Critical Care Nephrology · Two-Week Intensive · Lecture 2 of 9

Renal Hemodynamics, Shock & ICU Monitoring

Perfusion pressure, venous congestion and the vulnerable kidney — reading both sides of the gradient

40 minutes Nephrology Fellows Week 1

Based on Koyner, Handbook of Critical Care Nephrology (2021) & Ronco, Critical Care Nephrology (3e) · NTUH Yunlin Branch

Learning objectives

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

Explain why medullary oxygenation is uncoupled from renal blood flow, and why autoregulation is preglomerular only.
Compute and act on renal perfusion pressure — MAP − CVP, MAP − IAP — not MAP alone.
Choose a fluid-responsiveness test whose validity conditions your patient actually satisfies.
Defend a MAP target and match shock phenotype to vasopressor, quoting each trial's renal endpoint.
Recognise congestion, intra-abdominal hypertension and hypertensive emergency as pressure problems vasopressors cannot solve.

Koyner Ch 1–2, 13, 40, 42–43, 45 · Ronco Ch 4, 18, 109

Renal perfusion physiology

A high-flow, low-extraction organ whose metabolic demand is set by its own blood flow — and one region living permanently on the edge of hypoxia.

Ronco Ch 18 · Koyner Ch 2

The energy paradox: flow sets demand, not the other way round

1.2L/min RBF ≈ 20% of cardiac output

~99%of filtered Na⁺ reabsorbed — the mTAL does the hardest transport at the lowest PO₂

10–20mmHg medullary PO₂ vs ~50 in cortex

~10%of whole-body O₂

The kidney reverses the usual rule: ↑RBF → ↑GFR → ↑filtered Na⁺ → more ATP work.
Vasa recta countercurrent exchange shunts O₂ away from the medulla.

Why this matters at the bedside

Global O₂ extraction is low — a normal RBF says nothing about the medulla. Anaemia, sepsis and vasoconstrictors tip a region already at PO₂ 10–20.

Ronco Ch 18 (Beloncle, Piquilloud, Asfar) · Ronco Ch 10 · Koyner Ch 2 · Brezis M, Rosen S. N Engl J Med. 1995;332:647–655

Autoregulation: two loops, both preglomerular

Myogenic response — fast

Afferent stretch → depolarisation → L-type Ca²⁺ entry → constriction within ~300 ms.

Tubuloglomerular feedback — slower

Macula densa senses distal NaCl → adenosine → A₁ afferent constriction, ~1 s. Abolished by loop diuretics.

The point fellows miss

Autoregulation protects the preglomerular circulation only — a preserved GFR is no guarantee of tubular perfusion.

The human lower threshold is unknown, and likely higher than brain or heart.
Chronic hypertension shifts the curve right; blunted in sepsis, post-CPB, CKD, elderly.
NSAIDs block afferent dilation; ACEi/ARB block efferent tone — hypotension plus both disables the loop.

Ronco Ch 18 · Koyner Ch 2

Perfusion pressure: it is never just MAP

RPP = MAP − CVP APP = MAP − IAP (target ≥ 60 mmHg)
Use whichever back-pressure is higher. MAP 75 with CVP 18 = RPP 57.

The venous half of the gradient

The kidney is encapsulated: raised venous pressure collapses tubules at unchanged MAP. In ADHF, worsening renal function tracked CVP 18 vs 12 — cardiac index did not.

The abdominal half

Normal IAP 5–7 mmHg. IAH ≥12; ACS >20 with new organ failure. Oliguria is the earliest sign, before BP falls.

Ronco Ch 18 · Koyner Ch 43 · Mullens W et al. J Am Coll Cardiol. 2009;53:589 · Cheatham ML et al. J Trauma. 2000;49:621

Sepsis: the flow can be normal and the kidney still fails

Why "prerenal ischaemia" is the wrong model

Renal blood flow rose in 5 of 6 patients with severe sepsis.
The lesion is haemodynamic incoherence: macrocirculation restored, microcirculation not.
Tubular cells downshift metabolism — part of the GFR fall is adaptive.

The demand side rises at the same time

Fever, hypercatabolism, high filtered Na⁺ load after resuscitation
Mitochondrial injury and oxidative stress from DAMPs/PAMPs
Nephrotoxins, free haemoglobin, hyperglycaemia
Vasoconstrictor excess that lowers regional flow

Therapeutic consequence

Resuscitating past macrocirculatory adequacy does not reopen the microcirculation — it adds congestion. Choose an endpoint, not a ceiling.

