Previous hospital admissions? \200 Search your pathology system, and pull hospital notes. \200 Ask the patient s GP to check their records. 2. Ultrasound: Long-standing renal disease leads to loss of renal parenchyma and d renal size. Small (< 9 \200\223 10cm length), echo bright, often cystic kidneys are characteristic of CKD. 2 Normal-sized kidneys should arouse suspicion of AKI. A common exception is diabetic nephr opathy ( b p. 604). Lab \201 ndings suggesting AKI, rather than CKD These are rarely as h elpful as textbooks imply. Err on the side of caution (i.e. assume AKI until proven otherwi se). \200 Anemia might suggest chronic undersynthesis of erythropoietin by scarred kidney s: a normal Hb 6 argues against CKD, but anemia occurs in both AKI and CKD. d Ca 2+ and i PO 4 suggest established CKD-MBD ( b p. 232). Not so: disturbances of mineral metabolism can occur rapidly in AKI. \200 In many situations, particularly when renal si ze is normal, a kidney biopsy may be necessary to determine the nature of the renal lesion and the extent of rever sibility ( b p. 121). CHAPTER 2 Acute kidney injury (AKI) 112 AKI: priorities Make the patient safe Evaluate as for any critically unwell patient: airway , breathing, and circu- lation. The standard priorities of resuscitation initially override thoughts regarding underlying cause. 2 Does the patient require urgent level 2 or 3 care? Two additional speci \201 c questions must be addressed urgently: 2 How high is the K + ? \200 2 What is the volume status? Hyperkalaemia ( b p. 130) and p ulmonary oedema ( b p. 134) may prove rapidly lethal, if untreated. 3 Call for expert help. Care bundles and protocols, such as that provided by LAKIN (see Fig. 2.8), provide a helpful framework for prioritizing management. Look for a reversible cause Once the patient is stabilized, consider the following question s, as they may identify situations where relatively straightforward interventions can have a signi \201 cant impact. \200 Is it pre-renal ( b p. 114)? \200 Is the patient septic ? \200 Are there predisposing factors in the history? \200 Carefully assess the patient s volume and haemodynamic status. \200 Is invasive monitoring needed? Involve your criti cal care team if it is. Is it post-renal ( b p. 115)? Are there predisposing factors in the history? \200 Is there a palpable bladder or signi \201 cant urinary tract symptoms? \200 What does the urine look like \200\224 any haema turia? \200 Arrange an urgent USS. What is on the drug chart ( b p. 7)? \200 Stop all nephrotoxins, if possible. \200 Has any radiocontrast been administered? \200 Have you dipsticked the urine ( b p. 116)? \200 2 Do it now \200\224 you may forget later. AKI: PRIORITIES 113 AKI care bundle Institute in all patients with a 1.5 \227 rise in creatinine or oliguria (0.5 mL/kg/h) for >6 hours This is a medical emergency Full set of physiological observations Assess for signs of shock/hypoperfusion If MEWS trig gering, give oxygen, begin resuscitation, and contact critical care outreach team Fluid therapy in AKI Assess heart rate, blood pressure, jugular venous pressure, capillary refill (should be <3 s), conscious level. If hypovolaemic, give bolus fluids (e.g. 250 \200 \223500 mL) until volume replete with regular review of response. Middle grade review if >2 litres filling in oliguria. If the patient is euvolaemic, give maintenenance fluids (estim ated output plus 500 mL) and set daily fluid target. Monitoring in AKI Do arterial blood gas and lactate if venous bicarbonate is low or evidenc e of severe sepsis or hypoperfusion. Consider insertion of urinary catheter and measurement of hourly urine volumes. Measure urea, creatinine, bone, other electrolytes, and venous bi carbonate at least daily while creatinine rising. Measure daily weights, keep a fluid chart , and perform a minimum of 4-hourly observations. Perform regular fluid assessments and che ck for signs of uraemia. Investigation of AKI Investigate the cause of all AKI unless multi-organ failure or obvious precipitant Urine dipstick. If proteinuria is present, perform urgent spot urine protein c reatinine ratio (PCR). USS should be performed within 24 hours unless AKI cause is obvious or AKI is recovering or within 6 hours if obstruction with infection (pyonephrosis) is susp ected. Check liver function (hepatorenal), CRP, and CK (rhabdomyolysis). If platelets low, do blood movie/LDH/Bili/retics (HUS/TTP). If PCR high, consider urgent Bence \200\223Jones protein and serum free light chains. Supportive AKI care Treat sepsis \200\224in severe sepsis, intravenous antibiotics should b e administered within 1 hour of recognition. Stop NSAID/ACE/ARB/metformin/K-sparing diureti cs, and review all drug dosages. Give proton pump inhibitor and perform dietetic assessment . Stop antihypertensives if relative hypotension. If