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. 10 \200\223 15IU of soluble insulin (e.g. Actrapid ) in 50mL of 50% glucose IVI over 10 min (alternative: 5IU of soluble insulin in 50mL 20% glucose over 15min by syringe pump and repeated). 50% glucose is extremely viscous and irritant. Find a large vein, and \202 ush with saline afterwards. Effect within 15 \200\223 30min (peak 7 60min), lasts for 2 \200\223 4h. Expect a d of 0.5 \200\223 1.5mmol/L. Can be repeated after 4h. Check BMs regularly for 6h, and infuse 10% glucose IVI if d glucose. Sodium bicarbonate \200 If i K + in the presence of acidosis (HCO 3 \200\223 <16) and vo lume depletion. \200 i Na + /H + exchange l i intracellular Na + l i Na-K-ATPase activity (i.e. K + in for Na + out). Additional pH-independent mechanisms operate. 1.26% or 1.4% solutions as 200 \200\223 500mL over 15 \200\223 60min IVI. \200 In cardi ac arrest: 50mL of 8.4% (1 ampoule) IVI. \200 1 CAUTION: do not infuse bicarbonate soluti ons into the same cannula as calcium gluconate/carbonate unless thoroughly \202 ushed. Action within hours, not minutes. \200 Involves an appreciable Na + load (150mmol Na + ). 1 Volume overload. \200 Rapid correction of acidosis in a patient with d Ca 2+ may induc e tetany and seizures, as ionized calcium drops rapidly as pH i . CHAPTER 2 Acute kidney injury (AKI) 132 B 2-agonists (salbutamol, etc.) \200 10 \200\223 20mg (i.e. a large dose) of nebulized s albutamol will d K + by up to 1mmol/L but has limited additive bene \201 t beyond insulin/glucose (it acts via the same Na-K-ATPase and has a slower onset of action). \200 1 It may also precipitate angina or a rrhythmias in those with underlying cardiac disease and can cause an increase in lactate acid ( l worsening acidosis ). Once (if) the immediate arrhythmic danger is past, the aim should be to reduce total body p otassium to prevent further hyperkalaemic episodes. Urinary K + wasting: diuretics \200 Only useful in patients expected to pass urine and 6 urine into which K + can be excreted. Particularly useful if coexisting volume overload. Act on the renal tubule \200\224 K + loss as one of several effects. \200 Furosemide 40 \200\223 120mg IVI as a slow bolus or 10 \200\223 40mg/h to a maximum of 1000mg/day. Bume tanide offers a better absorbed oral alternative. \200 Effect depends on onset of diuresi s. Can lose substantial amounts of K + over 24h, with a UO >2L/day. Much less effective, as GFR deteriorates. Gut K + wasting: cation exchange resins Overused , particularly orally. \200 Exchange Na + /Ca 2+ for K + in the gut so actually removes K + , rather than just redistributing it. Calcium polystyrene sulfonate (CPS) (Calcium Resonium ) or sodium polystyrene sulphonate (SPS) (Resonium A or Kayexalate ). Can give 15g orally (supplied as a powder to be s uspended in water) up to qds or 15 \200\223 30g suspended in 2% methylcellulose and 100mL water rectally up to qds, retained for at least 2 (preferably >4) hours. May require saline irrigation through a catheter to remove the resin from the colon. \200 Rectal route is m ore effective, as there is more K + available for exchange: colonic [K + ] = 60 \200\223 9 0mmol/L, whereas upper GI tract = 5 \200\223 10mmol/L. \200 The constipating effect of t hese agents given orally may paradoxically prevent K + losses in the stool \200\224 equall y, the laxatives (e.g. lactulose 10 \200\223 20mL tds) given with these agents may be more ef \201 cacious than the agent itself! Modest effect seen within 24 \200\223 48h. \200 May cause colonic ulceration and necrosi s (recognized with SPS when given with sorbitol as a hyperosmotic laxative \200\224 previo usly a common practice in the USA. Post-op patients with an ileus are at highest risk). AKI MANAGEMENT: HYPERKALAEMIA 133 Extracorporeal K + wasting: dialysis \200 Consider if K + >6.0mmol/L, or rapidly rising, and renal function cannot be restored quickly. \200 Lowers K + within minutes. \200 Haemodialysis (HD) can process 20 \200\223 60L of blood against a dialysate K + of 1 \200\223 2mmol/L and is 6 a potent means of removing K + . Haemo \201 ltration ( b p. 174), with returned infusate free of K + , can achieve much the same thing although much slower. Peritoneal dialysis is effective but rarely indicated acutely ( b p. 188). \200 Requires dialysis access and transfer to a dialysing facility (which potentially introduces delays). 