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multidisciplinary guidelines renal replacement therapy intensive care medicine guideline

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mkdir -p "/tmp/workspace/rrt-guideline/notes" && python -c "import pdfplumber; p='/tmp/workspace/attachments/a7aa165e-8cf0-45c5-80d4-f5a44551a8af/multidisciplinary-guidelines-on-renal-replacement-therapy-in-intensive-care-medicine.pdf'; out='/tmp/workspace/rrt-guideline/notes/extracted.txt'; pdf=pdfplumber.open(p); f=open(out,'w',encoding='utf-8'); [f.write(f'\n\n===== PAGE {i+1} =====\n'+(page.extract_text() or '')) for i,page in enumerate(pdf.pages)]; f.close(); print('pages',len(pdf.pages),'out',out)"

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python -c "import re; p='/tmp/workspace/rrt-guideline/notes/extracted.txt'; s=open(p,encoding='utf-8').read(); pats=['RECOMMENDATION','Recommendation','recommendation','STATEMENT','Statement','statement']; out=[]; lines=s.splitlines(); [out.extend([f'{i+1}: '+lines[i+j] for j in range(-2,4) if 0<=i+j<len(lines)]) for i,l in enumerate(lines) if any(x in l for x in pats)]; open('/tmp/workspace/rrt-guideline/notes/recommendation_context.txt','w',encoding='utf-8').write('\n'.join(out)); print('matches',sum(any(x in l for x in pats) for l in lines),'contexts',len(out))"

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12849416

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12849416

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python -c "import re; s=open('/tmp/workspace/rrt-guideline/notes/extracted.txt',encoding='utf-8').read(); s=re.sub(r'\n===== PAGE \d+ =====\n','\n',s); lines=s.splitlines(); heads=[i for i,x in enumerate(lines) if re.match(r'^[1-7]\. (Start|Diffusion|Continuous|Anticoagulation|Dose|Pharmacotherapy|Stopping)',x.strip())]; out=[]; [out.extend(['\n### '+lines[i]]+[x for x in lines[i+1:(heads[n+1] if n+1<len(heads) else len(lines))] if re.match(r'\s*(?:[1-7]\.[0-9]+-|Table [0-9]|Recommendation|Statement)',x)]) for n,i in enumerate(heads)]; open('/tmp/workspace/rrt-guideline/notes/key_recommendations.txt','w',encoding='utf-8').write('\n'.join(out)); print(heads, len(out))"

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Detailed Notes: Multidisciplinary Guidelines on Renal Replacement Therapy in Intensive Care Medicine

Source: Meersch-Dini et al., Critical Care, DOI: 10.1186/s13054-025-05817-6. The guideline is a multidisciplinary German-Austrian consensus document for renal replacement therapy (RRT) in critically ill adults with dialysis-dependent acute kidney injury (AKI). The final open-access article is available through the PMC version.

1. Purpose and scope

Why the guideline was needed

RRT is commonly used in ICU patients with severe AKI. Important decisions remain variable in practice:

When to begin RRT
Which clearance method to use: diffusion, convection, or both
Whether continuous or intermittent therapy is preferable
Choice and monitoring of anticoagulation
Appropriate treatment dose
Drug dosing during RRT
When and how to discontinue RRT

How the guideline was developed

A multidisciplinary panel of 22 experts from 12 German-speaking professional societies was assembled.
Included intensivists, nephrologists, anesthesiologists, internists, surgeons, and patient representatives.
Evidence was identified through systematic searches of PubMed, Scopus, and Cochrane databases.
Recommendations were developed using:
- PICO clinical questions
- Modified Delphi process
- Nominal group and consensus conferences
- GRADE framework
- AGREE II guideline methodology
The panel produced 73 statements/recommendations, with 47 key recommendations summarized in the main paper.

Core message

RRT decisions should be based on the whole clinical picture, not on one laboratory value, one AKI stage, one biomarker, or one rigid timing threshold.

2. Starting RRT in ICU AKI

2.1 Absolute indications: start immediately

RRT should be initiated immediately if there are life-threatening disturbances in:

Fluid balance
- Severe fluid overload, especially pulmonary edema with hypoxemia or respiratory compromise
Electrolyte balance
- Especially severe or refractory hyperkalemia
Acid-base balance
- Severe metabolic acidosis not adequately controlled with medical treatment
Uremia
- Clinically significant uremic complications, for example encephalopathy, pericarditis, or severe symptoms attributable to kidney failure

Key principle

The document uses the classic emergency framework of hypervolemia, hyperkalemia, acidosis, and uremia. In such circumstances, delaying RRT to obtain further biomarkers or conduct a furosemide stress test is inappropriate.

2.2 Relative indications: individualize the decision

If RRT is expected to become necessary because of:

Deteriorating clinical condition
Progressive AKI course
Increasing metabolic complications
Significant pre-existing kidney disease
Poor renal reserve
Inability to maintain volume, electrolyte, or acid-base control conservatively

then it should be started without unnecessary delay.

However, in patients with non-life-threatening abnormalities or uncertainty about the need for RRT, the guideline supports:

Conservative medical management
Repeated clinical reassessment
Monitoring of volume status, urine output, potassium, pH/bicarbonate, urea, creatinine, and clinical complications

2.3 What should not trigger RRT by itself

Do not start RRT solely because of:

Isolated elevation of serum urea
Isolated elevation of serum creatinine
AKI stage alone, including KDIGO stage
A goal of accelerating renal recovery
A negative furosemide stress test alone
Novel AKI biomarkers alone

Why?

Trials comparing early versus delayed initiation have generally not shown a clear mortality benefit from routine early RRT. Also, many patients assigned to delayed strategies recover without ever requiring RRT. Thus, indiscriminate early treatment risks exposing patients to catheter-related, bleeding, hemodynamic, and infectious complications without definite benefit.

Furosemide stress test

A negative test suggests a greater likelihood of AKI progression but does not itself establish an indication for dialysis. It is a prognostic aid, not a treatment trigger.

3. Diffusion, convection, and combined methods

Definitions

Method	Main process	Main role
Diffusion	Solute movement down a concentration gradient	Efficient clearance of small solutes such as urea and potassium
Convection	Solute removal with ultrafiltrate flow, followed by replacement fluid	Removes small and middle molecules
Hemodiafiltration	Combination of diffusion and convection	Provides both mechanisms

Guideline position

For ICU patients with AKI who need RRT:

Diffusive, convective, and combined techniques produce similar patient outcomes.
No method has shown superiority for mortality, renal recovery, or hemodynamic stability.
The choice should depend on the treatment goal, local expertise, equipment, filter performance, and patient-specific circumstances.

Important practical points

Severe life-threatening hyperkalemia

Prefer a diffusive technique with high dialysate flow, if available.

Reason: Diffusion is more efficient for rapid removal of small molecules, especially potassium.

Sepsis

Diffusive, convective, or combined approaches can all be used. No modality has proven superior for survival in septic ICU patients requiring RRT.

Rhabdomyolysis

Do not initiate RRT merely because creatine kinase or myoglobin is high.
Start RRT only when there is AKI with a clear usual indication, such as refractory hyperkalemia, acidosis, fluid overload, or severe oliguria/anuria.
Convective or high cut-off approaches may remove more myoglobin, but evidence has not consistently shown better patient outcomes.

Predilution versus postdilution in hemofiltration

Either can be used.
Predilution may be preferred when filters repeatedly clot.
Predilution reduces hemoconcentration in the filter but requires a higher substitution volume to obtain similar solute clearance.
Postdilution can give more efficient clearance but may increase hemoconcentration and clotting risk.

4. Continuous, intermittent, and prolonged intermittent RRT

Definitions

Modality	Typical duration	Main characteristics
IHD: intermittent hemodialysis	4-6 hours	Rapid solute and fluid shifts
PIRRT/SLED: prolonged intermittent RRT	6-12 hours	Intermediate approach
CRRT: continuous RRT	~24 hours/day	Gradual and continuous solute/fluid removal

General recommendation

Continuous and intermittent modalities can be used equally in severe AKI with respect to survival. The modality should be selected according to the individual clinical situation.

When CRRT or prolonged RRT is preferred

Use continuous or prolonged modalities preferentially when there is:

Hemodynamic instability
High vasopressor requirement
Recurrent intradialytic hypotension
Need for slow, tightly controlled net ultrafiltration
Concern about rapid osmotic shifts
Increased intracranial pressure or cerebral edema risk

Rationale

CRRT provides slower and more stable correction of solute and fluid abnormalities. This reduces sudden changes in blood pressure, osmolality, urea concentration, and intravascular volume.

Increased intracranial pressure

RRT should be adapted to avoid dialysis disequilibrium and maintain appropriate serum osmolality.

Monitor regularly:

Serum osmolality
Sodium
Urea
Blood glucose

Rapid urea removal can lower extracellular osmolality, draw water into cells, and contribute to cerebral edema.

Thrombocytopenia

Intermittent and continuous therapies may both be considered. Thrombocytopenia alone does not dictate a specific modality.

Fluid overload

All modalities can achieve a negative fluid balance. Success depends more on individualized ultrafiltration targets and hemodynamic tolerance than on the modality itself.

Mobilization

CRRT should not delay early mobilization. Safe mobilization is possible even with CRRT and femoral access when proper protocols, trained staff, and monitoring are in place.

5. Anticoagulation during RRT

Why anticoagulation is used

Extracorporeal circuits activate coagulation and can clot. Anticoagulation helps preserve filter life and maintain prescribed treatment delivery.

Main options

Regional citrate anticoagulation
Systemic unfractionated heparin
Systemic low-molecular-weight heparin
Alternative agents for heparin-induced thrombocytopenia, such as argatroban

Citrate versus heparin

Regional citrate and systemic heparin are considered similar for major patient outcomes:

Mortality
Renal recovery
Transfusion frequency

When citrate is preferred

Regional citrate anticoagulation is preferred when:

Heparin is contraindicated
The patient has active bleeding
Bleeding risk is high
Systemic heparin is associated with poor filter life or repeated clotting

Citrate in shock or liver failure

Shock and liver failure are not absolute contraindications to citrate anticoagulation.

However, citrate can only be used safely with regular monitoring of:

Lactate
Ionized calcium
Total calcium
Acid-base status
Calcium replacement requirement
Evidence of citrate accumulation

Avoid or use extreme caution

Avoid citrate where possible in patients with:

Pronounced and progressive lactic acidosis due to shock
Severe liver failure with impaired citrate metabolism
Clinical or biochemical evidence of citrate accumulation

Citrate accumulation

If citrate accumulation occurs:

Stop citrate anticoagulation
Use RRT without anticoagulation or switch to heparin if appropriate
Use bicarbonate-buffered replacement/dialysate fluid

Heparin

LMWH and unfractionated heparin may both be used.
Unfractionated heparin is often preferred in ICU practice because it:
- Has a shorter half-life
- Is easier to monitor
- Is easier to stop or reverse if bleeding occurs

Heparin-induced thrombocytopenia type II

Stop all heparin products.
Argatroban can be considered.
It is hepatically metabolized and not significantly removed by standard dialysis filters.
In critically ill patients, especially those with liver dysfunction, a much lower initial dose may be needed.

6. Dose of RRT

CRRT dose

The recommended delivered CRRT dose is:

20-25 mL/kg/hour

This usually refers to the delivered effluent dose.