hypovolaemic, consider stopping diuret ics. Avoid radiological contrast if possible. If given, follow prophylaxis protocol. Causes Think \200\230STOP AKI \200\231 Sepsis and hypoperfusion, Toxicity (drugs/contrast) , Obstruction, Parenchymal kidney disease (acute GN) Fig. 2.8 The LAKIN AKI care bundle. Reproduced from London AKI network manual (2012), with permission. M http://www.londonAKI.net/clinical CHAPTER 2 Acute kidney injury (AKI) 114 Assessing AKI: clinical clues Pre-renal AKI History ( b p. 104) \200 Any cause of d intra vascular volume? Inadequate \202 uid intake, hemorrhage, GI losses, renal losses, skin losses, third-space losses. \200 Any cause of cardiac pump failure? \200 Any evidence f or sepsis? Clinical examination ( b p. 12) \200 Assessment of volume status is fundamenta l to diagnosis: BP: check lying and standing, if possible. \200 Heart rate: check lying and standing, if possible. \200 Peripheral perfusion: Warm with bounding pulse l vasodilatation (? sepsis). Cold and shut down with d capillary r e \201 ll l volume \200\224 \200\224 depletion or low cardiac output. d JVP: hypovolaemia or vasodilatation (may be i with pump failure). \200 Peripheral and p ulmonary oedema. \200 Urine output. Poor signs of volume depletion Dry mucous membranes (most sick patients mouth-breathe). \200 d skin turgor (better sign in children). Classically 1. Volume depletion (hypovolaemic or haemorrhagic shock): \200 (Postural) hyp otension. \200 May be peripherally shut down. \200 JVP d . 2. Poor cardiac output (card iogenic shock): \200 Hypotension with narrow pulse pressure. \200 Peripherally shut dow n (often very). \200 JVP i . 3. Systemic vasodilatation (septic shock): \200 Hypotensio n with i pulse pressure. \200 Peripherally warm. \200 JVP d . Intrinsic renal AKI Large renal vessels History \200 Cardiovascular: CV risk: smoking, diabetes, lipids, i BP, age. \200 CV disease: claudication and PVD, str oke, IHD. \200 CV intervention: invasive/endovascular radiological procedures, vascular surgery. ASSESSING AKI: CLINICAL CLUES 115 Source of emboli: AF, prosthetic valve, cardiomyopathy, thrombophilia tendency. Nephrotic syndrome: renal vein thrombosis ( b p. 590). Examination AF, missing pulses, dila ted heart, bruits, aortic aneurysm, ischaemic toes, i BP (though very non-speci \201 c), o edema (? nephrotic). Small renal vessels and glomeruli History No other cause evident; recent infection, particu larly skin or throat (post-streptococcal GN); symptoms suggesting a deep-seated infection ( fevers, night sweats); known systemic disorder, e.g. SLE, scleroderma, vasculitis; symptoms suggesting an underlying connective tissue disorder or vasculitis ( b p. 5). Examination R ash, i BP, oedema, synovitis, arthropathy, uveitis, mouth ulcers, epistaxis, hearing loss, stigmata of endocarditis, evidence of scleroderma or other connective tissue disorder, abno rmal respiratory \201 ndings (pulmonary-renal syndrome). Investigations Urinalysis ( b p. 116), abnormality in immunological/serological testing ( \200\230 renal \200\231 or \200\230nephritic/myeloma \200\231 screen) ( b p. 119), and r enal biopsy may be required ( b p. 121). Tubulointerstitium History Drugs ( b p. 7); system ic infection: many are associated, including TB ( b p. 698). Systemic diseases: myeloma, sa rcoidosis, Sj gren s syndrome, SLE, uveitis (tubulointerstitial nephritis and uveitis (T INU) syndrome ( b p. 581)). Examination Fever or rash, easy bruising in multiple myeloma. Investigations Eosinophiluria on urine microscopy/cytology, eosinophilia in peripheral bloo d (neither are universal). Post-renal ( b p. 730) History LUTS, prostate disease, urothelia l cancer, stones, pain, haematuria. Examination Palpable bladder? Visible haematuria? Investigation Early urinary tract imaging (usually USS) is essential. CHAPTER 2 Acute kidney injury (AKI) 116 Assessing AKI: urinalysis 2 The only excuse for not performing a urine dipstick is if a pat ient is completely anuric! Urinalysis \201 ndings can point to a diagnosis, particularly for glomerulone- phritis and other intrinsic renal lesions (see Fig. 2.9). \200 Perform a dipstick (yourse lf), and document the result . If there is signi \201 cant blood and protein on dipstick: (i) exclude a UTI; (ii) conside r an immunological/serological screen ( \200\230 renal \200\231 or \200\230nephritic/mye loma \200\231 screen, b p. 119). 