Critical Care Nephrology · Two-Week Intensive · Lecture 3 of 9

Fluids, Vasopressors, Diuretics & Blood Products

Prevention and conservative management of AKI — prescribing the four things we give every ICU patient without thinking

40 minutes Nephrology Fellows Week 1

Based on Koyner, Handbook of Critical Care Nephrology (2021) · NTUH Yunlin Branch

Learning objectives

By the end of this session you will be able to…

Choose a resuscitation fluid by mechanism and by trial evidence — and name the four times saline still wins.
Prescribe a volume, an endpoint and a stop rule, then de-resuscitate deliberately.
Run and interpret a furosemide stress test, and work a diuretic-resistance ladder to its end.
Write vasoactive prescriptions in norepinephrine-equivalent doses and know when to add a second agent.
Apply restrictive transfusion with its named exceptions, and feed the AKI patient properly.

Koyner Ch 8–15, 40, 42–43 · KDIGO AKI 2012 · Surviving Sepsis Campaign 2021

Fluids: which one

Every fluid is a drug with a composition, a dose, a distribution volume and a toxicity — start prescribing it that way.

Koyner Ch 10 · Ronco Ch 18

Where the infused fluid actually goes

~25%of a crystalloid bolus is still intravascular after equilibration — 1 L ≈ 200–250 mL of plasma expansion

1 : 1.4albumin-to-saline volume ratio actually needed in SAFE — not the 1:4 classical physiology predicted

40%of infused colloid left in plasma at 30 min in perioperative patients

2 µmendothelial glycocalyx layer — the real oncotic barrier, shed by sepsis, surgery, trauma and hypotension

The revised Starling principle

Fluid does not return to the capillary at the venous end. Filtration is one-way and is returned by lymphatics; the glycocalyx — not plasma albumin — sets the barrier. Two consequences: colloids never behave as the textbook says, and once the glycocalyx is damaged the "colloid advantage" disappears entirely. Even 20–25% albumin will not pull interstitial oedema back into the vessel.

Woodcock TE, Woodcock TM. Br J Anaesth. 2012;108:384–394 · Levick JR. J Physiol. 2004;557:704 · Rehm M et al. Anesthesiology. 2001;95:849 · Koyner Ch 10

The formulary — read the label before you hang the bag

Fluid	Na⁺	Cl⁻	K⁺	Buffer	Osmolarity	Note
Plasma	140	100–104	4	HCO₃⁻ 24	285–295	The target you are trying to imitate
0.9% saline	154	154	0	none	308	~50 mmol/L excess chloride; strong ion difference 0; pH 5.0–5.5
Lactated Ringer's	130	109	4	Lactate 28	~273	Contains Ca²⁺ 1.4 mmol/L; slightly hypotonic in vivo
Plasma-Lyte 148	140	98	5	Acetate 27 + gluconate 23	295	Mg²⁺ 1.5 mmol/L, no calcium — compatible with blood lines
Albumin 4–5%	~140	~128	0	varies	iso-oncotic	The SAFE fluid; behaves like a slow crystalloid
Albumin 20–25%	~130–160	low	0	varies	hyperoncotic	A concentrated drug, not a resuscitation fluid

Koyner Ch 10 (Table 10.2) · Ronco Ch 18 · values in mmol/L, osmolarity in mOsm/L

Chloride: the mechanism behind the trials

Every litre of saline delivers ~50 mmol more chloride than a litre of plasma
The filtered load overwhelms proximal reabsorption → distal NaCl rises → the macula densa triggers tubuloglomerular feedback → mesangial contraction and afferent vasoconstriction → renal blood flow and GFR fall
In denervated dog kidneys, chloride-containing fluids reduced RBF and GFR; sodium loads without chloride did not
Clinically: post-operative Cl⁻ >110 mmol/L is independently associated with longer stay and higher mortality

Strong ion difference (SID) of 0.9% saline = Na⁺ 154 − Cl⁻ 154 = 0
SID of plasma ≈ 40 → infusing SID 0 drives hyperchloraemic normal-anion-gap acidosis
Falling bicarbonate on day 2 of resuscitation is usually the fluid, not the sepsis. Check the chloride before you chase a lactate.

The before-and-after study that started it

Yunos et al: a chloride-liberal era followed by a chloride-restrictive era in 1,533 ICU patients. Injury/failure-grade AKI fell from 14% to 8.4%, and the odds ratio for kidney replacement therapy was 0.52 (95% CI 0.33–0.81).

Yunos NM et al. JAMA. 2012;308:1566–1572 · Wilcox CS. J Clin Invest. 1983;71:726 · McCluskey SA et al. Anesth Analg. 2013;117:412 · Koyner Ch 10

Balanced vs saline — the two positive trials

SMART · N Engl J Med 2018

15,802 ICU adults, cluster-randomised multiple crossover, balanced crystalloid (Ringer's lactate or Plasma-Lyte A) vs saline. MAKE30 14.3% vs 15.4% (OR 0.90, 95% CI 0.82–0.99; p = 0.04) — about 1 event avoided per 94 patients. Median study fluid was only ~1 L. Effect was largest in the sepsis subgroup.

SALT-ED · N Engl J Med 2018

13,347 non-critically ill emergency department adults at the same centre. Hospital-free days identical; MAKE30 4.7% vs 5.6% (adjusted OR 0.82). The signal survives outside the ICU.

Read the composite honestly

MAKE30 = death or new KRT or persistent creatinine >200% of baseline. In SMART the AKI-specific components did not reach significance on their own: stage 2/3 AKI, peak creatinine and KRT alone (2.5% vs 2.9%, p = 0.08) were no different. The composite moved; "balanced crystalloids prevent AKI" is more than the data say.

Semler MW et al. N Engl J Med. 2018;378:829–839 · Self WH et al. N Engl J Med. 2018;378:819–828 · Koyner Ch 8, 10

BaSICS, PLUS and the synthesis you should actually teach

BaSICS · JAMA 2021

11,052 Brazilian ICU patients, Plasma-Lyte vs saline. 90-day mortality 26.4% vs 27.2% (HR 0.97, 95% CI 0.90–1.05). Neutral overall — and in the pre-specified traumatic brain injury subgroup the balanced solution looked worse.

PLUS · N Engl J Med 2022

5,037 Australian and New Zealand ICU patients, Plasma-Lyte 148 vs saline. 90-day mortality 21.8% vs 22.0%; new KRT 12.7% vs 12.9%. Also neutral, in a sicker, longer-exposure population than SMART.