Ronco Ch 18 (Rector 1973; Brenner 1990) · Koyner Ch 2, 36 · Ince C. Crit Care. 2015;19:S8 · Pool R, Gomez H, Kellum JA. Crit Care Clin. 2018;34:63–80

Shock, monitoring & perfusion targets

Which numbers deserve a decision, which deserve only a trend, and which deserve to be ignored.

Koyner Ch 1–2, 10 · Ronco Ch 4, 21–26

Four haemodynamic patterns — one kidney at risk

MAP − CVP = CO × SVR. Shock means one term collapsed and the other failed to compensate.

Type	CO	SVR	Pulse pressure	CVP	ScvO₂	Renal mechanism
Hypovolemic	↓	↑	Narrow	↓	↓	Prerenal → ATN if uncorrected
Distributive	↑ / normal	↓↓	Wide	variable	↑ / normal	Microcirculatory failure; flow may be normal
Cardiogenic	↓↓	↑	Narrow	↑↑	↓↓	Congestion usually dominates low output
Obstructive	↓	↑	Narrow	↑↑	↓	Fix the obstruction, not the pressure

The one number that beats all monitoring

Each hour of delayed effective antibiotics: 7.6% higher mortality. No haemodynamic optimisation compensates for an undrained source.

Mixed shock is the ICU norm

Sepsis on HFrEF, vasoplegia on tamponade — one strategy cannot serve both.

Koyner Ch 1–2 (Table 2.1–2.2) · Kumar A et al. Crit Care Med. 2006;34:1589 · Vincent JL, De Backer D. N Engl J Med. 2013;369:1726

Perfusion endpoints: what each one actually measures

Signal	Target / signal	Where it fails
Urine output	Continuous perfusion + function readout	Blunted by diuretics; non-oliguric AKI common; ADH-driven oliguria is not hypoperfusion
Lactate	>2 mmol/L abnormal; recheck q2–4 h	Hepatic clearance ↓, β₂ agonism (epinephrine), metformin, thiamine deficiency
Capillary refill	<3 s; responds within minutes	Technique, temperature, vasopressor dose, dark skin, PVD
ScvO₂ / SvO₂	65–70% commonly targeted	Low in cardiogenic, normal-to-high in distributive despite dysoxia; the two are not interchangeable
Creatinine	Functional GFR	Lags 24–72 h; diluted by resuscitation; falls with muscle loss

Koyner Ch 1–2 · EGDT refuted by ProCESS/ARISE/ProMISe 2014–15

Capillary refill as a resuscitation target — the ANDROMEDA trials

ANDROMEDA-SHOCK · JAMA 2019

CRT- vs lactate-targeted: mortality 34.9% vs 43.4% (p = 0.06) — negative, but less organ dysfunction and less fluid.

ANDROMEDA-SHOCK-2 · JAMA 2025

CRT-guided vs usual care: win ratio 1.16 (p = 0.04). The win came from less organ support, not survival.

Why CRT is the exam sign to trust

The only physical-exam marker validated against lactate in an RCT — and it responds in minutes. Record it with the vitals.

Hernández G et al. JAMA. 2019;321:654 · Kattan E/Hernández G et al. JAMA. 2025 (ANDROMEDA-SHOCK-2) · Koyner Ch 1–2

The monitoring ladder — and where POCUS sits on it

Exam + NIBP — mottling, CRT, mentation. Free and repeatable.

Arterial line — continuous MAP, PPV/SVV, gases. Minimum on any vasopressor.

CVC — CVP as back-pressure, ScvO₂, drug and KRT access.

Echo — biventricular function, filling, tamponade. Repeat it.

CO/PA catheter — when the phenotype is unclear.

Heart

Empty, full or stunned?

IVC

Only at extremes — invalid when ventilated.

Lung

B-lines = extravascular water.

Kidney / veins

Hydronephrosis, cortical thickness, intrarenal venous flow.

Rule

POCUS answers binary questions well, continuous ones badly. Change a decision with it, don't generate a number.

Koyner Ch 1, 18 · Ronco Ch 21–26, 33

CVP and VExUS: the half of the gradient nobody monitors

Settle this first

Across 24 studies, CVP for volume responsiveness: AUC 0.56 — a coin flip. Never let it generate a fluid order.