1 Never transfer a dangerously hyperkalaemic patient \200\224 if they are not responding t o emergency measures, speak to your ITU ( b p. 123). Further management The aim is to prevent further dangerous rises. \200 Restrict oral K + intake to <2g per day. 2 Speak to your dietetic staff ( b p. 258). 1 K + content of enteral and parenteral feeds may need modi \201 cation. 1 No K + in IV \202 uids. \200 Avoid K + -sparing diuretics, ACE-I, ARB, spironolactone , and NSAIDs. \200 2 Refractory i K + is an indication for dialysis. \200 If i K + pers ists, despite dialysis, then: Review dietary intake and compliance. \200 Triple-check the drug chart. \200 Check for GI or occult bleeding (reabsorbed red cells are rich in K + ). Exclude concealed tissue or muscle damage (e.g. compartment syndrome). Review (and consider changing) dialysis access and dialysis adequacy ( b p. 181). Check dialysate K + concentration ( b p. 179). Blood transfusion 1 Caution is needed when administering a blood transfusion to a patient w ith AKI, particularly if oligo-anuric. The volume and K + content of red cell transfusions can precipitate pulmonary oedema and hyperkalaemia, respectively. If the patient requires r enal support, then transfusions are safest given during dialysis treatment ( 2 seek expert advice). CHAPTER 2 Acute kidney injury (AKI) 134 AKI management: pulmonary oedema Introduction Oliguric or anuric patients rapidly accumulat e salt and water unless (and even if) tightly \202 uid-restricted. Volume overload, often exacerbated iatro- genically, remains a relatively common presentation of AKI. In AKI, the heart is often structurally normal, but salt and water over- load push it inexo rably along the Starling curve. Many patients may also have poor underlying cardiac reserve ( l 1 mortality is high). Findings Cool, clammy, agitated patient. Tachycardia, tachypnoea, i JVP, i BP ( d BP in thi s context is worrying), gallop rhythm, respiratory crackles, and wheezes. Possibly: ascites , pleural effusions, and oedema. Investigations \200 Poor O 2 saturation. \200 Hypoxaemia on ABGs (PaO 2 <8kPa). \200 Widespread alveolar shadowing on CXR. Management \200 Sit the patient up, and stop all IV infusions. \200 Oxygen . Maintain S a O 2 >95%. It should be possible to achieve an FiO 2 >60% using a well-positioned high- \202 ow (e.g. Venturi) mask with an O 2 \202 ow rate of 6L/min. Combine with nasal prongs , if necessary. Masks with reservoir bags may allow FiO 2 >80%. Consider ward CPAP if avail able (e.g. Boussignac system). Opiates . Give IV diamorphine (1.25 \200\223 2.5mg) or morphine (2.5 \200\223 5mg) as an anxiolytic and a venodilator (+ 5mg metoclopramide as antiemetic). Can be repeated after 15min, but opiates will accumulate in AKI, so resist giving additional doses. Nitrates . If the systolic BP \211 90mmHg, start intravenous GTN 2 \200\223 10mg/h. Start low, and titrate every 10min, as tolerated. Give 2 puffs of subli ngual GTN while the pump is being set up. If systolic BP is <90mmHg ( 2 ? cardiogenic shock ), call your ITU and consider inotropic support. Diuretics ( b p. 144). Administer 80 \200\223 120mg furosemide bolus IV. If this initiates a diuresis, then repeat or start a continuous infusion (10 \200\223 40mg/h). 