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

Kidney Replacement Therapy II

Dose, anticoagulation, complications, drug dosing, blood purification and what happens after the machine is switched off

40 minutes Nephrology Fellows Week 2

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…

Write a CRRT prescription that delivers 20–25 mL/kg/h, and quantify the gap between prescribed and delivered.
Run regional citrate from first principles — dose per litre of blood, buffer arithmetic, the accumulation signal.
Attribute a clotting circuit to physics, access or pharmacology, and manage the complications the therapy itself creates.
Convert an effluent rate into a drug clearance and dose antimicrobials accordingly.
Appraise blood purification, ECMO-CRRT and poisoning indications honestly; liberate from KRT on evidence and plan post-AKI care.

Koyner Ch 15, 26, 28, 30, 33–36, 51, 56 · Ronco Ch 143, 154, 168 · KDIGO AKI 2012 (2026 AKI/AKD update in public review, March 2026)

Dose & delivery

Dose is a clearance the patient receives, not a number typed into a machine — and the two are never the same.

Koyner Ch 30 · KDIGO 2012 Section 5 · ATN · RENAL

Dose is delivered clearance — and the gap is where patients lose it

Delivered = Q_eff ÷ kg × (h/24) × F_predil
F_predil = Q_pw ÷ (Q_pw + Q_pre); Q_pw = Q_b × (1 − Hct)
Blood flow ≫ effluent, so effluent is urea clearance.

Thieves of dose: downtime, clotting, access dysfunction — ~16 h/24 h delivered
Even in RCTs the gap persists: RENAL delivered 33.4 vs 40 prescribed.
IHD metric: Kt/V_urea >1.2 per session.

Dose has four dimensions

Small solute: effluent rate
Middle molecule: cut-off
Volume: net UF rate
Time: hours actually connected

Urea was chosen because it is measurable — not because it is what matters.

Chen H, Palevsky PM. Koyner Ch 30 · Venkataraman R, Kellum JA, Palevsky P. J Crit Care. 2002;17:246–250 · Bellomo R et al. N Engl J Med. 2009;361:1627–1638 · Palevsky PM et al. N Engl J Med. 2008;359:7–20 · KDIGO AKI 2012 §5.8

The dose question is closed — and the answer is "enough, reliably"

ATN

n = 1,124. Intensive vs less-intensive: 60-day mortality 53.6% vs 51.5%.

RENAL

n = 1,508. CVVHDF 40 vs 25: 90-day mortality 44.7% in both arms.

IPD meta-analysis

No survival benefit from more dose, and a signal towards impaired recovery.

What to write

KDIGO: deliver 20–25 mL/kg/h effluent
Prescribe 25–30 and accept losses, or prescribe 25 and defend uptime — not both errors

When more dose is genuinely indicated

Hypercatabolism with uncontrolled K⁺ or acidosis
Tumour lysis
Poisoning
Citrate accumulation

Pitfall

Escalating effluent "because he is septic": no benefit, and it accelerates nutrient and antibiotic losses.

Palevsky PM et al. N Engl J Med. 2008;359:7–20 · Bellomo R et al. N Engl J Med. 2009;361:1627–1638 · Wang Y et al. Nephrol Dial Transplant. 2018;33:1017–1024 · KDIGO AKI 2012 §5.8 · Jörres A et al. Nephrol Dial Transplant. 2013;28:2940 (ERBP) · Koyner Ch 30

A CRRT prescription you could write tonight

70 kg, septic shock, anuric AKI, Hct 30% — CVVHDF with citrate (ACD-A).

Setting	Value	Why
Blood flow Q_b	150 mL/min	Sets citrate dose
ACD-A, pre-pump	239 mL/h	3 mmol/L blood
Dialysate, Ca-free	1,100 mL/h	Diffusive clearance
Replacement, post-filter	300 mL/h	Convective, low FF
Net UF	100 mL/h	1.4 mL/kg/h
Calcium chloride	titrated	Systemic iCa 1.0–1.2
Set change	72 h	If TMP rises

The arithmetic

Effluent 1,739→24.8 mL/kg/h (23.9 pre-dilution). 4 h off →19.9; 8 h →15.9.