Prescribed versus delivered dose

The actual delivered dose is often lower than the prescribed dose because of:

Circuit clotting
Machine downtime
Procedures and transport
Vascular access problems
Filter changes
Alarm-related interruptions

Therefore, a prescription around 25-30 mL/kg/hour may be required to reliably deliver 20-25 mL/kg/hour.

Intermittent dialysis dose

For IHD or prolonged intermittent therapy, dose should be individualized according to:

Dialysis membrane
Blood-flow rate
Dialysate-flow rate
Convective volume, if hemodiafiltration is used
Session duration
Frequency of sessions
Potassium concentration
Acid-base status
Catabolic state
Fluid balance

Dialysis disequilibrium syndrome

Particular attention is required when initiating intermittent treatment.

Mechanism

Rapid removal of urea reduces serum osmolality. Water then shifts into cells, especially brain cells, causing cerebral edema.

Possible manifestations

Headache
Nausea/vomiting
Restlessness
Confusion
Seizures
Reduced consciousness

Prevention

Avoid overly rapid initial urea removal
Adjust dialysis duration, flow rates, and solute clearance
Consider slower or continuous approaches in high-risk patients
Closely monitor neurological status and serum osmolality

High-volume hemofiltration

Do not routinely use high-volume hemofiltration for sepsis or septic shock.

High-volume hemofiltration was defined as approximately 50 mL/kg/hour or more.
Despite theories that it may remove inflammatory mediators, evidence is inconsistent and generally low quality.
No reliable survival benefit has been established.

7. Pharmacotherapy and antimicrobial dosing during RRT

Core pharmacokinetic principle

Drug dosing in RRT must account for:

Residual native kidney function
RRT modality and treatment intensity
Extracorporeal clearance
Nonrenal clearance
Volume of distribution
Protein binding
Severity of infection and likely pathogen
Fluid accumulation, edema, and hypoalbuminemia

Initial or loading dose

The initial anti-infective dose should not routinely be reduced simply because the patient has AKI or is receiving RRT.

Why?

Critically ill patients often have an increased volume of distribution due to:

Sepsis
Capillary leak
Fluid resuscitation
Edema
Hypoalbuminemia

This is especially important for hydrophilic drugs, such as:

Beta-lactams
Aminoglycosides
Vancomycin

Underdosing the first dose can delay adequate antimicrobial exposure in life-threatening infection.

Administration strategy

Continuous RRT

For time-dependent antibiotics, continuous or prolonged administration under therapeutic drug monitoring may improve pharmacokinetic/pharmacodynamic target attainment.

Intermittent hemodialysis

For IHD, short or prolonged infusion may be preferred over continuous administration.

Post-IHD supplemental doses

After IHD, give an additional dose when indicated by the drug’s pharmacokinetics, the dialysis dose, and evidence-based drug-specific recommendations.

Therapeutic drug monitoring

Use TDM whenever available for critical antibiotics in RRT patients, particularly:

Beta-lactams
Vancomycin
Aminoglycosides

TDM is especially important in patients with:

Multiple organ failure
Severe sepsis or septic shock
Unpredictable residual kidney function
High-intensity RRT
Long or interrupted RRT sessions
Marked fluid overload
Risk of toxicity or treatment failure

The guideline notes that TDM improves attainment of pharmacokinetic/pharmacodynamic targets, although a consistent mortality benefit has not been demonstrated.

8. Stopping or weaning RRT

General principle

Discontinue RRT when the original absolute indication has resolved and native kidney function appears sufficient to maintain:

Potassium control
Acid-base balance
Fluid balance
Uremic solute control
Clinical stability

Urine output

Urine output is a useful predictor of successful liberation from RRT.

A spontaneous urine output of approximately:

300-600 mL/day without diuretics

may suggest a reasonable possibility of successful discontinuation.

This is guidance rather than a universal threshold. The guideline cannot recommend one precise urine-output value for all patients.

Other factors suggesting weaning may fail

Persistent hyperkalemia

Potassium >5.5 mmol/L may indicate a higher risk of failure.
Investigate and correct causes before attempting weaning.

Persistent metabolic acidosis

A pH <7.3 may indicate higher risk of failure.
Identify and address the cause before discontinuing treatment.

Fluid overload

Correct significant fluid overload before stopping RRT where possible.

Kinetic GFR

Kinetic GFR based on endogenous clearance may be considered as an additional predictor of kidney recovery and concentrating capacity, but evidence remains limited.

Biomarkers

The guideline cannot recommend new kidney damage or functional biomarkers for predicting successful discontinuation.

Diuretics

Diuretics may be considered to increase urine output during discontinuation, but they should not be interpreted as proof of renal recovery. They do not replace assessment of solute clearance, potassium, acid-base status, and volume control.

Definition of successful discontinuation

The consensus considers cessation successful when RRT is not restarted for approximately 7 days after an intentional discontinuation attempt.

9. High-yield exam and clinical takeaways

Start RRT immediately for life-threatening fluid, electrolyte, acid-base, or uremic complications.
Do not dialyze solely because creatinine or urea is high.
AKI stage, biomarkers, and a negative furosemide stress test should not independently determine RRT initiation.
No clear survival advantage exists for diffusion versus convection.
For severe hyperkalemia, use high-flow diffusive dialysis if available.
CRRT, IHD, and PIRRT have similar survival outcomes overall.
Prefer CRRT or PIRRT for hemodynamic instability or concern about rapid osmotic shifts.
Use RRT carefully in increased intracranial pressure, with close osmolality and electrolyte monitoring.
Citrate and heparin have similar major patient outcomes, but citrate is useful with bleeding risk or poor filter life on heparin.
Shock or liver failure are relative, not absolute, contraindications to citrate.
Delivered CRRT dose: 20-25 mL/kg/hour.
High-volume hemofiltration is not recommended for sepsis or septic shock.
Do not routinely reduce the antimicrobial loading dose in ICU patients on RRT.
Use antibiotic TDM whenever feasible, especially for beta-lactams, vancomycin, and aminoglycosides.
Urine output of 300-600 mL/day without diuretics may support a trial off RRT, but assess the entire patient.
Persistent hyperkalemia, acidosis, or fluid overload predicts weaning failure.

Important caveat

These are detailed study notes, not a bedside protocol. Local ICU policy, modality availability, nephrology input, vascular access factors, and the patient’s hemodynamic and neurological condition must guide actual prescribing. The uploaded version was labeled an article-in-press manuscript, so the final published text should be checked for minor editorial changes.# Detailed Notes: Multidisciplinary Guidelines on Renal Replacement Therapy in Intensive Care Medicine

Source: Meersch-Dini et al., Critical Care (2025), DOI: 10.1186/s13054-025-05817-6.
Scope: Renal replacement therapy (RRT) for critically ill adults with acute kidney injury (AKI), particularly dialysis-dependent AKI in the ICU.

These notes summarize a guideline manuscript supplied by you. It was labelled “article in press,” so consult the final version and local ICU/nephrology protocol for clinical use.

1. Background and purpose

Why RRT matters in ICU

AKI is common in critical illness.
Severe AKI can produce life-threatening:
- Fluid overload and pulmonary edema
- Hyperkalemia
- Metabolic acidosis
- Uremic complications
RRT supports kidney function while the underlying illness is treated. It does not by itself reverse the cause of AKI.

Aim of the guideline

To update guidance on the use of RRT in ICU patients using current evidence and expert consensus.

Development process

Binational multidisciplinary panel from Germany and Austria.
Included intensivists, anesthesiologists, nephrologists, internists, surgeons, other professionals, and patient representatives.
Evidence searched in PubMed, Scopus, and Cochrane databases.
Recommendations developed using:
- PICO questions
- Systematic literature review
- Modified Delphi process
- GRADE approach
- Multiple full-panel consensus conferences

Seven areas addressed

Starting RRT
Diffusion versus convection
Continuous versus intermittent therapy
Anticoagulation
RRT dose
Pharmacotherapy during RRT
Stopping RRT

2. Starting RRT

Core principle

Start RRT for clinical indications, not just because creatinine or urea is high.

Absolute, urgent indications

RRT should be started immediately for life-threatening disturbance of:

Problem	Clinical examples
Fluid balance	Refractory fluid overload, pulmonary edema
Electrolytes	Severe or refractory hyperkalemia
Acid-base status	Severe metabolic acidosis not responsive to medical treatment
Uremia	Uremic complications such as encephalopathy, pericarditis, severe symptomatic uremia

Recommendation 1.1

Start RRT immediately in life-threatening fluid, acid-base, or electrolyte disturbances.

Relative indications and timing

If RRT is likely to become necessary because of the patient’s illness trajectory, underlying disease, or worsening AKI, it should not be unnecessarily delayed.

However, if there is no immediate threat and the need for RRT is uncertain:

Optimize conservative therapy.
Treat reversible causes.
Reassess frequently.
Avoid exposing patients to unnecessary catheterization and extracorporeal treatment.

Recommendation 1.2

If RRT is expected to become necessary based on clinical course and comorbidities, initiate it without further delay.

Recommendation 1.3

For non-life-threatening abnormalities or uncertain need for RRT, use conservative measures and reassess regularly.

What should not trigger RRT alone?

Isolated urea or creatinine elevation

A biochemical elevation alone, without symptoms or complications of kidney failure, is not a sufficient reason to initiate RRT.
The decision must integrate:
- Clinical examination
- Fluid status
- Potassium
- Acid-base status
- Urine output
- Uremic symptoms
- Overall trajectory and prognosis

Recommendation 1.5

RRT may be deferred in isolated elevation of serum urea or creatinine without clinical signs attributable to kidney failure.

Furosemide stress test

A poor diuretic response can predict AKI progression.
It does not by itself establish a need for RRT.

Biomarkers

Novel biomarkers may help risk-stratify AKI.
Current evidence does not support using biomarkers alone to decide when to start RRT.

Recommendation 1.7

Do not use biomarkers alone to make the RRT initiation decision.

Evidence on early versus delayed initiation

Trials and systematic reviews have not shown a consistent mortality benefit from routine early RRT before conventional clinical indications occur.
A major limitation is that many patients assigned to delayed initiation improve and never need RRT.
Therefore, indiscriminate early RRT may expose some patients to:
- Vascular access complications
- Bleeding
- Infection
- Hypotension
- Unnecessary treatment burden

Exam takeaway

Do not start RRT solely for KDIGO stage, creatinine, BUN, a failed furosemide stress test, or a biomarker result. Start for dangerous complications or a strongly anticipated clinical need.

3. Diffusion versus convection

Definitions

Diffusion

Solute transport occurs down a concentration gradient across a semipermeable membrane.
Particularly effective for small molecules:
- Urea
- Creatinine
- Potassium
Examples:
- Intermittent hemodialysis (IHD)
- Continuous venovenous hemodialysis (CVVHD)

Convection

Solutes are dragged across the membrane with water movement, called solvent drag.
Used in hemofiltration and hemodiafiltration.
Examples:
- Continuous venovenous hemofiltration (CVVH)
- Continuous venovenous hemodiafiltration (CVVHDF)

Main guidance

Diffusive, convective, and combined techniques have broadly similar patient outcomes in ICU AKI.

Recommendation 2.1

In AKI requiring RRT, diffusion, convection, or a combined method can be used because outcomes are similar.

Sepsis

For patients with sepsis requiring RRT:

No modality has proven superior for mortality or renal recovery.
Diffusion, convection, and combined methods can all be used.

Recommendation 2.3

Use diffusive, convective, or combined techniques equally in septic ICU patients needing RRT.

Severe hyperkalemia

Potassium is a small molecule and is cleared efficiently by diffusion.
In life-threatening hyperkalemia, if available, favor a diffusive technique with high dialysate flow.

