dose as above. Early intervention prevents avoidable pain and reduces disruption to the patient’s life. The patient should be observed closely until symptoms start to improve. The median time to the beginning of the relief of symptoms after concentrate infusion is 0.5–1.5 h, with complete resolution of symptoms after 24 hr. If symptoms persist at a high intensity 2 h after infusion, additional C1 INH concentrate should be given and alternative diagnoses should be considered.
  • No benefit from steroids or antihistamines!  Adrenaline has only a transient and modest effect.
  • Home therapy is recommended for children with frequent and debilitating attacks, under the condition of medically supervised training.
  • Recombinant C1-INH concentrate (Ruconest) similar.
  • Subcut bradykinin B2 receptor antagonist Icatibant safe, effective and convenient (subcut) for acute attacks. Less rapid onset but then you can do it yourself. Similar price. Theoretical risk of thrombosis

Short-term prophylaxis

Children don’t need prophylaxis as much as adults, but is recommended for surgery in the head and neck area. pdC1-INH is recommended, if not available, use danazol. Tranexamic acid can also be used.

Give C1-INH up to 24hrs before procedure (with/without further dose post-procedure), or else 48hr steroids/TA before and after.

Long-term prophylaxis

The only treatment option for long-term prophylaxis in children is pdC1-INH. Question is not just frequency of attacks but severity (laryngeal vs hand, for example).

Attenuated androgens worked but not available. Side effects not great, include weight gain, virilization, muslce cramps, jaundice. In children, stunts growth.

C1 inhibitor has short half life so needed every 2-3 days. Subcut works for prophylaxis! Costs £140K per year.

Berotralstat – oral kallikrein inhibitor – some GI upset, long QT. NICE/SMC approved. £10 000 per month so similar.

Lanadelumab – subcut monoclonal kallikrein inhibitor. 2-4 weekly. Similar cost.

At the current pediatric consensus meeting for German-speaking countries, several concerns were raised about these international consensus recommendations:

  • Experts strongly advocated taking body weight into account in treatment in pediatrics. Discomfort emerged as to whether appropriate dosing is possible for patients between 12 and 18 years of age with fixed doses established in adults.
  • For attenuated androgens, sufficient data are lacking on the long-term safety over decades of use Should there be a reason for its use in isolated cases, the initial dose (see above) should only be administered for a short period (e.g., for short-term prophylaxis prior to elective procedures).
  • Tranexamic acid (less effective than attenuated androgens) is recommended for long-term prophylaxis in patients for whom pdC1-INH is not available or in whom attenuated androgens are deemed unacceptable.  Side effects are nausea, vomiting, diarrhoea, muscle cramps. Thrombosis is theoretical risk, not seen in practice, in US restricted as evidence in animals of tumours, regular eye examination and LFTs recommended in BNF.

Autoimmune HAE can be treated with C1-INH but some are resistant due to rapid catabolism so icatibant seems a good option. HAE with normal C1-INH function do not respond to antihistamines or steroids but do respond to C1-INH, tranexamic acid, danazol.

[ Eur J Pediatr (2012) 171:1339–1348]

[Bowen et al. Allergy, Asthma & Clinical Immunology 2010, 6:24]

Gilbert’s syndrome

Common, Gastro, General paediatrics, OPD

Gilbert’s syndrome is an hereditary, chronic/episodic, mild unconjugated hyperbilirubinemia.  Due to impaired hepatic bilirubin clearance (glucuronyltransferase deficiency).  Otherwise liver function is normal.

It does not cause chronic liver disease. Non pruritic.  Jaundice may be provoked by fasting, surgery, dehydration, alcohol ingestion, infectious illnesses, heavy physical exertion, and lack of sleep.  Symptoms eg tiredness are due to exacerbating condition, not high bilirubin!

Common, 2–10% of the general population, many undiagnosed. At least 30% of people with Gilbert’s syndrome never develop symptoms.

Gilbert’s syndrome can be diagnosed when the person has:

  • Unconjugated hyperbilirubinemia (on at least 2 occasions, and not progressing).  Conj bilirubin may be sl high but always less than 20% of total.
  • Bilirubin is less than 3x upper limit of normal (approx 60).
  • No evidence of haemolysis (normal full blood count, reticulocyte count, blood film, Coombs’ test, haptoglobin level, and lactate dehydrogenase level).
  • Normal liver enzyme levels.
  • No clinical evidence of liver disease.
  • Commonly homozygous for allele 7.