Citrate rate = target × Q_b (L/h) ÷ mmol/L

Barker AB, Tolwani AJ. Koyner Ch 33, Table 33.3 · KDIGO 2012 §5.8 · Koyner Ch 30

The daily audit — and the fluid-removal ceiling nobody prescribes

Hours on therapy in 24 h — chart it.

Filter changes and the reason — the pattern names the fault.

Machine-logged effluent ÷ kg ÷ 24, corrected for pre-dilution.

Metabolic readout — urea, K⁺, PO₄, HCO₃⁻: the adequacy test.

24-h and cumulative balance against a written goal.

Net ultrafiltration rate: an unresolved U

Net UF >1.75 mL/kg/h tracked higher mortality
Rates <1.0 also track with more death
Both confounded — write a daily target

Pitfall

"Even balance" written once and never revised. Fluid removal is a drug — stop it during vasopressor escalation.

Murugan R et al. JAMA Netw Open. 2019;2:e195418 (RENAL secondary analysis) · Vijayan A, Palevsky PM. Am J Kidney Dis. 2012;59:569–576 · Koyner Ch 30

Anticoagulation, the circuit & its complications

The circuit and the patient have opposite interests. Regional citrate is the only strategy that serves both — if you understand the chemistry.

Koyner Ch 33 · Ronco Ch 143, 154, 168 · KDIGO 2012 §5.5 · RICH 2020

Choosing a strategy before choosing a drug

Situation	No liver failure	Severe liver failure
Low bleeding risk	Citrate or UFH	UFH or none
High bleeding risk	Citrate	None
HIT	Citrate or argatroban	Bivalirudin
Active bleed / neurosurgery	None or citrate	None

Key point

KDIGO: citrate first-line for CRRT without impaired citrate metabolism — not "liver disease" as a label. Many high-bleed patients previously got none.

Barker AB, Tolwani AJ. Koyner Ch 33, Table 33.1 · KDIGO 2012 §5.3.2.2

Circuit patency is physics before it is pharmacology

FF = Q_UF ÷ (Q_pw + Q_pre); keep <20–25% Above that the blood leaving the fibres will clot.

Post-dilution CVVH always has higher FF than CVVHD at same Q_b.
Fix: access → raise Q_b → pre-dilution → dialysate. Drug last.

Same dose, different filter life

CVVH 1,750/6,300 → FF 28% → clots. CVVHDF 400 convection → FF 6% → survives. Use CVVHDF.

Koyner Ch 33 · Joannidis M et al. Crit Care. 2007;11:218 · Ronco Ch 168

Systemic heparin: cheap, familiar, and paid for by the patient

How it is given

Bolus 25–50 U/kg, then 5–10 IU/kg/h
Target aPTT 45–60 s (or anti-Xa 0.3–0.6)
Half-life ~90 min, up to 3 h in kidney failure; protamine-reversible
"Heparin resistance" is usually low antithrombin

What it costs

Filter life tracks the aPTT, not the heparin dose: raising aPTT by 10 s cut clotting but raised bleeding 50%
Bleeding in 10–50% of series
HIT: platelets fall days 5–10
Argatroban: 100 µg/kg bolus, 1 µg/kg/min (0.5 in liver disease)

Koyner Ch 33, Table 33.2 · van de Wetering J et al. J Am Soc Nephrol. 1996;7:145–150 · Link A et al. Crit Care Med. 2009;37:105–110

Regional citrate: the whole chemistry in one slide

ChelatePre-filter citrate 3–4 mmol/L → iCa <0.35 — circuit only.

→

RemoveCa–citrate sieves — most lost in effluent.

→

MetaboliseLiver/kidney/muscle → 3 HCO₃⁻ each.

→

ReplaceSystemic Ca restores clotting; fluids Ca-free.