What CVP is genuinely for

The back-pressure term in RPP
A congestion signal: CVP >12–15 tracks AKI across cohorts
Waveform diagnosis: giant v-waves, RV failure, tamponade
Its trend during decongestion

VExUS: grading congestion, not estimating volume

Gate is a dilated IVC (≥2 cm), then hepatic, portal, intrarenal Doppler
Portal pulsatility ≥50% is severe; intrarenal continuous → biphasic → monophasic
≥2 severe patterns predicted post-cardiac-surgery AKI: HR 3.69
Caveat: derived in cardiac-surgical patients; unreliable in cirrhosis

Marik PE, Baram M, Vahid B. Chest. 2008;134:172 · Koyner Ch 1 · Beaubien-Souligny W et al. Ultrasound J. 2020;12:16 · Ronco Ch 109

Fluid responsiveness: ask a question the test can answer

Test	Threshold	AUC	Missing prerequisite
PPV	>12–15%	0.94	Vt ≥8 mL/kg, no spontaneous effort, sinus rhythm
SVV	>10–13%	0.84	As for PPV, plus a CO device
PLR	SV ↑ ≥10%	—	Stroke-volume measure; legs mobile
End-exp. occlusion	SV ↑ ≥5%	—	Tolerates 15-s ventilator hold
CVP	any	0.56	Nothing rescues it

How PPV lies

Raised IAP and pulmonary hypertension inflate PPV by stiffening the thorax — the false reading drives the fluid that raises the IAP.

Key point

About half of stable people are fluid-responsive. "Responsive" never means fluid is indicated.

Koyner Ch 1 (Table 1.1, adapted from Marik 2008) · Koyner Ch 2, 43 · Monnet X, Teboul JL. Crit Care. 2015;19:18 · Cherpanath TGV et al. Crit Care Med. 2016;44:981

The four phases of fluid therapy (ROSE)

ResuscitationMinutes–hours. Life-threatening shock; boluses; positive balance acceptable.

→

OptimisationHours. Titrate to organ perfusion; test responsiveness before every bolus.

→

StabilisationDays. Neutral balance; fluid only for ongoing losses. Maintenance and drug volumes now dominate.

→

EvacuationDays–weeks. Active de-resuscitation: diuretics or net ultrafiltration.

Common pitfall

Most ICU fluid is given in phases S and E — maintenance, drug diluents, flushes — long after the patient stopped being fluid-responsive. Positive cumulative balance independently predicts mortality in septic shock. Prescribe and audit it as deliberately as vasopressors.

Malbrain MLNG et al. Ann Intensive Care. 2018;8:66 · Koyner Ch 2, 10 · Tigabu BM et al. J Crit Care. 2018;48:153

Restrictive vs liberal fluids: two big trials, one uncomfortable answer

CLASSIC · NEJM 2022

Restrictive vs standard after ≥1 L: 90-day mortality 42.3% vs 42.1%. Separation only ~1.8 L — a trial of less, not none.

CLOVERS · NEJM 2023

Restrictive + early vasopressors vs liberal: 90-day death 14.0% vs 14.9%; stopped for futility; no KRT-free-day difference.

What to take to the bedside

Neither strategy is dangerous in the ranges tested. Settled as a protocol, not an individual answer: test responsiveness, respect the venous side, stop when the signal stops improving.

Meyhoff TS et al. N Engl J Med. 2022;386:2459 · Shapiro NI et al. N Engl J Med. 2023;388:499 · Koyner Ch 2, 10 · Surviving Sepsis Campaign 2026, Crit Care Med. 2026;54:725–812

MAP targets: 65 is a starting prescription, not a constant

SEPSISPAM · NEJM 2014

MAP 80–85 vs 65–70: mortality NS. Chronic-HTN subgroup: less KRT (31.7% vs 42.2%), more AF.

65 trial · JAMA 2020

Permissive hypotension (60–65) vs usual care: 90-day mortality NS.

What the physiology shows

MAP 60 → 75 improved renal O₂ delivery and GFR
MAP 65 → 75 raised UO; 75 → 85 did not
Time-integrated MAP <55 predicts mortality

Prescription, not dogma

Start 65 — SSC 2026 suggests 60–65 at ≥65. Trial 75–80 for chronic hypertensives or high CVP/IAP. Re-write it daily.