Recommendation 2.4

For severe life-threatening hyperkalemia, prefer high-dialysate-flow diffusive RRT over a convective method.

Predilution versus postdilution in hemofiltration

Feature	Predilution	Postdilution
Replacement fluid	Given before filter	Given after filter
Hemoconcentration in filter	Less	More
Filter clotting risk	Lower	Higher
Solute clearance efficiency	Lower for same volume	Higher
Best consideration	Repeated filter clotting	When maximizing clearance is important

Recommendation 2.2

Either pre- or postdilution may be used. Prefer predilution when filter clotting is recurrent.

Rhabdomyolysis

Myoglobin contributes to tubular injury and AKI.
Convective methods or high cut-off membranes may increase myoglobin removal.
But improved myoglobin clearance has not consistently improved patient outcomes.
Do not begin RRT solely because myoglobin is high.

Recommendation 2.5

Initiate RRT in rhabdomyolysis only when AKI has a clear RRT indication.

4. Continuous versus intermittent RRT

Modalities

Modality	Typical treatment pattern	Main characteristic
IHD	4-6 hours/session	Rapid solute and fluid removal
PIRRT/SLED	About 6-12 hours	Slower, prolonged intermittent therapy
CRRT	Continuous, usually 24 hours/day	Gradual, sustained solute and fluid removal

Mortality and renal recovery

No clear survival advantage of CRRT over intermittent RRT in unselected ICU patients with severe AKI.
Renal recovery is also broadly comparable.
Select a modality according to the patient’s hemodynamics, neurological status, fluid requirements, logistics, and staff expertise.

Recommendation 3.1

Continuous and intermittent RRT can be used equally for survival in severe AKI.

Recommendation 3.2

Individualize the modality to the clinical situation.

Hemodynamic instability

CRRT or prolonged intermittent therapy is generally preferred in patients who are:

Hypotensive
Receiving vasopressors
Unable to tolerate rapid fluid removal
At risk of intradialytic hypotension

Reason:

Slower fluid and solute shifts
Better hemodynamic tolerance

Recommendation 3.3

Prefer continuous or prolonged RRT in hemodynamically unstable patients to promote stability and reduce hypotension.

Raised intracranial pressure

Rapid decline in serum urea/osmolality can worsen cerebral edema and precipitate dialysis disequilibrium.

Recommendation 3.5

Increased intracranial pressure requires RRT adapted to preserve appropriate serum osmolality.

Monitor:

Serum osmolality
Sodium
Urea
Blood glucose

Avoid:

Abrupt urea removal
Large rapid osmotic shifts
Aggressive fluid shifts

Fluid overload

IHD, PIRRT, and CRRT can all create a negative fluid balance.
The key determinant is not the modality alone but a patient-specific ultrafiltration plan.
CRRT may facilitate steady fluid removal in unstable patients.

Recommendation 3.6

Any modality can be used for negative fluid balance. Tailor ultrafiltration to the individual patient.

Mobilization

CRRT should not automatically delay early mobilization.
Safe mobilization is feasible during CRRT with appropriately trained staff and line-safety procedures.

Recommendation 3.7

Do not delay or prevent early mobilization merely because the patient is receiving CRRT.

5. Anticoagulation in RRT

Goals

Anticoagulation should:

Maintain filter patency
Reduce circuit clotting
Minimize interruptions
Avoid bleeding and metabolic complications

Main options

Regional citrate anticoagulation (RCA)
Systemic unfractionated heparin (UFH)
Low-molecular-weight heparin (LMWH)
Alternatives in heparin-induced thrombocytopenia, such as argatroban

Citrate versus heparin

Citrate and systemic heparin have similar major patient outcomes, including mortality and renal recovery.
Citrate is useful when systemic anticoagulation is undesirable, particularly with bleeding risk.

Recommendation 4.1

Regional citrate and systemic heparin can be used equally regarding major patient outcomes.

Recommendation 4.2

Prefer regional citrate in patients with:

Heparin contraindication
Active bleeding
High risk of bleeding

Recommendation 4.3

If systemic heparin results in short filter life and inadequate delivery of therapy, consider switching to citrate.

Citrate in shock or liver failure

Older practice often treated liver failure and shock as contraindications to citrate. The guideline states they are not absolute contraindications.

However, citrate should only be used with close metabolic surveillance.

Monitor during RCA

Ionized calcium
Total calcium
Total calcium to ionized calcium relationship
Lactate
Acid-base balance
Evidence of citrate accumulation

Recommendation 4.4

Citrate can be used in shock or liver failure with regular lactate, ionized calcium, and total calcium monitoring.

Avoid or use extreme caution

Avoid citrate where possible in:

Pronounced progressive lactic acidosis
Shock with worsening lactate
Severe liver failure with impaired citrate metabolism

Recommendation 4.6

Avoid RCA if possible in progressive lactic acidosis related to shock and severe liver failure.

Citrate accumulation

Possible clues:

Increasing total calcium requirement
Worsening hypocalcemia despite calcium infusion
Rising total calcium relative to ionized calcium
Metabolic derangement
Rising lactate in the appropriate clinical setting

Recommendation 4.5

If citrate accumulation occurs:

Stop citrate.
Switch to no anticoagulation or heparin-based CRRT.
Use bicarbonate as buffering agent.

Heparin

UFH and LMWH may both be considered.
UFH is often favored in ICU because:
- Easier monitoring
- Shorter half-life
- More readily reversible

Recommendation 4.7

UFH and LMWH can both be used, but UFH is preferred when rapid adjustment and monitoring are needed.

Heparin-induced thrombocytopenia type II

Stop all heparin exposure.
Argatroban is a possible alternative.
It is hepatically metabolized, so dose reduction is needed in liver dysfunction.

Recommendation 4.8

Argatroban may be considered in acute HIT type II.

6. RRT dose

Continuous RRT dose

Recommendation 5.1

Deliver CRRT at 20-25 mL/kg/hour.

Important distinction

Prescribed dose is the dose ordered.
Delivered dose is what the patient actually receives.

Interruptions reduce delivered dose:

Filter clotting
Circuit changes
Procedures and transport
Imaging
Access problems
Machine downtime

Therefore, a slightly higher prescribed dose, such as 25-30 mL/kg/hour, may be required to achieve a delivered dose of 20-25 mL/kg/hour.

Intermittent RRT dose

Dose is individualized according to:

Dialysis membrane
Blood flow
Dialysate flow
Convective volume in hemodiafiltration
Duration of treatment
Frequency of sessions
Potassium concentration
Acidosis severity
Catabolic state
Fluid needs

Recommendation 5.2

Determine intermittent-dialysis dose using treatment parameters and clinical/laboratory targets, especially electrolyte and acid-base control.

Dialysis disequilibrium syndrome

Mechanism

Rapid urea removal lowers extracellular osmolality.
Water shifts into cells, especially brain cells.
Cerebral edema can occur.

Possible manifestations

Headache
Nausea/vomiting
Restlessness
Confusion
Seizures
Reduced consciousness

Higher-risk situations

Very high urea
First dialysis session
Rapidly delivered IHD
Acute neurological injury or raised intracranial pressure

Recommendation 5.3

When initiating RRT, assess risk of disequilibrium and adjust dose accordingly.

Practical approach:

Use gentler initial clearance.
Reduce blood and/or dialysate flow as appropriate.
Shorten first session.
Consider prolonged or continuous therapy where indicated.
Monitor neurological status and osmolality-related variables.

High-volume hemofiltration

Defined in this guideline as approximately 50 mL/kg/hour or more.
Proposed to remove inflammatory mediators in sepsis.
Evidence does not show a reliable survival benefit.
It increases complexity and may increase unintended removal of useful solutes or drugs.

Recommendation 5.4

Do not use high-volume hemofiltration routinely in sepsis or septic shock.

7. Pharmacotherapy during RRT

Why antibiotic dosing is difficult

Drug exposure in ICU patients receiving RRT is highly variable because of:

Residual renal function
Nonrenal clearance
RRT modality
Dialyzer membrane
Blood and dialysate flow
Effluent dose
Drug protein binding
Molecular size
Volume of distribution
Capillary leak, edema, hypoalbuminemia
Circuit downtime and interruptions

Loading dose

Principle

The initial dose depends mainly on the volume of distribution, not on renal clearance.

In severe critical illness:

Edema, capillary leak, and hypoalbuminemia commonly increase volume of distribution.
Hydrophilic drugs may distribute into expanded extracellular fluid, resulting in low initial plasma concentration.

Hydrophilic antibiotics include:

Beta-lactams
Aminoglycosides
Vancomycin

Recommendations 6.1-6.3

Base starting dose on the current volume of distribution.
Do not routinely reduce the initial anti-infective dose because the patient is receiving RRT.
Give the loading dose as a short infusion to achieve rapid effective concentration, even if continuous or prolonged infusion will follow.

Maintenance dose

Principle

Maintenance dosing depends on total clearance:

Total clearance = residual kidney clearance + extracorporeal/RRT clearance + nonrenal clearance

Recommendation 6.4

If effective levels are not known, calculate maintenance dose using estimated total clearance, including residual renal function and machine clearance.

Infusion strategy

Time-dependent antibiotics

Examples include many beta-lactams.

In CRRT, prolonged or continuous infusion may provide more reliable pharmacokinetic/pharmacodynamic target attainment, particularly if TDM is available.
In IHD, continuous infusion may be less suitable because dialysis interruption changes drug clearance. Short or prolonged infusion can be preferred.

Recommendations

6.5: Consider prolonged or continuous administration of time-dependent antibiotics in continuous RRT, ideally with TDM.
6.6: In IHD, short or prolonged infusion may be preferable to continuous infusion.
6.7: Following IHD, give a supplemental dose when required to restore therapeutic concentration, according to the drug’s pharmacokinetics and accepted dosing guidance.

Therapeutic drug monitoring

Recommendation 6.8

Use TDM when available for high-risk antibiotics in RRT, including:

Beta-lactams
Vancomycin
Aminoglycosides

The guideline also highlights evidence supporting TDM consideration for:

Linezolid
Colistin
Possibly daptomycin, tigecycline, and fluoroquinolones

Why TDM is important

TDM improves the probability of achieving pharmacokinetic/pharmacodynamic targets and can reduce nephrotoxicity, though a consistent mortality benefit has not been proven.

8. Stopping RRT and renal recovery

Principle

Stop RRT when the original indication has resolved and native kidney function is sufficient to maintain:

Potassium homeostasis
Acid-base balance
Fluid balance
Solute control

A successful discontinuation was considered as no restart of RRT within 7 days.

Urine output

Recommendation 7.2

Use urine output as a predictor of successful RRT discontinuation.

Recommendation 7.3

There is no exact mandatory urine output threshold. As practical guidance, spontaneous urine output of 300-600 mL/day without diuretics may suggest a reasonable chance of successful discontinuation.

Important:

Urine output predicts recovery but is not sufficient alone.
A patient may produce urine but still have inadequate clearance, persistent hyperkalemia, acidosis, or fluid overload.

Diuretics

Recommendation 7.1

Diuretics may be considered to increase urine output during RRT discontinuation.

But:

They do not prove renal recovery.
They should not substitute for reassessing clearance and complications.
They should not be used to force a trial off RRT in a patient with unresolved indications.

Other predictors and barriers

Kinetic GFR

Kinetic GFR based on endogenous clearance may be considered as an adjunctive predictor after stopping RRT.

