Lina Miyakawa1, Michael Bergman2, and Vikram Dhawan3
1 Icahn School of Medicine at Mount Sinai, New York, NY, USA
2 University of Virginia Health System, Charlottesville, VA, USA
3 Memorial Sloan Kettering Cancer Center, New York, NY, USA
Background
The prevalence of acute renal failure requiring RRT in the ICU is 5%.
There are three main modalities of artificial renal support in the ICU setting: intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT), and peritoneal dialysis.
Indications for RRT
Absolute indications
Relative indications
Metabolic abnormalities that cannot be controlled with conservative management
Metabolic acidosis (pH <7.1)
Hyperkalemia ([K+] >6.5 mmol/L or rapidly rising [K+])
Limited reserve to tolerate consequences of AKI (e.g. advanced CKD)
Complications from uremia (e.g. pericarditis, encephalopathy, coagulopathy)
Severity of underlying disease, affecting likelihood of recovery of kidney function
Toxicity from dialyzable drug/toxin
Timing of RRT initiation
The optimal time to initiate RRT in critically ill patients remains uncertain. There are different guidelines giving recommendations for the timing of initiation of RRT in the ICU (Table 51.1).
Table 51.1Guidelines in the USA and UK on when to initiate RRT in the ICU.
Kidney Disease Improving Global Outcomes (KDIGO) Consortium, USA
National Institute for Health and Care Excellence (NICE), UK
Initiate renal replacement therapy (RRT) emergently when life‐threatening changes in fluid, electrolyte, and acid–base balance exist
Discuss any potential indications for RRT with a nephrologist, pediatric nephrologist, and/or critical care specialist immediately to ensure that the therapy is started as soon as needed
Consider the broader clinical context, the presence of conditions that can be modified with RRT, and trends of laboratory tests – rather than single BUN and creatinine thresholds alone – when making the decision to start RRT
Refer adults, children, and young people immediately for RRT if any of the following are not responding to medical management:
Hyperkalemia
Metabolic acidosis
Complications of uremia (e.g. pericarditis or encephalopathy)
Fluid overload
Pulmonary edema
Base the decision to start RRT on the condition of the adult, child, or young person as a whole and not on an isolated urea, creatinine, or potassium value
Benefits of earlier dialysis
Drawbacks of earlier dialysis
Earlier control of metabolic derangements
Iatrogenic episodes of hemodynamic instability that may impede kidney recovery
Uncertain clearance of nutrients, trace elements, or vital medications (antibiotics, anticonvulsants)
Earlier management of fluid status/overload
Exposure to dialysis in patients who would spontaneously recover kidney function without dialysis
Potential beneficial immunomodulation
Increased health care costs
Procedure
Mechanisms of solute transport
Diffusion: hemodialysis:
Small molecular weight solutes move across a semipermeable membrane.
Particularly effective for urea, potassium, calcium, and bicarbonate.
Clearance decreases rapidly with increasing molecular size.
Does not clear protein‐bound substances.
Convection: hemofiltration:
Filtration of plasma water across semipermeable membrane as a result of hydrostatic pressure gradient (transmembrane pressure).
Amount of solute removed depends on amount of plasma water transported across the membrane and the size of the solute relative to the pore size of the membrane.
Effective in the removal of both small and large solutes.
Does not clear protein‐bound substances.
Convection and diffusion can occur simultaneously and as such any distinction is artificial.
Osmosis:
Primarily used for peritoneal dialysis.
Glucose solution is used as an osmotic agent (low peritoneal absorption).
Adsorption: hemoperfusion:
Binding of solutes to the hemodiaysis or hemofiltratioin membrane.
Primarily used for removal of drugs in acute poisoning.
Modes of RRT
Intermittent hemodialysis (IHD)
IHD is a diffusion‐based therapy. Blood is pumped through the compartment of the filter at a higher flow rate than with CRRT techniques, and dialysate is pumped in a counter‐current direction at very high flow rates to encourage solute exchange.
In IHD, solute clearance occurs mainly by diffusion, whereas volume is removed by ultrafiltration.
Traditionally, intensivists have managed AKI with IHD empirically delivered 3–4 times a week, lasting 3–4 hours per session. The main disadvantage of IHD is the risk of systemic hypotension caused by rapid electrolyte and fluid removal.