Differential is Crigler Najjar type 2 – can cause persistent jaundice in childhood (cf type 1 = severe jaundice in first few days of life).

No treatment is required.

Some drugs should be used with caution in people with Gilbert’s syndrome:

  • Atazanavir and indinavir.
  • Gemfibrozil.
  • Irinotecan.
  • Statins when combined with gemfibrozil.

[NICE clinical knowledge summary]

Parent/family information at https://childliverdisease.org/liver-information/childhood-liver-conditions/gilberts-syndrome/

Sudden Unexpected Death in Infancy (SUDI)

Child protection, Emergency medicine, General paediatrics, Sociology

Or Cot death?  Or SIDS (Sudden infant death syndrome)?

It is well recognised that some babies go to sleep apparently healthy, and then don’t wake up in the morning.  Even after a full post mortem (PM) investigation, no cause is found.  This unexplained phenomenon however has some very well recognised features eg age 2-6 months, prematurity, maternal smoking, poor socio-economic conditions, prone sleeping.

SUDI was originally defined by CESDI (Confidential Enquiry into Stillbirths and Deaths in Infancy) as death between 7 and 365 days where unexpected and unexplained at autopsy, during an acute illness that was not recognised as life-threatening, due to an acute illness of less than 24 h duration in a previously healthy infant (or death after this if life had only been prolonged by intensive medical care); definition also includes deaths from a pre-existing occult condition, and deaths from any form of accident, trauma or poisoning.

I find SUDI most useful for describing the initial situation one may find oneself in, particularly from the point of view of bereavement, need for medical and police investigation.  Interestingly, many of the same risk factors pertain to both deaths unexplained (ie SIDS, or strict SUDI) and to accidental deaths (with the exception of prone sleeping).

SIDS is the ICD recognized term, so is what is generally put on a death certificate.  However pathologists vary in their use of the terminology, some will use “Unascertained” to mean SIDS, others will use SIDS but reserve Unascertained for cases where there are additional factors that somehow cast doubt on the diagnosis.

Similarly, overlying (smothering) as a cause of SUDI is often inferred from the history, but may be specified on the death certificate to differentiate from SIDS.

PM finds a cause in about a 1/3 of cases) eg

  • Infection
  • Cardiomyopathy, anomalies of coronaries
  • Ion channelopathies
  • Metabolic disorders eg MCAD

See also Prevention, and Sudden unexpected postnatal collapse.

Nephrotic Syndrome

General paediatrics, Renal

Clinical picture, whereby kidneys leak protein, leading to hypoalbuminaemia. This results in oedema, particularly noticeable around the eyes, but also peripherally and as ascites. Mechanism is thought to be loss of negative charge on basement membrane. Usually idiopathic, mostly Minimal change glomerulonephritis. Otherwise can be focal segmental gomerulosclerosis (10-20%), secondary (eg HSP, SLE).

Mostly boys, 2 to 1 ratio. 5% go on to Chronic Renal Failure. Hypertension unusual so consider non minimal change glomerulonephritis if hypertensive at presentation. Classic features are:

  • Urinary protein:creatinine (PCR) more than 200mg/mmol (0.2g/mmol), and usually more than 500 (early morning sample is more reliable)
  • Strict definition is protein loss more than 1g/m2/d but noone collects 24hr urines anymore!
  • Low albumin (<25g/l)
  • Oedema
  • High Hb
  • Low Calcium

Check FBC, U&Es, creat, albumin, LFTs, varicella IgG (to check status before starting steroids), cholesterol, HBV/HCV, C3/4. Urinalysis, urine culture, protein:creatinine ratio. Urine sodium <10mmol/l indicates hypovolaemia.

Complications

  • Oedema – if symptomatic, give albumin (see below).
  • Intravascular depletion (despite massive oedema) – BP not useful as paradoxical hypertension may be seen; instead, judge by heart rate, perfusion, urinary sodium (<10 = hypovolaemia).
  • Infection – at risk due to loss of complement and immunoglobulins, esp cellulitis, primary pneumococcal peritonitis. Consider antibiotic prophylaxis with penicillin V if severe proteinuria.
  • Risk of thrombosis – loss of anti-thrombin III and other anti-coagulants, +/- hypovolaemia.  Esp renal vein thrombosis (pain, haematuria, worse renal function, palpable kidney. Do USS)
  • Hypocalcaemia – adjusted or ionised value.
  • Hyperlipidaemia  – characteristic, so part of diagnosis!  Only seen during flare, so only needs treated if other risk factors or frequent relapses.