2 Seek expert help. Note: 1 blood will often be present p ost-catheterization. Send an MSU for microscopy and culture. \200 uPCR or uACR if signi \201 cant dipstick pr otein. Urine biochemistry Included here for completeness only. While still beloved of postgraduate examiners, urine biochemistry is of limited value in everyday practice. (See Table 2.3.) In pre-renal AKI, tubular function is intact with avid salt retention, whereas, in establis hed ATN, the resorptive and concentrating capacity of the kidney is lost. Urinary biochemic al indices can 6 differentiate the two. \200 \200\230 Typical \200\231 pre-renal AKI: d u-Na + , i Ur, i SCr in the urine; u-osmolality high. \200\230 Typical \200\231 ATN: i u-Na + , d Ur and d SCr in the urine; u-osmolality relatively low. 1 Problems \200 Not suf \201 ciently sensitive or speci \201 c. Rarely in \202 uences management. \200 Diuretics confound the analysis ( l dilute urine with i Na + content). \200 There are exceptions that biochemically appear pre-renal but are not: hepatorenal syndrome, contrast nephropathy, early obstruction, acute GN, and vasculiti s. Table 2.3 Urine biochemistry in urinalysis Urine biochemistry Pre-renal ATN Urine speci \201 c gravity Urine osmolality (mOsm/kg H 2 O) Urine:plasma osmolality >1.020 <1.010 >500 <350 >1.5 <1.1 Urinary Na + (mmol/L) Fractional Na + excretion % (FE Na+ ) 1 best index! Fractional urea e xcretion % (FE urea ) Plasma urea:creatinine ratio <20 >40 <1 >2 <35 >35 >10 <15 Urine:plasma urea ratio >8 <3 Urine:plasma creatinine ratio >40 <20 Renal failure index 2 1 (urine Na + /plasma Na + )/(urine Cr/plasma Cr) x 100. 2 urine Na + /(urine creatinine/plasma creatinine) x 100. <1 >1 ASSESSING AKI: URINALYSIS 117 l a i t i t s r e t n o u b u T - a i r u n e t o r p a m s a l p a i s a r c s y d e d a r g - w o L r o a m o e y M i i e s a e s i d l r e h t o l l l e c l o c y l g s i s y l y h t a p o r h p e n a i r u ) e m o r d n y s l l a t s y r C e n e l y h t E r u o m u t ( s g u r D e t a r U s t s a c , N G e t u c a ( ) s i t i l d n a l l e c u c s a v l a i l r a l u n a r G N T A e h t i p e a i r u n b o l g o m e a H s t s a c a i r u n b o l g o y M i t n e m g P i i e n o l a F R A N G e t u c A l a n e r - t s o P - a i r u t a m e a H s i t i l a m u a r T - u c s a V - . I l a i t i t s r e t n K A n c i l s l i o b m e o r e h t A h p o n i s o E i s i t i r h p e n y p o c s o r c m e n i r u i e s a e s i d e t u c A l a m r o n b A i l a i t i t s r e t n s t s a c s i t i r h p e n o e y P - n o i t c u r t s b O s l l l l e c e c s i t i r h p e n i e t i h e t i h e t u c A d n a l W W s i s y l a n i r u e n i r u d n a F R A n y h t a p g n a o r c m d e r s t s a c c i t o b m o r h T - r o c i t i r h p e n ( ) e n i r u c h p r o m s y D i N G e t u c A i i a i r u n e t o r P y p o c s o r c i m s i t i l i s l l n o s g n d n \201 s i s y l a n i r U l l e c e c u c s a V - i e v i t c a s l l d e R d e R i e c i e v i t c a n i / n g n e b / d n a l B l a i t i t s r e t n o u b u T - e h T y e n d k F R A , F R A i l o b m e o r e h t A - a m r e d o r e l c S e h p o r t s a t a c i l a n e r - t s o P a m o e y M 9 2 l a n e r - e r P r a l u c s a V - i l a m r o N i . e s a e s i d l l , N T A . g i F CHAPTER 2 Acute kidney injury (AKI) 118 Assessing AKI: blood tests Managing AKI requires regular and informed testing. Order invest igations sensibly and cumulatively \200\224 do not just request everything listed here. He matology \200 FBC: d Hb develops early, typically 80 \200\223100g/L. 1 Haemolysis, GI bleeding. \200 i WCC: infection (rarely tissue infarction or vasculitis). Eosinophilia is a rare feature of TIN a nd cholesterol emboli. d WCC: severe sepsis (rarely SLE). d plt: DIC or thrombotic microangiopathy ( l check clotting and ask for a blood \201 lm). i plt: in \202 ammatory disorder, e.g. vasculitis. \200 Pancytopenia: ? marrow in \201 ltration (? myeloma or other malignancy). Clotting: ? Liver disease ( i INR) or DIC ( i PT, i APTT, i D-dimers). Group and save if anemic. \200 i ESR with any in \202 ammatory condition but esp. myelom a and SLE. \200 Blood \201 lm if d plts or ? microangiopathy: Fragmented red cells. If found, send LDH, haptoglobins, reticulocyte count. Biochemistry \200 U&E: i plasma Ur:Cr ratio may indicate pre-renal AKI (but see b p. 37). \200 i K + . 3 Needed urgently. \200 Na + usually normal; d Na + occurs if volume overload or diuretics. \200 d venous HCO 3 \200\223 l metabolic acidosis (if normal with normal O 2 saturation, then ABG may not be necessary). LFTs: d albumin may imply proteinuria and GN. \200 ? i bilirubin, ? hepatorenal syndrome ( b p. 156)? paracetamol overdose. 