Buffer

Q_b 150 → 27 mmol/h citrate ⇒ ~80 mmol/h HCO₃⁻ generated, ~40 delivered.

Sodium

4% citrate Na 420 → hyponatric fluid.

Calories

≈200 kcal/day — count it.

Koyner Ch 33 Fig 33.1 · Oudemans-van Straaten HM et al. Crit Care. 2012;16:249 · Ronco Ch 143

Monitoring the citrate patient — and catching accumulation

Measure	Target	Freq
Post-filter iCa	0.25–0.35	q6h
Systemic iCa	1.0–1.2	q6h
Total Ca / iCa	<2.5	2×/day
HCO₃, pH, AG	trend	q6h

Pitfall — the 02:00 miss

iCa falls, total Ca rises, ratio >2.5. More Ca is chelated, not missing.

Accumulation vs mismatch

Who: liver failure, lactate >4–5. Fix: cut citrate, raise effluent. Ratio normal + acidosis = too little citrate; alkalosis = too much.

L-CAT

Citrate feasible in liver failure at reduced target — avoid heparin in cirrhosis.

Koyner Ch 33 · Morabito S et al. Clin J Am Soc Nephrol. 2014;9:2173 · Schneider AG et al. Crit Care. 2017;21:281 · Slowinski T et al. Crit Care. 2015;19:349 (L-CAT)

Citrate troubleshooting at the bedside

What you see	Mechanism	First move
Clots, iCa >0.4	Too little citrate	Raise citrate; recheck 1 h
Clots, iCa on target	Access / high FF	Fix access; pre-dilution
Alkalosis	Citrate HCO₃ excess	Lower Q_b; cut buffer
Acidosis, ratio <2.5	Too little citrate	Raise Q_b; add HCO₃
Acidosis, ratio >2.5	Accumulation	Cut citrate, raise effluent
Hypernatraemia	Hypertonic citrate	Hypotonic fluid / ACD-A
iCa low / high	Replacement mismatch	Titrate Ca infusion
Low Mg / PO₄	Effluent loss	Replace daily

Koyner Ch 33 · Morabito S et al. Clin J Am Soc Nephrol. 2014;9:2173 · Schneider AG et al. Crit Care. 2017;21:281 · Ronco Ch 168

Citrate vs heparin: what the trials showed

RICH · JAMA 2020 (n=596)

Filter 47 vs 26 h; mortality 51.2 vs 53.6% (HR 0.79, p=0.054) — underpowered.

Bai — meta-analysis 2015 (11 RCTs, n=992)

Fewer circuit losses, bleeding RR 0.36; no survival difference.

Good citrate circuit

Most reach 72 h; <24 h = system problem (access→FF→citrate)
Uptime buys delivered dose

Limits

No proven survival benefit
Replace phosphate from day 1
Needs protocol + 6-hourly labs

Zarbock A et al. JAMA. 2020;324:1629 (RICH) · Bai M et al. Intensive Care Med. 2015;41:2098 · Koyner Ch 33

Complications: the circuit and the patient

Circuit — mechanical

Clotting: rising TMP, dark striations; loses blood plus dose
Blood leak: pink effluent — stop, do not return blood
Air embolism: via the subatmospheric pre-pump segment

Circuit — access & membrane

Recirculation: up to 20–30% with lines reversed
Access dysfunction: pressure alarms, positional flow
Bioincompatibility: AN69 bradykinin reaction on an ACE inhibitor

Patient

Haemodynamic: hypotension at connection; UF outrunning refill
Metabolic: hypophosphataemia, hypokalaemia, glucose swings
Nutritional: amino acids, phosphate, vitamins lost in effluent
Infective: CRBSI risk scales with catheter-days

Koyner Ch 33 · Druml W, Kalantar-Zadeh K. Koyner Ch 15, Table 15.3 · Ronco Ch 143, 154 · Leblanc M et al. Clin Nephrol. 1996;45:315–319 · Zarbock A et al. JAMA. 2020;324:1629–1639

