The coupling of adequate solute and UF control with satisfactory patient outcomes are the goals of RRT. Practical issues that include nursing scheduling and cost are coupled to the patient's presentation when selecting the RRT modality (Table 31–1).
Table 31–1Comparison of the RRT modalities. |Favorite Table|Download (.pdf) Table 31–1 Comparison of the RRT modalities.
|Modality ||10 Mode of Clearance ||BFR cc/min ||Dialysate ||RF ||Anticoagulation ||Time |
|IHD ||Diffusion ||250-400 ||Yes ||No ||Short heparin ||3-4 h |
|SLEDD ||Diffusion ||100-200 ||Yes ||No ||Long heparin || |
|CVVH ||Convection ||200-300 ||No ||Yes ||Continuous heparin/citrate ||24 h |
|CVVHD ||Both ||200-300 ||Yes ||Yes ||Continuous Heparin/citrate ||24 h |
|SCUF ||Convection ||100-200 ||No ||No ||Long heparin/citrate ||Variable |
In North America, peritoneal dialysis (PD) was extensively used into the 1990s to treat AKI in the ICU.36 PD requires placement of an intra-abdominal catheter, with continuous exchanges of high dextrose dialysate into the abdominal cavity. PD, therefore, is a continuous RRT. The high osmolarity dextrose generates UF, and hemodynamically it tends to fare better than IHD. Catheters were temporarily placed at the bedside by nephrologists, or Tenckhoff catheters were placed by surgeons. In the following decades, acute PD was largely abandoned due to inefficient solute clearance, infection concerns, and its contraindication in patients with abdominal problems or recent surgery. PD may also be difficult in ventilated patients or in severe obstructive lung disease.
Recently, the modality has been reassessed in the ICU setting, where the use of high-volume PD was examined.37 One study which excluded severely hypercatabolic patients, had few complications (7.5%) and 12% had peritonitis. In certain critically ill patients, PD may be a viable alternative,37 where its characteristic continuous slow clearance may better suit patients with elevated ICP.38
This is essentially conventional outpatient dialysis averaging 4 hours, 3 times per week, with blood flow rates (BFR) up to 400 cc/min. Due to the higher BFR and dialysate flow rates (DFRs) it is more likely to induce hypotension than other modalities. Therefore, the traditional arguments against using IHD in the ICU have been relatively less hemodynamic stability and clearance compared to continuous RRT. Furthermore, IHD is also a concern in situations where rapid changes in solute (sodium or potassium) or osmoles (elevated ICP) can be detrimental (see below). Financially, the use of roller blood pumps and rapid clearance requires skilled dialysis nursing, increasing costs.
Earlier studies demonstrated IHD a hemodynamic risk compared to continuous RRT (CRRT). Since then, advancements such as in-line bicarbonate baths and biocompatible membranes have improved IHD stability.30,39 Presently, IHD is the most commonly selected RRT in American ICUs, utilized in 57% of cases.40
Furthermore, in the severely ill, nephrologists can improvise IHD by slowing BFR, increasing hours and/or increasing its use to 6 d/wk. This increases net clearance while maintaining hemodynamic stability, essentially becoming sustained low-efficiency daily dialysis (SLEDD) (see later). What's more, adding a separate UF procedure (blood through the dialyzer without counter current dialysate, excising diffusion), facilitates volume removal with less hypotension. UF is better tolerated when solute and osmole clearance is not concomitant.
In the critically ill requiring the use of vasopressor agents, IHD may still be attempted by increasing the dose of the vasopressor as needed. The suggested guidelines in Table 31–2 can largely be met by most institutions.
Table 31–2Guidelines for IHD in critically ill patients.a |Favorite Table|Download (.pdf) Table 31–2 Guidelines for IHD in critically ill patients.a
Biocompatible, modified cellulosic membranes (not cuprophane)
Connect both sides of circuit simultaneously with .9% saline at start
Adjust dialysate sodium at 145, calcium 1.5 mmol/L
Limit maximum blood flow to 150 mL/min
Increase time on dialysis and/or days per week (6 days per week)
Dialysate temperature ≤ 37°C
Stop vasodilators; increase vasopressors as needed
Start with dialysis and then continue with ultrafiltration alone
Continuous Renal Replacement Therapy
Continuous modalities (see Table 31–1) are considered in hemodynamically unstable patients less likely to tolerate abrupt fluid shifts associated with IHD. CRRT is distinguished by lower BFR, allowing for greater stability in treating fluid overload. Indeed, fluid accumulation is more likely seen with IHD than CRRT.33 Also, acidosis and volume control are more consistent with CRRT. Both convective and diffusion modes of solute clearance can be utilized depending on CRRT type. Surprisingly, outcome benefits of CRRT over IHD have not been demonstrated.