Asfar P et al. N Engl J Med. 2014;370:1583 · Lamontagne F et al. JAMA. 2020;323:938 · Redfors B et al. Intensive Care Med. 2011 · Deruddre S et al. Intensive Care Med. 2007;33:1557–1562 · Dünser MW et al. Crit Care. 2009;13:R181 · Surviving Sepsis Campaign 2026, Crit Care Med. 2026;54:725–812 · Ronco Ch 18

SEPSISPAM n = 776; the KRT difference was day 1–7, p = 0.046. The 65 trial: n = 2,600, all aged ≥65, 90-day mortality 41.0% vs 43.8%, achieved MAP only 67 vs 72.6. Physiology detail: 75 → 90 added nothing to O₂ delivery, and 65 → 75 also lowered the resistive index. Accept a lower target if arrhythmia limits the drug, and always name the endpoint you are titrating to. 2 min. Both trials are about the tails: the chronic-HTN renal signal is an unadjusted subgroup (more AF), and the 65 trial never separated arms as planned — KRT did not differ. With high CVP/IAP, fix the gradient rather than the MAP alone. Physiology studies are tiny (n = 12, n = 11); KRT AUROC is highest below 75 mmHg. Cite them as physiology, not evidence of a target. Unadjusted 90-day was 41.0% vs 43.8% (p = 0.15), but Koyner Ch13 highlights an adjusted OR 0.82 (0.68–0.98) — have it ready if challenged.

Vasopressors & inotropes

What each agent does at the two arterioles, and what the trials actually showed for the kidney.

Koyner Ch 13 · Ronco Ch 4

First-line by phenotype, and how to compare doses

Shock	First-line	Escalation	Renal note
Distributive (sepsis)	Norepinephrine	Vasopressin 0.03 U/min → epinephrine → angiotensin II	Perfusion pressure protects; α-load does not
Cardiogenic	Norepinephrine + inotrope	Dobutamine, milrinone, mechanical support	Decongestion usually matters more
Hypovolemic	Volume/blood product	NE only as a bridge	Never mask ongoing bleeding
Obstructive	Relieve the obstruction	Pressor as a bridge	Pressure without flow perfuses nothing

Norepinephrine-equivalent dose (NEE)

epinephrine ×1 · phenylephrine ÷10 · dopamine ÷150 · vasopressin 0.04 U/min ≈ 0.1. Above ~0.5, escalate the diagnosis, not the dose.

Before you call it refractory, exclude

Occult haemorrhage · tamponade · abdominal compartment syndrome · acidaemia, ionised hypocalcaemia, adrenal insufficiency · line error.

Koyner Ch 2, 13 · Surviving Sepsis Campaign 2026, Crit Care Med. 2026;54:725–812 · Goradia S et al. J Crit Care. 2021;61:233

Norepinephrine — the workhorse, and its renal logic

Pharmacology

Potent α₁, modest β₁: MAP with little chronotropy
Preserves filtration fraction as RBF falls → GFR can hold while MAP recovers
Recruits unstressed splanchnic volume — "fluid-like" at low dose
Half-life ~2 min: titrate every few minutes

Practice points

Start early: CENSER showed faster shock control alongside fluids
Peripheral in a proximal large vein: ~2% extravasation — a bridge only
Extravasation: stop, aspirate, then phentolamine 5–10 mg
Rising dose + falling MAP = a diagnosis, not a titration problem

Koyner Ch 13 · Permpikul C et al. Am J Respir Crit Care Med. 2019;199:1097 (CENSER) · Surviving Sepsis Campaign 2026, Crit Care Med. 2026;54:725–812

Vasopressin — the sparing agent with a renal story that never closed

Rationale and dosing

V₁ vasoconstriction is catecholamine-independent and preserved in acidaemia
Preferential efferent constriction — a filtration-friendly profile
Fixed dose 0.03 U/min, not a rescue pressor. SSC 2026: second-line adjunct
Wean by 0.01 U/min every 30–60 min — abrupt stop causes hypotension

VASST · NEJM 2008

Vasopressin + NE vs NE: 28-day mortality 35.4% vs 39.3%, NS.

VANISH · JAMA 2016

Kidney-failure-free days: negative. KRT lower with vasopressin, but confined to non-survivors — a competing-risk artefact.

