Acute rise from baseline of serum urea and creatinine ±oliguria (Box 13.1).1 There are three basic mechanisms:
Acute rise from baseline of serum urea and creatinine ±oliguria (Box 13.1).1 There are three basic mechanisms:
Prerenal Hypoperfusion of kidney due to eg ↓BP, hypovolaemia, renal artery occlusion (mass, emboli).
Renal Intrinsic renal pathology eg glomerulonephritis, vasculitis, drugs.
Obstruction Obstruction of outflow tract (ureter, bladder, urethra) by eg enlarged prostate, single functioning kidney with calculi, pelvic mass, or surgery.
Acute tubular necrosis refers to irreversible renal damage with nephron loss that may occur due to prerenal or renal triggers, eg due to prolonged hypoperfusion or nephrotoxic drugs (NSAIDs, gentamicin, IV contrast).
►► Call for senior help early.
► Box 13.1 Features of different types of kidney injury
| Prerenal hypoperfusion | Oliguria, urine osmolality >500mOsmol/kg, urine Na+ <20mmol/L2 |
| Acute tubular necrosis | Oliguria/normal/polyuria, urine osmolality <350mOsmol/kg, urine Na+ >40mmol/L2 |
| Renal | Oligo/anuria, haematuria, ↑ BP |
| Obstruction | Oligo/anuria, hydronephrosis on USS; if urethral: painful anuria with palpable bladder |
| Chronic kidney disease | Oliguria/normal/polyuria, previous ↑creatinine, ↓Hb, ↓Ca2+, ↑ PO43−, small kidneys on USS, fatigue, nocturia |
History Previous renal or other medical problems, urine output, fluid intake, medications (?nephrotoxic), rashes, bleeding, lethargy, anorexia.
Examination Volume status (
p. 394), BP (compare to what is normal for patient from eg old obs charts), HR, JVP, basal creps, gallop rhythm, oedema, palpable bladder.
Investigations Urine Colour, hourly volume, dipstick, M,C+S, osmolality and Na+ ( pp. 604–605); blds FBC, U+E, LFT, CK, CRP, osmolality, ESR, clotting; ABG Beware acidosis or ↑K+; ► Urgent ECG ↑K+ causes flat P waves, wide QRS and tall, peaked T waves; CXR; urinary tract USS.
Treatment Insert catheter ( pp. 560–561) to monitor output; assess for and treat causes and serious complications:
Obstructed Catheter will relieve urethral obstruction; ureteric obstruction may require nephrostomy or stenting.
Shocked ↑HR, ↓BP, absent JVP; fluid resuscitate ( pp. 488–489) ±inotropes.
Overloaded Oedema, basal creps, ↑JVP: O2, furosemide ( p. 203), CXR.
Hyperkalaemia Insulin/glucose, Ca2+ gluconate, salbutamol ( p. 398).
Continue IV fluids unless overloaded (no KCl if ↑K+), stop nephrotoxic drugs ( p. 174)—this includes ACEi/metformin even if CCF/DM; monitor urine output; consider HDU referral for CVP monitoring.
Long-standing and irreversible reduction in GFR.3
Causes DM, ↑BP, chronic urinary retention, glomerulonephritis, nephritis, pyelonephritis, polycystic kidneys, vasculitis.
Symptoms Initially none; tiredness, weight loss, nausea.
Signs Initially none, may have signs of causative disease eg DM.
Results ↑urea, ↑creatinine, ↓eGFR,4↑cystatin C,4↓Hb, ↓Ca2+, ↑PO43–, ↑albumin:creatinine ratio (ACR p. 605), persistent haematuria, abnormal/small kidneys on USS; consider biopsy if cause unclear.
Treatment This involves regular monitoring. Tight control of BP ( p. 271) and DM, smoking cessation, ACEi, and avoidance of nephrotoxins slows the progression to ESRF. Review cardiovascular risk and need for statin and antiplatelet agent. Consider nephrology referral, eg for G4/G5 disease, ACR >70mg/mmol (or >30mg/mmol with haematuria), progressive eGFR decrease, or suspected rare/genetic cause. Management of complications includes correction of anaemia with iron infusions ±erythropoietin, dietary modification, and oral Ca2+ supplements/PO43− binders to prevent ↓Ca2+/↑PO43−, control of secondary hyperparathyroidism with vitamin D analogues. As patients near end-stage disease (Table 13.1), discuss wishes and suitability for dialysis (Box 13.2) or transplantation and make necessary arrangements (eg dialysis counselling, fistula creation).
Table 13.1 CKD classification
| eGFR (mL/min) | Stage |
| >90 | G1 |
| 60–89 | G2 |
| 45–59 | G3a |
| 30–44 | G3b |
| 15–29 | G4 |
| <15 | G5 (ESRF) |
Reduction in eGFR needs to be sustained >90d. Combine eGFR categories with ACR category (A1 <3mg/mmol; A2 3–30mg/mmol, A3 >30mg/mmol) for full classification.
Complications Vascular disease, anaemia, ↓Ca2+, renal osteodystrophy, ↑K+, fluid overload, immune compromise, peripheral neuropathy.
Prescribing p. 174; avoid nephrotoxic drugs (eg metformin, NSAIDs, gentamicin); reduce doses/frequency of renal excreted drugs (eg opioids, benzodiazepines, penicillins); see also pp. 394–397 for fluids.
Radiology Avoid IV contrast imaging except in an emergency since this is nephrotoxic; discuss carefully with nephrology and radiology. Where essential, use IV hydration and monitor renal function closely.
Box 13.2 Patients on dialysis
Approximately 15,000 UK patients are on haemodialysis, usually for 3–5h 3×/week via an arteriovenous fistula. Blood tests and BP measurements should never be made from a fistula arm. Placing fingers or a stethoscope bell gently over a fistula will confirm function if a gentle buzz is felt or heard. A further 5000 UK patients use peritoneal dialysis via an abdominal (Tenckhoff) catheter. Peritoneal infections in these patients can be devastating; if septic, a sample of dialysate should be inspected (?turbid) and sent for cell count, Gram stain, and culture; intraperitoneal antibiotics may be required. Always inform the renal team.
► Worrying features Weight loss, frank blood, or clots (?malignancy); ↑ BP, proteinuria (?nephritic syndrome p. 390).