Patients for which CRRT is preferred include those with hypotension as in severe sepsis, cirrhosis, liver transplant, and congestive heart failure (CHF). It also benefits patients with markedly elevated BUN and/or ICP due to gradual solute removal avoiding disequilibrium.
As implied, CRRT is administered continuously for as long as required. In actuality, due to interruptions for diagnostic and/or therapeutic interventions treatment time is closer to 18 hours. The long duration on the CRRT circuit cools the blood, resulting in reflexive vasoconstriction supporting hemodynamics.41 CRRT can be used in operating rooms during prolonged procedures such as liver transplantation, and requires frequent hemodynamic, laboratory and electrolyte assessments.
Continuous Arteriovenous Hemofiltration
Arteriovenous modalities (continuous arteriovenous hemofiltration [CAVH] and continuous arteriovenous hemodialysis [CAVHD]) required placement of catheters in an artery and central vein. This system utilized the patient's arterial pressure rather than a rolling pump for blood flow. CAVH is rarely used since the advent of continuous venovenous hemofiltration (CVVH) due to more invasive arterial access, variable BFR, and increased filter clotting issues.
Essentially through convection, clearance is dependent on large UF rates. To maintain hemodynamic and electrolyte stability large volumes (between 1 and 3 L/h) of electrolyte solutions are necessary. Frequent close attention to volume and electrolyte status is essential. Effluent flow is reported as mL/kg/h. The difference between infused volume and UF generated is the net fluid balance. Recent studies have not demonstrated superiority of a particular flow over another.29
REPLACEMENT FLUIDS:—Replacement fluids (RFs) are provided as prefilled sterilized bags by the equipment manufacturer. They have varying concentrations of sodium, magnesium, calcium, and potassium, and allow for modification. Either bicarbonate or lactate is the alkali source. Ideally, lactate-based RF should be avoided in liver failure and/or lactic acidosis, and periodic lactate measurements are needed with bicarbonate replacement when higher than 5 mmol/L.42 Bicarbonate has become the buffer of choice despite issues with storage and preparation.
The RF with the added clearance of solute has effects on blood composition and requires periodic monitoring of blood chemistries. It is added either before the dialyzer (predilution/inflow) or after blood has passed through the dialyzer (postdilution/outflow).
Predilution RF lowers (dilutes) solute concentration and theoretically decreases CVVH clearance efficiency. The UF is not 100% saturated with urea having been diluted by RF prior to passage through the dialyzer/filter. Advantages lie in requirements of low BFR and less clotting of circuit also due to the dilutional effect of the RF.
In postdilution outflow mode, UF rate should not be more than 20% of BFR to avoid excess hemoconcentration and clotting of the circuit. This requires higher BFR of 150 to 200 mL/min to achieve adequate fluid removal in excess of 25 L/d. Predilution inflow overcomes this problem at the expense of clearance efficiency but overall better treatment due to less clotting and more fluid processed for UF generation.43 As an example, 35 L of daily replacement fluid addition in predilution/inflow mode dilutes the blood by 15% at a BFR of 140 mL/min. (35 L/d = 24 mL/min; 24/140 + 24 = 15%).
Continuous Venovenous Hemodiafiltration
Diffusion is now introduced enhancing clearance, by running dialysate countercurrent to blood flow in the extracorporeal circuit. As a combined modality, it requires large volumes of RF in maintaining hemodynamic and electrolyte stability. Again, close attention to the volume and electrolyte status is essential. Comparing CVVH to continuous venovenous hemodiafiltration (CVVHDF) meta-analysis has failed to show any benefit in mortality, renal recovery, vasopressor use, or organ failure.44
All RRT requires anticoagulation to avoid circuit clotting that can result in blood loss, fluid administration to flush the circuit, and minimize blood loss. Treatment disruption to replace the circuit, associated costs for dialyzer and line changes, and resource utilization of personnel, since many institutions mandate dialysis staff to replace circuits. Due to lower BFRs, CRRT have higher clotting risks than IHD.
As in IHD, heparin is the preferred anticoagulant. It is intravenous (IV) bolus administered in the venous line, 2000 to 5000 units, allowing a few minutes to mix. Maintenance is 500 to1000 units/h infused by roller pump into the arterial line. Partial thromboplastin time (PTT) is measured via arterial and venous lines every 6 hours to maintain PTT 40 to 45 or greater than 65, respectively.