Persistent hyperkalemia

A potassium concentration above 5.5 mmol/L suggests a higher risk of failed RRT withdrawal.

Recommendation 7.5

Investigate persistent hyperkalemia before attempting weaning.

Persistent metabolic acidosis

A pH below 7.3 may predict failure of discontinuation.

Recommendation 7.7

Treat and investigate persistent metabolic acidosis before stopping RRT.

Fluid overload

Fluid overload should be corrected before attempting discontinuation.

Recommendation 7.8

Correct fluid overload before trialing RRT withdrawal.

Biomarkers

Current evidence is inadequate to recommend novel kidney injury or functional biomarkers for stopping RRT.

9. Practical ICU decision framework

A. Should RRT be started?

Assess for emergency indications:
- Refractory hyperkalemia
- Severe acidosis
- Pulmonary edema/fluid overload
- Uremic complication
If none:
- Treat reversible factors.
- Review fluid status, urine output, hemodynamics, trajectory, and comorbidity.
- Reassess regularly.
Do not initiate solely for:
- Creatinine
- Urea
- AKI stage
- Failed furosemide stress test
- Biomarker elevation

B. Which modality?

Hemodynamic instability: CRRT or PIRRT often favored.
Severe hyperkalemia needing rapid clearance: high-flow diffusive therapy if available.
Raised intracranial pressure: avoid rapid osmotic changes, use carefully adapted therapy.
Fluid removal: any modality can work, but tailor ultrafiltration rate.
Stable patient: IHD, PIRRT, or CRRT based on clinical goals and local capability.

C. Anticoagulation choice

Standard options: citrate or systemic heparin.
Bleeding risk or heparin contraindication: favor citrate if feasible.
Shock/liver failure: citrate may still be possible with close calcium and lactate monitoring.
HIT II: avoid heparin, consider argatroban.

D. Dose

CRRT delivered dose: 20-25 mL/kg/hour.
Anticipate downtime and prescribe enough to achieve this.
Avoid routine high-volume hemofiltration in septic shock.
Prevent dialysis disequilibrium in high-risk patients.

E. Antibiotics

Do not reduce loading dose merely because RRT is used.
Individualize maintenance dose according to total clearance.
Use TDM when available for high-risk drugs.

F. When to stop

Original indication resolved.
Adequate urine output and recovery trend.
No persistent hyperkalemia, acidosis, or fluid overload.
Monitor closely for at least the next week for restart requirement.

10. High-yield exam points

Emergency RRT indications: refractory hyperkalemia, severe acidosis, refractory fluid overload/pulmonary edema, and symptomatic uremia.
Creatinine alone is not an indication for RRT.
Routine “early” RRT before clinical indications does not have a consistent mortality benefit.
Diffusion and convection have similar overall outcomes in ICU AKI.
For life-threatening hyperkalemia, use a high-flow diffusive technique if possible.
CRRT has no established overall mortality superiority, but is often preferred in hemodynamic instability.
In raised intracranial pressure, avoid rapid osmotic shifts and monitor osmolality, sodium, urea, and glucose.
Citrate is preferred with bleeding risk or heparin contraindication, but requires calcium and metabolic monitoring.
Shock and liver failure are not absolute contraindications to citrate anticoagulation.
Target delivered CRRT dose: 20-25 mL/kg/hour.
Routine high-volume hemofiltration is not recommended for sepsis/septic shock.
Do not reduce the initial antibiotic loading dose merely due to RRT.
TDM is particularly useful for beta-lactams, vancomycin, and aminoglycosides.
Urine output helps predict successful liberation from RRT. A spontaneous output of 300-600 mL/day is a useful guide, not an absolute rule.
Persistent potassium >5.5 mmol/L, pH <7.3, or fluid overload should prompt caution before stopping RRT.

The guideline is available in the open-access full guideline article. A recent systematic review also suggests that lower CRRT intensity may be comparable to standard intensity, but this is post-guideline evidence and should be interpreted alongside local protocols (2026 review, PMID 41896891).

Find recent guidelines on antimicrobial dosing during RRT

Reading File

Quick answer

The most relevant recent guidance found in the material already reviewed is:

1. Multidisciplinary Guidelines on Renal Replacement Therapy in Intensive Care Medicine

Meersch-Dini et al., Critical Care, 2025. DOI: 10.1186/s13054-025-05817-6.
Open access: full guideline article

Its antimicrobial-dosing recommendations during RRT are:

Loading dose
- Base it on the patient’s current volume of distribution.
- Do not routinely reduce the initial dose simply because the patient is receiving RRT.
- Give the loading dose as a short infusion, even if subsequent therapy will use prolonged or continuous infusion.
Maintenance dose
- Individualize according to total drug clearance:
  - Residual kidney function
  - RRT/machine clearance
  - Nonrenal clearance
- Reassess after modality or dose changes, filter downtime, and recovery of native renal function.
Continuous RRT
- For time-dependent antimicrobials, prolonged or continuous infusion may improve PK/PD target attainment, ideally with therapeutic drug monitoring.
Intermittent hemodialysis
- Short or prolonged infusions may be preferred over continuous infusion.
- Give a post-dialysis supplemental dose when drug removal by dialysis makes it necessary.
Therapeutic drug monitoring
- Use TDM whenever available for high-risk or life-threatening infections, particularly for:
  - Beta-lactams
  - Vancomycin
  - Aminoglycosides
- The guideline additionally notes variable levels with linezolid and colistin, with possible consideration of TDM for daptomycin, tigecycline, and fluoroquinolones.

Practical interpretation

RRT dosing is not a simple “renal dose reduction.” In critically ill patients, initial underdosing is common because capillary leak, edema, hypoalbuminemia, and fluid resuscitation expand the volume of distribution. The loading dose is therefore usually standard or increased, while the maintenance dose is adjusted for the specific RRT prescription and residual function.

For background, the guideline cites KDIGO AKI guidance, but the 2025 multidisciplinary guideline is more directly applicable and more current for ICU RRT antimicrobial dosing.

Practical complete guidelines notes

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Definitions and classification: HFrEF, HFmrEF, HFpEF
Diagnostic pathway and natriuretic peptides
Four foundational HFrEF drug classes and titration
Diuretics and congestion management
Iron deficiency, atrial fibrillation, CKD, diabetes, and valvular disease
Device therapy: ICD and CRT
Acute heart failure algorithm
Advanced HF, transplantation, LVAD, and palliative care
Practical monitoring tables, contraindications, and follow-up schedule

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Objectives
Methods
Results
Interpretation
Limitations
Conclusions
Exam-ready key points# Detailed Notes: Multidisciplinary Guidelines on Renal Replacement Therapy in Intensive Care Medicine

These notes summarize a guideline manuscript supplied by you. It was labelled “article in press,” so consult the final version and local ICU/nephrology protocol for clinical use.

1. Background and purpose

Why RRT matters in ICU

AKI is common in critical illness.
Severe AKI can produce life-threatening:
- Fluid overload and pulmonary edema
- Hyperkalemia
- Metabolic acidosis
- Uremic complications
RRT supports kidney function while the underlying illness is treated. It does not by itself reverse the cause of AKI.

Aim of the guideline

To update guidance on the use of RRT in ICU patients using current evidence and expert consensus.

Development process

Binational multidisciplinary panel from Germany and Austria.
Included intensivists, anesthesiologists, nephrologists, internists, surgeons, other professionals, and patient representatives.
Evidence searched in PubMed, Scopus, and Cochrane databases.
Recommendations developed using:
- PICO questions
- Systematic literature review
- Modified Delphi process
- GRADE approach
- Multiple full-panel consensus conferences

Seven areas addressed

Starting RRT
Diffusion versus convection
Continuous versus intermittent therapy
Anticoagulation
RRT dose
Pharmacotherapy during RRT
Stopping RRT

2. Starting RRT

Core principle

Start RRT for clinical indications, not just because creatinine or urea is high.

Absolute, urgent indications

RRT should be started immediately for life-threatening disturbance of:

Problem	Clinical examples
Fluid balance	Refractory fluid overload, pulmonary edema
Electrolytes	Severe or refractory hyperkalemia
Acid-base status	Severe metabolic acidosis not responsive to medical treatment
Uremia	Uremic complications such as encephalopathy, pericarditis, severe symptomatic uremia

Recommendation 1.1

Start RRT immediately in life-threatening fluid, acid-base, or electrolyte disturbances.

Relative indications and timing

If RRT is likely to become necessary because of the patient’s illness trajectory, underlying disease, or worsening AKI, it should not be unnecessarily delayed.

However, if there is no immediate threat and the need for RRT is uncertain:

Optimize conservative therapy.
Treat reversible causes.
Reassess frequently.
Avoid exposing patients to unnecessary catheterization and extracorporeal treatment.

Recommendation 1.2

If RRT is expected to become necessary based on clinical course and comorbidities, initiate it without further delay.

Recommendation 1.3

For non-life-threatening abnormalities or uncertain need for RRT, use conservative measures and reassess regularly.

What should not trigger RRT alone?

Isolated urea or creatinine elevation

A biochemical elevation alone, without symptoms or complications of kidney failure, is not a sufficient reason to initiate RRT.
The decision must integrate:
- Clinical examination
- Fluid status
- Potassium
- Acid-base status
- Urine output
- Uremic symptoms
- Overall trajectory and prognosis

Recommendation 1.5

RRT may be deferred in isolated elevation of serum urea or creatinine without clinical signs attributable to kidney failure.

Furosemide stress test

A poor diuretic response can predict AKI progression.
It does not by itself establish a need for RRT.

Biomarkers

Novel biomarkers may help risk-stratify AKI.
Current evidence does not support using biomarkers alone to decide when to start RRT.

Recommendation 1.7

Do not use biomarkers alone to make the RRT initiation decision.

Evidence on early versus delayed initiation

Trials and systematic reviews have not shown a consistent mortality benefit from routine early RRT before conventional clinical indications occur.
A major limitation is that many patients assigned to delayed initiation improve and never need RRT.
Therefore, indiscriminate early RRT may expose some patients to:
- Vascular access complications
- Bleeding
- Infection
- Hypotension
- Unnecessary treatment burden

Exam takeaway

Do not start RRT solely for KDIGO stage, creatinine, BUN, a failed furosemide stress test, or a biomarker result. Start for dangerous complications or a strongly anticipated clinical need.

3. Diffusion versus convection

Definitions

Diffusion

Solute transport occurs down a concentration gradient across a semipermeable membrane.
Particularly effective for small molecules:
- Urea
- Creatinine
- Potassium
Examples:
- Intermittent hemodialysis (IHD)
- Continuous venovenous hemodialysis (CVVHD)

Convection

Solutes are dragged across the membrane with water movement, called solvent drag.
Used in hemofiltration and hemodiafiltration.
Examples:
- Continuous venovenous hemofiltration (CVVH)
- Continuous venovenous hemodiafiltration (CVVHDF)

Main guidance

Diffusive, convective, and combined techniques have broadly similar patient outcomes in ICU AKI.

Recommendation 2.1

In AKI requiring RRT, diffusion, convection, or a combined method can be used because outcomes are similar.

Sepsis

For patients with sepsis requiring RRT:

No modality has proven superior for mortality or renal recovery.
Diffusion, convection, and combined methods can all be used.

Recommendation 2.3

Use diffusive, convective, or combined techniques equally in septic ICU patients needing RRT.

Severe hyperkalemia

Potassium is a small molecule and is cleared efficiently by diffusion.
In life-threatening hyperkalemia, if available, favor a diffusive technique with high dialysate flow.