Koyner Ch 13 · Russell JA et al. N Engl J Med. 2008;358:877 · Gordon AC et al. JAMA. 2016;316:509 · Surviving Sepsis Campaign 2026, Crit Care Med. 2026;54:725–812

Epinephrine, dopamine, phenylephrine and the inotropes

Agent	Dose	Use	Evidence / renal caveat
Epinephrine	0.01–0.5 µg/kg/min	Refractory septic shock; anaphylaxis	No MAP advantage vs NE (CAT); don't chase β₂ lactate
Phenylephrine	0.1–10 µg/kg/min	NE-associated tachyarrhythmia	Reflex bradycardia; useful in AS/HOCM
Dopamine	—	Essentially never	SOAP II: no benefit, more arrhythmias
Dobutamine	2.5–20 µg/kg/min	Low CO with an adequate MAP	Vasodilates — can drop MAP; arrhythmogenic
Milrinone	0.125–0.75 µg/kg/min	RV failure, pulmonary hypertension	Renally cleared — accumulates in AKI
Levosimendan	0.05–0.2 µg/kg/min	Selected low-output states	Low-quality evidence; avoid if SBP <85

Koyner Ch 13 (Table 13.1) · De Backer D et al. N Engl J Med. 2010;362:779 (SOAP II) · Myburgh JA et al. Intensive Care Med. 2008;34:2226 (CAT) · Friedrich JO et al. Ann Intern Med. 2005;142:510

Angiotensin II and refractory vasoplegia

ATHOS-3 · NEJM 2017

Angiotensin II vs placebo in vasodilatory shock. MAP response 69.9% vs 23.4%. In KRT patients, 28-day survival 53% vs 30% — post hoc. Thrombosis 13.5% vs 5%.

Where it plausibly belongs

High-renin, low-ACE phenotypes: ARDS, ECMO, post-cardiotomy, chronic ACEi
Renin as a selection biomarker — no RCT has randomised on it
Restores efferent tone — coherent but unproven

Other rescue moves, ranked by evidence

Hydrocortisone 200 mg/day — faster shock resolution (ADRENAL)
Methylene blue 1–2 mg/kg — avoid with serotonergics, G6PD deficiency
Correct calcium, acidaemia, thiamine, thyroid before a fourth drug

Khanna A et al. N Engl J Med. 2017;377:419 · Tumlin JA et al. Crit Care Med. 2018;46:949 · Venkatesh B et al. N Engl J Med. 2018;378:797 · Annane D et al. N Engl J Med. 2018;378:809 · Koyner Ch 13

The kidney in specific contexts

Cardiorenal, hepatorenal, the ventilator, the abdomen and the hypertensive extreme — the consult service's daily work.

Koyner Ch 3, 40, 42–43, 45 · Ronco Ch 109, 121–122, 128

Cardiogenic shock: quantify it before you treat it

CPO (W) = MAP × CO / 451 PAPi = (PASP − PADP) / RAP
CPO couples pressure and flow; PAPi tests RV pulsatility against preload.

Numbers that change management

CPO <0.6 W — the strongest haemodynamic correlate of mortality
PAPi ≤0.9 flags severe RV dysfunction — a flag, not a rule
CVP/PCWP >0.6 — RV-dominant; the kidney fails from congestion
SCAI A–E: stage on admission and at 24 h

The nephrology reading

CPO 0.5 W + CVP 20 = two renal problems, only one of which responds to inotropes. If flow is the lesion, support it; otherwise decongest.

Fincke R et al. J Am Coll Cardiol. 2004;44:340 (SHOCK registry) · Korabathina R et al. Catheter Cardiovasc Interv. 2012;80:593 · Baran DA et al. Catheter Cardiovasc Interv. 2019;94:29 (SCAI) · Koyner Ch 40

Cardiorenal syndrome type 1: decongestion is the renal therapy

Forward failure — the minority mechanism

Low CO → low RPP → prerenal. But improving cardiac index does not improve kidney function outside cardiogenic shock — WRF occurs without hypotension.

Backward failure — the dominant mechanism

↑CVP → renal venous/interstitial pressure → tubular and capillary collapse → hypoxia → SNS/RAAS → Na⁺ retention → higher CVP. Only volume removal opens the loop.