In patients with heparin-induced thrombocytopenia direct thrombin inhibitors are used.45 Argatroban is preferred in renal patients at 0.5 to 1 μg/kg/min, due to its liver metabolism.46 Lepirudin is renal eliminated and may be administered as bolus or infusion (0.005-0.025 mg/kg/h). A target activated partial thromboplastin time (aPTT) greater than 1.5 to 2 times normal avoids excessive bleeding and ensures anticoagulation. Fresh frozen plasma is employed for reversal of bleeding attributed to these direct thrombin inhibitors.
Anticoagulation should be reviewed daily between intensivist and nephrologist, and if contraindicated, heparin-free treatments are possible. In SLEDD periodic, every 15 to 30 minutes, saline flushes are instituted. In CVVH, RF is infused prefilter to avoid hemoconcentration.47 Heparin-free extracorporeal circuits on average clot over 8 hours. Decrease in dialysate/serum BUN levels to less than 0.6 may indicate imminent clotting.
Regional citrate avoids systemic anticoagulation, and is superior in circuit survival and bleeding complications.9 Citrate can be administered either before or after blood has been exposed to the filter. Commercially available solutions include ACD-A which has 3% trisodium citrate, citric acid, and dextrose. Using calcium-free RF decreases the amount of citrate required for anticoagulation. Periodic assessment of bicarbonate levels and ionized Calcium (iCA), both from the extracorporeal circuit and patient, is mandatory to avoid serious hypocalcemia. The citrate administration or calcium supplementation is titrated to keep the postfilter iCA between 1.21 and 1.45 mmol/L. Infusion of calcium into circuit avoids delivery of hypocalcemic blood to patient. Citrate toxicity can be a concern in patients with liver disease or lactic acidosis.48
Staffing CRRT requires intense attention to patient care, necessitating one-to-one nurse-to-patient ratios. Elevating the head of the bed or turning the patient can compromise flow and risk clotting, making positioning an issue. In the case of femoral access, better flow is obtained in the supine position.47 Also, some institutions require hemodialysis staff to assist at CRRT commencement, interruption, or termination.
Equipment CVVH equipment is smaller in size since water purification filters in RRT requiring dialysate (IHD, CVVHDF, or SLEDD) are not necessary. The basic operating principle is similar to IHD as a blood pump is utilized to circulate blood through the dialyzer/filter to generate UF (see Figure 31–3). CVVH machines are now equipped with temperature regulation mechanisms resulting in added hemodynamic effects of vasoconstriction at lower temperatures. The febrile response to infection can therefore be missed. Despite impressive advancements in practicality and compactness of machines, it is still necessary to interrupt CRRT for transportation.
Access Any preexisting ESRD access can be utilized for CRRT. In AKI requires placement of a double-lumen catheter in either the femoral or internal jugular (IJ) vein regardless of RRT. These catheters have staggered openings allowing blood flow out from the patient via the proximal (insertion site) opening and return via the distal opening. This arrangement diminishes the degree of mixing or recirculation, and hence, inefficiency.
In general, site selection for catheter placement follows similar risks such as bleeding and infection. Subclavian and left IJ veins are avoided when possible due to the angulation necessary for proper placement and flow. The stiffer catheter risks vessel injury, compromising blood flow and clotting. Furthermore, the subclavian catheter can cause stenosis resulting in high venous pressures, making the creation of a permanent AV access difficult. Up to 14% of AKI patients may need permanent chronic dialysis.5,8
Sustained Low-Efficiency Daily Dialysis
Also called extended dialysis (ED), it is a hybrid of CRRT and IHD. It is increasingly utilized throughout the world,49 as well as in the United States, where about 25% of ICU providers reported using SLEDD in 2007.40
SLEDD generally runs daily for 8 to 10 hours with low DFR (200-400 cc/min) and BFR (150-200 cc/min). It can utilize the IHD machinery with added software to support a lower BFR allowing for a more gradual solute and/or fluid removal. Time on SLEDD can be extended up to 24 hours, to provide for greater clearance according to perceived needs by providers.50 The filters have smaller surface areas (1 m2 compared with 1.5 m2 for IHD), lower UF coefficients (10 mL/h/mm of Hg compared with 45), and lower K0As (maximal theoretical clearance of dialyzer of 600 mL/min compared with 1000 mL/min), but are similarly composed of polysulfone.