Recommendation 2.4

For severe life-threatening hyperkalemia, prefer high-dialysate-flow diffusive RRT over a convective method.

Predilution versus postdilution in hemofiltration

Feature	Predilution	Postdilution
Replacement fluid	Given before filter	Given after filter
Hemoconcentration in filter	Less	More
Filter clotting risk	Lower	Higher
Solute clearance efficiency	Lower for same volume	Higher
Best consideration	Repeated filter clotting	When maximizing clearance is important

Recommendation 2.2

Either pre- or postdilution may be used. Prefer predilution when filter clotting is recurrent.

Rhabdomyolysis

Myoglobin contributes to tubular injury and AKI.
Convective methods or high cut-off membranes may increase myoglobin removal.
But improved myoglobin clearance has not consistently improved patient outcomes.
Do not begin RRT solely because myoglobin is high.

Recommendation 2.5

Initiate RRT in rhabdomyolysis only when AKI has a clear RRT indication.

4. Continuous versus intermittent RRT

Modalities

Modality	Typical treatment pattern	Main characteristic
IHD	4-6 hours/session	Rapid solute and fluid removal
PIRRT/SLED	About 6-12 hours	Slower, prolonged intermittent therapy
CRRT	Continuous, usually 24 hours/day	Gradual, sustained solute and fluid removal

Mortality and renal recovery

No clear survival advantage of CRRT over intermittent RRT in unselected ICU patients with severe AKI.
Renal recovery is also broadly comparable.
Select a modality according to the patient’s hemodynamics, neurological status, fluid requirements, logistics, and staff expertise.

Recommendation 3.1

Continuous and intermittent RRT can be used equally for survival in severe AKI.

Recommendation 3.2

Individualize the modality to the clinical situation.

Hemodynamic instability

CRRT or prolonged intermittent therapy is generally preferred in patients who are:

Hypotensive
Receiving vasopressors
Unable to tolerate rapid fluid removal
At risk of intradialytic hypotension

Reason:

Slower fluid and solute shifts
Better hemodynamic tolerance

Recommendation 3.3

Prefer continuous or prolonged RRT in hemodynamically unstable patients to promote stability and reduce hypotension.

Raised intracranial pressure

Rapid decline in serum urea/osmolality can worsen cerebral edema and precipitate dialysis disequilibrium.

Recommendation 3.5

Increased intracranial pressure requires RRT adapted to preserve appropriate serum osmolality.

Monitor:

Serum osmolality
Sodium
Urea
Blood glucose

Avoid:

Abrupt urea removal
Large rapid osmotic shifts
Aggressive fluid shifts

Fluid overload

IHD, PIRRT, and CRRT can all create a negative fluid balance.
The key determinant is not the modality alone but a patient-specific ultrafiltration plan.
CRRT may facilitate steady fluid removal in unstable patients.

Recommendation 3.6

Any modality can be used for negative fluid balance. Tailor ultrafiltration to the individual patient.

Mobilization

CRRT should not automatically delay early mobilization.
Safe mobilization is feasible during CRRT with appropriately trained staff and line-safety procedures.

Recommendation 3.7

Do not delay or prevent early mobilization merely because the patient is receiving CRRT.

5. Anticoagulation in RRT

Goals

Anticoagulation should:

Maintain filter patency
Reduce circuit clotting
Minimize interruptions
Avoid bleeding and metabolic complications

Main options

Regional citrate anticoagulation (RCA)
Systemic unfractionated heparin (UFH)
Low-molecular-weight heparin (LMWH)
Alternatives in heparin-induced thrombocytopenia, such as argatroban

Citrate versus heparin

Citrate and systemic heparin have similar major patient outcomes, including mortality and renal recovery.
Citrate is useful when systemic anticoagulation is undesirable, particularly with bleeding risk.

Recommendation 4.1

Regional citrate and systemic heparin can be used equally regarding major patient outcomes.

Recommendation 4.2

Prefer regional citrate in patients with:

Heparin contraindication
Active bleeding
High risk of bleeding

Recommendation 4.3

If systemic heparin results in short filter life and inadequate delivery of therapy, consider switching to citrate.

Citrate in shock or liver failure

Older practice often treated liver failure and shock as contraindications to citrate. The guideline states they are not absolute contraindications.

However, citrate should only be used with close metabolic surveillance.

Monitor during RCA

Ionized calcium
Total calcium
Total calcium to ionized calcium relationship
Lactate
Acid-base balance
Evidence of citrate accumulation

Recommendation 4.4

Citrate can be used in shock or liver failure with regular lactate, ionized calcium, and total calcium monitoring.

Avoid or use extreme caution

Avoid citrate where possible in:

Pronounced progressive lactic acidosis
Shock with worsening lactate
Severe liver failure with impaired citrate metabolism

Recommendation 4.6

Avoid RCA if possible in progressive lactic acidosis related to shock and severe liver failure.

Citrate accumulation

Possible clues:

Increasing total calcium requirement
Worsening hypocalcemia despite calcium infusion
Rising total calcium relative to ionized calcium
Metabolic derangement
Rising lactate in the appropriate clinical setting

Recommendation 4.5

If citrate accumulation occurs:

Stop citrate.
Switch to no anticoagulation or heparin-based CRRT.
Use bicarbonate as buffering agent.

Heparin

UFH and LMWH may both be considered.
UFH is often favored in ICU because:
- Easier monitoring
- Shorter half-life
- More readily reversible

Recommendation 4.7

UFH and LMWH can both be used, but UFH is preferred when rapid adjustment and monitoring are needed.

Heparin-induced thrombocytopenia type II

Stop all heparin exposure.
Argatroban is a possible alternative.
It is hepatically metabolized, so dose reduction is needed in liver dysfunction.

Recommendation 4.8

Argatroban may be considered in acute HIT type II.

6. RRT dose

Continuous RRT dose

Recommendation 5.1

Deliver CRRT at 20-25 mL/kg/hour.

Important distinction

Prescribed dose is the dose ordered.
Delivered dose is what the patient actually receives.

Interruptions reduce delivered dose:

Filter clotting
Circuit changes
Procedures and transport
Imaging
Access problems
Machine downtime

Therefore, a slightly higher prescribed dose, such as 25-30 mL/kg/hour, may be required to achieve a delivered dose of 20-25 mL/kg/hour.

Intermittent RRT dose

Dose is individualized according to:

Dialysis membrane
Blood flow
Dialysate flow
Convective volume in hemodiafiltration
Duration of treatment
Frequency of sessions
Potassium concentration
Acidosis severity
Catabolic state
Fluid needs

Recommendation 5.2

Determine intermittent-dialysis dose using treatment parameters and clinical/laboratory targets, especially electrolyte and acid-base control.

Dialysis disequilibrium syndrome

Mechanism

Rapid urea removal lowers extracellular osmolality.
Water shifts into cells, especially brain cells.
Cerebral edema can occur.

Possible manifestations

Headache
Nausea/vomiting
Restlessness
Confusion
Seizures
Reduced consciousness

Higher-risk situations

Very high urea
First dialysis session
Rapidly delivered IHD
Acute neurological injury or raised intracranial pressure

Recommendation 5.3

When initiating RRT, assess risk of disequilibrium and adjust dose accordingly.

Practical approach:

Use gentler initial clearance.
Reduce blood and/or dialysate flow as appropriate.
Shorten first session.
Consider prolonged or continuous therapy where indicated.
Monitor neurological status and osmolality-related variables.

High-volume hemofiltration

Defined in this guideline as approximately 50 mL/kg/hour or more.
Proposed to remove inflammatory mediators in sepsis.
Evidence does not show a reliable survival benefit.
It increases complexity and may increase unintended removal of useful solutes or drugs.

Recommendation 5.4

Do not use high-volume hemofiltration routinely in sepsis or septic shock.

7. Pharmacotherapy during RRT

Why antibiotic dosing is difficult

Drug exposure in ICU patients receiving RRT is highly variable because of:

Residual renal function
Nonrenal clearance
RRT modality
Dialyzer membrane
Blood and dialysate flow
Effluent dose
Drug protein binding
Molecular size
Volume of distribution
Capillary leak, edema, hypoalbuminemia
Circuit downtime and interruptions

Loading dose

Principle

The initial dose depends mainly on the volume of distribution, not on renal clearance.

In severe critical illness:

Edema, capillary leak, and hypoalbuminemia commonly increase volume of distribution.
Hydrophilic drugs may distribute into expanded extracellular fluid, resulting in low initial plasma concentration.

Hydrophilic antibiotics include:

Beta-lactams
Aminoglycosides
Vancomycin

Recommendations 6.1-6.3

Base starting dose on the current volume of distribution.
Do not routinely reduce the initial anti-infective dose because the patient is receiving RRT.
Give the loading dose as a short infusion to achieve rapid effective concentration, even if continuous or prolonged infusion will follow.

Maintenance dose

Principle

Maintenance dosing depends on total clearance:

Total clearance = residual kidney clearance + extracorporeal/RRT clearance + nonrenal clearance

Recommendation 6.4

If effective levels are not known, calculate maintenance dose using estimated total clearance, including residual renal function and machine clearance.

Infusion strategy

Time-dependent antibiotics

Examples include many beta-lactams.

In CRRT, prolonged or continuous infusion may provide more reliable pharmacokinetic/pharmacodynamic target attainment, particularly if TDM is available.
In IHD, continuous infusion may be less suitable because dialysis interruption changes drug clearance. Short or prolonged infusion can be preferred.

Recommendations

6.5: Consider prolonged or continuous administration of time-dependent antibiotics in continuous RRT, ideally with TDM.
6.6: In IHD, short or prolonged infusion may be preferable to continuous infusion.
6.7: Following IHD, give a supplemental dose when required to restore therapeutic concentration, according to the drug’s pharmacokinetics and accepted dosing guidance.

Therapeutic drug monitoring

Recommendation 6.8

Use TDM when available for high-risk antibiotics in RRT, including:

Beta-lactams
Vancomycin
Aminoglycosides

The guideline also highlights evidence supporting TDM consideration for:

Linezolid
Colistin
Possibly daptomycin, tigecycline, and fluoroquinolones

Why TDM is important

TDM improves the probability of achieving pharmacokinetic/pharmacodynamic targets and can reduce nephrotoxicity, though a consistent mortality benefit has not been proven.

8. Stopping RRT and renal recovery

Principle

Stop RRT when the original indication has resolved and native kidney function is sufficient to maintain:

Potassium homeostasis
Acid-base balance
Fluid balance
Solute control

A successful discontinuation was considered as no restart of RRT within 7 days.

Urine output

Recommendation 7.2

Use urine output as a predictor of successful RRT discontinuation.

Recommendation 7.3

Important:

Urine output predicts recovery but is not sufficient alone.
A patient may produce urine but still have inadequate clearance, persistent hyperkalemia, acidosis, or fluid overload.

Diuretics

Recommendation 7.1

Diuretics may be considered to increase urine output during RRT discontinuation.

But:

They do not prove renal recovery.
They should not substitute for reassessing clearance and complications.
They should not be used to force a trial off RRT in a patient with unresolved indications.

Other predictors and barriers

Kinetic GFR

Kinetic GFR based on endogenous clearance may be considered as an adjunctive predictor after stopping RRT.

Persistent hyperkalemia

A potassium concentration above 5.5 mmol/L suggests a higher risk of failed RRT withdrawal.

Recommendation 7.5

Investigate persistent hyperkalemia before attempting weaning.