2 If no incr ease in urine output, seek specialist help without delay. Renal replacement therapy . Oligo-anuric patients are likely to need renal support ( b p. 1 72). 1 If renal facilities are not on site, then ensure the patient is \201 t for transfe r \200\224 discuss with your ITU ( b p. 123). AKI MANAGEMENT: PULMONARY OEDEMA 135 How to give loop diuretics in AKI \200 A bolus of 80 \200\223 120mg IV furosemide can be administered initially. \200 If no response, then call for expert help. Consider 250mg ( 25mL ampoule) furosemide IV, made up to 50mL (syringe driver) or 100mL (infusion pump) at a rate not exceeding 4mg/min to avoid ototoxicity. Bumetanide 5mg is an alternative. \200 If this initiates a diuresis, give a further 250mg. \200 If no response, further doses ar e likely to be futile. ( 2 Dialysis?) \200 If there is a reasonable, but transient, respo nse, then a continuous infusion 10 \200\223 40mg/h over 24h may promote ongoing diuresis. Consider respiratory support if: \200 Continuing severe breathlessness. \200 Falling re spiratory rate (tiring patient). \200 PaO 2 <8KPa, rising PaCO 2 . \200 Worsening acido sis (pH <7.2). \200 Inform your ITU team about the patient before these occur. Continuous positive airways pressure (CPAP) Provides a constant positive pressure support t hroughout the respiratory cycle (typically 5 \200\223 10cmH 2 O), allowing delivery of a h igher FiO 2 (80 \200\223 100%) and decreasing the work of breathing. 1 Patients must be co nscious, able to protect their airway, and possess suf \201 cient respiratory muscle stren gth. Endotracheal intubation and mechanical ventilation Requires critical care transfer. PEEP \200\224 a preset pressure is added to the end of expiration to prevent airway/alveolar col lapse and open up atelec- tatic and \202 uid- \201 lled lung. Venesection \200 Exceptional circumstances and Hb \211 100g/L and SBP \211 120mmHg. \200 250mL blood removed from a large vein with venesection kit. \200 Ideally, the blood should be saved to transfuse back when the patient is more stable. CHAPTER 2 Acute kidney injury (AKI) 136 AKI management: electrolytes and acidosis Hyperphosphataemia \200 d urinary PO 4 excretio n l i serum PO 4 . ( b p. 237). \200 Likely to be a potential issue in more persistent AK I, such as established ATN. Particularly marked elevations occur (early) in rhabdomyolysis ( b p. 152), tumor lysis syndrome ( b p. 160), and haemolysis (tissue injury and cell death l release of intracellular PO 4 ). Acute i PO 4 is important because it: Contributes to d Ca 2+ (by a poorly understood mechanism). \200 Encourages s hyperparathy roidism. \200 Promotes soft tissue/vascular calci \201 cation. \200 Makes the patient feel itchy, uncomfortable, and anorexic. \200 May cause arrhythmias. Treatment (see also b p. 246) \200 Dietary restriction of phosphate (<800mg/day, b p. 258). This requires a careful balance against an adequate protein and calorie intake \200\224 speak t o your dietitian. PO 4 removal through dialysis or haemo \201 ltration. \200 Oral phosphate binders (reduc e intestinal absorption of phosphate): \200 If both d Ca 2+ and i PO 4 , start calcium ca rbonate (usually 500mg calcium per tablet) or calcium acetate (250mg calcium). If PO 4 <2.4mmol/L, one tablet with each meal. \200 If PO 4 >2.4mmol/L, two tablets with each meal. If serum Ca 2+ \211 2.4mmol/L, use a non-calcium-containing binder (e.g. sevelamer HCl (0 .8 \200\223 2.4g with meals) or Alu-cap (1 \200\223 2 capsules with meals). Severe i PO 4 is unlikely to correct until the patient dialyses or recovers independent renal function. If the patient is being NG or parenterally fed, liaise with your dietitian. Hypocalcaemia Relatively common in prolonged or severe AKI. Usually in the corrected range of 1.6 \200\223 2.0mmol/L. Caused mainly by d 1,25-dihydroxyvitamin D 3 synthesis but also by i PO 4 . Clinical sequelae (e.g. paraesthesiae, tetany, and seizures) are rare, partly because concomitant acidosis protects by increasing the ratio of ionized to protein-bound C a 2+ . 