Detail to carry in discussion: a clotted adult circuit loses roughly 150–200 mL of blood plus the dose. Blood leak is fibre rupture at high TMP — stop and do not return the blood. Air is entrained through the subatmospheric pre-pump segment via loose connectors, cracks or unclamped ports. Recirculation averages ~4% IJ, 5% subclavian, ~8% femoral, and 20–30% with reversed lines — check line configuration first. Access dysfunction: pressure alarms, positional flow, fibrin sheath (catheter design and tip position — Lecture 8). AN69 bradykinin reaction: flushing, hypotension, bronchospasm within minutes of connection on an ACE inhibitor. Haemodynamic: circuit volume and cool fluid cause connection hypotension; net UF can outrun plasma refill; rapid electrolyte shifts cause arrhythmia. Metabolic: RICH hypophosphataemia 15.4% vs 6.2%, near-universal with phosphate-free fluid — weakens the diaphragm. Nutritional: ~0.2 g amino acids per litre effluent, protein loss up to 20 g/day with some membranes, plus water-soluble vitamins, selenium, thiamine. Infective: every extra catheter-day scales CRBSI risk — an argument for stopping early. 90 seconds.

The therapy as the problem: temperature and dialytrauma

Pitfall — the patient who cannot mount a fever

CRRT cools; the septic patient may stay normothermic. Never use temperature to exclude infection — use white-cell trend, vasopressors, cultures, catheter site.

Cooling can reduce vasodilation and vasopressor need
Costs: shivering, impaired coagulation, masked infection

Dialytrauma

Collective harm of the therapy itself — heat loss, electrolyte and nutrient losses, enhanced drug clearance, bioincompatibility, catheter-days, intradialytic hypotension. It may delay renal recovery: use the lowest effective dose, gentlest net UF, earliest stop.

Maynar Moliner J, Honoré PM, Sánchez-Izquierdo Riera JA, et al. The dialytrauma concept. Blood Purif. 2012;34:177–180 · Wang Y et al. Nephrol Dial Transplant. 2018;33:1017–1024 · Ronco Ch 143 · Koyner Ch 34

Detail: room-temperature fluid at 2 L/h removes substantial thermal energy — in RICH, culture-proven infection occurred in more than half of patients in both arms, so temperature is useless for screening. Cooling can be used deliberately (targeted temperature management) but the costs are shivering with higher oxygen consumption, impaired coagulation and masked infection — warm deliberately or cool deliberately, never drift. Dialytrauma is the sum of heat loss, electrolyte and divalent ion loss, water-soluble vitamin and trace element loss, enhanced antibiotic clearance, membrane bioincompatibility, catheter-days and repeated intradialytic hypotension. Its most important consequence is delayed renal recovery through recurrent hypoperfusion of a recovering kidney and the higher-dose signal from the individual-patient-data meta-analysis — the argument for the lowest effective dose, the gentlest net ultrafiltration rate that meets the goal, and the earliest reasonable stop. 60 seconds.

Drugs & nutrition on CRRT

A patient on 25 mL/kg/h is not anuric to a drug — they clear like someone with CKD stage 3b, around the clock, and almost nobody prescribes as if that were true.

Koyner Ch 15, 26 · Ronco Ch 073, 078

What governs removal — and why the ICU gets it wrong

CL_total = CL_non-renal + CL_kidney + CL_CRRT · CL_CRRT ≈ Q_eff × S (S≈free fraction)
1,750 mL/h = 29 mL/min — matters when ≥25–30% of total.

Cleared

Small, unbound, low V_d; high Q_eff

Not cleared

Large V_d / bound — but low albumin raises free

Rules

Load fully (V_d); adjust maintenance; measure

Pitfall — "renal dose" never revisited

Ceftazidime 53% at target, cefepime 0%; pip-tazo troughs ×10.5.