How to decongest without flinching at the creatinine

Stepped diuresis (CARRESS-HF): IV furosemide 2.5× home oral dose, divided, target 3–5 L/24 h; add metolazone if missed. DOSE: bolus = infusion. Cr rise with haemoconcentration or falling NT-proBNP = decongestion, not injury. SCUF only for true failure.

Koyner Ch 40 · Mullens W et al. J Am Coll Cardiol. 2009;53:589 · Felker GM et al. N Engl J Med. 2011;364:797 (DOSE) · Bart BA et al. N Engl J Med. 2012;367:2296 (CARRESS-HF) · Ronco Ch 109

Hepatorenal physiology: vasodilation in the wrong compartment

Portal hypertension → splanchnic vasodilation → effective arterial volume falls
Compensatory RAAS/SNS/ADH → intense renal vasoconstriction, bland sediment, low FeNa
Cirrhotic cardiomyopathy removes cardiac compensation; SBP is the classic trigger
HRS-AKI (ICA 2019): cirrhosis with ascites + KDIGO AKI, no response to albumin 1 g/kg/day × 2 d

CONFIRM · NEJM 2021

Terlipressin + albumin in HRS-1: reversal 32% vs 17%. More respiratory failure; 90-day survival unchanged.

Angeli P et al. J Hepatol. 2019;71:811 (ICA) · Wong F et al. N Engl J Med. 2021;384:818 (CONFIRM) · Koyner Ch 42 · Ronco Ch 128

Lung–kidney crosstalk: the ventilator is a haemodynamic drug

Mechanical

Positive intrathoracic pressure ↓ venous return and CO — low-grade obstructive shock
High PEEP ↑ CVP and raises IAP: a double hit on the venous side of RPP
Proning raises IAP — measure bladder pressure if oliguria follows
Neurohormonal: ↑renin, ↑ADH → Na⁺ and water retention within hours

Gas exchange and biotrauma

Hypoxaemia → renal vasoconstriction; hypercapnia → acidaemia and blunted pressor response
Ventilator-induced lung injury releases IL-6/TNF — biotrauma causes tubular apoptosis
Lung-protective ventilation is kidney-protective — and invalidates PPV/SVV

Koyner Ch 3–4 · Husain-Syed F et al. Am J Respir Crit Care Med. 2016;194:402 · Ronco Ch 121–122

Intra-abdominal hypertension: the pressure nobody measures

Grade	IAP	Action
I	12–15	Bed <30°, avoid hip flexion, analgesia, stop over-resuscitation
II	16–20	NG/rectal decompression, prokinetics, NM blockade
III	21–25	Percutaneous drainage; negative balance
IV	>25	Decompressive laparotomy if organ failure

Measure intravesically, supine, end-expiration; repeat q4 h. WSACS goal: IAP <15, APP ≥60.

Why it is a nephrology problem

Capillary compression and impaired venous outflow, plus direct renal-vein compression
IVC compression mimics hypovolaemia and inflates PPV — treatment worsens the disease
IAH independently predicts mortality: RR 1.85
Oliguria appears around IAP 15 — before BP moves

Koyner Ch 43 · Kirkpatrick AW et al. Intensive Care Med. 2013;39:1190 (WSACS) · Malbrain MLNG et al., multicentre analysis of 1,669 patients (cited in Koyner Ch 43) · Ronco Ch 18

The other extreme: hypertensive emergency

SBP >180 or DBP >120 with target-organ damage → fibrinoid necrosis
Renal face: haematuria, proteinuria, rising Cr, TMA
Exclude renal artery stenosis, phaeochromocytoma, cocaine
Many are volume depleted — diuretics are not routine

Hour 1: ≤20–25% mean BP ↓ → 160/100–110 at 2–6 h → <140/90 at 24–48 h
Aggressive lowering converts an emergency into ischaemic AKI.

Aortic dissection

SBP 100–120, HR <60; β-blockade before any vasodilator.

Intracerebral haemorrhage

INTERACT2: <140 in 1 h is safe.

Scleroderma renal crisis

Titrated ACEi, not a drip; up to half recover function.

Preeclampsia

Labetalol or nifedipine + magnesium; delivery is definitive.