What to say on rounds

Pooled across SMART, BaSICS and PLUS, the most likely truth is a small absolute benefit — well under 1% — with a very low probability of harm. It is not a large effect. But balanced crystalloid costs the same, requires no monitoring, and avoids an iatrogenic acidosis. Free upside with no downside is still worth taking: balanced by default, saline by indication.

Zampieri FG et al. JAMA. 2021;326:818–829 · Finfer S et al. N Engl J Med. 2022;386:815–826 · Hammond NE et al. NEJM Evid. 2022;1(2) · Koyner Ch 10

Four times 0.9% saline is still the right prescription

Hypochloraemic alkalosis

Chloride-depletion alkalosis after vomiting, nasogastric loss or aggressive diuresis. The high chloride content is the therapy — balanced solutions will not correct it.

Brain injury & raised ICP

Lactate is not an effective osmole, so Ringer's is functionally hypotonic and can worsen cerebral oedema. Saline or hypertonic saline; BaSICS gave a matching clinical signal.

Hypercalcaemia & blood lines

Ringer's contains calcium — it worsens hypercalcaemia and can antagonise the citrate in a blood product line. Plasma-Lyte contains no calcium and is safe with blood.

Significant liver failure

Lactate needs hepatic conversion to bicarbonate. In fulminant failure or advanced cirrhosis, choose an acetate-buffered solution or saline.

Two myths worth killing

Ringer's lactate does not cause lactic acidosis — the salt is sodium lactate, not lactic acid — though it does raise the measured lactate, so stop using lactate as a resuscitation endpoint while it is running. And Ringer's is not contraindicated in hyperkalaemia: it contains 4 mmol/L of potassium, and saline's non-anion-gap acidosis shifts more potassium out of cells than Ringer's ever adds.

Koyner Ch 10 · Zitek T et al. J Emerg Med. 2018;55:313 · O'Malley CMN et al. Anesth Analg. 2005;100:1518

Albumin: an expensive fluid with three real indications

What the trials showed

SAFE (n = 6,997): 4% albumin vs saline, 28-day mortality 20.9% vs 21.1%. No benefit, no harm overall; septic subgroup trended better
ALBIOS (n = 1,818): 20% albumin daily to keep serum albumin ≥3 g/dL in severe sepsis. Higher MAP and lower net balance, but 28-day mortality 31.8% vs 32.0%; no difference in AKI or KRT
SSC 2021 keeps albumin as a weak suggestion for patients needing large crystalloid volumes

Where it does harm

Traumatic brain injury — contraindicated. The SAFE trauma signal was driven entirely by TBI; the post hoc analysis found 24-month mortality 33.2% vs 20.4% with albumin (RR 1.63, p = 0.003)
Hyperoncotic (20–25%) albumin in shock was associated with more doubling of creatinine or dialysis (OR 5.99) and higher ICU mortality in a propensity-matched cohort — plausibly by raising glomerular oncotic pressure and slowing filtration
No evidence of benefit in burns, trauma or malnutrition

Finfer S et al. N Engl J Med. 2004;350:2247 · SAFE-TBI. N Engl J Med. 2007;357:874 · Caironi P et al. N Engl J Med. 2014;370:1412 · Schortgen F et al. Intensive Care Med. 2008;34:2157 · Koyner Ch 10

Albumin in cirrhosis — the one place it changes the disease

Spontaneous bacterial peritonitis — 1.5 g/kg on day 1 plus 1 g/kg on day 3 alongside antibiotics. Renal impairment fell from 33% to 10% and in-hospital mortality from 29% to 10%. This is the highest-yield albumin order in medicine.

Large-volume paracentesis >5 L — 6–8 g of albumin per litre of ascites removed, to prevent post-paracentesis circulatory dysfunction.

Diagnosing HRS-AKI — 1 g/kg/day (maximum 100 g) for 2 days with diuretics withheld. No response, no shock, no nephrotoxin, bland sediment: that is the diagnosis, by exclusion.

Treating HRS-AKI — 20–40 g/day with a vasoconstrictor (terlipressin, or norepinephrine titrated to a 10–15 mmHg MAP rise in the ICU). Stop at day 5–7 if creatinine has not moved.

Long-term outpatient albumin in decompensated cirrhosis reduced SBP, other infections, HRS-1 and kidney dysfunction, and improved survival in a large randomised trial — an outpatient decision, but know it exists.

Sort P et al. N Engl J Med. 1999;341:403–409 · Caraceni P et al. Lancet. 2018;391:2417 (ANSWER) · Angeli P et al. J Hepatol. 2019;71:811 (ICA) · Koyner Ch 42

Starches and gelatins: settled, and settled against

6S · N Engl J Med 2012

804 patients with severe sepsis, HES 130/0.42 vs Ringer's acetate. 90-day mortality 51% vs 43% (RR 1.17, p = 0.03) and more KRT (22% vs 16%, p = 0.04). The trial that ended the argument.

CHEST · N Engl J Med 2012

7,000 ICU patients, 6% HES 130/0.4 vs saline. 90-day mortality 18.0% vs 17.0% (p = 0.26) but more KRT: 7.0% vs 5.8% (RR 1.21, p = 0.04), with a post hoc dose–response for AKI.

CRISTAL · JAMA 2013

2,857 patients with hypovolaemic shock, institution's colloid of choice vs crystalloid. No difference at 28 days; lower 90-day mortality with colloids (30.7% vs 34.2%) — the lone positive result, unblinded, with mixed colloids. Not enough to reopen the question.

Pitfall — the "shortcut" colloid

HES causes osmotic nephrosis: proximal tubular vacuolisation and swelling, plus coagulopathy. KDIGO recommends against synthetic colloids for volume resuscitation. Gelatins have never shown outcome benefit and carry an anaphylaxis risk — they are not the safe compromise they are marketed as.

Perner A et al. N Engl J Med. 2012;367:124 · Myburgh JA et al. N Engl J Med. 2012;367:1901 · Annane D et al. JAMA. 2013;310:1809 · KDIGO AKI 2012 · Koyner Ch 8, 10

How much — and preventing the injury

Restrictive and liberal strategies barely differ in mortality; what kills is fluid nobody ever decided to give.

Koyner Ch 8–10 · Ronco Ch 18

De-resuscitation: the phase we skip

Lecture 2 introduced the ROSE frame — Resuscitation, Optimisation, Stabilisation, Evacuation. Almost all ICU fluid is given in S and E, and almost no one prescribes the E phase at all.

CountYesterday's true intake: boluses, maintenance, drug diluents, line flushes, nutrition, blood products, citrate. Most units under-count by 1–2 L/day.