Jang SM, Mueller BA. Koyner Ch 26 · Roberts DM et al. Crit Care Med. 2012;40:1523 · Lewis SJ et al. Semin Dial. 2014;27:441

Cheat sheet — effluent 20–25 mL/kg/h, anuric

Agent	On CRRT	Note
Vancomycin	Load 20–25, then 15–20 mg/kg q24h	AUC/MIC 400–600
Piperacillin–tazobactam	4.5 g q8h extended	Time > MIC
Meropenem	1 g q8h (2 g if MIC≥2)	ESKD dose ≠ CRRT
Cefepime	2 g q12h (q8h Pseudo)	Neurotoxic
Fluconazole	400–800 mg q24h	Freely sieved
Levetiracetam	500–1,000 mg q12h	Seizure if underdosed
Colistin	Increase maintenance	Needs more
Aminoglycosides	Extended interval	Level-guided

Koyner Ch 26 Tables 26.1–26.2 · Trotman RL et al. CID. 2005;41:1159 · Heintz BH et al. Pharmacotherapy. 2009;29:562 · Rybak MJ et al. Am J Health-Syst Pharm. 2020;77:835

Nutrition on CRRT — the hidden ledger

Target	Value
Energy	20–25 kcal/kg/day (max 30)
Protein on KRT	1.2–1.5 g/kg/day (to 1.7 if hypercatabolic)
Glucose	2–3 g/kg/day; target <180 mg/dL
Water-soluble vitamins	Twice RDA; extra thiamine
Selenium, zinc, copper	Supplement — cleared by CRRT
Phosphate	Anticipate depletion; replace

Count both sides

Out: ~10–15 g/day amino acids; phosphate, magnesium, selenium, thiamine, vitamin C
In: citrate ~200 kcal/day, plus dextrose and buffer calories — un-counted, they overfeed
Triglycerides >800 mg/dL impair therapy and clot the filter — watch propofol

Druml W, Kalantar-Zadeh K. Koyner Ch 15, Table 15.4 · Ronco Ch 073, 143

Blood purification, ECMO & poisoning

A beautiful hypothesis, twenty years of trials, and a short list of indications that actually survived.

Koyner Ch 28, 34–36 · Ronco Ch 100, 160, 193 · EXTRIP

Blood purification in sepsis: what the trials showed

Mediator removal hypothesis; families: endotoxin/cytokine adsorption, oXiris, plasma exchange
Reality: production + refill → plasma level barely falls

IVOIRE 2013 (n=140)

High vs standard volume: 37.9 vs 40.8% mortality — NS.

EUPHAS 2009 (n=64)

Polymyxin B 32 vs 53% (HR 0.43, stopped early).

EUPHRATES 2018 (n=450)

Sham-controlled: no difference.

Verdict

No routine purification (SSC 2026 against). CRRT = organ support.

Joannes-Boyau O et al. Intensive Care Med. 2013;39:1535 · Cruz DN et al. JAMA. 2009;301:2445 · Dellinger RP et al. JAMA. 2018;320:1455 · Becker S et al. Crit Care. 2023;27:215 · SSC 2026

Therapeutic plasma exchange: where it does earn its place

Established ICU indications

TTP — start daily exchange on clinical suspicion
Anti-GBM — exchange plus immunosuppression; urgent in alveolar haemorrhage
ANCA vasculitis — for alveolar haemorrhage / severe kidney disease
Myasthenic crisis, Guillain–Barré, selected rejection, hyperviscosity

Where it does not

Sepsis — no overall mortality benefit in trials
Myeloma cast nephropathy — routine exchange unsupported
Cost: hypocalcaemia, factor and immunoglobulin depletion, drug removal, donor reactions

Koyner Ch 34 · Rimmer E et al. Crit Care. 2014;18:699 · Walsh M et al. N Engl J Med. 2020;382:622–631 (PEXIVAS) · Ronco Ch 160

