Search

Last updated: Lupus Nephritis…
on 26 Aug 2016

Renal Replacement Therapy on ICU

Background

Nicholas Sangala and Marlies Ostermann  -  Review Date Jun 2016

Acute Kidney Injury (AKI) is a common complication of acute illness occurring in 13-18% of all hospitalised patients and up to 35% of patients in the Intensive Care Unit (ICU).­ It is associated with an increase in hospital mortality, length of stay, and is an independent risk factor for chronic kidney disease (CKD) including the need for long-term maintenance dialysis at discharge [1,2,3,4,5,6]. Renal replacement therapy (RRT) is not a cure for AKI, but is a supportive treatment that averts the immediate life threatening complications of AKI; whilst a diagnosis and definitive treatment is sought - and allows time for recovery of renal function following resolution of the original insult.­ Between 3-6% of critical care patients will require a period of RRT, and the in-hospital mortality, in this population of patients, is between 50-70% [7,8,9,10].­ Use of RRT on the ICU is therefore a relatively common occurrence, yet the evidence base on which intensive care physicians base their practice is varied in both quality and quantity. In this chapter we will review the latest guidance and the evidence base behind it.


The Principles

­

Renal replacement therapy in the intensive care setting involves the use of an extracorporeal circuit to ‘clean’ blood of solute, and remove excess plasma water.­ The mechanism of solute clearance involves diffusion (haemodialysis), convection (haemofiltration), or a combination of the two (haemodiafiltration).­­ All of the above mechanisms allow for the removal of excess plasma water from blood down a hydrostatic pressure gradient, a process called ultrafiltration. ­

Continuous Veno-venous Haemodialysis (CVVHD)

Using the principal of diffusion, haemodialysis ‘cleans’ blood by running it through a cylindrical semipermeable membrane bathed in dialysate flowing in the opposite direction. This counter current mechanism optimises the concentration gradient between blood and dialysate at all times allowing for the rapid diffusion of solute.­ By generating a transmembrane pressure gradient between the blood and the dialysate, plasma water is forced through the membrane from blood into the dialysate (ultrafiltrate) exiting the circuit as waste. Haemodialysis can be provided as an intermittent modality [eg intermittent haemodialysis (IHD)] or continuously [eg continuous veno-venous haemodialysis (CVVHD)]

Continuous Veno-venous Haemofiltration (CVVH)

Haemofiltration relies on the process of convection as the mechanism for cleaning blood.­ Convection is the movement of solute alongside the plasma water removed during ultrafiltration.­ The clearance of solute via convection depends not only on the volume of ultrafiltrate removed, but also on the ease with which individual molecules can pass through the semipermeable membrane.­ This is dependent on both the size of the molecule in question, and the porousness of the membrane itself, and is quantified as the Sieving Coefficient (SC). A sieving coefficient of 1 equates to the free passage of a molecule across the membrane. In contrast, a sieving coefficient of 0 describes a molecule that is unable to pass through the membrane.

As plasma water is forced across the membrane, the concentration of solute in the ultrafiltrate will at best be equal to the concentration of the solute in the blood, as is the case if the SC is 1.­ As the SC decreases, so too does the concentration of the substance in the ultrafiltrate.­ In order to effectively ‘clean’ blood of solute by convection, large volumes of ultrafiltration are needed. This necessitates the return of a balanced, ultrapure crystalloid solution to the patient, in effect exchanging the ‘dirty’ ultrafiltrate with a ‘clean’ solution. Replacement can occur before blood passes through the filter (‘pre-dilution’) or after blood passes through the filter, (‘post-dilution’) or, as is usually the case, a combination of both.­

Continuous Veno-venous Haemodiafiltration (CVVHDF)

Haemodiafiltration is a combination of haemodialysis (diffusive clearance), and haemofiltration (convective clearance). Haemodialysis effectively becomes haeomodiafiltration by increasing the transmembrane pressure and thereby increasing the ultrafiltration volume, and with it the convection of solutes.­ Diffusive clearance continues as described prior, down a concentration gradient maintained by the counter current flow of dialysate.­ The removal of larger volumes of ultrafiltrate necessitates volume replacement with a balanced, ultra pure crystalloid solution to maintain blood volume. ­Replacement can occur before blood passes through the filter (‘pre-dilution’) or after blood passes through the filter (‘post-dilution’) or, as is usually the case, a combination of both.­ Haemodiafiltration, like haemodialysis has the potential for rapid solute clearance. It can be provided as an intermittent therapy or continuously as continuous veno-venous haemodiafiltration (CVVHDF). ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­

Peritoneal Dialysis

Peritoneal dialysis (PD) is an option for treating patients with AKI, and in some countries is the only form of treatment available in the intensive care setting.­ The principles of PD have been covered in an earlier chapter. Although it is an option, PD does not offer the control afforded to intensivists by CVVH, CVVHDF or CVVHD.­ This is particularly true with respect to control of fluid balance but also with the element of clearance control.­ Setting aside these issues, there are also practical implications. For example, PD catheter insertion is an option not available to many postoperative patients.­ Despite this, there are situations where it may be the only option.