→

SubtractWhich of those are obligatory? Concentrate infusions, convert to enteral drugs and feeding, and stop maintenance fluid the moment enteral intake starts.

→

Prescribe a balanceName a target for the next 24 h — "−1 L" is an order; "even" is not. Once shock has resolved and lactate is clearing, negative is the default.

→

Choose the toolLoop diuretic first, ultrafiltration only when the kidney genuinely cannot excrete the sodium load (Lecture 8).

Key point

Fluid is prescribed in millilitres and removed in litres. The evacuation phase needs the same daily attention, the same explicit target and the same reassessment loop you already give to the vasopressor.

Malbrain MLNG et al. Ann Intensive Care. 2018;8:66 · Koyner Ch 10 (Table 10.5) · Ronco Ch 18

Restrictive vs liberal: two big trials, one flat result

CLASSIC · N Engl J Med 2022

1,554 adults with septic shock after initial resuscitation, randomised to restrictive vs standard IV fluid. Median IV fluid in ICU 1,798 mL vs 3,811 mL — a genuine 2 L separation. 90-day mortality 42.3% vs 42.1%. No difference in serious adverse events or ischaemic events.

CLOVERS · N Engl J Med 2023

1,563 patients with sepsis-induced hypotension, restrictive (vasopressor-first) vs liberal fluid for 24 h. Fluid given: 1,267 mL vs 3,400 mL. 90-day in-hospital death 14.0% vs 14.9%; stopped early for futility. Neither strategy harmed.

The honest reading

Within the range these trials tested, the exact volume does not decide survival. What that licenses is not indifference — it is permission to give early norepinephrine instead of a fourth litre without fearing you are harming the patient. The 30 mL/kg SSC bolus remains a starting point for the undifferentiated patient, not a target to be completed in someone who is already congested.

Meyhoff TS et al. N Engl J Med. 2022;386:2459–2470 · Shapiro NI et al. N Engl J Med. 2023;388:499–510 · Evans L et al. Crit Care Med. 2021 (SSC) · Koyner Ch 10

Fluid accumulation: the exposure that is associated with death

>10%fluid accumulation over baseline body weight — the threshold associated with mortality across cohorts

~2×adjusted odds of death with fluid overload at KRT initiation in PICARD

−136 vs +6,992mL net balance, conservative vs liberal arm of FACTT — more ventilator-free days, no excess shock

1.31 vs 0.17L/day mean fluid balance, non-survivors vs survivors with AKI in a 601-patient ICU cohort

Pitfall — chasing urine output with boluses in established ATN

In an established tubular injury, a bolus given "for the urine output" produces neither urine nor benefit; it produces interstitial oedema, a rising CVP, a falling renal perfusion pressure and a diluted creatinine that hides the injury. If the patient is not fluid-responsive and not hypovolaemic, the fluid reflex is the diagnosis to treat.

Bouchard J et al. Kidney Int. 2009;76:422–427 (PICARD) · ARDSNet FACTT. N Engl J Med. 2006;354:2564 · Teixeira C et al. Crit Care. 2013;17:R14 · Koyner Ch 8–10

The fluid challenge, done properly

Dose: 4 mL/kg (or 250–500 mL) balanced crystalloid over 10–15 min
Measure: stroke volume or VTI before and after — never blood pressure alone
Positive: ≥10% rise in stroke volume · mini-challenge = 100 mL over 1 min, ≥6% rise
If you cannot measure stroke volume, you have not done a fluid challenge — you have given fluid.

Testing changes what you give

In the FRESH trial, resuscitation guided by passive leg raise cut 72-hour fluid balance by 1.4 L and reduced KRT (5.1% vs 17.5%) and mechanical ventilation (17.7% vs 34.1%). Validity conditions for each test were covered in Lecture 2 — use the one that is valid for that patient.

Where the litres actually come from

Maintenance infusions, antibiotic and sedative diluents, line flushes, enteral and parenteral nutrition, citrate and replacement fluid on CKRT, blood products. Reduce tonicity where you can, concentrate the drugs, and move to the enteral route early — that is where a negative balance is really won.

Douglas IS et al. Chest. 2020;158:1431–1445 (FRESH) · Monnet X, Teboul JL. Ann Intensive Care. 2016;6:111 · Koyner Ch 1, 10

The KDIGO prevention bundle — staged, not one-size

High risk, no AKI yet — discontinue all nephrotoxic agents where possible; ensure volume status and perfusion pressure; consider functional haemodynamic monitoring; monitor creatinine and urine output; avoid hyperglycaemia; consider alternatives to iodinated contrast.

Stage 1 — all of the above, plus a non-invasive diagnostic workup: sediment, ultrasound, drug review, bladder pressure if the abdomen is tense.

Stage 2 — check drug dosing against the current (non-steady-state) GFR, consider ICU admission, consider invasive diagnostic workup, avoid nephrotoxic imaging.

Stage 3 — avoid subclavian catheters if future vascular access matters; consider KRT (timing in Lecture 8).

The thirteen risk factors worth memorising

Age, baseline creatinine/CKD, diabetes, heart failure, hypertension · sepsis or SIRS, high severity score, vasopressor or inotrope use, nephrotoxic drugs, high-risk surgery, emergency surgery, intra-aortic balloon pump, long cardiopulmonary bypass time. Nephrotoxic = contrast, aminoglycosides, amphotericin B, vancomycin, NSAIDs, ACEi/ARB.

KDIGO AKI 2012 · Cartin-Ceba R et al. Crit Care Res Pract. 2012;2012:691013 · Koyner Ch 8

Does the bundle work? Three trials that say "partly"

PrevAKI · Intensive Care Med 2017

276 cardiac surgery patients with a raised urinary [TIMP-2]×[IGFBP7], randomised to a protocolised KDIGO bundle. AKI within 72 h 55% vs 72% (p = 0.004); stage 2/3 AKI 30% vs 45% (p = 0.009). No mortality difference; 882 patients had to be screened to randomise 276.

BigpAK · Ann Surg 2018

121 patients after major abdominal surgery, same biomarker-triggered design. All-stage AKI 32% vs 48% (p = 0.07, missed); stage 2/3 AKI 7% vs 20% (p = 0.04), with shorter ICU and hospital stay.

INPRESS · JAMA 2017

298 high-risk surgical patients: keep systolic pressure within 10% of the pre-operative value using an arterial line and norepinephrine, vs treating only below 80 mmHg. Kidney dysfunction 32.7% vs 49% (p = 0.01) — a number needed to treat of 7.