Detail: TTP — daily exchange is the emergency, start on clinical suspicion with steroids and caplacizumab/rituximab per protocol. Anti-GBM — exchange plus immunosuppression, urgent for diffuse alveolar haemorrhage or dialysis-requiring disease. ANCA vasculitis — reserve for diffuse alveolar haemorrhage or the most severe kidney disease; PEXIVAS (n = 704) showed no reduction in death or ESKD overall. Sepsis — meta-analysis of four small trials (194 patients) showed no overall mortality benefit; the adult-subgroup signal (RR 0.63) is not practice-changing. Myeloma cast nephropathy — any benefit appears confined to biopsy-confirmed cast nephropathy with light-chain-guided dosing. Count the cost: citrate load, coagulation-factor and immunoglobulin depletion, removal of the antibiotics and monoclonals you just gave, reactions to donor plasma. 60 seconds.

CRRT on ECMO: three ways to connect, three sets of problems

Configuration	Advantage	Problem
Separate circuit, own catheter	Independent control; familiar alarms	Another catheter under anticoagulation
In-line haemofilter	Cheap, no extra access	External pumps for balance — errors >800 mL reported
CRRT machine spliced in	Easy ports; oxygenator traps bubbles and clots	Pressure alarms unless ports chosen deliberately

Numbers that explain the alarms

Half of ECMO patients need KRT; AKI on ECMO ≈ four-fold mortality
CRRT expects venous pressure 0 to +20 mmHg; ECMO runs −100 to +300 mmHg
ECMO anticoagulation usually protects the KRT circuit; otherwise use citrate
Cannula "chatter" = UF outpacing refill

Koyner Ch 35, Figures 35.1–35.2 · Tymowski CD, Augustin P, Houissa H, et al. CRRT connected to ECMO: managing high pressures. ASAIO J. 2017;63:48–52

Detail: separate circuits with their own catheter give independent flow and ultrafiltration control with familiar alarms, but add a large catheter under systemic anticoagulation and air entrainment risk at cannulation. An in-line haemofilter is cheap with a small priming volume and no extra access, but relies on external infusion pumps for balance — errors over 800 mL have been reported and there is no effluent metering. A CRRT machine spliced into the ECMO circuit uses pre- and post-oxygenator ports easily and the oxygenator acts as a bubble and clot trap, but there is blood loss at high-pressure connections and air entrapment at low-pressure ones. About half of ECMO patients need KRT; AKI on ECMO carries roughly a four-fold increase in mortality. Early capillary leak means poor tolerance of fluid removal; cannula chatter means ultrafiltration is faster than the patient can refill. 90 seconds.

Poisoning: which toxins, and why

Dialysable = small + V_d <1 + binding <80% + low native clearance IHD preferred; add CRRT for rebound (lithium, metformin).

Poison	Dialyse when	Stop when
Methanol / EG	Coma, visual loss, pH ≤7.15, persisting acidosis	<20 mg/dL + better
Salicylate	AMS, level >100 mg/dL	≥6 h HD or <19 mg/dL
Lithium	CNS any level; >4.0 mmol/L with kidney impairment	<1.0 mmol/L, recheck 12 h
Valproate	Oedema/shock; >1,300 mg/L	Clin better / 50–100 mg/L
Metformin	Shock, pH <7.0, lactate >20 mmol/L	Acidosis resolved
Do not dialyse	Tricyclics, digoxin, cocaine

EXTRIP Workgroup (Koyner Ch 28) · Roberts DM et al. Crit Care Med. 2015;43:461 · Decker BS et al. Clin J Am Soc Nephrol. 2015;10:875 · Juurlink DN et al. Ann Emerg Med. 2015;66:165–181

Liberation, recovery & the rest of the consult

The machine is the easy part. The highest-yield thing in this lecture happens after it is switched off — or when you decide it never should have been switched on.

Koyner Ch 51, 56 · Ronco Ch 023, 028 · KDIGO 2012 §3.5 · ADQI

Liberation from KRT: the numbers behind the decision

Signal	Threshold
UO off diuretics	>400 mL/day — best predictor
2-h CrCl	>23 mL/min (sens 76, spec 84)
24-h CrCl	>15 mL/min — strongest model
Cr falling between sessions	Any sustained fall — free

Off-diuretic UO >400 beats on-diuretic >2,300 (not clearance).