1 i transaminases may be of muscle origin l check the CK. Ca 2+ and PO 4 : i Ca 2+ is a cause of AKI (? myeloma, sarcoidosis, malignancy). \200 d Ca 2+ and i PO 4 a re present in most cases. CRP for infection or in \202 ammation. Procalcitonin if available. \200 Creatine kinase (CK) if rhabdomyolysis likely. \200 Urate if tumor lysis or pre-eclampsia possible. \200 Lactate to assess tissue ischaemia or underperfusion. Microbiology Culture urine and bloo d if any clinical suspicion of sepsis. Arterial blood gas ABG and lactate are necessary if venous HCO 3 \200\223 is low (or unavailable) or there is evidence of sepsis, hypotension, or clinical deterioration. Minimum AKI panel \200 Urine dipstick. \200 FBC, U&E, Ca 2+ , phosphate, albumin, LFT, CK, and CRP. \200 Venous HCO 3 \200\223 or ABG. ASSESSING AKI: BLOOD TESTS 119 Immunological/serological testing (the \200\230renal \200\231 or \200\230nephritic/myelom a \200\231 screen) (Some) of these may be needed if intrinsic AKI (besides ATN) is sus- pec ted (e.g. active urine 9 systemic symptoms). However, common sense is required. There is no role for the re \202 ex ordering of these in the majority of AKI (costly and require care ful clinical correlation). Anti-nuclear antibodies (ANA) The serological hallmark of many autoimmune diseases. Further de \201 ned by speci \201 c target antigens. Where clinical suspicion is strong, the spe ci \201 c assay may be necessary despite a negative ANA ( b p. 42). 1 False +ve ANAs are c ommon. Anti-neutrophil cytoplasmic antibodies (ANCA) Autoantibodies directed against components of neutrophil cytoplasm, characteristic of small vessel vasculitis ( b p. 642). Two patterns: \200 Cytoplasmic (cANCA): antigen usually proteinase 3 (PR3). \200 Perinuclear (pANCA) : antigen usually myeloperoxidase (MPO). Anti-glomerular basement membrane antibody (anti-GBM) Highly sensitive and speci \201 c fo r anti-GBM disease ( b p. 656). Anti-streptolysin O titres (ASOT) Post-streptococcal GN is the historical prototype for the acute nephritic syndrome, though incidence is falling ( b p. 548). Sensitive for the diag- nosis of streptococcal pharyngitis but less so for skin in fections. Protein electrophoresis (serum and urine) Plasma cell dyscrasias: serum protein electrophor esis (SPEP), urine pro- tein electrophoresis (UPEP), serum free light chains (SFLC). Immunoglobulins (IgG, IgA, and IgM) Diffuse increase in vasculitis, SLE (and other connecti ve tissue disor- ders), and HIV infection. Immune paresis in myeloma. Rheumatoid factor (RhF) May be +ve in RA associated vasculitis ( b p. 669) or cryoglobulina emia ( b p. 634). Viral serology Hep B is associated with PAN ( b p. 652), hepatitis C with mixed essential cryoglobulinaemia ( b p. 686). HIV may present in many ways involving the kidney. 2 It is desirable to know the viral status prior to haemodialysis. Cryoglobulins ( b p. 634) Consider if unexplained rash, peripheral neuropathy, hypocomplemen- taemia, known hep C, known lymphoproliferative disorder, or +ve RhF (a useful screening test). The sampl e needs to be transported at 37 C, so bleed the patient and transportation the sample yo urself (in a water bath \200\224 an armpit is 2nd best) within minutes. Warn the lab it is coming. Antiphospholipid antibodies Associated with the primary antiphospholipid syndrome ( b p. 66 4). Liaise with your haemostasis laboratory. CHAPTER 2 Acute kidney injury (AKI) 120 Assessing AKI: imaging CXR 3 Perform a CXR (urgently if tachypnoea, d O 2 sats, haemoptysis , sus- pected infection, or signi \201 cant associated primary lung disease). The key \201 ndings are pulmonary oedema, respiratory infection, and pul- monary hemorrha ge (all l air space shadowing that may look identical). However, additional useful information may be gathered: \200 Cardiac contour \200\224 ? LVH consistent with long-standing i BP, ? pericardial effusion. Hilar lymphadenopathy, lytic lesions. Renal ultrasound 3 Perform an USS of the renal tract as soon as possible (within hours if s uspected pyonephrosis). Imaging rarely makes a speci \201 c diagnosis but has two principal aims: To exclude obstruction ( b p. 732). \200 To con \201 rm the presence of two kidneys and measure renal length. Renal length is used as a surrogate for the time course of renal impa irment. Long-standing CKD l parenchymal scarring, loss of renal volume and length. \200 > 10 \200\223 11cm = normal ( 6 probable AKI). \200 <8 \200\223 9cm ( 9 acquired cysts) s uggests CKD. Isotope studies in AKI \200 Certainly not \201 rst-line but (very) occasionally helpful : Acute loss of renal perfusion associated with renal artery occlusion or embolism can be diagnosed with nuclear renography (e.g. MAG 3 scan). Cortical necrosis (after severe haemorrhagic shock, particularly post-partum) will be demonstrated. AKI accompanying early vascular complications in the immediate post-transplantation setting can be evaluated. In experienced hands, recovery from ATN can be assessed, though it is rarely clinically useful. In partial obstruction, delayed transit in the ureteric phase can be helpful. ASSESSING AKI: HISTOLOGY 121 Assessing AKI: histology Role of the renal biopsy in AKI (see also b p. 82) Required in a m inority of cases only. Consider once pre- and post-renal factors have been addressed and wh ere \200\230non-ATN \200\231 intrinsic AKI is sus- pected. In ATN, the prognosis for rena l recovery is generally good, and