Those with minimal change tend to be responsive to steroids and do not need a biopsy. But if atypical or unresponsive (allow 4 weeks) then biopsy indicated; or if:

  • Age under 1 yr, over 10yrs
  • Hypertensive
  • Elevated creatinine
  • Macroscopic haematuria (microscopic sometimes seen with minimal change)

Treatment

  • Steroids – Cochrane suggests at least 3 months.  PREDNOS trial did not find benefit from 16 weeks cf 8 (median time to relapse 139 vs 87 days. RHC protocol is:
    • 60mg/m2 for 4 weeks (max 80mg)
    • 40mg/m2 alt days for 4 weeks (max 60mg)
    • Wean by 5-10mg/m2 weekly for a total of 12 weeks treatment
  • Low salt diet, fluid restriction eg 50-70%.  Beware thirst driving consumption of wet foods to cheat restriction! Or drinking with tooth brushing, showering.
  • Albumin: not for low albumin itself, but for hypovolaemia or severe, symptomatic oedema (esp scrotal, where skin starts to break down). If shock, give 4.5% albumin as resuscitation fluid (without diuretic!). Otherwise, 1g/kg 20% albumin (=5ml/kg) over 4-6 hours, with IV frusemide (2mg/kg) mid-infusion.
  • Diuretics – not usually regular.  Some need, metazolone and spironolactone are synergistic with frusemide.
  • Varicella protection – check serology at diagnosis.  Vaccinate when on low dose; consider vaccinating close contacts.  May need post exposure prophylaxis if susceptible.

Remission defined as 3 consecutive days neg or trace protein. Most remit within 1 month, refer if no response by then – allow 8/52 before labelling steroid resistant .

Prognosis

1/3 no relapse, 1/3 infrequent, 1/3 frequent. Nephrotic relapse defined as 3+ protein for 3 days, but also refer if 2+ for 7 days. Treat relapse with prednisolone 2mg/kg until proteinuria suppressed for 3 days, then taper over 4-8 weeks.  In frequent relapsers (ie 2+ within first 6 months, or 4+ within any 12 month period), may become steroid dependent (ie relapses during weaning) so consider Levamisole (2.5mg/kg alternate days, SE reversible neutropenia), cyclophosphamide, ciclosporin etc.

As with any condition requiring high dose steroids, remember vaccinations, varicella, bones.

Children with steroid-resistant nephrotic syndrome who are homozygous or compound heterozygous for NPHS2 (podocin) mutations do not respond to standard steroid treatment and have a reduced risk for recurrence of nephrotic syndrome (with focal segmental glomerulosclerosis) after renal transplantation. Available through UK Genetic Testing Network for children with nephrotic syndrome that is resistant to treatment with steroids, presents in the first 3 months of life or has a histological picture of focal segmental glomerulosclerosis on renal biopsy.

Sudden Unexpected Postnatal Collapse

Neonatology

Identified as a group by BPSU, led by Julie-Clare Becher in Edinburgh.  As with SUDI, previously well appearing baby suddenly suffers cardiorespiratory failure, with death or severe neurological disability as a result.

Her 2011 report highlighted an association with prone position and breast feeding.  One third of of cases had an underlying pathological or clinical condition but over half probably due to accidental suffocation, frequently unrecognised by parents themselves.

Some suggestion that cases are underreported, and that cases are increasing due to increased early skin-skin practices without adequate supervision.  In a big survey from Sweden, most happen within first 2 hours of birth, often during first breast feeding attempt.

The process of referral to procurator fiscal, bereavement support, prolonged delay in post mortem report etc is common to SUDI, even if only a few of the underlying risk factors are shared.

A BAPM protocol is available, detailing elements of history eg family tree, drug/alcohol/smoking history, obstetric history; plus investigations eg Kleihauer, placental histology, skeletal survey, PHOX2B gene (congenital central hypoventilation syndrome), fibroblast culture from skin biopsy.  In a death, most if not all should be done routinely by pathology.

In terms of prevention, standard SUDI precautions are emphasized – avoid prone position, co-bedding, head covering, beware sedating drugs etc.  Education of parents regarding warning signs and upper airway control.  Better non-obtrusive monitoring.

[Arch Dis Child Fetal Neonatal Ed 2012;97:F30−F34. doi:10.1136/F30 adc.2010.208736; Translational Stroke Research , Volume 4, Issue 2, pp 236-247]