1 Rapid correction of acidosis with oral or IV HCO 3 \200\223 can precipitate sympt omatic d Ca 2+ . Calcium is supplemented orally (as \200\230Hyperphosphataemia \200\231 section) \200\224 the dual phosphate-binding role of calcium salts helps to make life simple. IV Ca 2+ (e.g. calcium gluconate) is virtually never required. If Ca 2+ <2.0mmol/L (and PO 4 <1.5mmol/L), start alfacalcidol (or calcitriol) 0.25 \200\223 0.5 micro- grams PO daily. AKI MANAGEMENT: ELECTROLYTES AND ACIDOSIS 137 1 In rhabdomyolysis ( b p. 152), Ca 2+ can precipitate in injured muscle, causing necrosis and ischaemic contractures \200\224 resist the administration of Ca 2+ unless symptomatic hypocalcaemia. Other electrolyte abnormalities found with AKI Hypokalaemia. Rare in AKI but can accompany non-oliguric ATN caused by tubular toxins (e.g. aminoglycosides, amphotericin, cisplatin). May also develop as GFR recovers, especially in the context of polyuria. Hypomagnesaemia. d Mg 2+ occasionally complicates non-oliguric ATN. Usually asymptomatic but can l neuromuscu lar instability, cramps, arrhythmias, resistant d K + , and resistant d Ca 2+ . Metabolic acidosis \200 AKI is usually associated with a raised anion gap metabolic acido sis: \200 As GFR falls, unmeasured anions (such as HSO 4 \200\223 and HPO 4 \200\223 ) from dietary and metabolic sources accumulate. As H + is buffered, HCO 3 \200\223 is consumed. \200 The struggling kidney is unable to reclaim \201 ltered HCO 3 \200\223 from the urine (proximal tubule) or generate new HCO 3 \200\223 (through production and excretion of NH 4 + ). The degree of acidosis is usually modest in uncomplicated AKI (serum HCO 3 \200\223 >10, pH >7.2) but more problematic in the critically ill where it ma y contribute to circulatory compromise. 1 If unexpectedly severe, consider s cause \200 \224 especially lactic acidosis (sepsis, cardiogenic shock), ketoacidosis (diabetes and alc ohol), and poisoning (salicylates, methanol, ethylene glycol). Acidosis per se may be an indication for dialysis, particularly if pH <7.0 \200\223 7.1 or evidence of cardiovascular compromise. CHAPTER 2 Acute kidney injury (AKI) 138 AKI management: other strategies Anemia 2 Do not always assume anemia is part of the uraemi c syndrome. Beware bleeding \200\224 especially from the GI tract \200\224 and haemolysis . An Hb of 7 8 \200\223 11g/dL is a frequent \201 nding in AKI \200\224 it does not help to distinguish between AKI and CKD. Major contributing factors are impaired erythropoiesis ( d renal EPO production), d red cell lifespan, haemolysis ( i red cell fragility), haemodi lution (from \202 uid overload), and blood loss. Treatment with an ESA is rarely effectiv e in AKI ( b p. 220), so transfu- sion may be necessary, particularly if d cardiovascular r eserve means d Hb is poorly tolerated. See b p. 133 for blood transfusion in oligo-anuric p atients. Bleeding Acute renal insuf \201 ciency may be associated with a bleeding tendency s to pla telet dysfunction. Uraemic toxins disrupt the interaction between platelet GPIIb/IIIa and a dhesion molecules, such as von Willebrand factor (vWF) and \201 brinogen. i platelet nitr ic oxide synthesis may also inhibit aggregation. Clinical manifestations are typically mild (e.g. spontaneous bruising, bleeding at venepunc ture sites) though occasionally more troublesome ( 1 GI tract). Usually manifest if urea >2 5mmol/L for several days. INR, APTT, and platelet count are usually normal (if abnormal l look for other causes). The bleeding time (if measured) is prolonged. Correcting bleeding tendency \200 The two situations that require speci \201 c intervent ion are: Active bleeding or poorly controlled persistent