Think about Macroscopic UTI, tumours, stones; Microscopic with red cells UTI, bladder, renal or prostate tumour, stones, recent catheterization, glomerulonephritis/nephritic syndrome, endocarditis, clotting abnormality, sickle cell, TB, schistosomiasis, trauma, strenuous exercise, PV bleeding ( pp. 510–513); Microscopic without red cells (haemoglobinuria) haemolytic anaemia, myositis, rhabdomyolysis, trauma, ischaemia; Red discolouration Rifampicin, beetroot.
Ask about Urine colour and volume, clots, dysuria, frequency, urgency, fever, abdominal pain, hesitancy, poor stream, recent trauma or catheterization, weight loss, malaise, lethargy, menstruation; PMH Kidney disease, stones, prostate disease, cancer, clotting disorders, sickle cell; DH Nephrotoxic drugs (eg NSAIDs, gentamicin), rifampicin, anticoagulants.
Obs BP, HR, temp, fluid balance.
Look for ↑BP, haematuria and proteinuria suggest nephritic syndrome ( p. 390); inspect the urine; rashes, bruises, splinter haemorrhages, palpate for suprapubic or loin tenderness or masses; PR: enlarged prostate; PV bleeding.
Investigations Urine Dipstick may not distinguish red cells and haemoglobin, microscopy (for red cell or protein casts), culture; blds FBC, U+E, LFT, Ca2+, ESR, CRP, clotting; consider G+S, autoantibodies (anti-GBM, ANCA, ANA, anti-DNA), complement, PSA, USS Urinary tract.
Management Macroscopic (red/pink urine) Resuscitate ( p. 492), if heavy consider inserting a three-lumen catheter for bladder wash-out, discuss with urology to exclude malignancy (IVU, cystoscopy, CT).
Microscopic (urine looks normal, red cells on dipstick or microscopy):
• With nitrites/white cells Treat as a UTI/pyelonephritis ( p. 498), check urine once infection has cleared to be sure haematuria has resolved
• Without proteinuria This suggests urological tumour or stones ( pp. 301–302), refer to urology (urgently if >50yr) for CT-KUB ±cystoscopy
• With proteinuria This suggests glomerular pathology, refer to nephrology and check BP, urinary output, urine casts, autoantibodies, complement, urine protein:creatinine, 24h urine collection for protein, renal USS.
Haemoglobinuria Haemolytic anaemia ( p. 408), rhabdomyolysis (Box 13.3).
Box 13.3 Rhabdomyolysis
First described in crush victims during the Blitz, this involves muscle necrosis after crush injuries or after lying on a hard surface for prolonged periods (eg elderly patients who fall and are unable to get up). Myocyte contents are nephrotoxic and lead to renal failure with ↑↑↑ CK (but normal troponins), with haemoglobinuria. Treatment is as for AKI ( p. 386), with management of hyperkalaemia ( p. 398) ± surgical debridement.
► Worrying features ↑ BP, oliguria, haematuria, ↑↑protein, oedema.
Think about Transient Physical exertion, fever, UTI, vaginal discharge, recent ejaculation; Extra-renal causes Orthostatic, hypertension, CCF; Primary renal disease Glomerulonephritis; Multisystemic disease Vasculitis, lupus, endocarditis, myeloma, hepatitis C, pre-eclampsia.
Ask about Recent exercise, vaginal discharge, pregnancy, dysuria, frequency, urgency, urine output, fever, haematuria, arthralgia or rash, malaise, lethargy, oedema, orthopnoea, recent URTI/tonsillitis; PMH Kidney disease, ↑BP, heart disease, cholesterol, DM; DH Nephrotoxic drugs (eg NSAIDs, gentamicin).
Obs BP, HR, RR, temp, fluid balance, blood glucose.
Look for Evidence of the underlying pathology: oedema, basal creps, ↑JVP, suprapubic or loin tenderness, palpable kidneys or uterus, rashes/arthralgia, splinter haemorrhages.
Investigations Urine Dipstick (protein, blood, nitrites, leucocytes; repeat early in morning to exclude postural proteinuria), check β-hCG, microscopy (for casts), culture, electrophoresis, spot albumin:creatinine ratio—a more practical initial investigation than a 24h collection for protein ( p. 605); blds FBC, U+E, LFT, triglycerides, ESR, CRP, autoantibodies (anti-GBM, ANCA, ANA, anti-DNA), complement, cryoglobulins, serum electrophoresis; USS Kidneys/urinary tract.
• Fever/exercise/transient Repeat urine dipstick normal, no treatment
• Orthostatic Age <30yr, no protein in early morning, no treatment
• UTI Dysuria, frequency, urine nitrites/leucocytes, culture +ve ( p. 498)
• Pre-eclampsia Pregnancy, ↑BP ±oedema ( p. 518)
• Myeloma >60yr, bone pain, urine Bence Jones, ↑Ca2+ ( p. 403)
• Nephrotic Oedema, ↓albumin, ↑triglycerides ( p. 390)
• DM Tight glycaemic and BP control, ACEi ( p. 336).
See Box 13.4 for tumour lysis syndrome.
Box 13.4 Tumour lysis syndrome
The destruction of malignant cells during chemotherapy causes release of intracellular contents which may overwhelm renal elimination and extracellular buffers; the resulting metabolic derangement, together with the precipitation of uric acid crystals within the tubules, can cause AKI. Risk factors include pre-existing renal impairment with high-grade tumours, lymphoma, or leukaemia. Onset is generally within 3d of chemotherapy, with oliguria, muscle cramps, tingling, weakness, tetany, and seizures. Blood tests will show ↑K+, ↑ PO43−, ↓Ca2+, ↑urate, ↑urea, ↑creatinine.
Treatment Involves recognition of at-risk patients and prophylactic IV hydration and allopurinol started 24–48h prior to therapy with careful monitoring of electrolytes during therapy. If the syndrome still develops, attempt hyperhydration with IV fluids, allopurinol, bicarbonate, K+ restriction, and PO43− binding under advice from the renal team. Dialysis may be necessary to prevent worsening renal failure, refractory hyperkalaemia, and ultimately arrhythmias and cardiac arrest.
Box 13.5 Nomenclature
To overcome those palpitations that you experienced as a student, remember that the wide range of primary and secondary pathologies affecting glomeruli all share a limited repertoire of clinical manifestations (eg nephrotic syndrome). These pathological processes also share a limited repertoire of histological features and in the absence of a definitive diagnosis, nephrologists will often refer instead to the pattern seen on biopsy (eg membranous glomerulonephritis).
Inflammation of the glomeruli triggered by an immunologic mechanism results in tissue damage, often with proliferation of basement membrane, mesangial cells, or capillary endothelium.