Key point

Permit recovery. Resume is easy; delayed recovery is not.

Trial off

Net UF zero → balance holds?
Stop; observe 48–72 h with restart triggers
Poor recovery: age, CKD, proteinuria, prolonged anuria

Uchino S et al. Crit Care Med. 2009;37:2576 (BEST) · Fröhlich S et al. J Crit Care. 2012;27:744 · Viallet N et al. Ann Intensive Care. 2016;6:71 · Koyner Ch 51

When recovery does not come: prognosis, trials and limits

Older AKI patients starting dialysis in hospital do badly: median survival 0.7 years in one cohort
AKI on pre-existing CKD drives permanent dependence — two-thirds or more in two studies
Withholding and withdrawing are ethically equivalent; offer a time-limited trial when prognosis is uncertain

Clinical momentum

Intubation → vasopressors → KRT → tracheostomy — each reasonable, the sum never discussed. Ask: what is this therapy for, and by when will we know?

Ellison K, Holley JL. Koyner Ch 56, Table 56.2 & Box 56.1 · Kruser JM et al. Ann Am Thorac Soc. 2017;14:426–431 · Scherer JS, Holley JL. Clin J Am Soc Nephrol. 2016;11:344–353 · Renal Physicians Association. Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis. 2nd ed. 2010

Post-AKI care: the risk and the letter that changes it

~30%readmitted AKI

80%never told they had AKI

<10%seen by nephrology

1.53HR/ albuminuria stratum

Name AKI — summary and patient

Peak stage, cause, KRT dates

Nephrotoxin review — stop NSAIDs, re-escalate renally cleared drugs

RAS — restart when stable

Cr + ACR within 3 mo — proteinuria = strongest predictor

Sick-day rules + follow-up date

Risk

CKD even after mild, recovered AKI
Heart failure association
Nephrology follow-up → lower mortality

Heung M. Koyner Ch 51 · Hsu CY et al. JAMA Intern Med. 2020;180:402 (ASSESS-AKI) · KDIGO 2012 §3.5 · ADQI AKD statements

Case 1 · The circuit that will not survive the shift

62 M, septic shock, day 3 — post-dilution CVVH 25 mL/kg/h via 16 cm femoral catheter. Third filter in 18 h; nurse asks to increase heparin.

70 kgQ_b 120Hct 34%1,750 mL/h postTMP 280→340aPTT 52 sPlt 96→41Day 5 heparin

Two errors — name both, calculate the number, fix in order.

Think 60 s · next slide

Koyner Ch 33 · Ronco Ch 154, 168 · KDIGO 2012 §5.3.2.2

Case 1 — fix the physics before the pharmacology

FF 37%No drug keeps 37% open.

→

Drop itCVVHDF + pre-dilution → single digits.

→

AccessFemoral <20 cm: ~26% recirc; swap ≥24 cm.

→

4TsPlt >50% day 5 → stop heparin, HIT work-up.

→

Drug lastCitrate first-line; argatroban if needed.

Key point

Clotting on adequate drug = physics: access → flows → FF → drug.

Koyner Ch 33 · Ronco Ch 154, 168 · KDIGO 2012 §5.3.2.2

Case 2 · VAP not responding

68 M, 80 kg, CVVHDF. Pseudomonas tracheal, mero MIC 2. "Renal failure" doses day 0 unchanged. Day 4 febrile — team wants broader agent.

Eff 2,000 mL/hMero 500 q12hVanco 1 g q24h no loadTrough 8.4Alb 21UO 60/dT 38.9WBC 22

Effluent → clearance. Judge the orders and the escalation.

Hands up — change antibiotic?