Persistent metabolic acidosis

A pH below 7.3 may predict failure of discontinuation.

Recommendation 7.7

Treat and investigate persistent metabolic acidosis before stopping RRT.

Fluid overload

Fluid overload should be corrected before attempting discontinuation.

Recommendation 7.8

Correct fluid overload before trialing RRT withdrawal.

Biomarkers

Current evidence is inadequate to recommend novel kidney injury or functional biomarkers for stopping RRT.

9. Practical ICU decision framework

A. Should RRT be started?

Assess for emergency indications:
- Refractory hyperkalemia
- Severe acidosis
- Pulmonary edema/fluid overload
- Uremic complication
If none:
- Treat reversible factors.
- Review fluid status, urine output, hemodynamics, trajectory, and comorbidity.
- Reassess regularly.
Do not initiate solely for:
- Creatinine
- Urea
- AKI stage
- Failed furosemide stress test
- Biomarker elevation

B. Which modality?

Hemodynamic instability: CRRT or PIRRT often favored.
Severe hyperkalemia needing rapid clearance: high-flow diffusive therapy if available.
Raised intracranial pressure: avoid rapid osmotic changes, use carefully adapted therapy.
Fluid removal: any modality can work, but tailor ultrafiltration rate.
Stable patient: IHD, PIRRT, or CRRT based on clinical goals and local capability.

C. Anticoagulation choice

Standard options: citrate or systemic heparin.
Bleeding risk or heparin contraindication: favor citrate if feasible.
Shock/liver failure: citrate may still be possible with close calcium and lactate monitoring.
HIT II: avoid heparin, consider argatroban.

D. Dose

CRRT delivered dose: 20-25 mL/kg/hour.
Anticipate downtime and prescribe enough to achieve this.
Avoid routine high-volume hemofiltration in septic shock.
Prevent dialysis disequilibrium in high-risk patients.

E. Antibiotics

Do not reduce loading dose merely because RRT is used.
Individualize maintenance dose according to total clearance.
Use TDM when available for high-risk drugs.

F. When to stop

Original indication resolved.
Adequate urine output and recovery trend.
No persistent hyperkalemia, acidosis, or fluid overload.
Monitor closely for at least the next week for restart requirement.

10. High-yield exam points

Emergency RRT indications: refractory hyperkalemia, severe acidosis, refractory fluid overload/pulmonary edema, and symptomatic uremia.
Creatinine alone is not an indication for RRT.
Routine “early” RRT before clinical indications does not have a consistent mortality benefit.
Diffusion and convection have similar overall outcomes in ICU AKI.
For life-threatening hyperkalemia, use a high-flow diffusive technique if possible.
CRRT has no established overall mortality superiority, but is often preferred in hemodynamic instability.
In raised intracranial pressure, avoid rapid osmotic shifts and monitor osmolality, sodium, urea, and glucose.
Citrate is preferred with bleeding risk or heparin contraindication, but requires calcium and metabolic monitoring.
Shock and liver failure are not absolute contraindications to citrate anticoagulation.
Target delivered CRRT dose: 20-25 mL/kg/hour.
Routine high-volume hemofiltration is not recommended for sepsis/septic shock.
Do not reduce the initial antibiotic loading dose merely due to RRT.
TDM is particularly useful for beta-lactams, vancomycin, and aminoglycosides.
Urine output helps predict successful liberation from RRT. A spontaneous output of 300-600 mL/day is a useful guide, not an absolute rule.
Persistent potassium >5.5 mmol/L, pH <7.3, or fluid overload should prompt caution before stopping RRT.

1. Multidisciplinary Guidelines on Renal Replacement Therapy in Intensive Care Medicine

Meersch-Dini et al., Critical Care, 2025. DOI: 10.1186/s13054-025-05817-6.
Open access: full guideline article

Its antimicrobial-dosing recommendations during RRT are:

Loading dose
- Base it on the patient’s current volume of distribution.
- Do not routinely reduce the initial dose simply because the patient is receiving RRT.
- Give the loading dose as a short infusion, even if subsequent therapy will use prolonged or continuous infusion.
Maintenance dose
- Individualize according to total drug clearance:
  - Residual kidney function
  - RRT/machine clearance
  - Nonrenal clearance
- Reassess after modality or dose changes, filter downtime, and recovery of native renal function.
Continuous RRT
- For time-dependent antimicrobials, prolonged or continuous infusion may improve PK/PD target attainment, ideally with therapeutic drug monitoring.
Intermittent hemodialysis
- Short or prolonged infusions may be preferred over continuous infusion.
- Give a post-dialysis supplemental dose when drug removal by dialysis makes it necessary.
Therapeutic drug monitoring
- Use TDM whenever available for high-risk or life-threatening infections, particularly for:
  - Beta-lactams
  - Vancomycin
  - Aminoglycosides
- The guideline additionally notes variable levels with linezolid and colistin, with possible consideration of TDM for daptomycin, tigecycline, and fluoroquinolones.

Practical interpretation

For background, the guideline cites KDIGO AKI guidance, but the 2025 multidisciplinary guideline is more directly applicable and more current for ICU RRT antimicrobial dosing.A complete set of practical heart-fI can prepare complete practical notes, but I have not extracted or reviewed the attached “ESC 2026 heart failure.pdf” in the available context. I should not label any recommendations as ESC 2026 without reading the document.

Please send the request again without the quick-answer instruction, and I will produce structured notes covering:

Definitions and classification: HFrEF, HFmrEF, HFpEF
Diagnostic pathway and natriuretic peptides
Four foundational HFrEF drug classes and titration
Diuretics and congestion management
Iron deficiency, atrial fibrillation, CKD, diabetes, and valvular disease
Device therapy: ICD and CRT
Acute heart failure algorithm
Advanced HF, transplantation, LVAD, and palliative care
Practical monitoring tables, contraindications, and follow-up scheduleA complete ESC heart-failure guide is broad. I can structure it as a practical study and bedside reference, but the most useful depth depends on your goal.A complete practical ESC heart-failure guide covers:

Definitions and classification
- HFrEF, HFmrEF, HFpEF, improved EF
- Acute versus chronic HF
- NYHA functional class and congestion/perfusion profiles
Diagnosis and initial assessment
- Symptoms, signs, ECG, chest imaging, echocardiography
- Natriuretic peptides
- Cause and precipitant evaluation
Chronic HFrEF treatment
- Four foundational drug classes
- Diuretic strategy
- Initiation, titration, monitoring, adverse effects, contraindications
- Add-on therapies
HFmrEF and HFpEF
- Diuretics, SGLT2 inhibitors, blood-pressure control
- Atrial fibrillation, obesity, diabetes, CKD, coronary disease, amyloidosis, and valvular disease
Acute heart failure
- Emergency assessment and phenotype-based management
- Oxygen/ventilation, IV diuretics, vasodilators, inotropes, vasopressors
- Cardiogenic shock and discharge planning
Devices and interventions
- ICD, CRT, revascularization, valve intervention
- AF ablation and cardiac monitoring
Advanced HF
- Referral criteria
- LVAD, transplantation, palliative and end-of-life care
Practical follow-up
- Laboratory and clinical monitoring
- Patient education, fluid/salt advice, vaccination, exercise and rehabilitation
- Red flags requiring urgent review

I can build detailed notes on one section at a time to keep them accurate and clinically usable. Reply with the number you want first, for example: “3” for complete chronic HFrEF treatment notes.

Reading File

Browsing Directory

Searching the Web

ESC 2026 heart failure guidelines definition classification HFrEF HFmrEF HFpEF

Searching PubMed

heart failure classification ejection fraction

Finding Sources

Reading File

Reading Web Page

https://www.escardio.org/guidelines/clinical-practice-guidel…

Browsing Directory

~/attachments/a7aa165e-8cf0-45c5-80d4-f5a44551a8af

Running Command

mkdir -p "/tmp/workspace/esc-hf/notes" && python -c "import pdfplumber; p='/tmp/workspace/attachments/a7aa165e-8cf0-45c5-80d4-f5a44551a8af/ESC 2026 heart failure .pdf'; out='/tmp/workspace/esc-hf/notes/extracted.txt'; pdf=pdfplumber.open(p); f=open(out,'w',encoding='utf-8'); [f.write(f'\n===== PAGE {i+1} =====\n'+(page.extract_text() or '')) for i,page in enumerate(pdf.pages)]; f.close(); print('pages=',len(pdf.pages))"

Searching Content

"Definitions and classification" in ~/esc-hf/notes

Searching Content

"Classification of HF" in ~/esc-hf/notes

Searching Content

"HF with reduced" in ~/esc-hf/notes

Reading File

Running Command

python -c "import re; p='/tmp/workspace/esc-hf/notes/extracted.txt'; lines=open(p,encoding='utf-8').read().splitlines(); [print(f'{i+1}: {x}') for i,x in enumerate(lines) if re.match(r'^(?:[1-9]|10)\.\s',x.strip()) or any(k in x.lower() for k in ['definition of heart failure','classification and stages','heart failure classification','terminology'])][:]"

Reading File

Finding Sources

Reading File

Searching Content

"Table 3" in ~/esc-hf/notes

Searching Content

"NYHA" in ~/esc-hf/notes

Reading File

Reading Web Page

https://www.escardio.org/news/news-room/congress-news/2026-e…

Reading File

ESC 2026 Heart Failure Notes: 1. Definition and Classification

Primary source: 2026 ESC Guidelines for the Management of Heart Failure, European Heart Journal, DOI 10.1093/eurheartj/ehag100. The major 2026 change is a simplified two-phenotype system, with HFmrEF no longer a separate category. See the ESC guideline summary.

1. Definition of heart failure

ESC definition

Heart failure (HF) is a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality that results in either:

Elevated intracardiac pressures, and/or
Inadequate cardiac output at rest and/or during exercise.

A diagnosis requires more than symptoms alone. It should be supported by:

Symptoms and/or signs compatible with HF
Objective evidence of cardiac dysfunction and/or congestion
Diagnostic tests supporting the syndrome, usually natriuretic peptides and echocardiography

Key implication

HF is not synonymous with low LVEF.

A patient can have:

HF with reduced LVEF
HF with normal or preserved LVEF
Predominantly right-sided HF
HF due to valvular, myocardial, pericardial, rhythm-related, congenital, or systemic disease

2. Symptoms and signs of HF

Typical symptoms

More typical symptoms	Less specific symptoms
Exertional breathlessness	Fatigue
Orthopnoea	Weakness
Paroxysmal nocturnal dyspnoea	Reduced exercise tolerance
Ankle swelling	Cough, particularly nocturnal
Reduced exercise capacity	Wheeze
Bendopnoea	Dizziness or syncope
Abdominal bloating/early satiety	Confusion, especially in older adults

Bendopnoea means breathlessness when bending forward, for example while tying shoelaces. It can suggest elevated filling pressures.