Some important histological types and associated causes and clinical features are listed in Table 13.2 (see also Boxes 13.5–13.7).
Table 13.2 Classification of glomerulonephritis
| Biopsy | Presentation | Causes | Management |
| Minimal change (normal by light microscopy) | Nephrotic syndrome (commonest cause in children) | ?T-cell mediated podocyte damage | Majority steroid responsive; very few progress to ESRF |
| Membranous | Heavy proteinuria ±nephrotic syndrome | Idiopathic (70%); malignancy, connective tissue disease, drugs | ⅓ stabilize with immunosuppression; ⅓ remit spontaneously; ⅓ progress to ESRF |
| Focal segmental glomerulosclerosis | Proteinuria ±nephrotic syndrome; CRF | Idiopathic; secondary causes include heroin abuse and HIV | Primary disease may respond to steroids but significant progression to ESRF; secondary disease managed with ACEi |
| Mesangioproliferative | Haematuria (often <72h after URTI); nephritic syndrome | Idiopathic IgA deposition | Majority self-limiting but 20–40% progress to ESRF; ACEi ±steroids |
Box 13.6 Nephrotic syndrome
Defined as >3g proteinuria/24h with hypoalbuminaemia and oedema. Hypercholesterolaemia, ↓IgG, and hypercoagulability may also feature. Causes include primary glomerulonephritis as above (typically minimal change or membranous disease) but also extra-renal causes including DM, anti-GBM disease, malaria, pre-eclampsia and drugs (eg gold, penicillamine, NSAIDs). Treatment is of the underlying cause along with diuretics, active treatment of infection, ±anticoagulants.
Box 13.7 Nephritic syndrome
Characterized by ↑BP, oliguria, and haematuria. This may classically be seen around 3wk after a streptococcal throat infection as a self-resolving glomerulonephritis, but is also associated with some much more aggressive pathologies including vasculitis and anti-GBM disease.
Causes Enlarged prostate, postoperative, pain, anticholinergics, spinal pathology/MS (painless), pregnancy, constipation, UTI.
Symptoms Suprapubic pain + urge to urinate, anuria/oliguria, delirium.
Signs Palpable distended bladder (dull to percussion and tender), check leg power/reflexes and tone, perianal sensation, and prostate on PR.
Investigations Bladder scan if unsure or simply pass a catheter.
Management ► Urgent catheterization ( pp. 560–561), record residual volume of urine (normal bladder size is 400–500mL, consider acute-on-chronic retention if >1L); urine dipstick and send for M,C+S; stool chart ±laxatives; urgent MRI spine if new lower limb neurology and diminished perianal sensation/tone ( p. 361). Beware post-obstructive diuresis: pay close attention to fluid balance and electrolytes. Once reversible precipitants addressed, attempt a trial without catheter (TWOC) with close monitoring for recurrence of retention. If this occurs, reinsert catheter and treat as chronic retention.
Complications AKI, chronic obstruction.
Causes Obstruction (prostate), DM, MS, dysfunctional bladder.
Symptoms Incontinence, dribbling, poor stream, recurrent UTI.
Signs Palpable distended bladder (usually non-tender), enlarged prostate.
Investigations blds FBC, U+E, PSA, Ca2+, PO43−.
Management Do not catheterize unless in pain or anuric (acute on chronic retention); refer to urology to investigate cause; options include TURP, intermittent self-catheterization, anti-androgens (eg finasteride), or alpha-blockers (eg tamsulosin).
Complications Chronic kidney disease, recurrent UTI.
• Stress Leakage on exercise/coughing/laughing
• Urge Severe and sudden urgency (often due to detrusor instability)
• Overflow Urine volume exceeds bladder capacity (eg chronic retention)
• Functional Restricted mobility so unable to get to toilet in time.
Causes UTI, detrusor instability, neurological problem (eg MS, DM), diuretics + reduced mobility; ♀: uterine prolapse, weak pelvic muscles, pelvic mass; ♂: post-prostate surgery.
Ask about Urgency, frequency, leakage, dysuria, poor stream, haematuria, fluid intake (including caffeine consumption late in the day), effects on lifestyle, obstetric history, and previous pelvic surgery or trauma, DM, chronic cough, faecal incontinence. If acute presentation with new leg weakness, suspect spinal cord compression ( p. 361).
Look for Abdo/pelvic masses, prolapse ( pp. 158–159); assess leakage on coughing.
Investigations Urine MSU, glucose, urinary diary, urodynamics studies. ♂: blds PSA (take prior to checking prostate size and nodularity by PR).
Treatment General Weight loss, less caffeine, stop smoking, treat prolapse; Stress incontinence Fluid restriction, pelvic floor exercises, transvaginal tape; Detrusor instability Behavioural therapy (bladder drill), tolterodine 2mg/12h PO; Overflow See ‘Chronic urinary retention’ earlier in this topic; Functional Aid mobility.
► Worrying features Low urine output <0.5mL/kg/h (Table 13.3) sustained >4h or despite adequate fluid, ↑HR, systolic BP <100mmHg, ↑K+, ↑creatinine, acidosis.
►► Do not ignore patients with very low urine output, they will be among the sickest in the hospital. It is usually easier to treat fluid overload than AKI, although patients with underlying CKD and CCF will need your closest attention for regular review and fluid management.
Table 13.3 Classification of low urine output*
| Volume in 1h | Volume in 24h | |
| Normal urine output | >60mL (>1mL/kg) | >1600mL |
| Low urine output | <30mL (<0.5mL/kg) | <800mL |
| Oliguria | <17mL | <400mL |
| Anuria | <4mL | <100mL |
| Absolute anuria | None | None |
*Volumes are defined for adult patients; paediatric values are based upon weight.
Think about Severe AKI, shock; Most likely Hypovolaemia, hypotension, urinary retention, blocked catheter, prostatic hypertrophy; Other Rhabdomyolysis, chronic kidney disease, renal vascular problems (eg thrombosis, emboli), urethral trauma.
Ask about Abdominal pain, hesitancy, poor stream, fluid balance (oral and IV intake, vomiting, diarrhoea, stoma output, leaking wounds, fever/sweating), breathlessness, orthopnoea, postural dizziness; PMH Kidney disease, solitary functioning kidney, prostate disease, ↑BP, heart disease, DM; DH Nephrotoxic drugs (eg NSAIDs, gentamicin, ACEi, IV contrast).
Obs BP, HR, RR, fluid balance, CVP if possible.