Koyner Ch 45 · Anderson CS et al. N Engl J Med. 2013;368:2355 (INTERACT2) · Whelton PK et al. Hypertension. 2018;71:e13 · van den Born BH et al. Eur Heart J Cardiovasc Pharmacother. 2019;5:37

Titratable agents that respect the kidney

Agent	Dose	Use	Renal / ICU note
Nicardipine	5 mg/h, ↑2.5 q5–15 min	First-line	No renal dose change; reflex tachycardia
Clevidipine	1–2 mg/h, double q90 s	Ultra-short alternative	Lipid emulsion — count calories
Labetalol	10–20 mg then 0.5–2 mg/min	Dissection, pregnancy	Avoid in decompensated HF
Esmolol	50–200 µg/kg/min	Dissection, tachyarrhythmia	Half-life ~9 min
Nitroglycerin	5–200 µg/min	Pulmonary oedema, ischaemia	Venodilator; limited BP effect
Nitroprusside	0.25–3 µg/kg/min	Last resort only	Avoid in kidney failure — thiocyanate
Fenoldopam	0.1–1.6 µg/kg/min	Historic interest	RCT stopped for futility

Koyner Ch 13, 45 · Bove T et al. JAMA. 2014;312:2244 (fenoldopam)

Cases & wrap-up

Three consults, three different answers to the same question: "the creatinine is up — what do I do?"

Koyner Ch 1–2, 40, 43

Case 1 · Septic shock, MAP 60, creatinine rising

68 M, pneumococcal pneumonia, ICU day 1; 3 L crystalloid; ventilated, Vt 6, sinus rhythm.

NE 0.2 µg/kg/minMAP 60CVP 8PPV 17%Lactate 4.1ScvO₂ 74%UO 15 mL/hCRT 4 sCr 1.1 → 1.9

Bolus, more NE, or an inotrope?

TestPLR with a stroke-volume measure — valid at Vt 6

→

ActSV ↑ ≥10% → 250–500 mL. No rise → NE to MAP 65–70

→

ReassessAt 30–60 min: MAP, CRT, UO, lactate, CVP

→

StopWhen the perfusion signal stops improving

Koyner Ch 1–2 · Hernández G et al. JAMA. 2019;321:654 · Surviving Sepsis Campaign 2026 · Monnet X, Teboul JL. Crit Care. 2015;19:18

Case 2 · Cardiorenal syndrome — is this kidney underperfused?

70 F, HFrEF EF 25%, admitted with orthopnoea, home furosemide 40 mg bd. JVP to the jaw, bilateral B-lines in 6 zones, 4+ oedema.

Cr 1.0 → 2.2 mg/dLMAP 78CVP 16IVC 2.4 cm, non-collapsingPortal pulsatility 60%Monophasic intrarenal venous flowNT-proBNP 11,400

RPP = 78 − 16 = 62 mmHg. Do you raise the MAP, or lower the CVP?

Koyner Ch 40 · Mullens W et al. J Am Coll Cardiol. 2009;53:589 · Beaubien-Souligny W et al. Ultrasound J. 2020;12:16 (VExUS) · Felker GM et al. N Engl J Med. 2011;364:797 (DOSE)

Case 3 · The tense abdomen

52 M, severe acute pancreatitis, day 3, cumulative balance +8 L. Distended, tense abdomen; anuric 4 h. The team wants to give fluid because "the PPV is 22% and the IVC looks small".

MAP 62CVP 20Bladder pressure 26 mmHgNE 0.3 µg/kg/minPlateau pressure 34Lactate 3.8Cr 2.8

Compute the abdominal perfusion pressure. Then explain why both the PPV and the IVC are lying.

Koyner Ch 43 · Kirkpatrick AW et al. Intensive Care Med. 2013;39:1190 (WSACS) · Cheatham ML et al. J Trauma. 2000;49:621

Quick poll — think like a specialist

62 M, chronic hypertension, septic shock day 2. NE 0.35, MAP 66, CVP 15, lactate 2.4 and falling, CRT 2 s, urine 0.2 mL/kg/h × 5 h, Cr 1.3 → 2.4. Hyperdynamic LV. Bladder pressure 11.