Slow low efficiency daily dialysis is a variant of IHD that is associated with less hypotension; compared with IHD, both blood flow and dialysate rates are substantially slower (100–200 mL/min).
Continuous veno‐venous hemodialysis (CVVHD)
CVVHD is a diffusion‐based therapy. Blood is pumped through the blood compartment of the filter and dialysate flows counter‐currently (Figure 51.1). The counter‐current flow optimizes the diffusion gradient and thus the resulting clearances.
With CVVHD, dialysate flow is less than the blood flow, corresponding to clearances closely related to dialysate flow.
Continuous veno‐venous hemofiltration (CVVH)
CVVH is a convection‐based therapy. Blood is pumped through the blood compartment of the filter and a significant filtrate flow is produced by action of the filtrate pump.
Filtrate flow requires compensation by infusion of a substitution fluid to the blood flow pre‐ or post‐filter. This way, high filtrate flows can be generated that enhance solute removal.
Continuous veno‐venous hemodiafiltration (CVVHDF)
CVVHDF combines the use of both diffusion and convection therapies. Blood is pumped through the blood compartment of the filter and dialysate flows counter‐currently.
The counter‐current flow optimizes the diffusion gradient.
In addition, a substitution fluid is infused into the blood flow either pre‐ or post‐filter. This is paralleled by filtration of plasma water across the membrane resulting in convective clearance.
Pros and cons of intermittent versus continuous RRT
There are no definitive data supporting one technique over another, although meta‐analyses tend to support potential survival and renal recovery benefit with continuous treatments.
The optimal mode of RRT depends on the therapeutic aim.
Continuous therapies may be associated with less hypotension and disequilibrium syndromes (Table 51.2).
Intermittent therapies mainly rely on diffusion, thus necessitating high dialysate flow rates to maintain high concentration gradients.
Continuous therapies mainly rely on convection, performed as a low efficiency technique.
Table 51.2Differences between intermittent and continuous renal replacement therapy.
More hypotension and dialysis disequilibrium syndrome from fluid shifts
Less hypotension and dialysis disequilibrium syndrome
For stable patients, volume and solute removal can be accomplished with intermittent dialysis.
For unstable patients, continuous therapies can be utilized.
Slow continuous ultrafiltration can be used in unstable patients who require volume removal.
Anticoagulation during CRRT
For most patients, CRRT is performed without anticoagulation.
CRRT may require anticoagulation to prevent clotting of the circuit. Clotting leads to interruption in the time on CRRT and therefore reduction in effectiveness.
Unfractionated heparin or low molecular weight heparin can be used to prevent clotting in the extracorporeal circuit.
Regional citrate anticoagulation can be used and has less risk of bleeding. It cannot be used in liver failure or lactic acidosis and patients must be monitored for citrate accumulation.
Complications of RRT
The most common complications of RRT are hypotension and cardiac arrhythmia.
Hypotension tends to be more problematic with IHD than with continuous forms of RRT. For this reason CRRT is preferred when patients are hemodynamically unstable.
In the BEST Kidney Study, new onset or worsening of hypotension complicated RRT in 18% of patients and arrhythmias occurred in 4%.
Concurrent use of vasopressors and elevated lactate levels increase the risk of dangerous arrhythmias during RRT.
Use bicarbonate dialysate to correct acidosis for prevention of arrhythmias.
Maintain potassium and calcium at appropriate levels.
Use of dialysate with potassium <2 mmol/L should be avoided.
Prognois
Prognosis for treated patients
Overall hospital mortality of ICU patients with AKI requiring dialysis ranges from 40% to 60%.
Among survivors, dialysis dependence at hospital discharge is about 14%.
There are a paucity of data indicating superiority between intermittent and continuous modalities with regard to long‐term outcome:
Mortality is similar in both intermittent and continuous modalities.
No evidence‐based guidelines exist for selecting CRRT versus IHD with regard to residual renal function recovery.
Table 51.3Causes and treatment of complications of RRT.