Look for Volume status ( p. 394), oedema, unrecorded leakage from wounds, stomas, or surgical drains; palpable bladder, suprapubic pain, loin pain, enlarged prostate, evidence of infection or haemorrhage.
Investigations Urine Colour, dipstick, M,C+S; septic screen, if not responding to fluid challenges call for senior help and send urine for osmolality ( p. 605) and Na+; blds FBC, U+E, CK, osmolality; Bladder scan If retention or a blocked catheter is suspected; USS renal tract Will allow full assessment for structural causes, request a Doppler USS if renal artery stenosis/embolism is suspected.
Treatment Insert a urinary catheter ( pp. 560–561) and ask the nurses to keep an hourly fluid balance including any diarrhoea, vomiting, and fluid loss from wounds. Consider asking for a catheter flush if already catheterized. Assess the patient and if in doubt treat as hypovolaemia with a fluid challenge (eg 500mL 0.9% saline over 10–15min p. 395) and review in 1–2h. Beware post-obstructive diuresis if in retention/blocked catheter.
If urine output is still low despite treatment Then get further senior advice. If a patient is volume depleted, it may need considerable fluid volumes to improve output, but assess frequently for volume overload. Always rule out urinary tract obstruction. Indiscriminate use of IV furosemide simply to improve output may make the fluid balance chart look better, but does nothing for your patient.
Table 13.4 Common causes for low urine output
| History | Examination | Investigations | |
| Hypovolaemia ( p. 393) |
Low fluid input, excess losses, post-op | Negative fluid balance, ↑HR, ↓JVP, ±↓BP (postural) | ↑urea, concentrated urine, ↑ urine osmolality |
| Septic shock ( p. 494) |
Malaise, symptoms of infection, acute illness | ↑HR, ↓BP, ↑RR, exclude haemorrhage | May have ↑↓WCC, ↑CRP, ±↑lactate |
| Acute kidney injury ( p. 386) |
Severe illness, untreated low urine output | May be dehydrated or shocked | New-onset ↑urea and creatinine, ↑CK if rhabdomyolysis |
| Chronic kidney disease ( p. 387) |
↑BP, lethargy, anorexia, previous kidney problems, DM | Pale, anaemic, oedema, bruising, peripheral neuropathy | Persistent ↑urea and creatinine, small kidneys on USS |
| Urinary retention ( p. 391) |
Lower abdominal pain, previous prostate problems | Palpable bladder, often anuric, enlarged prostate | Full bladder on scan, relief on catheterization |
This is by far the most common cause of low urine output in in-patients.
Symptoms, signs, investigations See Table 13.4 (see also Box 13.8).
Treatment Increase fluid input; the rate of rehydration depends on the patient. If urine output is >0.5mL/kg/h simply increase the rate of current IV fluids. If <0.5mL/kg/h consider a fluid challenge ( p. 395) and prescribe some quick fluids to follow, eg 0.9% saline 1L/4h; review the patient in 1–2h.
Complications AKI.
Prescribing of fluid volumes that exceed the ability of the kidneys to excrete may lead to iatrogenic fluid overload (eg failure to identify obstructive uropathy or cardiac failure as cause of low output).
Symptoms, signs, investigations ( p. 394.)
Treatment ( p. 288 ‘Pulmonary oedema’.) For mild overload reduce or stop IV fluids and review in a few hours; ask the nurses to record hourly obs and contact you if the patient’s RR rises. If you are certain of overload, ensure no evidence of obstruction before trying 40mg furosemide IV. This will cause a diuresis in most patients, but potentially contribute towards AKI if the patient was hypovolaemic. In certain settings (eg sepsis + cardiogenic shock) the patient may be intravascularly volume depleted, but symptomatically fluid overloaded—this requires senior assessment for HDU/ICU and inotropic support.
Complications Pulmonary oedema.
⇄ Box 13.8 Causes of low urine output covered elsewhere
HR, postural hypotension, and low urine output (<0.5mL/kg/h) are sensitive signs of hypovolaemia while orthopnoea suggests overload.5
Table 13.5 Assessing volume status
| History | Examination | Investigations | |
| Mild–moderate fluid deficit (eg <1500mL in adult) | ↓urine output, headache, thirst or poor oral intake, excessive fluid loss (eg diarrhoea, vomiting) | ↑HR,* postural BP drop,† urine output <0.5mL/kg/h, dry mucous membranes, capillary refill >2s, ↓JVP | Dark urine, ↑urine osmolality; blds: ↑urea, ↑PCV/haematocrit, ↑albumin, ↑serum osmolality |
| Severe hypovolaemia (as for mild plus …) | Drowsy, obtunded | Oliguria/anuria, ↓BP<100mmHg, sunken eyes, decreased skin turgor | ↑creatinine |
| Fluid overload | Cardiac history, excess fluids, SOB, orthopnoea, cough, sputum (white/frothy), swelling | ↑RR, ↓O2 sats, ↑JVP, bilateral basal crackles, pitting oedema,‡ gallop rhythm (3rd heart sound) | Pulmonary oedema on CXR ( pp. 596–597), abnormal ECG ( pp. 586–588—LVH, MI), ↑CVP |
*Including upper range of normal, ie >90/min; remains slow if taking β-blockers or other rate-limiting drugs (eg verapamil, diltiazem, digoxin).
†A drop of >20mmHg systolic/10mmHg diastolic is significant.
‡Ankles if sitting, sacrum if in bed.
Fluid balance This is calculated by measuring a patient’s urine output and fluid input along with any losses from vomit, diarrhoea, or drains. The patient must be catheterized for accurate measurement.
Insensible losses These are unrecordable fluid losses, eg sweating and breathing. 500–1000mL is usually lost each day, but this increases with pyrexia (from sweating), tachypnoea, and burns; this loss will not be apparent from the fluid chart. Litres of fluid can be lost from burns and wound seepage which is missed unless the bandages are inspected.
Third-space fluids Also called ‘fluid sequestration’; inflammation and injury causes capillary permeability to increase so that fluid and protein leak from the blood vessels (intravascular space) causing oedema. The patient is intravascularly hypovolaemic despite normal fluid balance and fluid should be replaced according to clinical signs, especially urine output. It is common in sepsis, pancreatitis, and after major operations.