Meersch M et al. Intensive Care Med. 2017;43:1551–1561 · Göcze I et al. Ann Surg. 2018;267:1013 · Futier E et al. JAMA. 2017;318:1346 · Koyner Ch 8

What does not prevent AKI — and why we keep trying

Intervention	The theory	The verdict
"Renal-dose" dopamine	D₁-mediated renal vasodilation, natriuresis	Meta-analysis of 61 RCTs (n = 3,359): more urine, no change in KRT or death. SOAP II: arrhythmias 24.1% vs 12.4% vs norepinephrine. Dead.
Fenoldopam	Selective D₁ agonist, renal vasodilation	667-patient Italian trial stopped for futility; hypotension 26% vs 15% (p = 0.001). No renoprotective effect.
Furosemide	Less mTAL transport → less medullary O₂ demand	No prevention in cardiac surgery; no faster recovery after haemofiltration. Volume control only.
Mannitol	Tubular flushing, osmotic washout of casts	No prevention evidence outside intracranial hypertension; risks hyperosmolar AKI, dysnatraemia and volume expansion.
N-acetylcysteine + bicarbonate	Antioxidant, alkalinised tubular fluid	PRESERVE (n = 5,177): neither works for contrast-associated AKI. Stop ordering both.
Statins	Anti-inflammatory, endothelial stabilisation	Positive only in non-ICU contrast cohorts; no protective effect in critically ill ARDS patients.
Levosimendan · erythropoietin · selenium · remote ischaemic preconditioning · aspirin/clonidine	Various	All negative in adequately powered critical care or perioperative trials.

Friedrich JO et al. Ann Intern Med. 2005;142:510 · De Backer D et al. N Engl J Med. 2010;362:779 (SOAP II) · Bove T et al. JAMA. 2014;312:2244 · Weisbord SD et al. N Engl J Med. 2018;378:603 (PRESERVE) · Koyner Ch 8 (Table 8.3)

Diuretics & the furosemide stress test

Loop diuretics buy you volume control and prognostic information — never renal protection.

Koyner Ch 9, 12, 40

Loop pharmacology — and the arithmetic that follows from it

Loop diuretics are organic anions, >95% albumin-bound, so they are barely filtered. They must be secreted into the tubule by OAT1/OAT3 in the proximal tubule to reach the NKCC2 target
In AKI and CKD, uraemic anions (indoxyl sulfate, p-cresol) competitively block OAT secretion — the same plasma level delivers less drug to the lumen. That is why the dose must rise
Threshold and ceiling: below the threshold concentration nothing happens; above the ceiling nothing more happens. So double the dose to find the threshold — do not shorten the interval
Bioavailability: furosemide 40–60% (erratic), bumetanide 80%, torsemide >90%. Oral furosemide in a congested gut is a lottery — use IV in the ICU

Equivalence

Furosemide 40 mg IV ≈ bumetanide 1 mg ≈ torsemide 20 mg. Oral furosemide 80 mg ≈ 40 mg IV.

Starting doses

Naive, preserved GFR: 40 mg IV. Prior loop exposure or AKI: 1–1.5 mg/kg, or double the home dose. Infusion after a loading bolus: 5–20 mg/h.

Daily IV total (acute decompensated heart failure, DOSE high-dose arm) = 2.5 × total daily home oral dose
A patient on furosemide 80 mg twice daily at home needs ~400 mg IV/day to be "high-dose" — not the 40 mg the admitting team wrote.

Ellison DH. Clin J Am Soc Nephrol. 2019;14:1248 · Huang X et al. Am J Physiol Renal Physiol. 2016;310:F958 · Felker GM et al. N Engl J Med. 2011;364:797 · Koyner Ch 12 (Table 12.1)

What loop diuretics do and do not do in AKI

What they genuinely deliver

Volume control: relief of congestion, lower CVP, better renal perfusion pressure
Space for obligatory intake — nutrition, antibiotics, blood products
Avoidance of intubation, or of dialysis started purely for volume
In FACTT, AKI patients in the conservative arm got more furosemide (80 vs 23 mg/day), accumulated less fluid, and the strategy was protective
Prognostic information — the furosemide stress test

What they do not deliver

No prevention of AKI (cardiac surgery, angiography)
No treatment of established AKI, no shortening of KRT
No improvement in kidney recovery after haemofiltration
Converting oliguric to non-oliguric AKI is cosmetic — it does not change survival
Real toxicity: hypovolaemia, hypokalaemia, hypomagnesaemia, metabolic alkalosis, hyperuricaemia, tinnitus and ototoxicity at high peak levels

How to reconcile the two columns

KDIGO recommends against diuretics to prevent or treat AKI, and for their use to manage volume overload. The old association between diuretics and mortality (Mehta, JAMA 2002) is confounding by indication; when diuretics are used to achieve a negative balance, the association reverses (adjusted HR 0.25 in a 601-patient multicentre cohort). Prescribe them to a volume target, never to a creatinine.

KDIGO AKI 2012 · Mehta RL et al. JAMA. 2002;288:2547 · Teixeira C et al. Crit Care. 2013;17:R14 · van der Voort PH et al. Crit Care Med. 2009;37:533 · Koyner Ch 9, 12

The furosemide stress test — a functional biomarker you already own

Dose: 1.0 mg/kg IV if loop-diuretic naive · 1.5 mg/kg IV if prior loop exposure
Replace urine mL for mL with crystalloid — the test is isovolaemic by design
Measure the 2-hour urine output. Cut-off: 200 mL (i.e. 100 mL/h)
≥200 mL = the tubule can still respond → low risk of progression. <200 mL = high risk of stage 3 AKI or KRT.

The evidence

Chawla 2013 (n = 77, early AKI): AUC 0.87 for progression to stage 3 — better than any single damage biomarker in the same cohort
Rewa 2019, multicentre prospective (n = 92): same 200 mL cut-off, sensitivity 73.9%, specificity 89.9%. Hypotension occurred in 9.8%
Also validated to predict delayed graft function after deceased-donor transplantation

How to act on the result

Pass — de-escalate monitoring, continue conservative management, do not rush access
Fail — plan dialysis access, review drug dosing and potassium/acid–base trajectory, book the family conversation early
The FST is prognostic, not therapeutic. A pass is not permission to keep giving fluid; a fail is not an order to start KRT tonight

Pitfall — running the test on the wrong patient

The FST is invalid and dangerous in a hypovolaemic or hypotensive patient — you will convert a prerenal state into ischaemic ATN and blame the kidney. Optimise volume and perfusion pressure first, replace urine millilitre for millilitre, and do not run it in someone with obstruction or an unrecognised bleed.