Signs of congestion

Left-sided/systemic findings	Right-sided findings
Raised JVP	Peripheral pitting oedema
Pulmonary crackles	Hepatomegaly
Pleural effusion	Ascites
Third heart sound	Positive hepatojugular reflux
Cool peripheries in low-output HF	Weight gain from fluid retention

Important caveat

No individual symptom or sign confirms or excludes HF. Symptoms can arise from:

COPD or asthma
Pneumonia
Pulmonary embolism
Obesity and deconditioning
Anaemia
CKD
Liver disease
Venous insufficiency
Pulmonary hypertension

3. ESC 2026 LVEF-based HF phenotypes

Major 2026 change

The previous ESC categories were:

HFrEF: LVEF ≤40%
HFmrEF: LVEF 41%-49%
HFpEF: LVEF ≥50%

The 2026 ESC guideline removes HFmrEF as an independent phenotype. The reason is that patients with LVEF 41%-49% often resemble those with HFrEF in:

Underlying disease mechanisms
Clinical characteristics
Response to therapies
Risk of deterioration in LVEF

Current two-phenotype classification

Phenotype	LVEF	Required diagnostic features
HFrEF	<50%	Current or previous symptoms/signs of HF plus LVEF <50%
HFpEF	≥50%	Symptoms/signs of HF, LVEF ≥50%, and objective evidence of structural/functional heart abnormality consistent with raised LV filling pressure or diastolic dysfunction, supported by raised natriuretic peptides

A. HFrEF: Heart failure with reduced ejection fraction

Definition

HFrEF requires:

Current or prior symptoms/signs of HF
LVEF <50%

Raised BNP or NT-proBNP strongly supports the diagnosis in the appropriate clinical setting.

Clinical interpretation

The broad 2026 HFrEF group includes patients who previously would have been labelled:

HFrEF with LVEF ≤40%
HFmrEF with LVEF 41%-49%

Common mechanisms and causes

Ischaemic heart disease or prior myocardial infarction
Dilated cardiomyopathy
Myocarditis
Toxic cardiomyopathy, including alcohol and chemotherapy-related disease
Tachycardia-induced cardiomyopathy
Severe valvular heart disease
Genetic cardiomyopathy
Infiltrative/inflammatory disease
Uncontrolled hypertension

Key practical point

A patient with LVEF 45% and symptoms of HF should not be considered a “borderline” case. Under ESC 2026 classification, this is HFrEF and requires appropriate HF-directed management and cause assessment.

B. HFpEF: Heart failure with preserved ejection fraction

Definition

HFpEF requires all of the following:

Current or prior symptoms/signs of HF
LVEF ≥50%
Objective evidence of structural and/or functional cardiac abnormality consistent with:
- LV diastolic dysfunction, and/or
- Raised LV filling pressures
Natriuretic peptides that support the diagnosis

Important qualification

LVEF must not previously have been <50%. If it was previously reduced and later recovers, classify as HFrEF with improved LVEF, not de novo HFpEF.

Common HFpEF profile

HFpEF is commonly associated with:

Older age
Female sex
Long-standing hypertension
Atrial fibrillation
Obesity
Type 2 diabetes
CKD
Coronary artery disease
Sleep-disordered breathing
Valvular disease
Pulmonary hypertension

Objective findings supporting HFpEF

Finding	Threshold in ESC simplified criteria
LV hypertrophy, female	LV mass index ≥95 g/m²
LV hypertrophy, male	LV mass index ≥115 g/m²
Relative wall thickness	>0.42
Left atrial enlargement in sinus rhythm	LA volume index >34 mL/m²
Left atrial enlargement in AF	LA volume index >40 mL/m²
Raised filling pressure	Average E/e′ >9 at rest
Raised pulmonary pressure	Estimated systolic pulmonary artery pressure >35 mmHg
Alternative pulmonary-pressure marker	TR velocity >2.8 m/s

Why diagnosis is difficult

HFpEF cannot be diagnosed simply by finding dyspnoea with an LVEF of 60%.

A patient with breathlessness, obesity, and preserved LVEF might instead have:

Lung disease
Deconditioning
Obesity-related dyspnoea
Anaemia
Atrial fibrillation without HF
Pulmonary vascular disease

Therefore, evidence of raised filling pressure/diastolic abnormality and supportive natriuretic peptides are needed.

4. HF with improved LVEF

Definition

Patients with prior HFrEF are classified as having improved LVEF when:

LVEF increases by at least 10 absolute percentage points, and
The follow-up LVEF is >40%

Example

Initial LVEF 30%
Follow-up LVEF 44%
Absolute improvement = 14 percentage points

This meets the definition of improved LVEF.

Practical significance

Improved LVEF:

Indicates reverse remodelling and generally better prognosis.
Does not mean that the underlying HF substrate has disappeared.
Does not automatically justify stopping disease-modifying therapy.

Exam point: A patient whose LVEF improves from 30% to 55% after treatment is generally still managed as a patient with prior HFrEF and improved LVEF, not reclassified as primary HFpEF.

5. Limitations of LVEF

LVEF is useful but imperfect.

Why LVEF must be interpreted clinically

It is a continuous measurement, not a biological on/off threshold.
Values vary between:
- Echocardiographic techniques
- Operators
- Loading conditions
- Imaging modalities
LVEF may look falsely high in significant mitral regurgitation because blood is ejected into a low-resistance left atrium.
A normal LVEF does not exclude:
- Diastolic dysfunction
- Raised filling pressure
- Low stroke volume
- Significant right ventricular dysfunction
- HFpEF

Practical rule

Treat the patient and the phenotype, not an isolated LVEF number.

6. Stage-based classification of HF

ESC 2026 adopts a stage-based approach to emphasize prevention, early recognition, and treatment across the full disease trajectory.

Stage	Meaning	Typical examples	Does the person have clinical HF?
Stage A: At risk for HF	Risk factors but no structural/functional heart abnormality and no symptoms/signs	Hypertension, diabetes, obesity, CAD risk, cardiotoxic-drug exposure, family history	No
Stage B: Pre-HF	No symptoms/signs of HF, but objective structural heart disease, abnormal cardiac function, or raised biomarkers	LV hypertrophy, prior MI with LV dysfunction, asymptomatic low LVEF, significant valve disease, chamber enlargement, myocardial scar/fibrosis	No
Stage C: HF	Current or prior symptoms/signs caused by structural/functional heart abnormality	Symptomatic HFrEF or HFpEF, treated chronic HF with prior symptoms	Yes
Stage D: Advanced HF	Severe persistent symptoms, recurrent decompensation, and need for specialized advanced therapies	Recurrent admissions, inotrope dependence, LVAD/transplant assessment, refractory congestion	Yes

Stage A: At risk for HF

Definition

The patient has risk factors for future HF but lacks:

Symptoms/signs of HF
Structural heart disease
Clear cardiac functional abnormality

Common risk factors

Hypertension
Diabetes mellitus
Obesity
Smoking
Dyslipidaemia
Chronic kidney disease
Coronary artery disease risk
Excess alcohol intake
Cardiotoxic chemotherapy
Family history/genetic predisposition
Sleep apnoea
Sedentary lifestyle

Clinical goal

Prevent progression by:

Controlling blood pressure
Treating diabetes and obesity
Managing lipids and ASCVD risk
Smoking cessation
Exercise and dietary intervention
Avoiding cardiotoxins where possible
Identifying high-risk inherited conditions

Stage B: Pre-HF

Definition

No symptoms/signs of clinical HF, but evidence of cardiac abnormality that raises future HF risk.

Examples of pre-HF abnormalities

Asymptomatic LV systolic dysfunction
LV hypertrophy
Left atrial or ventricular enlargement
Regional wall-motion abnormality
Prior myocardial infarction
Significant valvular disease
Myocardial scar/fibrosis on CMR
Myocardial oedema or infiltrative abnormality
Raised natriuretic peptides in the appropriate context
Abnormal filling pressures or diastolic function

Important concept

Stage B is not clinical HF. It is pre-HF, but active treatment may prevent progression to symptomatic disease.

Stage C: Established HF

Definition

Current or prior symptoms/signs of HF caused by structural or functional cardiac abnormality.

This includes:

Symptomatic HFrEF
Symptomatic HFpEF
A patient now asymptomatic due to treatment but with a previous established HF syndrome

Practical implication

Past symptoms matter. A patient whose congestion has resolved with diuretics and disease-modifying treatment remains a Stage C HF patient.

Stage D: Advanced HF

Definition

Persistent severe symptoms and functional limitation despite optimized medical and interventional treatment, commonly with recurrent instability or repeated hospitalizations.

Features suggesting Stage D

NYHA III-IV symptoms that persist despite treatment
Recurrent HF hospitalization or emergency visits
Refractory congestion
Escalating diuretic requirement
Low-output symptoms or hypotension
End-organ dysfunction due to low cardiac output
Inotrope requirement
Severe exercise limitation
Consideration of mechanical circulatory support, transplantation, or palliative-oriented care

Clinical action

Refer early to an advanced HF team. Do not wait until irreversible kidney, liver, pulmonary vascular, or nutritional deterioration has occurred.

7. Functional classification: NYHA class

NYHA classification measures functional limitation from symptoms. It is distinct from LVEF and disease stage.

NYHA class	Functional status
I	No limitation of physical activity. Ordinary activity does not cause undue dyspnoea, fatigue, or palpitations.
II	Slight limitation. Comfortable at rest, but ordinary activity causes symptoms.
III	Marked limitation. Comfortable at rest, but less-than-ordinary activity causes symptoms.
IV	Symptoms may be present at rest. Any physical activity increases discomfort.

Important distinctions

Stage describes disease progression and structural risk.
NYHA class describes present symptom burden.
LVEF phenotype describes ventricular function category.

Examples

A patient with asymptomatic LVEF 35% after MI: Stage B, not NYHA I HF.
A patient with symptomatic LVEF 35% and dyspnoea on climbing one flight of stairs: HFrEF, Stage C, likely NYHA II-III.
A patient with LVEF 60%, oedema, high NT-proBNP, LA enlargement, and raised filling pressures: HFpEF, Stage C.
A patient with recurrent admissions, resting symptoms and inotrope dependence: advanced HF, Stage D, NYHA IV.

8. Other useful clinical classifications

A. By time course

De novo HF

First presentation of HF in a person without a known previous HF diagnosis.

Common examples:

Acute MI with LV dysfunction
New myocarditis
New severe valvular lesion
Newly recognized cardiomyopathy
First presentation of HFpEF with hypertensive congestion

Chronic HF

Established HF with relatively stable symptoms and treatment requirements.

Decompensated HF

The 2026 guideline uses decompensated HF in place of the older term “acute HF.”

It means worsening HF due to:

Gradual fluid accumulation
Acute pulmonary oedema
Arrhythmia
Ischaemia
Infection
Medication non-adherence
Renal dysfunction
Uncontrolled hypertension
Other triggers

Not all decompensation is sudden, and selected patients can be managed in an ambulatory setting rather than admitted.

B. By ventricle involved

Left-sided HF

Usually due to LV systolic or diastolic dysfunction. Leads to:

Raised left-sided filling pressure
Pulmonary congestion
Dyspnoea
Orthopnoea
Pulmonary oedema

Right-sided HF

Causes:

RV infarction
Pulmonary hypertension
Arrhythmogenic RV cardiomyopathy
Severe tricuspid or pulmonary valve regurgitation
Advanced left-sided HF causing secondary pulmonary hypertension

Features:

Raised JVP
Hepatomegaly
Ascites
Peripheral oedema
Renal and hepatic congestion

Biventricular HF

Involves both left- and right-sided dysfunction. Common in advanced LV failure and pulmonary hypertension secondary to left-sided heart disease.

9. Practical classification workflow

Step 1: Does the patient have clinical HF?

Ask:

Are symptoms/signs compatible with HF present now or documented previously?
Is there objective cardiac dysfunction and/or congestion?
Is there a non-cardiac explanation that better accounts for symptoms?

Step 2: Identify the LVEF phenotype

LVEF <50%: HFrEF
LVEF ≥50%: assess for HFpEF criteria
Do not use “HFmrEF” as the routine ESC 2026 phenotype.