Key Points:

  1. Haemodialysis utilises diffusion to remove waste from blood.
  2. Haemofiltration utilises convection to remove waste from blood.
  3. Haemodiafiltration uses both convection and diffusion to remove waste from blood.

Timing Modality and Dosing on ICU

Timing of RRT

The issue of optimal timing of initiation of RRT is an important question which has led to many debates. It is less an issue of ‘time’ per se, but more the complexity of defining exactly when, during a course of an illness complicated by AKI, the benefits of RRT outweigh any potential harm.­ In patients with the life threatening complications of hyperkalemia, fluid overload, severe metabolic acidosis, or uraemic pericarditis, the indication for RRT is absolute - and the benefit is clear.­ In this setting the objective is to correct the immediate life-threatening abnormalities, and to avoid additional organ dysfunction by providing ongoing renal support. ­

The difficulty arises in the much more common scenario of a critically ill patient with AKI who is yet to reach any of the above described thresholds.­ Here, the aim of initiating RRT is to prevent the development of life-threatening complications that may occur as AKI progresses, and to prevent any additional organ dysfunction. This may develop as a result of AKI; for example, cardiac failure or respiratory failure. AKI itself is not a diagnosis but merely a description of a syndrome that occurs as a result of numerous underlying causes. The progression of AKI is therefore both highly variable and unpredictable - depending on the cause.

At present, the biochemical markers used to measure renal function are sufficient in the context of chronic kidney disease (CKD), or even an acute deterioration in renal function that occurs over days or weeks. But, in the context of acute circulatory collapse and multi organ failure, they are not able to acutely reflect the severity of renal dysfunction; nor are they able to identify patients who will progress to the point of acute renal failure requiring RRT.­ Consequently, patients who receive RRT ‘early’ in their disease course may never have reached the thresholds discussed above.­ However, whether or not delaying RRT until ‘later’ in the disease is detrimental to the patient remains unclear.

The Evidence

Unsurprisingly, given the complexity of the issue, there are only 2 randomised controlled trials and most of the evidence stems from prospective and retrospective cohort studies.­ These studies tend to suggest an outcome benefit in those who receive RRT ‘early’, though defining ‘early’ is not straightforward. A recent study by Bagshaw et al (2009) highlights the complexity of the problem [11]. ­They prospectively studied the outcomes of patients admitted to ICU who required RRT, but separated them into those who received RRT ‘early’ and those who received it ‘late’.­ Using the same population of patients, they varied their definitions of ‘early’ and ‘late’ utilising either blood urea nitrogen (BUN) levels (early being a BUN <24.2μmol/L), serum creatinine (Cr) levels (early being a Cr <309μmol/L), or the timing of initiation with respect to days in ICU (early 0-2 days, delayed 2-5 days, late >5 days).­ In this study, timing based on BUN showed no significant difference in mortality; but there was a significant increase in patients’ dependence on RRT at discharge compared to the ‘late’ group.­

When the same patients were analysed from the serum creatinine perspective, those in the late group had a significantly lower mortality compared to the early group (53.4% vs 71.4%) but again had higher rates of RRT dependence at discharge.­ Finally, those treated early in their ICU stay faired better than those with delayed or late initiation of RRT with mortality rates being 58.9%, 62.1% and 72.8% respectively. The authors concluded that timing of initiation of RRT is modifiable and may influence patient survival but is highly dependent on the definitions used. It is important to note that in this study, there are many other variables that were not controlled for, including modality and dose of RRT.­ Shiao et al (2009) performed a similar prospective study in patients who required RRT following abdominal surgery [12].­ They defined ‘early’ and ‘late’ based on the RIFLE criteria, early being RIFLE-Risk or no AKI, late being RIFLE-Injury or RIFLE-Loss.­ Again, modality of RRT was not standardised, neither was dose. ­Late initiation of RRT was found to be an independent predictor of hospital mortality, a finding supported by an earlier study by Liu et al in 2006 [13]

There have been 2 randomised control trials (RCTs) addressing the issue, the first and larger trial published in 2002, followed by a smaller trial in 2004 [14,15]Bouman et al randomised 106 patients with multi-organ failure and AKI to receive ‘early’ CVVH (25ml/kg/hr) or ‘late’ CVVH (25ml/kg/hr).­ Patients in the ‘early’ arm commenced CVVH within 12 hours of meeting inclusion criteria (average 7hrs). ­The inclusion criteria were a urine output <30ml/hr for more than 6 hours or a creatinine clearance of <20ml/min. Those in the ‘late’ arm commenced CVVH only when the following thresholds were met; uraemia (serum urea >40μmol/L), hyperkalaemia (K >6.5mmol/L), or fluid overload.­ The average time to initiation of RRT in this arm was 41.8hrs (21.4-72) with an average urea at initiation being 37.4μmol/L compared to 17.1μmol/L in the early arm. ­