Chawla LS et al. Crit Care. 2013;17:R207 · Rewa OG et al. J Crit Care. 2019;52:109–114 · McMahon BA et al. Biomarkers. 2018;23:61 · Koyner Ch 12

Diuretic resistance — work the ladder to its end

Is it resistance, or an under-dose? — Check the route (IV, not oral), the actual dose reached, and the urine sodium. A spot urine Na⁺ <50–70 mmol/L two hours after a loop dose, or urine output <100–150 mL/h in the first 6 h, means the prescription failed — not the kidney.

Double to the ceiling — 40 → 80 → 160 → 200 mg IV furosemide equivalents. Doubling finds the threshold; adding an extra dose at a sub-threshold level does nothing.

Convert to infusion after a loading bolus, 5–20 mg/h. DOSE showed no efficacy advantage over q12h bolus, but the lower peak concentration is the argument that matters in AKI: less ototoxicity.

Correct what blunts the response — hypovolaemia despite oedema, NSAIDs, high sodium intake, and above all metabolic alkalosis with hypochloraemia: add acetazolamide 250–500 mg IV, which also adds proximal natriuresis.

Sequential nephron blockade — metolazone 2.5–10 mg PO or chlorothiazide 500 mg IV, given 30 minutes before the loop dose, to block the hypertrophied distal convoluted tubule ("braking phenomenon"). Add an MRA where potassium allows. Watch sodium, potassium and magnesium daily.

Albumin co-administration — physiologically attractive, clinically marginal: the meta-analysis found only a small increase in sodium excretion and urine output. Reserve for serum albumin below ~2 g/dL, and do not let it delay the next rung.

Stop and reconsider — if the nephron cannot excrete the sodium load, more diuretic is not the answer. Ultrafiltration or KRT is (Lecture 8). Keep ultrafiltration rates ≤250 mL/h to avoid haemodynamic compromise.

Hoorn EJ, Ellison DH. Am J Kidney Dis. 2017;69:136 · Mullens W et al. Eur J Heart Fail. 2019;21:137 · Kitsios GD et al. J Crit Care. 2014;29:253 · Koyner Ch 12, 40

DOSE and CARRESS-HF — the two decongestion trials to quote

DOSE · N Engl J Med 2011

308 patients with acute decompensated heart failure, 2×2 factorial. Bolus q12h vs continuous infusion: no difference in symptoms or creatinine. High dose (2.5× home oral) vs low dose (1×): greater diuresis and a non-significant symptom benefit (p = 0.06), with more transient worsening renal function (23% vs 14%, p = 0.04) that resolved by 60 days without any survival penalty.

CARRESS-HF · N Engl J Med 2012

188 patients with ADHF and worsening renal function: ultrafiltration vs a stepped pharmacological algorithm. The bivariate endpoint at 96 h favoured stepped care (creatinine +0.23 vs −0.04 mg/dL, p = 0.003); weight loss was equivalent (5.5 vs 5.7 kg); serious adverse events were more frequent with ultrafiltration (72% vs 57%, p = 0.03).

Key point

A creatinine rise during effective decongestion — falling NT-proBNP, rising haematocrit, falling CVP and improving intrarenal venous flow — is haemoconcentration, not injury, and is associated with better outcomes. Stop the diuretic for hypotension or true hypovolaemia, not for a number.

Felker GM et al. N Engl J Med. 2011;364:797–805 · Bart BA et al. N Engl J Med. 2012;367:2296–2304 · Metra M et al. Circ Heart Fail. 2012;5:54 · Koyner Ch 40

Vasoactive prescribing

Lecture 2 argued which agent; this is how to write the order, compare the dose and get off it.

Koyner Ch 13, 42 · Ronco Ch 4

Norepinephrine: writing the actual prescription

The order

Working range 0.05–0.5 µg/kg/min; standard concentration 4 mg in 250 mL = 16 µg/mL
Titrate every 3–5 minutes to the MAP target you wrote down — and rewrite that target daily
Start it alongside fluids, not after them: CENSER showed faster shock control with early norepinephrine
Peripheral administration through a proximal large vein is acceptable short-term (extravasation ~2% under controlled conditions), but no guideline endorses it — arrange central access
Extravasation: stop, aspirate, and infiltrate phentolamine 5–10 mg in 10–15 mL saline subcutaneously as soon as possible

Escalation, not dose creep

At ~0.25–0.3 µg/kg/min, add vasopressin 0.03 U/min rather than climbing further on a single agent
Wean vasopressin by 0.01 U/min every 30–60 min — abrupt withdrawal causes marked hypotension
A rising dose with a falling MAP is a missed diagnosis: bleeding, tamponade, severe acidaemia, adrenal insufficiency, intra-abdominal hypertension, or the line is not in the vein

NEE (µg/kg/min) = norepinephrine + epinephrine + phenylephrine/10 + dopamine/150 + vasopressin (U/min) × 2.5 + angiotensin II (ng/kg/min)/10
Use norepinephrine-equivalent dose to compare patients and days. Above ~0.5 µg/kg/min mortality rises steeply — escalate the diagnosis, not just the infusion.

Koyner Ch 13 (Table 13.1) · Permpikul C et al. Am J Respir Crit Care Med. 2019;199:1097 (CENSER) · Goradia S et al. J Crit Care. 2021;61:233 · SSC 2021

Second-line and rescue agents — dose and practical caveat

Agent	Dose	Prescribing point that matters at the bedside
Vasopressin	0.01–0.04 U/min, fixed	Catecholamine-sparing; do not titrate as a rescue pressor; wean slowly. Watch digital and mesenteric ischaemia, hyponatraemia
Epinephrine	0.01–0.5 µg/kg/min (bolus 1 mg IM in anaphylaxis)	CAT trial: no MAP or mortality advantage over norepinephrine, but more lactic acidosis and tachycardia. The lactate is β₂-driven glycolysis — do not resuscitate to it
Phenylephrine	0.1–10 µg/kg/min, or 50–100 µg bolus	For norepinephrine-associated tachyarrhythmia or high-output hypotension. Reflex bradycardia and falling cardiac output; needs higher doses for the same MAP
Dopamine	Restricted use only	SOAP II: double the arrhythmia rate vs norepinephrine. SSC restricts it to highly selected low-arrhythmia-risk patients. There is no "renal dose"
Angiotensin II	Start 20 ng/kg/min, titrate	ATHOS-3: MAP response 69.9% vs 23.4% on ≥0.2 µg/kg/min NEE; KRT-subgroup survival signal is hypothesis-generating. FDA warning for thrombosis (DVT 13.5% vs 5%) — give prophylaxis
Dobutamine	2.5–20 µg/kg/min	β₂ vasodilation below 5 µg/kg/min can drop the MAP. Continuous ECG; arrhythmogenic; not for routine acute heart failure
Milrinone	0.125–0.75 µg/kg/min	Renally cleared — accumulates in AKI, and the long half-life means hypotension you cannot switch off. Reduce or avoid without KRT