histological veri \201 cation will not alter management. The principal aims of biopsy are to: Establish a tissue diagnosis. \200 Assess prognosis (is renal function salvageable?). \200 Guide therapy. Potential indications \200 Unexplained AKI (initial work-up unhelpful/equivocal). \200 Suspected glomerular disease: Haematuria 9 casts, signi \201 cant proteinuria, marked i BP ( 1 control BP \201 rst). Serological or other evidence of systemic disease: For example, ANCA, ANA, anti-GBM, paraprotein. Suspected thrombotic microangiopathy (HSP/TTP). \200 Presumed ATN persists (e.g. >2 weeks , esp. if dialysis-dependent). \200 Pre-existing glomerular disease. \200 Suspected TIN /drug allergy. \200 Suspected atheroembolic disease. \200\230Non-ATN \200\231 intrinsic renal disease presenting as AKI \200 Acute primary GN ( b p. 536). \200 Systemic vasculitis affecting the kidney ( b p. 638). \200 Infection -associated GN ( b p. 548). \200 Thrombotic microangiopathies ( b p. 574). \200 Acute T IN ( b p. 580). \200 Myeloma cast nephropathy ( b p. 622). \200 Atheroembolic disease ( b p. 590). CHAPTER 2 Acute kidney injury (AKI) 122 AKI management: a checklist Despite a multitude of potential causes, several general princi ples apply to the management of AKI. See AKI bundle on b p. 113. Where can I \201 nd information on ? \200 Resuscitating volume deplete pre-renal AKI? ( b p. 124) \200 Managing hyperkalaemia? ( b p. 131) \200 Managing volume overload and pulmonary oedema? ( b p. 134) \200 Managing acidosis? ( b p. 136) \200 Maintaining nutrition? ( b p. 140) \200 Instituting dialysis? ( b p. 172) \200 Speci \201 c cause s of AKI: \200 ATN? ( b p. 106) \200 Hepatorenal syndrome? ( b p. 156) \200 Contrast nephrotoxicity? ( b p. 148) \200 Tumor lysis? ( b p. 160) \200 Septic shock and AKI? ( b p. 168) Post-renal failure and acute obstruction? ( b p. 730) Have you \200 Seen the result of the serum K + and acted appropriately? \200 Asse ssed the patient s volume status and: Satis \201 ed yourself that, clinically and radiologically, the patient is not in pulmonary oedema? Adequately corrected volume depletion? Taken a full history and examined the patient from head to toe? \200 Excluded a palpable bladder? \200 Seen a list of all the patient s drugs? If they are an inpatient, have you checked their drug chart, including the \200\230prn \200\231 side? Stopped nephrotoxins, if possible? \200 Performed a urinalysis and sent an MSU for M,C+S? \200 Arranged an urgent ultrasound? \200 Checked the Hb 9 sent a group and save? \200 Tried to \201 nd any historical tests of renal function? \200 Checked serum Ca 2+ and PO 4 9 written up a phosphate binder? \200 Checked acid \200\223 base status and interv ened appropriately? \200 Arranged for the patient to be nursed in a suf \201 ciently hig h dependency environment, with strict monitoring of \202 uid intake and output? Spoken to your dietitian? \200 Discussed the patient with your local renal unit if needs be? \200 If intrinsic AKI is suspected, sent off a nephritic and myeloma screen? AKI MANAGEMENT: A CHECKLIST 123 Questions you will be asked when referring to a renal unit \200 What \200\231s the story? \200 What \200\231s the potassium? \200 What \200\231s the patient \200\231s volume an d haemodynamic status? Are they dehydrated, overloaded, or about right? How do you know? Is there anything else of note on clinical examination? \200 What \200\231s the patient \200\231s acid \200\223 base status? \200 What drugs has the patient been on? \200 Wha t did the urine dipstick show? \200 Has the patient had a renal ultrasound? \200 Is the patient passing urine? How much? \200 Do you have any record of a previous eGFR/serum cr eatinine? \200 What comorbidity does the patient have? \200 Is the patient \201 t for transfer? Are you sure (see Fig. 2.10 below)? See Fig. 2.10 for LAKIN guidelines on transf erring to a renal unit. Transfer from ward to kidney unit (interhospital transfer) The following is a guideline for whether patients are safe to transfer from a ward to a kid ney unit in another hospital. All AKI 3 patients or patients with complications should also be assessed as safe for transfer by a middle grade doctor and, if necessary, by the home c ritical care team Hyperkalaemia No ECG changes. K<6.0mmol/L. If K lowered to <6.0 after presentation this mus t be potentially sustained (e.g bicarbonate therapy or dialysis/CVVH) not transient therapy (insulin and dextrose). Renal acidosis pH >7.2. Venous bicarbonate >12mmol/L. Lactate <4mmol/L. Respiratory Respiratory rate >11 and <26/min. Oxygen saturations >94% on not more than 35% oxygen. If patient required acute CPAP must have been independent of this treatment for 24 hrs. Circulatory Heart rate >50/min and <120/min. Blood pressure >100mmHg systolic. MAP >65mmHg. Lactate <4mmol/L. (Lower BP values may be accepted if it has been firmly established these are pre-morbid.) Neurological Alert on AVPU score or GCS >12. If criteria not met, emergency referral to local critical care Once stabilized follow ITU t o acute kidney unit transfer policy. Fig. 2.10 LAKIN guidelines for transfer to a renal unit. Reproduced from London AKI network manual (2012), with permission. M http://www.londonAKI.net/clinical CHAPTER 2 Acute kidney injury (AKI) 124 AKI management: volume replacement \200\224which \202 uid? Prompt \202 uid resuscitatio n reverses pre-renal AKI. However, there is increasing evidence that \202 uid overload is harmful and 6 needs to be avoided. 