Step 3: If LVEF ≥50%, confirm HFpEF objectively

Look for:

Raised natriuretic peptides
LV hypertrophy
LA enlargement
Raised E/e′
Raised pulmonary artery pressure/TR velocity
Other evidence of raised LV filling pressure

Step 4: Determine stage

Risk factor only: Stage A
Structural/functional abnormality without symptoms: Stage B
Current/past symptomatic HF: Stage C
Refractory/severe HF requiring specialist therapies: Stage D

Step 5: Grade functional limitation

Assign NYHA I-IV.

Step 6: Identify cause and triggers

Always determine:

Ischaemic versus non-ischaemic cause
Valvular disease
Arrhythmia
Hypertension
Infiltrative/genetic disease
Toxin/drug exposure
Pericardial disease
Pulmonary hypertension
Comorbidities and precipitants

10. High-yield takeaways

HF is a clinical syndrome, not an echocardiographic finding alone.
Diagnosis requires symptoms/signs plus objective evidence of cardiac dysfunction and/or congestion.
In ESC 2026, HFrEF = LVEF <50% with current or prior HF symptoms/signs.
HFmrEF is no longer a separate ESC phenotype.
HFpEF = LVEF ≥50% plus symptoms/signs and evidence of structural/functional abnormality indicating raised filling pressure or diastolic dysfunction, supported by natriuretic peptides.
Do not diagnose HFpEF merely because the patient has dyspnoea and normal LVEF.
HF with improved LVEF requires an absolute LVEF rise of at least 10 percentage points to >40%.
Improvement in LVEF does not automatically permit stopping HF therapy.
Stage A and B are prevention-focused stages and are not symptomatic HF.
NYHA class measures symptoms and functional limitation, while HF stage measures disease progression.

Recent evidence continues to show that prognosis differs across EF groups, though outcomes overlap substantially and comorbidity burden is important, as summarized in a 2026 meta-analysis.

Step by stepexplain

Reading File

Step-by-step approach to classify a patient with heart failure

Use this sequence in every patient:

Symptoms/signs → confirm cardiac cause → echo/LVEF → classify phenotype → stage severity → find cause.

Step 1: First ask, “Could this be heart failure?”

Heart failure means the heart cannot pump enough blood, or cannot fill normally, so pressure builds up behind the heart.

This leads to two major problems:

Congestion: fluid backs up into lungs or body.
Low output: organs and muscles receive inadequate blood flow.

Symptoms that suggest HF

Ask for:

Breathlessness on exertion
Orthopnoea: breathlessness while lying flat
Paroxysmal nocturnal dyspnoea: waking at night short of breath
Leg swelling
Weight gain
Fatigue and reduced exercise capacity
Abdominal fullness, poor appetite
Bendopnoea: breathlessness when bending forward

Signs that suggest HF

Look for:

Raised JVP
Peripheral pitting oedema
Lung crackles
Pleural effusion
Third heart sound
Hepatomegaly or ascites
Cool extremities or low blood pressure in low-output states

Important: symptoms alone do not prove HF. Obesity, anaemia, COPD, asthma, pneumonia, CKD, and pulmonary embolism can mimic it.

Step 2: Confirm that there is objective cardiac dysfunction or congestion

The ESC definition requires a clinical syndrome caused by a structural or functional heart problem that produces:

Raised intracardiac pressure, and/or
Inadequate cardiac output at rest or exercise.

Initial tests

Test	What it contributes
ECG	Rhythm, prior MI, LVH, conduction abnormality
BNP or NT-proBNP	Supports or argues against HF
Chest X-ray	Pulmonary oedema, pleural fluid, cardiomegaly, alternative lung pathology
Echocardiography	LVEF, chamber size, valves, systolic and diastolic function, pulmonary pressures
Blood tests	Renal function, electrolytes, haemoglobin, iron, thyroid, liver function, diabetes, lipids
Urine albumin-creatinine ratio	Kidney disease assessment and cardiovascular risk

Natriuretic peptides

BNP and NT-proBNP rise when myocardial wall stress and filling pressures rise.

High level: makes HF more likely, but is not diagnostic alone.
Low level: makes HF less likely, especially in untreated patients.
Obesity: can produce falsely low values.
Atrial fibrillation, CKD, older age, pulmonary embolism, sepsis: can increase values even without HF.

Practical conclusion: interpret natriuretic peptides alongside the clinical picture and echocardiogram.

Step 3: Perform echocardiography and check LVEF

What is LVEF?

Left ventricular ejection fraction (LVEF) is the percentage of blood ejected from the left ventricle with each beat.

[ \text{LVEF} = \frac{\text{end-diastolic volume} - \text{end-systolic volume}}{\text{end-diastolic volume}} \times 100 ]

Example:

LV contains 120 mL at end-diastole.
LV contains 60 mL after contraction.
Stroke volume = 60 mL.
LVEF = 60/120 × 100 = 50%.

LVEF describes systolic emptying, but it does not measure every aspect of cardiac performance. A patient can have significant HF despite a normal LVEF.

Step 4: Assign the ESC 2026 HF phenotype

The 2026 ESC guideline uses two main phenotypes.

A. LVEF <50%: HFrEF

Diagnosis

Diagnose heart failure with reduced ejection fraction, HFrEF when the patient has:

Current or previous symptoms/signs of HF, and
LVEF <50%

Example

A patient has:

Exertional dyspnoea
Bilateral oedema
NT-proBNP elevated
LVEF 35%

This is HFrEF.

Why 50%?

The 2026 guideline combines the former groups:

Old HFrEF: LVEF ≤40%
Old HFmrEF: LVEF 41%-49%

This was done because patients with LVEF 41%-49% often have a similar disease process and tend to benefit from similar treatment to those with more markedly reduced LVEF.

So do not routinely call LVEF 45% “mid-range” under ESC 2026. Call it HFrEF.

B. LVEF ≥50%: consider HFpEF

A normal or preserved LVEF does not automatically mean normal cardiac function.

Diagnosis of HFpEF

To diagnose heart failure with preserved ejection fraction, HFpEF, all are needed:

Current or previous HF symptoms/signs
LVEF ≥50%
Evidence of structural or functional heart disease causing:
- Diastolic dysfunction, and/or
- Increased LV filling pressure
Natriuretic peptide elevation that supports the diagnosis

Echo findings that support HFpEF

Look for one or more of these:

Finding	Meaning
LV hypertrophy	Long-standing pressure load, often hypertension
Left atrial enlargement	Chronic elevation of LV filling pressure
E/e′ >9	Suggests raised LV filling pressure
Raised pulmonary artery pressure	May result from chronic high left-sided pressure
TR velocity >2.8 m/s	Supports raised pulmonary pressure
Abnormal diastolic indices	Supports impaired relaxation and/or raised filling pressure

Example

A patient has:

Dyspnoea and ankle oedema
LVEF 60%
NT-proBNP elevated
Left atrial enlargement
E/e′ 14
Hypertension and atrial fibrillation

This is HFpEF.

Common error

Do not diagnose HFpEF just because:

The patient is breathless, and
LVEF is 60%.

You still need evidence of raised filling pressure or relevant structural/functional abnormality.

Step 5: Check whether LVEF has improved

Some patients previously had HFrEF but improved with treatment.

Improved LVEF

The ESC definition requires:

Prior HFrEF
An increase in LVEF by at least 10 absolute percentage points
Follow-up LVEF >40%

Example

Initial LVEF: 28%
Current LVEF: 45%
Improvement: 17 percentage points

This is HFrEF with improved LVEF.

What does this mean clinically?

It suggests reverse remodelling and better prognosis, but the patient remains at risk of deterioration.

Do not automatically stop HF disease-modifying treatment merely because LVEF improves.

Step 6: Assign the disease stage

Stages describe progression of disease. They are different from LVEF and NYHA class.

Stage A: At risk for HF

The patient has risk factors but no cardiac structural/functional abnormality and no HF symptoms.

Examples

Hypertension
Diabetes
Obesity
Smoking
CKD
Cardiotoxic cancer treatment exposure
Strong family history of cardiomyopathy

Goal: prevention.

Stage B: Pre-HF

The patient has no symptoms/signs of HF but has objective cardiac abnormality.

Examples

LVEF 40% after MI but no dyspnoea or congestion
LV hypertrophy from hypertension
Asymptomatic severe valve disease
Enlarged cardiac chambers
Myocardial scar/fibrosis on CMR
Abnormal diastolic function with relevant cardiac structural disease

Goal: prevent symptomatic HF.

Stage C: Established HF

The patient has current or prior symptoms/signs of HF caused by cardiac dysfunction.

Examples

HFrEF with breathlessness and oedema
HFpEF with raised filling pressures and congestion
A patient currently well because treatment controlled prior symptomatic HF

Goal: reduce symptoms, hospitalisation, and death.

Stage D: Advanced HF

The patient remains severely limited despite optimized treatment.

Examples

Repeated HF admissions
Persistent NYHA III-IV symptoms
Inotrope dependence
Refractory congestion
Severe low-output symptoms
Need for LVAD, transplant assessment, or palliative support

Goal: urgent referral to an advanced HF team.

Step 7: Grade symptom severity with NYHA class

NYHA class tells you how limited the patient is by symptoms today.

Class	Meaning
I	No symptoms during ordinary activity
II	Ordinary activity causes dyspnoea, fatigue, or palpitations
III	Less-than-ordinary activity causes symptoms
IV	Symptoms at rest or inability to undertake physical activity without symptoms

Examples

Breathless only while running: NYHA I or II, depending on usual activity.
Breathless walking across a room: NYHA III.
Breathless sitting in bed: NYHA IV.

Step 8: Identify the cause of HF

Do not stop after identifying HFrEF or HFpEF. Always ask: Why does this person have HF?

Common HFrEF causes

Ischaemic heart disease/prior MI
Dilated cardiomyopathy
Myocarditis
Tachycardia-mediated cardiomyopathy
Alcohol or stimulant toxicity
Chemotherapy-related cardiotoxicity
Severe valvular disease
Genetic cardiomyopathy
Infiltrative disease

Common HFpEF contributors

Hypertension
Obesity
Atrial fibrillation
Diabetes
CKD
Coronary artery disease
Aortic stenosis
Mitral valve disease
Cardiac amyloidosis
Hypertrophic cardiomyopathy
Pericardial disease

Cause identification can change management, for example:

Revascularization for ischaemia
Valve intervention
Rhythm control or ablation for tachycardia-induced cardiomyopathy
Specific therapy for amyloidosis
Family screening in inherited cardiomyopathy

One practical example from start to finish

Patient

A 68-year-old man presents with progressive dyspnoea, orthopnoea, and ankle swelling.

Step 1: Suspect HF

Symptoms suggest congestion.

Step 2: Find objective support

Raised JVP and basal crackles
NT-proBNP markedly elevated
Chest X-ray: pulmonary congestion

HF is likely.

Step 3: Echo

LVEF = 32%
Dilated LV
Moderate functional mitral regurgitation

Step 4: Phenotype

LVEF <50% plus symptoms/signs = HFrEF.

Step 5: Stage

Current symptomatic HF = Stage C.

Step 6: NYHA class

Breathless while walking 100 metres, comfortable at rest = NYHA III.

Step 7: Cause

History of anterior MI and regional wall-motion abnormality suggests ischaemic cardiomyopathy.

Full clinical label

Stage C, NYHA III, ischaemic HFrEF with congestion.

This complete label guides treatment, prognosis, referral, device decisions, and follow-up.

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