Koyner Ch 13 · Myburgh JA et al. Intensive Care Med. 2008;34:2226 (CAT) · De Backer D et al. N Engl J Med. 2010;362:779 · Khanna A et al. N Engl J Med. 2017;377:419

Terlipressin in HRS-AKI: real benefit, real respiratory cost

CONFIRM · N Engl J Med 2021

300 patients with HRS-1, terlipressin plus albumin vs placebo plus albumin. Verified HRS reversal 32% vs 17% (p = 0.006). No survival benefit at 90 days — and respiratory failure occurred in 11% vs 2%, driving deaths from respiratory causes in the terlipressin arm.

How to give it

1 mg IV every 6 h; escalate to 2 mg every 6 h if creatinine has not fallen ≥25% by day 4. Continuous infusion 2 mg/24 h titrated to 12 mg/24 h is better tolerated where available
Always with albumin 20–40 g/day, after the 1 g/kg diagnostic challenge
Stop at day 5–7 without response, on starting KRT, or for adverse effects
Predictors of response: MAP rise >5 mmHg, creatinine <5 mg/dL and bilirubin <10 mg/dL at the start

Before you write it

Screen oxygenation. Avoid in hypoxaemia, in ACLF grade 3, and in anyone whose respiratory reserve is marginal — the albumin volume compounds it
Monitor SpO₂ continuously and cap the daily albumin
Terlipressin is unavailable in many countries: norepinephrine plus albumin, titrated to a 10–15 mmHg MAP rise, performs comparably in ICU patients
On the ward: midodrine 7.5–12.5 mg three times daily plus octreotide 100–200 µg subcutaneously three times daily — weaker, but available

Wong F et al. N Engl J Med. 2021;384:818–828 (CONFIRM) · Angeli P et al. J Hepatol. 2019;71:811 · Koyner Ch 42 (Table 42.2)

Blood products, nutrition & glycaemia

Three prescriptions the consultant nephrologist is expected to have an opinion about — and usually does not.

Koyner Ch 11, 14–15

Restrictive transfusion is the default

TRICC · N Engl J Med 1999

838 euvolaemic ICU patients, threshold 7 g/dL vs 10 g/dL. 30-day mortality 18.7% vs 23.3% (p = 0.11); in-hospital mortality 22.2% vs 28.1% (p = 0.05). Restrictive was better in patients under 55 and with APACHE II ≤20.

TRISS · N Engl J Med 2014

998 patients with septic shock, 7 vs 9 g/dL. 90-day mortality 43.0% vs 45.0% (RR 0.94, 95% CI 0.78–1.09; p = 0.44) — no difference, with a median of 1 vs 4 units transfused. Half the blood, the same outcome.

TRICS III · N Engl J Med 2017

5,243 cardiac surgery patients: restrictive (<7.5 g/dL intra-operatively) was non-inferior to liberal, and AKI rates were identical — despite pre-operative anaemia being a well-established risk factor for cardiac-surgery-associated AKI.

Hébert PC et al. N Engl J Med. 1999;340:409–417 · Holst LB et al. N Engl J Med. 2014;371:1381–1391 · Mazer CD et al. N Engl J Med. 2017;377:2133 · Cochrane review of 31 trials, 12,587 patients: RR 0.97 for death, 43% less transfusion exposure · Koyner Ch 11

The exceptions — and MINT, which moved one of them

MINT · N Engl J Med 2023

3,504 patients with myocardial infarction and haemoglobin <10 g/dL, restrictive (7–8) vs liberal (≥10). 30-day death or recurrent MI 16.9% vs 14.5% (RR 1.15, 95% CI 0.99–1.34; p = 0.07) with more cardiac deaths in the restrictive arm. It did not prove restrictive transfusion is safe in acute MI — so transfuse the ischaemic myocardium more liberally.

Transfuse above 7

Acute coronary syndrome or ongoing myocardial ischaemia; symptomatic anaemia with a fixed cardiac output.

Transfuse to physiology

Active major haemorrhage — treat the bleeding rate, not the haemoglobin, which lags. Massive transfusion protocol at 1:1:1 (PROPPR).

Transfuse less

Potential transplant candidates — minimise pRBC exposure to limit allosensitisation. Non-acute anaemia: transfuse for symptoms, not for a threshold.

Pitfall — TACO, the transfusion reaction nephrologists cause

Transfusion-associated circulatory overload occurs in 1–2% of transfusions and is the commonest cause of transfusion death. AKI and CKD are named risk factors. It is distinguished from TRALI by its rapid response to a diuretic — so in a suspected reaction, an early trial of furosemide is worth more than the harm of unnecessary diuresis. One unit, slowly, then recheck: a single unit is ~350 mL and ~250 mg of iron, and should raise the haemoglobin about 1 g/dL.

Carson JL et al. N Engl J Med. 2023;389:2446–2456 (MINT) · Holcomb JB et al. JAMA. 2015;313:471 (PROPPR) · Koyner Ch 11 (Table 11.2)

Platelets, plasma and cryoprecipitate — the thresholds

Product	Threshold / indication	Nephrology note
Platelets — prophylaxis	≤10 × 10⁹/L in a hospitalised patient	Rising thresholds have no evidence; treat the bleeding risk, not the count
Platelets — central line	>20 × 10⁹/L	A tunnelled dialysis catheter is a central line; ultrasound guidance matters more than the count
Platelets — LP or elective surgery	≥50 × 10⁹/L	Not required before cardiopulmonary bypass unless platelet dysfunction is documented
Platelets — kidney biopsy	Most nephrologists want ≥100 × 10⁹/L	Custom, not evidence — the supporting data are genuinely absent
Fresh-frozen plasma	Massive transfusion (≥10 units RBC/24 h); warfarin with intracranial haemorrhage	Highest TRALI risk of any product. Do not use it to "correct" an INR before a line in a non-bleeding patient
Cryoprecipitate	Fibrinogen <100 mg/dL with bleeding or DIC	Pooled from 5 donors; enriched in fibrinogen, factor VIII and factor XIII
Prothrombin complex concentrate	Warfarin reversal, factor deficiency	Faster and lower-volume than FFP — the better choice in a fluid-overloaded AKI patient

AABB platelet guidelines 2015 · Koyner Ch 11 · citrate toxicity from massive transfusion causes ionised hypocalcaemia and QT prolongation — the same chemistry as regional citrate anticoagulation (Lecture 9)

Uraemic bleeding — a stepwise toolkit

Correct the correctable — stop antiplatelets and anticoagulants where the indication allows; treat severe anaemia (a higher red cell mass pushes platelets toward the vessel wall and improves primary haemostasis); correct acidaemia and ionised hypocalcaemia.