2 The key to achieving euvolaemia is repeated clinical assess- ment of a patient s volume status. Which \202 uid? Crystalloids See Table 2.4 for composition of cystalloids. Isotonic saline 0.9% isotonic remains the benchmark against which other solutions are measu red. However, despite its other pseudonyms, it is neither \200\230nor- mal \200\231 nor \200\230physiological \200\231 . In fact, there is evidence that it may be harmful. Excess ive use of saline can result in hyperchloraemic acidosis. X Although the morbidity associat ed with this condition is probably low (isotonic saline has been in use for 50 years), it h as informed a move towards the use of balanced solutions. Balanced crystalloids Refer to solutions with an electrolyte composition closer to plasma. The 2009 British consensus guidelines on intravenous \202 uid therapy for adult surgical patients recommended the use of balanced crystalloids over saline. Furthermore, the recent UK AKI consensus statement includes the recommendation that balanced crystalloids are used, unless patients are hypochloraemic or hyperkalaemic (balanced crystalloid solutions, such as Hartmann \200\231s and Ringer \200\231s solutions, contain 5mmol/L K + and must be used with caution). X Critics of such guidelines say that, while the move to balanced crystalloi ds is unlikely to cause harm, bene \201 ts are likely to be marginal only. Hypotonic crystalloids 0.45% ( \200\230 half normal \200\231 ) saline and 5% glucose dist ribute rapidly throughout total body water and are of limited use for the restoration of in travascular volume. Avoid unless true water depletion (hypernatraemia, b p. 788). Sodium bi carbonate \200\230 Weak \200\231 NaHCO 3 solutions (e.g. 1.26% or 1.4%) can be useful in volume-depleted, acidotic (pH <7.15) 9 hyperkalaemic patients ( b p. 131). Use with crystal loid, e.g. in a ratio of 1L NaHCO 3 to every 2 \200\223 3L of NaCl. 1 Avoid stronger (4.2% or 8.4%) solutions, and monitor for d Ca 2+ . AKI MANAGEMENT: VOLUME REPLACEMENT \200\224WHICH FLUID? 125 Table 2.4 Composition (mmol/L) of commonly available crystalloids Electrolyte Plasma (typical) Isotonic saline Example balanced crystalloid, e.g. Hartmann s, Ringer s lactate Sodium 140 154 131 Potassium 5 0 5 Chloride 100 154 111 Calcium 2.2 0 2 Magnesium 1 0 1 Bicarbonate 24 0 0 Lactate 1 0 29 Synthetic colloids Solutions contain oncotically active ingredients (e.g. hydroxyethyl star ch or gelatin) that remain in the intravascular compartment and pull in extravascular water . Effective volume expanders, but evidence suggests that starch-containing solutions may wo rsen AKI. Examples include Gelofusine and Haemaccel \200\224 both gelatin-based. The use of \211 1000 \200\223 1500mL may deplete clotting factors and i bleeding risk. Seve re allergic reactions have been reported to all types of colloid. 2 The recent UK consensus statement on AKI and guidelines from the European Society of Intensive Care Medicine recom mends that colloid (including gelatin-based) solutions be avoided. Human albumin solutions \200\230 Physiological colloid \200\231 . Expensive. Although a C ochrane meta-analysis con- cluded that its use was associated with i mortality in the criti cally ill, the more recent (and well-designed) SAFE study suggested equivalence with saline (and bene \201 t in the subgroup of patients with sepsis). Many favor its use when volume depletion occurs in the context of hypoalbuminaemia. Proven bene \201 t also in AKI in th e context of cirrhosis with spontaneous bacterial peritonitis ( b p. 158). The results of t he Albumin in Severe Sepsis and Septic Shock (ALBIOS) study, in which patients with severe sepsis were randomized to either albumin or crystalloid for resuscitation, will be availabl e in 2013. \200 Isotonic (4 \200\223 5%). Usually 100 \200\223 500mL bottles. Used to r estore circulatory volume. Concentrated (20 \200\223 25%). Usually 50 \200\223 100mL bottles. Used to expand circulatory volume when general salt and water restriction is desirable, i.e. an oedematous , hypoalbuminaemic patient who is intravascularly depleted (e.g. nephrotic syndrome, cirrho sis). CHAPTER 2 Acute kidney injury (AKI) 126 AKI management: volume replacement \200\224how much? See Figs 2.11 and 2.12 for guidelines on \202 uid therapy and AKI complica- tions, respectively. How much \202 uid? The volume required to restore euvolaemia is the volume that improves clinical signs of \202 uid depletion. These include: \200 Reducing tachycardia. \200 Improved peripheral perfusion. \200 Rising BP ( 2 check for postural drop, if possible). If d BP, despite apparently adequate \201 lling, consider cardiogenic or septic shock. Visible JVP. \200 Improving UO. 1 Beware volume overload: i P, i BP, i RR, basal lung cra ckles, d O 2 sats. How quickly? Resuscitation See b p. 168 for initial management of severe sepsis and sepsis-induced shock. In other situations, the aim is to infuse \202 uids ( 9 blood products) rapidly to restore BP and tissue perfusion. If in doubt, trial of 200 \200\223 300 mL crystalloid fast IVI, and reassess clinical parameters. Repeat, as required . Replacement If the patient is not shocked, the optimal infusion rate depends on: (i) degree of hypovolaemia; (ii) ongoing losses; (iii) whether oligo-anuric; (iv) CV status. The following is a rough guide to getting things underway ( 1 slower in the elderly and in those with poor LV function): \200 First liter over 2h, then reassess. \200 Second liter over 4h, then reassess. \200 Third liter over 6h, then reassess . In the face of ongoing losses (e.g. diarrhea), input should aim to exceed measured and unmeas ured (insensible, 7 30mL/h) losses by 100mL/h. If you think you may have overdone it, stop \202 uids and reassess the patient. Maintenance Once euvolaemic, and assuming no other losses, match UO + 30mL on an hourly bas is. Insensible losses will be higher in a febrile patient. 2 Reassess the patient at least twice a day. AKI MANAGEMENT: VOLUME REPLACEMENT \200\224HOW MUCH? 127 When do you need a central line? \200 Not often; however, bedside assessment can be probl ematic. Although generally straightforward when the patient is profoundly volume-depleted, it is mu ch more dif \201 cult to judge when a patient is at the point of euvolaemia and 6 no longe r in need of \202 uid. Despite this, clinical assessment remains the cornerstone \200\224 it is an important skill and improves with practice. If you are not experienced enough to assess volume status clinically, then you are unlikely to be experienced enough to use invasive monitoring correctly. If in doubt, speak to your critical care. \200 Stand-alone CVP measurements do not correlate well with intravascular volume status (although trends following a \202 uid bolus may be helpful). 2 Putting a central lines into a hypovolaemic patient is not easy and offers a signi \201 cant risk of complication. The UK consensus AKI statement does not advocate a CVP line for the routine management of AKI. However, a CVP may be useful in AKI in conjunction with: \200 Septic shock and capillary leak. \200 Cardiogenic shock or where the CV status is precarious and you feel it would b e dangerous, or unwise, to give signi \201 cant \202 uids without a more accurate baseli ne and continuous monitoring. The need for vasoactive medications (e.g. noradrenaline). \200 There are other non-invasi ve tests that are being increasingly used to assess volume status, e.g. IVC diameter on ult rasound ( b p. 13.) CHAPTER 2 Acute kidney injury (AKI) 128 Fluids Adult resuscitation or replacement fluids Adult maintenance fluids Baseline requirements 50 \200\223100mmol sodium, 40 \200\22380mmol potassium, and 1.5 \200 \2232.5L water per 24 hours Oral, enteral, or parenteral route Give according to clinical scenario General volume replacement or expansion Give balanced crystalloid solutions (Hartmann \200 \231s solution/Ringer \200\231s lactate) These contain small amounts of potassium. Avoid in hyperkalaemia. If AKI, only use these if close (HDU) monitoring of potassium or Colloids A void high molecular weight (>200kDa starches in severe sepsis due to risk of AKI Assess vit al signs, postural blood pressure, capillary refill, JVP, and consider invasive or non-inva sive measurement using flow-based technology Adjust estimated requirements according to changes in sensible or insensible losses Insensible losses Respiration Perspiration Metabolism Increase in pyrexia or tachypnoea (ma inly water) Sensible losses (measurable) Surgical drains Vomiting Diarrhea Urine (variable amounts of e lectrolytes) Hemorrhage Give blood and blood products Balanced crystalloid or colloid may be given while blood awaited Clinical assessment as above Regular assessment of volume and hydration status Daily weights Fluid charts Measured elect rolytes Severe free water losses (hypernatraemia) 5% glucose or 4%/0.18% glucose/saline Available parenteral solutions (if required) Hartmann \200\231s solution/Ringer \200\231s l actate Normal saline 5% glucose 0.4%/0.18% dextrose/saline