Complication
Etiology
Management
Hypotension
Intravascular volume depletion Antihypertensive/nitrates prior to dialysis Allergic reaction to dialyzer Left ventricular dysfunction Autonomic dysfunction Others: myocardial infarction, sepsis, cardiac tamponade, bleeding
Infusion of normal saline Reduction of ultrafiltration rate
Active bleeding/coagulopathy
Exacerbated by anticoagulation Platelet dysfunction from uremia
Minimize or hold heparin dosage IV desmopressin (0.3 μg/kg in 50 mL saline every 4–8 hours), IV conjugated estrogen (0.6 mg/kg/day for 5 days), or intranasal desmopressin
Clotting of the extracorporeal circuit during dialysis
Air in circuit or poor priming of heparin line Inadequate blood flow caused by needle or catheter positioning Clotting Frequent blood flow interruptions
Arteriovenous fistula results in reduced blood flow to hand
Severe symptoms: surgical or radiologic revision Mild symptoms: improve with time
Dialysis‐associated pericarditis
Dialysis associated (different from uremic pericarditis)
Intensification of dialysis to 6–7 times/week Minimize or discontinue anticoagulation Treatment failure or evidence of tamponade: pericardiectomy
Dialysis disequilibrium
Occurs in first few treatments More common in profoundly uremic patients Due to CNS edema from rapid osmolar shifts Symptoms: nausea, emesis, headache, confusion, seizures
Lower blood flows and shorter treatment duration during initial sessions
Anaphylactic and anaphylactoid reactions
Anaphylaxis: IgE mediated Anaphylactoid: release of mast cell mediators Usually ~5–20 minutes into hemodialysis Drug induced (e.g. iron dextran) Bradykinin‐mediated reactions
Stop hemodialysis without return of extracorporeal blood to patient Epinephrine, antihistamines, corticosteroids, respiratory support Using gamma ray or steamed filters may prevent hypotension (first use) Mild symptoms (e.g. chest/back pain) (20–40 minutes into hemodialysis) may improve over time and hemodialysis does not need to be stopped
Fever and pyrogenic reactions
Water or bicarbonate dialysate Improperly sterilized dialyzers Use of central venous dialysis catheters Cannulation of infected arteriovenous grafts or fistulae
If hemodynamically unstable, hold dialysis and initiate supportive measures (vasopressor, fluid bolus) Infectious work up (e.g. catheter sites or arteriovenous graft) Prompt use of antibiotics
Follow‐up tests and monitoring
Drug clearance increases with RRT. Monitor drug levels (e.g. antibiotics, anticonvulsants) to ensure adequate therapeutic levels.
Continuous modalities require the patient to be bedbound, and thus will need vigilant nursing protocols to prevent pressure ulcers.
Reasons for discontinuation of RRT in the ICU
There are a paucity of data on optimal timing for discontinuation but the following are reasons for stopping RRT in the ICU:
Increase in urine output is the most common determinant of kidney function recovery and thus successful weaning from dialysis.
Decrease in BUN and creatinine.
Improved metabolic state.
Improved fluid overload.
Withdrawal of therapy.
Reading list
Augustine JJ, Sandy D, Seifert TH, Paganini EP. A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF. Am J Kidney Dis 2004; 44:1000–7.
Bellomo R, Ronco C. An introduction to continuous renal replacement therapy. In: Bellomo R, Baldwin I, Ronco C, Golper G (eds), Atlas of Hemofiltration. London: Bailliere Tindall, 2001, pp. 1–9.
Oudemans‐van Straaten HM, et al. (eds) Acute Nephrology for the Critical Care Physician. New York: Springer, 2015.
Uchino S, et al. Discontinuation of continuous renal replacement therapy: a post hoc analysis of prospective multicenter observational study. Crit Care Med 2009; 37:2576–82.
Uchino S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294(7):813–18.
Vinsonneau DCC, et al. A prospective, multicentre, randomized clinical trial comparing continuous venovenous hemodiafiltration to intermittent hemodialysis for the treatment of acute renal failure in intensive care unit patients with multiple organ dysfunction syndrome. Lancet 2006; 368:379–85.
Figure 51.1 Continuous veno‐venous hemodialysis (CVVHD) circuit. The dialysate runs in a counter‐current to blood flow within the hemofilter chamber, promoting solute exchange.
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