Dialyse — removing the uraemic milieu is the only intervention that treats the cause. Everything below is a bridge.

Desmopressin 0.3 µg/kg IV over 30 min (or 3 µg/kg intranasally) — releases von Willebrand factor multimers. Onset ~1 h, duration 4–8 h, and tachyphylaxis after 2 doses. Watch for hyponatraemia; restrict free water afterwards.

Cryoprecipitate, 10 units — onset ~1 h, duration 4–24 h. Reserve for active bleeding: it carries all the risks of a pooled allogeneic product.

Conjugated oestrogens 0.6 mg/kg/day IV for 5 days — onset ~6 h, peak effect at 5–7 days, effect lasting up to 2 weeks. The right choice for recurrent or angiodysplastic gastrointestinal bleeding, where DDAVP's 8 hours are useless.

Tranexamic acid — effective but renally cleared. Dose-reduce in kidney failure; accumulation causes seizures and thrombosis.

Hedges SJ et al. Nat Clin Pract Nephrol. 2007;3:138–153 · Koyner Ch 11, 14 (Table 14.1, coagulopathy of kidney disease)

Feeding the AKI patient

Target	Prescription	Why
Energy	20–25 kcal/kg/day (max 30); 20 if >60 years	Energy expenditure is set by the underlying illness, not by AKI. Early high-energy intake may worsen kidney function; calculation formulae overestimate
Protein — no KRT	0.8–1.2 g/kg/day	The "amino acid paradox": a high protein load during active injury raises urea and can aggravate damage. Permissive hypoalimentation at 60–80% of expenditure is reasonable in stage 2–3
Protein — on KRT	1.2–1.5 g/kg/day; up to 1.7 if hypercatabolic	Includes 0.2 g/kg/day to replace therapy losses. ASPEN's 2.0–2.5 g/kg/day rests on a single study and risks hyperammonaemia
KRT losses	~2 g amino acids per hour on IHD; ~0.2 g per litre of effluent on CKRT — roughly 10 g/day at 2 L/h. Protein loss up to 20 g/day across high-flux membranes	This is the arithmetic behind the extra 0.2 g/kg/day. Albumin is lost too
Route	Enteral first, started early at a trophic rate and advanced slowly; prokinetics early	AKI impairs gastrointestinal motility; enteral feeding improves kidney perfusion in animal models
Micronutrients	Water-soluble vitamins 2× RDA; thiamine before feeding starts; selenium up to 600 µg/day on CKRT; supplement phosphate routinely	CKRT strips water-soluble vitamins and trace elements. Hypophosphataemia delays ventilator weaning and worsens survival

The one rule to take away

Never restrict protein to postpone dialysis. You will not defer the dialysis and you will catabolise the patient. Also count the hidden calories: citrate on CKRT contributes roughly 200 kcal/day, and propofol is a lipid infusion — check triglycerides, because levels >800 mg/dL clot the filter.

Koyner Ch 15 (Tables 15.3–15.4) · Fiaccadori E et al. Clin Nutr. 2021 (ESPEN, kidney disease) · KDIGO AKI 2012

Glucose and the metabolic environment

NICE-SUGAR · N Engl J Med 2009

6,104 ICU patients, intensive control (81–108 mg/dL) vs conventional (≤180 mg/dL). 90-day mortality 27.5% vs 24.9% (OR 1.14; p = 0.02) with severe hypoglycaemia in 6.8% vs 0.5%. Tight control kills.

BICAR-ICU · Lancet 2018

Sodium bicarbonate for severe metabolic acidaemia (pH ≤7.20) in the ICU: neutral overall, but in the pre-specified AKIN 2–3 stratum 28-day mortality was lower (46% vs 63%) and fewer patients needed KRT. In severe AKI with severe acidaemia, bicarbonate is reasonable while you decide about dialysis.

Pitfall — the target you actually write

Aim for 140–180 mg/dL (7.8–10.0 mmol/L). Because glucose has a diurnal swing, some units aim at 150 to stay reliably under 180. Hyperglycaemia damages the endothelium and amplifies kidney injury, but hypoglycaemia is the poison — and in AKI, insulin clearance falls, so the same infusion rate that was safe on day 1 is not on day 3. Correct potassium, magnesium and phosphate at the same time: their depletion augments kidney injury experimentally.

NICE-SUGAR Study Investigators. N Engl J Med. 2009;360:1283–1297 · Jaber S et al. Lancet. 2018;392:31–40 · Koyner Ch 15 (Table 15.1)

Cases & wrap-up

Two consults where the correct answer is to stop doing something, and one poll where the number decides the plan.

Koyner Ch 10, 12, 36, 40

Case 1 · 64 M, urosepsis, hour 4

Presented with obstructive pyelonephritis; the stone has been stented, antibiotics are running. He has already had 30 mL/kg of 0.9% saline in the emergency department.

MAP 62NE 0.18 µg/kg/minLactate 3.8Cr 1.0 → 2.1 mg/dLUO 0.2 mL/kg/h × 5 hCVP 12PLR ΔSV +4%Cl⁻ 112HCO₃⁻ 18anion gap 11

The intern wants "another litre because he is still oliguric". What do you do about the volume, the acidosis and the urine output?

Think 60 seconds · answer on the next slide

Case 1 — four decisions, not one

Stop the volumePLR +4% is a negative test. The next litre will raise the CVP, lower the renal perfusion pressure and buy nothing.

→

Fix the pressureTitrate norepinephrine to MAP 65; add vasopressin 0.03 U/min at ~0.25–0.3 µg/kg/min instead of escalating a single agent.

→

Name the acidosisCl⁻ 112 with a normal anion gap is iatrogenic hyperchloraemic acidosis. Switch to balanced crystalloid; do not treat it as worsening sepsis.