Potassium usually added addition ally Hypochloraemia (vomiting, NG drainage) Give normal saline (Potassium repletion usually also required) Fig. 2.11 AKI \202 uid therapy. Reproduced from London AKI network manual (2012), with pe rmission. M http://www.londonAKI.net/clinical AKI MANAGEMENT: VOLUME REPLACEMENT \200\224HOW MUCH? 129 AKI complications Hyperkalaemia, acidosis, pulmonary oedema, reduced conscious level Begin medical therapy and get help Local critical care team and Local nephrology team (if onsite) Hyperkalaemia Medical therapy of hyperkalaemia is a transient measure pending imminent reco very in renal function or transfer to kidney unit or critical care for renal replacement th erapy. If ECG change, give calcium gluconate 10mL 10%. If bicarbonate <22mmol/L and no flui d overload, give 500mL 1.26% sodium bicarbonate over 1 hour. K >6.5mmol/L or ECG changes, g ive insulin 10IU in 50mL of 50% glucose over 15 minutes and salbutamol 10mg nebulized (caut ion with salbutamol in tachycardia or ischaemic heart disease). Insulin/glucose and salbuta mol reduce ECF potassium for <4 hours only. Acidosis Medical therapy of acidosis with bicarbonate reserved for emergency management of hyperkalaemia (as above) pending specialist help. pH <7.15 requires immediate critical care referral. Pulmonary oedema Sit the patient up and give oxygen (60 \200\223100% unless contraindicated ) If haemodynamically stable, give furosemide 80mg IV. Consider repeat bolus and infusion a t 10mg/hour If haemodynamically stable, commence GTN 1 \200\22310mg/hour titrating dose. Reduced conscious level Manage uraemic coma as per all reduced consciousness (airway manage ment) pending critical care transfer and emergency renal replacement therapy. These are holding measures prior to specialist help from critical care or nephrology servic es Fig. 2.12 AKI complications from London AKI network manual. Reproduced from London AKI netw ork manual (2012), with permission. M http://www.londonAKI. net/clinical CHAPTER 2 Acute kidney injury (AKI) 130 AKI management: hyperkalaemia In excitable tissues, i K + l depolarization of the membrane resting poten- tial l Na + channel inactivation l d membrane excitability l neuromuscu- lar depression and cardiac dysrhythmias. What represents a dangerous i K + ? \200 Chronically hyperkalaemic patients may tolerate i K + of 6.0 \200\223 7.0mmol/L ( 2 but treat if >6.5mmol/L). 1 However, an acute i K + in AKI is much less likely to be tolerated, particularly if: (i) elderly; (ii) associated cardiac disease (esp. arrhythmias); (iii) oli guria (cannot excrete i K + ). Closely monitor ( l cardiac monitor, repeat serum K + 2 \200\223 4-hourly) all patients wi th i K + acutely >6.0mmol/L, and commence treatment to enhance K + wasting. 3 Treat to urgently lower serum K + if \211 6.5mmol/L. 1 Although U&E are often repeated to exclude haemolysis or artifact, this should cause delays l put on a cardiac monitor, and start treatment. The hyperkalaemic ECG ECG manifestations of i K + are manifold (see Fig. 2.13). 1 Mild ECG changes can progress to life-threatening disturbances very quickly. All may be exacerbated by coexisting d Ca 2+ and acidosis. 1 A normal ECG does not rule out cardiac instability. \200 Peaking of T waves ( \200\230 tenting \200\231 ). \200 Flattening and disappearan ce of P waves. \200 Prolonged PR interval ( p heart block). \200 Progressive widening o f the QRS complex. Rising K+ Deepened S waves and merging of S and T waves. Idioventricular rhythm. \200 Sine wave pattern. \200 VF and asystolic cardiac arrest. Peaked T Loss of P Reduced R y t i r e v e S Wide QRS T R S Sine wave Fig. 2.13 The ECG changes of hyperkalaemia. AKI MANAGEMENT: HYPERKALAEMIA 131 3 Treatment of dangerous hyperkalaemia The following d serum K + acutely but DO NOT d overa ll elevated total body K + . Additional measures, described on b pp. 132 \200\223133, are 6 also required. Calcium \200 If K + \211 6.5mmol/L or ECG changes. \200 2 Ca 2+ is cardioprotective \200\224 it does not d K + . \200 Antagonizes membrane K + effects by poorly understood m echanisms. 10mL 10% calcium gluconate (usually 1 ampoule \200\224 calcium gluconate contains 220 mol Ca 2+ /mL), or 5mL 10% calcium chloride (usually half an ampoule \200\224 CaCl 2 contains 680 mol Ca 2+ /mL). Give over 2 \200\223 5min. Repeat if no ECG improvement after 5min (up to 40mL calcium gluconate). Acts within minutes, but protective effect lasts <1h . \200 1 Can induce digitalis toxici ty ( l a pragmatic approach: halve the initial dose, and give more slowly if taking digoxin). Insulin and glucose \200 If K + \211 6.5mmol/L or ECG changes. \200 Insulin binds to its cellular receptor and i Na-K-ATPase activity, moving K + into cells. Glucose alone will d K + through endogenous insulin release, but ins ulin/glucose is more effective.