Koyner Ch 26 Tables 26.1–26.2 · Heintz BH et al. Pharmacotherapy. 2009;29:562 · Lewis SJ et al. Semin Dial. 2014;27:441

Case 3 · Hour 20 of citrate in liver failure

54 F, cirrhosis, decompensated, NE 0.35, lactate 7.8. CVVHD citrate Q_b 150, eff 1,600. Ca infusion ↑×2 overnight, iCa still falling.

iCa 0.86Total Ca 2.35pH 7.24HCO₃ 17AG 22Post iCa 0.28Na 141

Ratio? What is happening, first change — and at hour 0?

Think 45 s

Koyner Ch 33 · Morabito S et al. Clin J Am Soc Nephrol. 2014;9:2173 · Slowinski T et al. Crit Care. 2015;19:349 (L-CAT)

Quick poll

Day 12 CRRT — off vasopressors 48 h, source controlled, UO 950 mL/day off diuretics, Cr plateau, K/HCO₃ normal, balance at target. Timed CrCl 26 mL/min.

A. Raise effluent to 30 to "clear" · B. Stop now, observe 48–72 h with restart triggers; book Cr + ACR at 3 mo · C. Furosemide infusion to test · D. Thrice-weekly HD ×2 wks to "protect"

Hands up — which changes 1-year outcome?

Uchino S et al. Crit Care Med. 2009;37:2576 (BEST) · Fröhlich S et al. J Crit Care. 2012;27:744 · Koyner Ch 51

Closing the arc: nine lectures, one way of thinking

Recognise (L1, L4)

Stage with KDIGO; use biomarkers and imaging to separate haemodynamic from structural injury.

Perfuse and protect (L2, L3)

Test before giving fluid; choose the vasopressor for the phenotype; remove the nephrotoxin.

Correct the milieu (L5–L7)

Electrolytes and acid–base are the daily work — and why a patient needs the machine.

Support and stop (L8, L9)

Start when the patient demands it; prescribe a dose, defend the circuit, dose the drugs, stop as early as safely possible.

The through-line

What is this kidney being asked to do, and what is stopping it? Machines are the last answer, never the first.

Critical Care Nephrology two-week intensive, Lectures 1–9 · Koyner, Handbook of Critical Care Nephrology, 2021 · Ronco, Critical Care Nephrology, 3rd ed.

Key takeaways

Effluent = clearance: 20–25 mL/kg/h delivered — prescribe higher or defend uptime.
More dose ≠ better; net UF ~1.0–1.75 mL/kg/h, both ends confounded.
Citrate: total/iCa >2.5 = accumulation — cut citrate, raise effluent.
RICH: citrate 47 vs 26 h, less bleeding — replace phosphate day 1.
Clotting on drug = physics: keep FF <25%; access → flows → drug last.
CRRT ≈30 mL/min 24/7: load fully, TDM.
No routine blood purification — SSC 2026 against.
Liberate on UO >400 off diuretics / CrCl >23; hand off: nephrotoxins, Cr + proteinuria 3 mo.

References & further reading

Where to go deeper

ATN/RENAL 2008/09 · Wang IPD 2018 · Murugan net UF 2019.
RICH 2020;324 · Bai 2015 · L-CAT 2015.
Roberts CRRT antibiotics 2012 · Rybak vanco 2020.
IVOIRE 2013 · EUPHRATES 2018 · CytoSorb 2023 · SSC 2026.
BEST Kidney 2009 · Fröhlich CrCl 2012 · Viallet 2016.
ASSESS-AKI 2020 · Scherer trials 2016 · RPA 2nd ed.
KDIGO 2012 · KDIGO 2026 draft · Koyner 2021 · Ronco 3e · EXTRIP.

Critical Care Nephrology · Two-Week Intensive · Course complete

Thank you

Nine lectures, two weeks, one habit: ask what the kidney is being asked to do — then be the person on the round who knows the number.

NTUH Yunlin Branch Nephrology · Based on Koyner, Handbook of Critical Care Nephrology (2021) and Ronco, Critical Care Nephrology (3rd ed.)