CVP lines Central venous pressure measurements are used primarily in ICU and HDU since they require a central line ( pp. 548–549). By recording the pressure in the line at the level of the right atrium, an estimate of filling state is obtained. The normal range is 1–7mmHg (1–9cmH2O); high pressure suggests fluid overload or heart failure while a low CVP suggests hypovolaemia. Trends are more important than absolute values; the CVP should rise with a fluid challenge; hypovolaemia has been corrected once this rise persists after the challenge has finished, or when there is no further rise in CVP with subsequent fluid challenges.
Rapid restoration of circulating volume is vital, particularly for those with evidence of severe hypovolaemia (Table 13.5). Give high-flow O2, establish IV access, and begin emergency management ( p. 488–489). (See Box 13.9.)
Fluid challenge This implies rapid delivery of a bolus of fluid with monitoring for effects to guide further fluid management. A bolus of 500mL crystalloid, eg 0.9% saline IV (250mL if frail or heart problems, 10mL/kg in children), is infused over <15min. Reassess immediately: if evidence of hypovolaemia persists, consider further 250–500mL fluid boluses. Large volumes may eventually be needed, but seek senior help and involve ICU early.
Box 13.9 Choice of fluid in resuscitation
Choice of synthetic resuscitation fluid has historically split into a debate between the use of crystalloids (aqueous solutions of mineral salts) and colloids (containing larger, insoluble molecules). Although colloids might theoretically exert an osmotic load keeping more fluid in the circulation, this effect may be overstated and must be set against the higher cost of colloids. Trial data have firmly come down in favour of the use of crystalloids, with evidence of increased rates of renal failure6 and death7 associated with colloid resuscitation. Evidence for choice of crystalloid is less robust, and both 0.9% saline and physiological salt solutions represent reasonable choices. Of course, blood represents a highly physiological replacement fluid when used in haemorrhage, but is rarely a practical or necessary choice in other settings. Human albumin solutions should offer the same osmotic benefits as proposed for colloids, but in ICU study data any survival advantage appears small and limited to patients with severe sepsis.8
Prescribing ‘routine’ fluids is a common task for foundation doctors, and one your seniors are unlikely to take much interest in until you make a mistake. When asked to prescribe fluids, always consider why a patient is on fluids, what their electrolyte needs are (look at recent blood result), and whether further fluids should be given (is the patient able to drink?). If in any doubt, assess the patient for RR, JVP, and basal lung crepitations.
Maintenance requirements Typically adults require 25–30mL of water/kg/24h to cover their urine output and insensible losses (sweat, respiration, stool). This equals about 2–2.5L per day for a 70–80kg adult.9 Several additional sources of fluid losses may occur in acutely ill patients:
Recordable Polyuria, NG aspirate, diarrhoea, vomiting, drains.
Insensible Wound leakage, pyrexia, tachypnoea, burns.
Third space ( p. 394), eg pancreatitis, post-op.
As much as possible, intake should come through the GI tract—always maximize PO intake, and consider using NG fluids as an alternative to IV where inadequate PO intake persists ≥3d. Alternatively, for an elderly patient managing insufficient volumes PO and who has no need for an IV cannula, 1L 0.9% saline SC overnight (12h) may be all that is required. Always explore with seniors which patients need to remain NBM.
Estimating fluid requirements 24h requirements can best be estimated from review of an accurate fluid balance chart. This is especially useful in patients at risk of fluid overload. Three components need to be considered:
• Recorded losses over last 24h (from fluid chart)
• Estimate of insensible losses (usually 0.5–1.5L/24h)
• Estimate of fluid deficit (from history, examination, obs and fluid chart).
Where a fluid balance chart is not available, estimate needs as:
• Estimate of maintenance requirement from weight (25–30mL/kg/24h)
• Additional fluids if significant insensible losses are expected (0.5–1.5L/24h)
• Estimate of fluid deficit (from history, examination, obs).
Beware groups of patients who may need less fluids than estimated: elderly/frail, low BMI, heart problems, CKD, partial oral intake.
Electrolyte and glucose requirements Estimation of electrolyte requirements should take into account current U+E, medications (especially diuretics and supplements), and fluid loss. Basic maintenance requirements are:
Table 13.6 shows the electrolyte content of some commonly used IV fluids. Due to the potential to trigger dysrhythmias, the maximal safe rate of potassium administration outside of HDU/ICU is 10mmol/h.
Table 13.6 Electrolyte constituents of common IV fluids
| Na+ (mmol/L) | K+ (mmol/L) | Cl− (mmol/L) | |
| 5% glucose* | 0 | 0/20/40 | 0 |
| Glucose saline† | 30 | 0/20/40 | 30 |
| 0.9% saline‡ | 154 | 0/20/40 | 154 |
| Hartmann’s | 131 | 5 | 111 |
| Packed red cells: | |||
| Fresh | 15 | 0.3 | 150 |
| At expiry date | 10 | 6.0 | 150 |
*Glucose has 2 stereoisomers. The D-isomer is known as dextrose, which is the form found in infusion fluids. In practical usage, ‘dextrose’ and ‘glucose’ are interchangeable, since alternative isomers of glucose are not prescribable, although can be a source of some confusion.
†0.18% saline/4% glucose.
‡1l 0.9% saline/24h already exceeds daily Na+ requirements. Large volume saline infusions result in hyperchloraemic metabolic acidosis and potential overload of renal sodium excretion capacity.
Prescribing Having decided the 24h fluid and electrolyte requirement, convert total needs into suitable 500–1000mL bags to run at appropriate rates. If there is any deficit, the initial bags should be run more quickly to correct hypovolaemia. Where safe, prescribe the fluids so that they run out during the normal working day to reduce work for those on-call; if careful review is required before further fluid prescribing, this should be indicated on the chart.
A maintenance fluid regimen suitable for an otherwise well hospitalized patient who is NBM awaiting surgery is shown in Fig. 13.1. Although this may be appropriate for an adult with a healthy heart and kidneys, indiscriminate use of this regimen could lead to fluid overload.
Fig. 13.1 Example of a maintenance fluids regimen.
Patients may leave surgery with hypovolaemia due to blood loss and third-space loss; they may require more fluids to make up this deficit. Despite lysis of cells during surgery causing a release of K+, most postoperative patients who remain NBM will still require supplementary KCl in their postoperative fluid replacement after 24h.
Intestinal fluid losses Most intestinal fluids have a composition similar to 0.9% saline with 20mmol/L of KCl and should be replaced with this. For the exact composition of different intestinal fluids consult the BNF.