oozing. \200 Prior to an invasive procedu re (including renal biopsy). Management \200 Stop aspirin, clopidogrel, anticoagulants. \200 Correct anemia (transfu sion of packed cells). A haematocrit (Hct) \211 25 \200\223 30% will help to reduce bleeding time. DDAVP (desmopressin): a synthetic analog of ADH that probably acts by i amount of available vWF. Easy to administer and often bene \201 cial. G ive 0.3 micrograms/kg IV in 100mL of 0.9% NaCl over 30min. Effective within 1h, lasts 4 \200\223 24 h. Less effective on repetitive dosing. Can also be given subcutaneously (same dose) and intranasally (3 micrograms/kg). 1 Rarely causes coronary vasospasm \200\224 avoi d if unstable angina. Cryoprecipitate: 10 units every 12 \200\223 24h. Not usually required unless more severe bleeding. Dialysis: improves bleeding time, presumably through removal of uraemic toxins. 2 Dialysis usually requires anticoagulation to prevent clotting of the extr acorporeal circuit ( b p. 182). AKI MANAGEMENT: OTHER STRATEGIES 139 Infection \200 2 Sepsis is an important cause of morbidity and mortality in AKI ( 7 75% m ortality if AKI + sepsis). It occurs in three contexts: \200 AKI is the consequence of a speci \201 c infection (e.g. post-infectious GN, endocarditis, malaria, leptospirosis, hantavirus). Septicaemia l circulatory compromise l pre-renal AKI l ATN. \200 Localized or systemic in fection arises in those with pre-existing AKI. Approach \200 Take signs of infection, such as fever, i WCC, i CRP, seriously \200\224 a s a minimum, re-examine the patient thoroughly. Culture (and re-culture) blood, urine, sputum, and other secretions. \200 Make use of ima ging. Repeat CXRs frequently. If the source of sepsis remains obscure, consider abdominal/chest/pelvis CT. Attention to microbiological detail: chase up samples; review sensitivities; carefully consider antibiotic options, and speak to your microbiologist regu larly about resistance patterns. 1 Many antimicrobials require dose adjustment in renal impairment ( b p. 878). Strict aseptic technique for central venous line, dialysis catheter, and bladder catheter i nsertion. Consider prophylactic antibiotics when inserting a line or catheter into a febril e patient. Do not leave bladder catheters in place longer than necessary. In the majority o f cases, accurate monitoring of UO does not require a catheter. Antibiotic cover for remova l if the urine is a likely source of sepsis. Inspect IV cannula sites regularly, and look under dressings. \200 Remove all lines as so on as feasible. \200 3 Treat proven infection aggressively. CHAPTER 2 Acute kidney injury (AKI) 140 AKI management: nutrition Pre-existing and hospital-acquired malnutrition l i morbidity and mortal- ity in the critically ill. Preventing malnutrition preserves muscle function (incl uding) respiratory, i wound healing, and i resistance to infection. General rules \200 If pre-existing nutritional status is normal and a normal diet is like ly to be resumed in \211 5 days, support is not initially indicated. If the patient is malnourished, ignore this 5-day rule and start feeding. \200 If hyperca tabolic (sepsis, trauma, burns), initiate support early. \200 Some protocols avoid feedin g within \201 rst 24h: evidence that feeding during the \200\230insult phase \200\231 i O 2 requirements and worsens tissue injury). \200 Modify nutritional support as GFR changes and with dialysis initiation. \200 Do not overprescribe \200\224 you can have too much of a good thing. \200 Enteral feeding is a lways preferable to parenteral (although they are not mutually exclusive). Step 1: determine the nutritional status of the patient \200 Body weight: recent unintent ional loss >10% body weight is a bad sign. \200 Determine BMI (kg/height in m 2 ). Normal range 20 \200\223 25kg/m 2 . \200 Beware \202 uid retention falsely i weight. \200 