A. Raise the MAP target to 80–85
B. Add vasopressin 0.03 U/min and trial a MAP of 75
C. Give 500 mL — CVP 15 with oliguria means under-filling
D. Start dobutamine for inadequate cardiac output

Hands up — then defend it against the trial that seems to support the others

Asfar P et al. N Engl J Med. 2014;370:1583 · Lamontagne F et al. JAMA. 2020;323:938 · Redfors B et al. Intensive Care Med. 2011 · Deruddre S et al. Intensive Care Med. 2007;33:1557–1562 · Surviving Sepsis Campaign 2026, Crit Care Med. 2026;54:725–812

Three pitfalls that undo good haemodynamics

Pitfall 1 — treating MAP and ignoring the back-pressure

MAP is displayed continuously; CVP and IAP are not. Read both ends of the gradient before every fluid or pressor change.

Pitfall 2 — using a valid test in an invalid patient

The monitor prints a number whether or not its assumptions hold. A confidently wrong number is worse than none.

Pitfall 3 — reading a rising creatinine as failed decongestion

During effective decongestion, a creatinine rise with haemoconcentration carries a better prognosis. Stop when congestion is gone, not when the creatinine moves.

Koyner Ch 1–2, 40, 43 · Marik PE et al. Chest. 2008;134:172 · Koyner Ch 40 (DOSE/CARRESS post hoc)

Key takeaways

Renal demand is set by renal blood flow; autoregulation is preglomerular only.
Prescribe perfusion pressure, not MAP: RPP = MAP − CVP; APP = MAP − IAP (≥60).
CVP: AUC 0.56 for responsiveness, excellent for congestion — never a volume estimate.
Match the test to the patient: PPV needs Vt ≥8 and sinus rhythm; otherwise PLR.
Norepinephrine first, vasopressin second, dopamine dead. Start MAP 65; 75 captures most of the renal gain.
Congestion injures kidneys — cardiorenal syndrome, IAH and high PEEP need pressure removed.

References & further reading

Where to go deeper

Asfar P, et al. SEPSISPAM. N Engl J Med. 2014;370:1583.
Lamontagne F, et al. 65 trial. JAMA. 2020;323:938.
Russell JA, et al. VASST. N Engl J Med. 2008;358:877.
Gordon AC, et al. VANISH. JAMA. 2016;316:509.
Hernández G, et al. ANDROMEDA-SHOCK. JAMA. 2019;321:654.
Meyhoff TS, et al. CLASSIC. N Engl J Med. 2022;386:2459.
Mullens W, et al. J Am Coll Cardiol. 2009;53:589.
Beaubien-Souligny W, et al. VExUS. Ultrasound J. 2020;12:16.

Full list: (1) Koyner et al., eds., Handbook of Critical Care Nephrology, Wolters Kluwer 2021, Ch 1–3, 13, 40, 42–43, 45; (2) Ronco et al., eds., Critical Care Nephrology 3e, Elsevier 2018, Ch 4, 10, 18, 109, 121–122, 128; (3) Asfar P et al., N Engl J Med 2014;370:1583–1593 (SEPSISPAM); (4) Lamontagne F et al., JAMA 2020;323:938–949 (65 trial); (5) Russell JA et al., N Engl J Med 2008;358:877–887 (VASST); (6) Gordon AC et al., JAMA 2016;316:509–518 (VANISH); (7) De Backer D et al., N Engl J Med 2010;362:779–789 (SOAP II); (8) Khanna A et al., N Engl J Med 2017;377:419–430 (ATHOS-3); (9) Hernández G et al., JAMA 2019;321:654–664 and JAMA 2025 (ANDROMEDA-SHOCK-2); (10) Meyhoff TS et al., N Engl J Med 2022;386:2459–2470 (CLASSIC); (11) Shapiro NI et al., N Engl J Med 2023;388:499–510 (CLOVERS); (12) Mullens W et al., J Am Coll Cardiol 2009;53:589–596; (13) Beaubien-Souligny W et al., Ultrasound J 2020;12:16 (VExUS); (14) Marik PE et al., Chest 2008;134:172–178; (15) Kirkpatrick AW et al., Intensive Care Med 2013;39:1190–1206 (WSACS); (16) Wong F et al., N Engl J Med 2021;384:818–828 (CONFIRM); (17) Surviving Sepsis Campaign 2026, Crit Care Med 2026;54(4):725–812, superseding SSC 2021, Crit Care Med 2021;49:e1063–e1143.

Critical Care Nephrology · Two-Week Intensive

Thank you

Questions & discussion — tomorrow we turn this physiology into prescriptions.

Next: Lecture 03 — Fluids, Vasopressors, Diuretics & Blood Products