Heart problems Patients with previous heart disease are more prone to fluid overload and pulmonary oedema. Simple attention to fluid balance prevents problems in the majority of patients. If fluid overload develops, the patient may require a ↓Na+ diet, daily weights, and fluid restriction (eg 1.5L/24h). There is no logic to the routine prescribing of furosemide alongside maintenance fluids.
Chronic liver failure Excess Na+ may cause ascites. Restrict Na+ by using 5% glucose; 1.5L/24h fluid restriction is sometimes required. If fluid resuscitation is required use salt-poor albumin (a blood product, see BNF). Recheck U+E regularly to ensure not becoming hyponatraemic.
Acute kidney injury Ensure adequate and timely administration of crystalloids to correct for any hypovolaemia. Avoid additional K+ unless hypokalaemic. Further IV fluids should be determined by fluid balance ±CVP in HDU/ICU, along with regular repeat U+E.
Chronic kidney disease A reduction in glomerular filtration rate (GFR) means that the kidney cannot excrete as much water, Na+, or K+. In mild CKD excess fluids and Na+ should be avoided, though acute deterioration in renal function is usually a sign of hypovolaemia. In severe CKD, restriction of Na+, K+ and fluid (eg 1.5L/24h) is required.
►► If in doubt Reassess and seek senior advice. Fluid prescribing is complex, the condition of your patient will change and there is no substitute for reassessing prior to prescribing the next bag of any fluid.
Milk volume Babies >5d require 150mL/kg milk each day.
Maintenance Calculate daily fluid (oral/IV) requirements from Table 13.7.10
Table 13.7 Maintenance fluids in children
| Weight | Fluids/kg/24h | Fluids/kg/h | Expected 24h volume |
| First 10kg | 100mL/kg/24h | 4mL/kg/h | 0–1000mL |
| 10–20kg | 50mL/kg/24h | 2mL/kg/h | 1000–1500mL |
| Above 20kg | 20mL/kg/24h | 1mL/kg/h | 1500–3000mL |
Example 23kg child: (10 × 100mL) + (10 × 50mL) + (3 × 20mL) = 1560mL/24h.
| ► Airway | Check airway is patent; consider manoeuvres/adjuncts |
| ► Breathing | If no respiratory effort—CALL ARREST TEAM |
| ► Circulation | If no palpable pulse—CALL ARREST TEAM |
►► Call for senior help early if patient deteriorating.
(K+<2.5mmol/L or <3mmol/L with ECG changes.)
• ECG changes Arrhythmias, prolonged PR interval, ST depression, small/inverted T waves, U waves (after T wave)
• 15L/minO2 if SOB or sats <94%
• Monitor defibrillator’s ECG leads, BP, pulse oximeter
• Venous access, take bloods for urgent repeat U+E, Mg2+
• ReplaceK+, 40mmol/L KCl in 1l 0.9% saline IV unless oliguric
(K+ ≥7mmol/L or >5.3mmol/L with ECG changes.)
• ECG changes Arrhythmias, flat P waves, wide QRS, tall/tented T waves
• Monitor defibrillator’s ECG leads, BP, pulse oximeter
• Venous access, take bloods for urgent repeat U+E
• If ECG changes seen or K+ ≥7mmol/L (arrhythmias p. 254):
• 10mL of 10% calcium gluconate IV over 2min, repeat every 15min up to 50mL (five doses) until K+ corrected
• ABG to exclude severe acidosis (Box 13.10)
► Box 13.10 Life-threatening causes
►► Hypokalaemia (K+<3.5mmol/L.)
► Worrying features ↓GCS, chest pain, palpitations, abnormal ECG.
Causes Vomiting, diarrhoea, most diuretics, steroids, and Cushing’s, inadequate replacement in fluids, alkalosis, Conn’s syndrome.
Symptoms Weakness, cramps, palpitations, nausea, paraesthesia.
Signs Muscle weakness, hypotonia, arrhythmias.
Investigations blds Recheck U+E looking for coexisting electrolyte imbalances, in particular ↓Mg2+
ABG If alkalosis suspected
ECG T wave flattening or inversion, U waves, ST depression, atrial arrhythmias.
Treatment If K+ ≥2.5mmol/L with no ECG changes add 20–40mmol KCl to IV fluids or give Sando-K® 2 tablets/8h PO and monitor U+E; consider writing up Sando-K® only for 3–5d to prevent continuous unmonitored treatment. Replace any concurrent ↓Mg2+ (eg 8mmol MgSO4 in 100mL 0.9% saline IV over 1h). If K+ <2.5mmol/L or ECG changes see treatment plan p. 398.
►► Hyperkalaemia (K+ >5.3mmol/L.)
► Worrying features ↓GCS, chest pain, palpitations, abnormal ECG.
Causes Haemolysed samples (likely if several hours taken to reach lab), AKI, CKD, K+-sparing diuretics (spironolactone, amiloride), ACEi, trauma, burns, excess K+, large blood transfusions, Addison’s disease.
Symptoms Palpitations, dizziness, chest pain.
Signs Assess haemodynamic stability, irregular pulse, stigmata of CKD.
Investigations blds Urgent repeat U+E; if K+<7mmol/L with no new ECG changes or the sample is reported as haemolysed then await the repeat sample, otherwise follow the treatment plan ( p. 398); if on digoxin, check levels since digoxin toxicity will worsen hyperkalaemia; ABG For acidosis if AKI ECG Initially peaked T waves, later broad QRS and flat P waves, ultimately VF.
Treatment Ca2+ gluconate protects the heart against ↑K+. Salbutamol and insulin move K+ into cells to reduce plasma levels in the short term (1–2h) after which a rebound increase may occur. Furosemide (with IV fluids if necessary) or calcium polystyrene sulfonate (takes 24h, give with lactulose 30mL/6h PO) enhance K+ excretion. If refractory or acidotic, dialysis may be necessary ( p. 387). Stop any causative or nephrotoxic medication.
Hyponatraemia (Na+ <133mmol/L.)
► Worrying features ↓GCS, irritable, seizures, ↑HR, ↓BP.
Ask about Diarrhoea, vomiting, abdo pain, tiredness, urine frequency, quantity and colour, thirst, constipation, SOB, cough, chest pain, weakness, head trauma; PMH Heart, liver or kidney problems; DH Diuretics, opioids, antipsychotics, amiodarone, proton pump inhibitors, SSRIs, IV fluids.
Look for Assess fluid balance and volume status ( p. 394), basal creps, oedema (legs and sacrum), ascites, focal neurology, conscious level (if Na+ <120mmol/L the patient may become irritable or confused, <110mmol/L there may be seizures or coma).