Serum albumin (<30g/L is worrying), though in \202 ammation may be a confounder. Pre-albumin, transferrin, and cholesterol can also be used. Subjective global assessment (SGA): combines clinical parameters with albumin, anthropometry, clinical judgment, and other metrics ( b p. 258). Step 2: estimate energy requirements \200 Standard formulas (>200 published), e.g. Scho \201 eld, 3 revolve around gender-based, weight-adjusted formulas. Ask your dietitian. Energy expenditure in \200\230uncomplicated \200\231 AKI is usually within the normal ran ge, and energy requirements for those with \200\230complicated \200\231 AKI are generally determined by associated disorders (e.g. sepsis). It is rare for energy requirements to ex ceed 130% basal. 2 Broadly speaking: \231\202 should receive 25 \200\223 30 non-protein kcal/kg/day and \231\200 20 \200\223 25kcal/kg/day. Step 3: estimation of protein (and amino acid) requirements \200 Depends on associated ca tabolic stress. Hypercatabolism l i Ur, which can be used to estimate nitrogen balance. Rul es of thumb: \200 For \200\230uncomplicated \200\231 AKI, daily protein or amino acid r equirement is near the recommended allowance of 0.8g/kg/day for normal adults. In \200\230complicated \200\231 AKI, the requirement is 7 1.0 \200\223 1.2g/kg/day. \200 If dialysis is necessary, add 0.2g/kg/day. Critically ill patients may need more (up to 1.5g/kg/day); \211 1.5g/kg/day may aggravate the situation by stimulating formation of urea and other nitrogenous waste products. AKI MANAGEMENT: NUTRITION 141 Step 4: decide on route of administration See Table 2.5. Step 5: ensure volume and electrolyte content appropriate for AKI \200 Low volume and low electrolyte feeds are often necessary. \200 Requirements may change as renal support is initiated (and will depend on whether intermittent dialysis or CRRT). Consider high dose vitamin administration (e.g. Pabrinex ) if pre- existing malnutrition. Reference 3. Scho \201 eld WN (1985). Predicting basal metabolic rate, new standards and r eview of previous work. Human Nutrition Clinical Nutrition , 39 , 5 \200\223 41. CHAPTER 2 Acute kidney injury (AKI) 142 , s p m a r c e t y l o r t c e e l a n m o d b a i d e g d o l s i d n o i t a r i p s a , a e s u a n l / r e p y h s n o i t a c i l : l , a m e a c y l g o p y h . a n i t s e t n o r t s a G . s e i t i l a m r o n b a a e o h r r a d i . : l a n o m u e n p , a c n a h c e M n o i s n e t s i d i : c i l : s u o i t c e f n I i o b a t e M p m o C i i . e b u t d n a d e h s i r u o n l a m a e v o b a y a m . o t e d e k c e h c . i ( g n d e e f e r : s n o i t c i r t s e r d n a , 4 r o i r p ) d e e f i n e m g e r e h t I . K A n y l p p a . t n e m e c n e m m o c O P , + K f i i d e t c e r r o c e b d r a d n a t s - n o n y r a s s e c e n n i s n o i t c i r t s e r t n e v e r p o T i s n r e c n o C t s u m d e r o e m o r d n y s e v r e s b O e m u o V , t n e i t a p l i a t + 2 g M 4 d n a l O P e b + K A . t s n a g a a i r e t c a b e t a r e o t f s n a t n a m g n d e e f i o y t i r g e t n f i i h t i l l u f e s u s t c e t o r p w n o i t a t n e m e p p u S i l G n a c f s k n i r d o n o i t a c o l s n a r t i . r o o p s t n e i t a p l a r u t c u r t s i . t e d d n a i n o i t i r t u n e t i t e p p a t u g l a r e t n E l a r o n a s e t o N l y n a M e h t e h t t s e r . t n e t n o c e b u t y l l a c \201 c e p s o r p e N l e w o b G N i l a n e r y g r e n e f h 4 w o o n o i t i s o p . e a l u m r o g e . . ) R X C r o H p ; e c r u o s e b a l i a v a d n a l l l A s e t u o r f . n e t o r p h / L m 0 3 g n d e e f t c e r r o c i ? t i a v o N . i h 4 2 e r a . ) s i t r a v o N n i e t a r i p s a ( n o i t a r t s i n m d A y r e v e s \200\231 t a h t s e d o M I t a l a r e t n E , ) s s o R ( e r u s n E K A r o t r a