→

Leave the urine aloneObstruction is relieved; this is evolving septic ATN. No boluses, no furosemide for oliguria. Consider an FST at 24 h for prognosis, not for therapy.

Key point

"He's still oliguric" is not an indication for anything. Test fluid responsiveness, name the acid–base disorder, and separate the perfusion problem from the tubular problem — they need opposite treatments.

Koyner Ch 10, 12, 36 · Semler MW et al. N Engl J Med. 2018 · Shapiro NI et al. N Engl J Med. 2023 · SSC 2021

Case 2 · 74 F, HFrEF (EF 30%), hospital day 5

Home furosemide 80 mg twice daily. Admitted with orthopnoea; currently on furosemide 80 mg IV twice daily. She has gained 7 kg since admission and remains breathless with a raised JVP.

Cr 1.4 → 2.3 mg/dLNa⁺ 129K⁺ 3.2HCO₃⁻ 34Cl⁻ 91Albumin 2.6 g/dLCVP 18UO 900 mL/daySpot urine Na⁺ 12 mmol/LCumulative +6 L

Is this diuretic resistance, or a bad prescription? Write your next three orders — and say what you will not do.

Think 60 seconds · answer on the next slide

Case 2 — measure the natriuresis before you call it resistance

Urine Na⁺ 12 mmol/L two hours after a loop dose is a failed prescription, not a failed kidney. The target is >50–70 mmol/L, with urine output >100–150 mL/h in the first 6 h
Her IV dose is 160 mg/day; the DOSE high-dose equivalent for a 160 mg/day home dose is ~400 mg/day
HCO₃⁻ 34 with Cl⁻ 91 is contraction alkalosis with chloride depletion — it directly blunts the loop response
The creatinine rise with a CVP of 18 is congestive, not ischaemic. Decongest and watch NT-proBNP and haematocrit, not the creatinine (Lecture 2)

What not to do

Do not order ultrafiltration first — CARRESS-HF: same weight loss, worse creatinine, 72% vs 57% serious adverse events
Do not stop the diuretic because the creatinine rose
Do not give albumin as a diuretic adjuvant here — the evidence is marginal and it will not fix an under-dose

The three orders

1. Furosemide 160 mg IV bolus, then infusion 10–20 mg/h. 2. Chlorothiazide 500 mg IV (or metolazone 5 mg) 30 minutes before the loop dose. 3. Acetazolamide 250–500 mg IV for the alkalosis, with potassium and magnesium replaced first and rechecked at 6 hours.

Mullens W et al. Eur J Heart Fail. 2019;21:137–155 · Felker GM et al. N Engl J Med. 2011;364:797 · Bart BA et al. N Engl J Med. 2012;367:2296 · Koyner Ch 12, 40

Quick poll

Day 3 of KDIGO stage 2 AKI after pancreatitis. De-resuscitated to a neutral balance, MAP 74 off vasopressors, CVP 9, no obstruction. She received furosemide two days ago. You give furosemide 1.5 mg/kg IV and replace urine millilitre for millilitre. Two-hour urine output: 130 mL.

A. Repeat the test at a higher dose · B. High risk of progression to stage 3 or KRT — plan access and monitoring · C. Start a furosemide infusion to force the output up · D. Give 500 mL of crystalloid and repeat the test

Hands up — then say what you would change in the next 24 hours

Answer B. 130 mL is below the 200 mL / 2 h threshold, which predicts progression to stage 3 AKI or KRT with a specificity near 90%. The dose was correct (1.5 mg/kg because she is not diuretic-naive) and the patient was euvolaemic and normotensive, so the test is valid. A is wrong: the FST is a single standardised challenge, not a titration — repeating it at a higher dose has no validated cut-off. C is wrong: the test is prognostic, and forcing urine output does not change the trajectory of the injury or improve recovery. D is wrong and harmful — she is euvolaemic; giving fluid to make the test "pass" is exactly the fluid creep this lecture is about. Teaching point: act on the information — secure access, review every renally cleared drug, recheck potassium and acid–base, and start the conversation about KRT timing (Lecture 8) — but do not start dialysis on a stress test alone.

Key takeaways

Balanced crystalloid by default, saline by indication — the effect is small (SMART 14.3% vs 15.4%; BaSICS and PLUS neutral) but it is free, and hyperchloraemic acidosis is entirely iatrogenic.
Albumin earns its cost in SBP, large-volume paracentesis and HRS-AKI; it is contraindicated in traumatic brain injury; starches are finished.
CLASSIC and CLOVERS say the exact volume rarely decides survival — but >10% fluid accumulation is independently associated with death, so prescribe the evacuation phase as deliberately as the resuscitation.
Diuretics give volume control, never renal protection. The furosemide stress test (1.0 or 1.5 mg/kg; 200 mL in 2 h; AUC 0.87) is the best functional biomarker you already own.
Before calling it diuretic resistance, measure the natriuresis, double to the ceiling, correct the alkalosis and block the distal tubule — ultrafiltration is the last rung, not the first.
Restrictive transfusion at 7 g/dL everywhere except acute myocardial ischaemia (MINT), glucose 140–180 mg/dL, protein 1.2–1.5 g/kg/day on KRT — and never restrict protein to defer dialysis.

References & further reading

Where to go deeper

Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults (SMART). N Engl J Med. 2018;378:829–839.
Zampieri FG, Machado FR, Biondi RS, et al. Effect of intravenous fluid treatment with a balanced solution vs 0.9% saline solution on mortality in critically ill patients (BaSICS). JAMA. 2021;326:818–829.
Finfer S, Micallef S, Hammond N, et al. Balanced multielectrolyte solution versus saline in critically ill adults (PLUS). N Engl J Med. 2022;386:815–826.
Meyhoff TS, Hjortrup PB, Wetterslev J, et al. Restriction of intravenous fluid in ICU patients with septic shock (CLASSIC). N Engl J Med. 2022;386:2459–2470.
Chawla LS, Davison DL, Brasha-Mitchell E, et al. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013;17:R207.
Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure (DOSE). N Engl J Med. 2011;364:797–805.
Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome (CONFIRM). N Engl J Med. 2021;384:818–828.
Koyner JL, Topf JM, Lerma EV, eds. Handbook of Critical Care Nephrology. Wolters Kluwer; 2021 (Ch 8–15, 40, 42–43).

Critical Care Nephrology · Two-Week Intensive

Thank you

Questions & discussion — bring a fluid balance chart from your own unit and we will price it.

Next: Lecture 04 — Biomarkers, Risk Scores & Imaging in AKI