Investigations BLDS FBC, U+E, LFT, CRP, plasma osmolality; Urine Send paired sample for osmolality and Na+; assess underlying cause as in Fig. 13.2 (also see Box 13.12).
Fig. 13.2 Assessment of hyponatraemia.
Spurious ↓ Na+ (pseudohyponatraemia) This can be caused by taking blood from an arm with IV fluids running, a lipaemic sample (labs should detect this) or osmotically active substances in the blood, eg in hyperglycaemia. Discuss with lab if unsure.
Box 13.11 Syndrome of inappropriate ADH secretion (SIADH)
In this condition, inappropriate hypothalamic release of ADH leads to euvolaemic hyponatraemia. Beware of overcalling this diagnosis, which requires a careful workup:
• Concentrated urine despite dilute plasma (ie urine osmolality >plasma): generally plasma osmolality <275mosm/kg and urine osmolality >500mosm/kg
• Normal adrenal and thyroid function (check TSH and short Synacthen® test).
Causes include malignancy (lung, pancreas, lymphoma), lung infections, CNS infections or vascular events, drugs (eg SSRIs, tricyclics, carbamazepine, antipsychotics) or idiopathic. Management requires fluid restriction (initially 1L/24h) ±ADH antagonists (eg demeclocycline 300mg/12h PO).
Treatment Although acute hyponatraemia (<48h duration) can be rapidly corrected, chronic hyponatraemia (or where the time course is unclear) should be corrected slowly to prevent fluid overload or osmotic demyelination. Aim for a rise of no more than 10mmol/L/24h. Get senior help if seizures or coma (the rare situation where it may be necessary to raise Na+ rapidly by ~5mmol/L using hypertonic saline) or if Na+ <120mmol/L. In all patients monitor fluid balance closely with catheter, regular obs and possibly CVP. Repeat U+E daily, or more frequently if neurological signs. Assess cause using Fig. 13.2 and treat accordingly.
• Hypovolaemic Replace lost fluid with 0.9% saline according to degree of dehydration ( p. 396); severe hypovolaemia should be corrected ( p. 492) and takes precedence over hyponatraemia. Try to establish the cause of fluid loss and treat accordingly. Stop diuretics
• Normovolaemic or mild overload Slow 0.9% saline IV eg 1L/8–10h, Na+ levels should rise over a few days. If urine osmolality >500mOsmol/kg consider SIADH (see Box 13.11)
• Oedematous Urine Na+ usually <10mmol/L, identify and treat the underlying cause (see relevant chapter).
⇄ Box 13.12 Causes of hyponatraemia covered elsewhere
Hypernatraemia (Na+ >146mmol/L.)
► Worrying features ↓GCS, ↑HR, ↓BP.
Causes Fluid loss (diarrhoea, burns, fever, glycosuria eg DM, diabetes insipidus) or inadequate intake (impaired thirst response in elderly or hypothalamic disease); more rarely excess Na+ (iatrogenic, Conn’s syndrome).
Symptoms Anorexia, nausea, weakness, hyperreflexia, confusion, ↓GCS.
Signs Assess fluid balance, volume status ( p. 394), neurological deficit.
Investigations blds Plasma osmolality (likely to be raised); Urine Osmolality (>400mOsmol/kg if fluid loss, <400mOsmol/kg if excess Na+, or in diabetes insipidus, normal range 350–1000mOsmol/kg); consider CT Head or MRI If suspect central cause.
Cells rapidly adapt to raised osmolality of extracellular fluid by retention and production of intracellular osmolytes. This prevents osmotic fluid losses from inside the cell, but if extracellular Na+ concentration rapidly corrected, osmotic forces will now drive fluid into cells, causing lysis resulting in neurological damage and death.
Hence aim for slow correction of Na+ (10mmol/L/24h at the very most). Treatment is guided by volume status:
• Hypovolaemic Give 0.9% saline 1L/6h (prevents sudden Na+ shifts) until normovolaemic
• Normovolaemic Encourage oral fluids or 5% glucose 1L/6h. Monitor fluid balance and plasma Na+; consider a urinary catheter.
Hypocalcaemia (Corrected Ca2+<2.2mmol/L.)
Although >99% calcium is stored in bones, and most of the remainder is intracellular, extracellular calcium is critical for neuromuscular and cardiac function. Albumin binds around 40% of extracellular calcium, so hypoalbuminaemia may give falsely low recordings of serum calcium; always check the ‘corrected calcium’. Gut, renal, and bone calcium handling is critically regulated by vitamin D, which requires hydroxylation in functioning kidneys and liver to be active, and by PTH.
► Worrying features ↓GCS, chest pain, palpitations, ↓BP, abnormal ECG.
Causes Vitamin D deficiency (elderly, Asians, Africans, chronic kidney disease, intestinal malabsorption eg coeliac, Crohn’s), hypoparathyroid, acute pancreatitis, alkalosis, ↓Mg2+, alcoholism.
Symptoms Spasm of hands and feet (carpopedal), twitching muscles, tingling around the mouth, fatigue, depression, dry skin, coarse hair.
Signs Hyperreflexia, tetany, Trousseau’s (spasm of hand from inflated BP cuff) and Chvostek’s (unilateral twitching of face from tapping facial nerve 2cm anterior to auditory meatus), ↓BP, bradycardia, arrhythmias.
Investigations Blds U+E, Ca2+, PO43−, Mg2+, albumin, ALP, PTH, vitamin D ECG Prolonged QT, ST abnormalities, arrhythmias.
Treatment Treat arrhythmias according to p. 254. If tetany is severe give 10mL 10% Ca2+ gluconate IV over 10min. Always assess for and correct coexistent ↓Mg2+. If Ca2+ deficit is mild and the patient is asymptomatic, monitor. Prolonged ↓Ca2+ will need vitamin D replacement and Ca2+ supplements, eg Calcichew-D3 Forte® one tablet/24h PO.
Complications Arrhythmias, seizures, cataracts, bone fractures.
Primary hypoparathyroidism ↓PTH, despite ↓Ca2+.
Causes Iatrogenic (neck surgery, irradiation), autoimmune, metal overload.
Investigations ↓Ca2+, ↓PTH, ↑ PO43−.
Treatment Vitamin D, eg calciferol 1–2.5mg/24h PO.
Pseudohypoparathyroidism Genetic resistance to PTH, presents with ↓Ca2+ but high PTH and dysmorphic features (short stature, strabismus, short 4/5th metacarpals, low IQ, obesity);11 treat as hypoparathyroid.