t S W n ( f i i e s n e d - n o i t i r t u N y r a t n e m e p p u S 5 2 g n d e e f . t e d i e l b a T l a r e t n E e t u o R i l : l a r O l a r o p i s AKI MANAGEMENT: NUTRITION 143 e s o l c . g n i r o t i n o m y r o t a r o b a l . c t e s e r i u q e r . n o i t c e f n : n o i t r e s n , x a r o h t o m u e n p : i i c i l r e t e h t a C r e t e h t a C o b a t e M t s i s s a t n e m e c a l p e r ) F H V V C . g n d e e f i l a n e r . y l w o l s . g e ( f . o y r e v i l s u o u n i t n o C s e u q n h c e t d e e f e d i t r a t S e h t y g r e n e n e v g y l n a m e r a o s t n u o m a i i a . y l l a u s u e r u s a e m m r e t - t r o h s e b a v ( l l a . s n e v n u r i w o n a c i t e e m l l a m y l l a r t n e c s i l . ) e n a l a r e h p i r e p o t n d e e f d n a t s u m N P T s s t n e m e r i u q e r . e v a h y l t n e r r u c n o c t o n o d a i l , y t i l a l o m s o e b i s s o p d e t a c d e d l a r e t n e l n e v g s d p i y e h T i i i l l l e b u F V f o f I a I i d n a e h t s a / g 1 \211 y l l a u s u ( s e t y l o r t c e e , , d e d d a e s o c u l g o t n e t f o r e t t a l y r o t a r i p s e r n , ) r e v i l . ) a m e a d p i 2 O C s e s u a c l a i t n e s s e l a i t n e s s e \200\231 y l l a n o i t i d n o c d e s u i y t t a f ( e r a l s a e r a i , s t n e m e e ) n n e v g i l r e p y h r e d n a m e r d e n b m o c g n i s a e r c n i ( s d p L e h t ( s i s e n e g o p i l u s n y a d / g k / g 5 > h g u o h t l a i i i i i y l l a p c n i r p l a i t n e s s e - n o n i l s e m . ) I K A a m e a c y l g r e p y h d o v a o t i e c a r t i i i l : s d c a i t e m o s e h t n o i t c u d o r p f , ) s d n a m e d . o t x e t n o c y r a s s e c e n i \200\230 , s n m a t i V e m o c e b e d v o r p : y g r e n E y a d / g k i o n m A i d n a ( i d n a l a r e t n e r a P CHAPTER 2 Acute kidney injury (AKI) 144 AKI management: myths Loop diuretics Theory. (i) i urinary \202 ow \200\230washes out \200\231 cellular debris, casts, and nephro- toxins from tubules; (ii) blockade of active t ransportation processes l d tubular O 2 consumption and protects against ATN; (iii) vasodil ator action l i RBF. Evidence. None to suggest improved renal or patient outcome in any AKI setting. In particular, the natural history and prognosis of ATN remains unchanged. Some s tudies have suggested harm . May increase diuresis, however, assisting the management of \202 uid balance and preventing pro- gressive volume overload. 2 Given as part of the treat ment of pulmo- nary oedema ( b p. 134). 1 The only indication for diuretics is volume overl oad. Mannitol An osmotic diuretic, previously used for the prevention of ATN in high-risk CV sur gery. A lack of evidence means the practice is in decline. Can para- doxically cause pulmon ary oedema through volume expansion. Avoid. Dopamine Previously widely used for the prevention and treatment of AKI. A lack of evidence for ef \201 cacy and potential risk of harm have led most to abandon this practice. You s hould do the same. Theory. Dopamine (DA) is synthesized in the proximal tubule from cir- cu lating L-dopa and helps regulate Na + excretion and renal vasodilata- tion through speci \201 c DA1 and DA2 receptors. Exogenously administered \200\230low-dose \200\231 dopamine should l renal vasodilatation l i RBF l i natriuresis and mild i GFR. All would be of pote ntial bene \201 t in AKI, although evi- dence suggests these mechanisms may not remain int act in renal insuf- \201 ciency. (See Table 2.6.) Table 2.6 Dopamine effects Micrograms/ kg/min Effect Selective DA (mainly DA1) receptor activation l i renal (and mesenteric) blood \202 ow Bo th DA and B 1 receptors are activated, the latter l i cardiac output (mainly by i SV). B 1 effect predominates. Starts to activate A adrenoreceptors. A adrenergic (vasoconstrictive) effect takes over with i SVR. 0.5 \200\223 3 3 \200\223 10 10 \200\223 20 >20 AKI MANAGEMENT: MYTHS 145 Evidence. Largely anecdotal or from inadequate studies. Larger trials (e.g. ANZICS) have fa iled to show bene \201 t. 1 It may cause harm : tachycardia, arrhythmias, myocardial ischa emia, blunted hypoxaemic drive, splanchnic vasoconstriction ( l bacterial translocation), d igital ischaemia, impaired pituitary function, electrolyte disturbances (even at \200\230r enal \200\231 dose), impaired T cell function. Dopamine accumulates in renal failure. Other \200\230renoprotective \200\231 agents Fenoldopam \200 Dopaminergic agonist that acts through DA1 receptors (without signi \201 cant A or B adrenergic activity) to produce afferent and efferent arteriolar vasodilatatio n. Preserves renal blood \202 ow and tissue oxygenation in animal studies. \200 Human stud ies (mainly small) have yielded variable results in several clinical contexts, including AKI prevention post-cardiac surgery. Larger randomized studies are awaited. In the meantime, fenoldopam use is not recommended in the KDIGO (2012) guideline. Atrial natriuretic peptides \200 ANP l d tubular Na + reabsorption, i afferent arteriolar vasodilatation, and d RAS activation. Tested in a post-surgical context in multiple studies, but overall quality of study evidence is variable and inconsistent. Can induce signi \201 cant, and potentially harmful, hypotension. \200 Other natriuretic peptides have been tried, e.g. brain natriuretic peptide (nesiritide) and urodilatin. Not recommended in KDIGO (2012) guideline. N-acetylcysteine \200 Most widely studied in the context of contrast-induced AKI ( b p. 150). NAC is a modi \201 ed form of the amino acid L-cysteine, a precursor of glutathione. NAC is a potent free radical scavenger and antioxidant that also possesses vasodilator prop erties (via nitric oxide availability). Shown to reduce ischaemic and nephrotoxic ATN in animal studies but clinical evidence lacking. Not recommended in KDIGO (2012) guideline. CHAPTER 2 Acute kidney injury (AKI) 146 AKI: hope for the future? Phases of ATN (see also b p. 108) There are four pathophysiologic al/temporal phases of ATN that can help to conceptualize where pharmacological intervention s might be targeted and applied. Initiation phase Characterized by aberrant vascular reactivity, diminished renal perfusion, and widespread oxidative injury. Extension phase A proin \202 ammatory state, with macrophage activation, in \202 ammatory medi- ator release, and stimulation of epithelial and endothelial cells. Maintenance phase Restoration of tubular cell integrity through the division of adjacent tu bu- lar cells and the differentiation of local (kidney) and systemic (haematopoi- etic \200\224 X ) stem cells. Repair phase Normal tubular cell function is restored. Very broadly speaking, therapeutic interventions can, therefore, attempt to decrease vascul ar reactivity, moderate in \202 ammation, preserve cell via- bility, and augment cell repa ir. Putative agents are shown in Table 2.7. Many of these are currently being studied in animal models of renal ischaemia-reperfusion injury, but bene \201 t in human AKI is yet to be d emon- strated. There are many potential reasons for this: AKI is a heterogeneous condition (both in terms of the type of patient affected and the underlying cause); study endpoints ( such as mortality) are often confounded, and, until recently, there was no agreed consensus de \201 nition of AKI. Furthermore, late detection of AKI prevents timely administration. It is hoped that novel AKI biomarkers will facilitate earlier intervention ( b p. 94). AKI: HOPE FOR THE FUTURE? 147 Table 2.7 Putative therapeutic strategies in AKI Pathogenic mechanism targeted Interventions currently of unproven bene \201 t in humans Ameliorate renal vasoconstriction