SLEDD's hybrid properties support hemodynamics, enhance clearance, and increase convenience while lowering costs. This, as well as its versatility, accounts for a rising popularity.49 For instance, it often is utilized overnight (nocturnal dialysis) when the probability for interruption from procedures or radiologic examinations is less likely. Such maneuvers better guarantee the prescribed dialysis without interruption. Still another important benefit is the decreased need for heparin, not being continuous.
Most importantly, these benefits come without compromising outcomes in AKI as compared to CRRT.49 In a recent study,50 the net 24-hour UF and fluid balances were similar between CVVH and SLEDD, as were hypotensive episodes. Furthermore, SLEDD was associated with a fewer days on mechanical ventilation and in the ICU.
Sustained continuous UF and fluid removal in severe CHF
Though technically not RRT, extracorporeal modalities for UF are considered in severe CHF with diuretic resistance. In such patients renal impairment is not the overwhelming reason to initiate sustained continuous UF (SCUF) but rather as an alternative to diuretics. To date various studies, the UNLOAD and others, have not demonstrated any renal or length-of-stay advantages.51 SCUF should probably be relegated to patients who failed medical therapy and are awaiting cardiac transplant (see Table 31–1).52
Unfortunately, significant questions involving RRT, namely the exact clearance provided, how much is necessary and when to provide it are poorly understood. Dosing should indicate a measured effectiveness of the ridding of waste products from a given volume of blood.14 Urea kinetic modeling, which is ESRD based, is questionable in assessing efficacy in the critically ill, given their increased catabolism and urea Vd.14,26
Treatment dosing (volume of fluid processed) utilizes urea generation (g) over 24 hours (the difference in BUN levels 24 hours apart + loss in urine in nonoliguric AKI) as a marker, divided by the target BUN (g/L). For a 60-kg individual, water compartment is 33 L (0.55% of body weight). Total body urea = BUN level in g/L X's body water (add edema volume to this). The difference between 2 values 24 hours apart + urine loss of urea is total urea generation (g) in 24 hours. If urea production is 16 g/d and target BUN is 40 mg/dL (0.4 g/L), 16/0.4, 40 L of fluid needs to be processed to achieve the clearance and maintain BUN at 40 mg/dL. This however is not generally done when utilizing these modalities. In fact most providers are uncertain of prescribed dosing.53
Past RRT trials have not used urea clearance as a study goal. Guidelines suggest a CRRT KT/V of 3.9/wk or an effluent volume of 20 to 25 mL/Kg/h.54 To achieve this a higher prescription of 25 to 30 mL/kg/h may be necessary. What's more, CVVHDF studies suggest using doses at 35 mL/kg/h.
Antibiotic Management The most common cause of AKI in the ICU remains sepsis8 and despite advances, the mortality has not appreciably improved.3,6,13,29 Though the reasons are likely multifactorial, recent attention on antibiotic (AB) dosing during RRT has identified an important shortcoming (Table 31–3).55 High-flux membranes with larger surface areas and increased time on RRT (CRRT or SLEDD) remove ABs more efficiently compared to IHD. In these forms of RRT, eGFR provided may be up to 30 mL/min and as many as 25% of patients are not making pharmacokinetic targets.55 Furthermore, difficulties in dosing are further compounded when considering modality variability and intermittent usage.56 Given data supporting improved mortality with adequate AB dosing, this is a legitimate concern for septic patients on RRT.
Table 31–3Suggestions to consider when antibiotics (ABs) are to be used.a |Favorite Table|Download (.pdf) Table 31–3 Suggestions to consider when antibiotics (ABs) are to be used.a
ABs are either time dependent (TD) or concentration dependent (CD) and should be approached and adjusted accordingly.
For TD ABs (beta-lactams, linezolid, vancomycin, erythromycin) increase the frequency of the dose to maintain levels. In TD ABs, it is the time spent above the MIC that is crucial.
For CD ABs (fluoroquinolones, aminoglycosides, metronidazole, daptomycin, colistin) increasing the dose maintains levels. In CD ABs it is desirable to have high peaks and low troughs to enhance bactericidal activity while diminishing toxicity.
The Vd in AKI is altered, often higher than normal. It may be preferable to give the first 1 or 2 doses as if the patient's renal function is normal, then adjust to function. In CRRT assume creatinine clearances of 30 cc/min.
Use therapeutic monitoring where possible.
Other systems such as ECMO and nonoliguric patients may increase AB clearances.