Rickets/osteomalacia Rickets is the childhood equivalent of osteomalacia, both characterized by vitamin D deficiency or defect in metabolism.
• Features↓Ca2+, ↓ PO43−, ↑ ALP, decreased urine Ca2+, crush fractures, spontaneous fractures (eg of ribs), rickets rosary (prominent costochondral junctions), long bone bowing and Looser’s zones (pseudofractures, perpendicular to cortex, common in femoral/humeral necks) on X-ray
• Treatment This depends on cause, but usually simply by intake of adequate diet (egg yolk, milk, some fortified cereals); may require calciferol and Ca2+ supplements (eg Calcichew-D3 Forte® one tablet/24h PO).
Hypercalcaemia (Corrected Ca2+ >2.6mmol/L.)
► Worrying features ↓GCS, chest pain, palpitations, ↑HR, ↓BP, abnormal ECG.
Causes Primary/tertiary hyperparathyroidism, malignancy (myeloma, bone metastases, PTH-related peptide secreting tumours), excess vitamin D supplements, sarcoidosis.
Symptoms Bones (bone pain ±fractures), Stones (renal), Moans (depression), Groans (abdo pain). Also vomiting, constipation, weakness, tiredness, thirst, polyuria, weight loss.
Signs Hypertension, arrhythmias, dehydrated (shock if severe), cachexia, bony tenderness secondary to a local lesion—especially along spine.
Investigations blds FBC, U+E, Mg2+, Ca2+, PO43−, ALP; send paired sample for PTH (may have to be on ice—discuss with lab); consider ESR, serum and urine electrophoresis; ECG Short QT, arrhythmias; CXR; bone scan.
Treatment This depends upon IV fluids to correct any volume deficit, then further fluid rehydration with coadministration of 40mg/12h PO or IV furosemide; consider catheterization and CVP monitoring to assess fluid balance; monitor U+E, Ca2+, and Mg2+ daily. IV bisphosphonates (eg pamidronate 30mg in 300mL 0.9% saline over 3h) are useful in refractory hypercalcaemia. Investigate and treat the cause.
Complications AKI, arrhythmias, osteopenia, renal stones, peptic ulcers, pancreatitis.
Primary hyperparathyroidism ↑PTH from parathyroid tumour. Investigations ↑PTH, ↑Ca2+, ↑ALP, ↓ PO43−. Treatment Correct ↑Ca2+ then parathyroidectomy.
Secondary hyperparathyroidism ↑PTH caused by ↓Ca2+; treat the underlying cause of ↓Ca2+ ( p. 402).
Tertiary hyperparathyroidism Same presentation and treatment as primary, but caused by a parathyroid adenoma due to prolonged secondary hyperparathyroidism. Seen in end-stage renal failure.
Myeloma Plasma-cell malignancy secreting monoclonal immunoglobulins. Presentations include asymptomatic hypercalcaemia, renal failure, bleeding, infection or fracture.
Investigations ↑ ESR, ↑Ca2+, normal ALP, often a degree of renal impairment, monoclonal immunoglobulin band in urine or plasma (>30g/L, or >10% plasma cells on bone marrow biopsy else MGUS p. 410). Treatment Correct ↑Ca2+ as above and with pamidronate IV; give adequate analgesia. Attempted cure requires bone marrow transplant. Lesions can be treated palliatively with radiotherapy or chemotherapy. Complications Infection, CKD, haemorrhage.
Paget’s disease Excess bone remodelling leads to structurally disorganized and weakened bone prone to fracture and deformity. Typically found in axial bones of elderly.
Features ↑ ALP, Ca2+ normal (but may be raised if immobile), lytic lesions and coarse trabeculations on X-ray. Treatment Analgesia, bisphosphonates, surgery for fractures and nerve entrapment. Complications Fractures, osteoarthritis, osteosarcoma (rare), cranial nerve compression (eg new deafness), high output heart failure.
Bone mets Five cancers commonly metastasize to bone—these can be remembered as ‘BLT with Kosher Pickle’: Breast Lung Thyroid Kidney Prostate.
1 May be defined as any of: ↑creatinine of ≥26 μmol/L in ≤48h, or ≥50% in 7d (if recent bloods unavailable consider baseline values plus clinical history); or↓urine output <0.5 mL/kg/h for >6h (adults) or >8h (children); or ≥25% ↓eGFR in 7d (children only).NICE guidelines available at 
guidance.nice.org.uk/CG169
2 In prerenal states, the hypoperfused kidney attempts to conserve water and electrolytes, passing waste solutes as a maximally concentrated urine low in sodium. With tubular necrosis, concentrating ability is lost. Calculating the fractional excretion of sodium (FENa) corrects for dilution by relating sodium concentrations to creatinine (Cr): FENa = (UrineNa/PlasmaNa)/(UrineCr/PlasmaCr) × 100. FENa>1% supports a diagnosis of ATN.
3 NICE guidelines available at guidance.nice.org.uk/CG182 See also the UK renal association website www.renal.org/home.aspx for useful educational material and links.
4 There are various methods of giving an estimated GFR (eGFR). Until recently most labs use variations on a formula developed by the Modification of Diet in Renal Disease (MDRD) study group which combine age, sex, race, and serum creatinine. More recently, NICE has recommended a formula derived by the CKD-Epidemiology Collaboration (CKD-EPI) that uses the same variables. Serum cystatin C measurements increase accuracy of CKD diagnosis in those with borderline eGFR (G3a) but no other markers of kidney disease (eg ACR A1).
5 NICE guidelines available at guidance.nice.org.uk/CG174
6 Myburgh JA, et al. NEJM 2012;367:1901 available free at www.nejm.org/doi/full/10.1056/NEJMoa1209759
7 Perner A, et al.NEJM 2012;367:124 available free at www.nejm.org/doi/full/10.1056/NEJMoa1204242
8 SAFE study investigatorsNEJM 2004;350:2247 available free at www.nejm.org/doi/full/10.1056/NEJMoa040232
9 Paediatric fluid requirements are on p. 397.
10 Children are especially prone to iatrogenic electrolyte disturbances, especially hypo- and hypernatraemia, both of which can be fatal. Therefore, fluid choice requires specialist advice; 5% glucose + 0.45% saline is safe in most situations.
11 Patients with the morphological appearance of pseudohypoparathyroidism but normal Ca2+ and PTH, are said to have pseudopseudohypoparathyroidism. This is also the longest real word in the Oxford English Dictionary.