There was no difference in ICU, hospital or 28-day mortality and no difference in rates of renal recovery. Four patients in the late arm recovered renal function without needing RRT.­ The second study (by Sugahara et al) ­involved 28 patients post cardiac surgery.­ Here, the criterion for ‘early’ RRT was a urine output less than 30mls/hr for 3 consecutive hours with a rise in serum creatinine by 0.5mg/dL/day, compared to the ‘conventional’ group that had a urine output of less 20ml/hr for 2 consecutive hours in the presence of deteriorating renal function.­ The modality of RRT in this study was CVVHD.­ Interestingly, 8 patients who were randomised were subsequently excluded as their urine output improved during the ‘observational’ period.­ 14-day survival was superior in the ‘early’ group (12/14) compared with only 2 survivors in the ‘conventional’ group. ­The causes of death in these patients were not reported.

When considering the evidence, it must be acknowledged that most of the data stem from either prospective or retrospective cohort studies. The most robust RCT compared extremes of management with respect to timing, and failed to show any difference between ‘late’ and ‘early’ initiation of RRT. The remaining non-RCTs, tend to suggest a benefit in early initiation of RRT whether based on BUN levels or RIFLE/AKIN criteria [16].­ The recent guideline by the Kidney Diseases Improving Global Outcome (KDIGO) committee recognises the lack of definitive evidence by suggesting timing of RRT should be very much based on the individual clinical need of each patient; and take into account the goals of therapy alongside the trends in markers of renal function.

The KDIGO guideline (2012) suggests:

  • Initiate RRT emergently when life-threatening changes in fluid, electrolyte, and acid-base balance exist.
  • 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.

Similarly, the recent NICE AKI guideline (2013) recommends:

  • Refer adults, children and young people immediately for RRT if any of the following are not responding to medical management: hyperkalaemia, metabolic acidosis, symptoms or complications of uraemia (ie. pericarditis or encephalopathy), fluid overload, pulmonary oedema.
  • 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.

The following algorithm may serve as a guide when deciding whether to start RRT for AKI (Ostermann M et al, 2012 [17]

­


RRT Modality: Intermittent versus Continuous

Having taken the decision that a patient requires renal support, the next question is that of modality.­ The broad options are intermittent renal replacement therapy (IRRT) in the form of intermittent haemodialysis/haemodiafiltration, or continuous renal replacement therapy (CRRT) in the form of CVVHD, CVVH, or CVVHDF.­ Ever since the introduction of CRRT in the 1970s, there has been a general perception that CRRT was superior to IRRT for numerous theoretical reasons. These include: slower more protracted solute removal preventing disequilibrium syndrome and cerebral oedema; better control of fluid balance; and perhaps most importantly, better hemodynamic stability than IRRT [18,19,20]. CRRT is not however without complications, in particular the need for anticoagulation, the risk of hypothermia, and the requirement for prolonged immobilisation of the patient.­

Additionally, CRRT is associated with higher costs than IRRT.­ IRRT also has benefits. For example, rapid solute clearance in a shorter time period that reduces the risk of hypothermia and the need for anticoagulation, and allows for more time for both diagnostic and therapeutic interventions and rehabilitation. Worldwide and in the UK, CRRT has become the most commonly used form of RRT in critical care [20,21].­ The first few studies comparing the modalities were largely retrospective. These generally found a benefit to continuous therapies over intermittent.­ They were followed by numerous randomised controlled trials that quickly questioned the theoretical advantages associated with continuous therapies.

The Evidence

In 1996, Misset et al performed a randomised cross-over study to directly compare the haemodynamic profile of critically ill patients with AKI receiving continuous or intermittent therapy [22].­ At that time, IHD was performed using a veno-venous single pump extracorporeal circuit, whereas continuous therapy required both venous and arterial cannualation – continuous arterio-venous haemofiltration­ (CAVH).­ Of the 27 patients randomise, 16 were suffering from sepsis and multi organ failure (MOF), 7 had MOF post cardiac surgery and 4 had MOF associated with congestive cardiac failure.­ Each patient received both therapies – either IHD followed by CAVH, or CAVH followed by IHD. There was no significant difference between the haemodynamic profiles of each patient before and after cross-over. This was the first RCT to cast doubt on the preconceived belief that continuous therapy was superior to intermittent, though the outcome measures were limited to haemodynamic parameters and not morbidity or mortality.­

John et al performed a more detailed study of haemodynamics in 2001 [23].­ This study, randomising patients to IHD versus CVVH, also looked at surrogate markers of tissue perfusion and hypoxia as well as haemodynamic parameters.­ IHD was associated with a slight fall in systolic blood pressure and mean arterial pressure (MAP) that normalised after discontinuation of therapy. There was, however, no difference in the number of severe hypotensive episodes necessitating fluid bolus +/- escalation of inotropes between either group. Interestingly, cardiac output fell upon initiation of both types of RRT, but the fall was sustained in the CVVH group, whereas it returned to baseline in the IHD group following its discontinuation. Despite these differences in haemodynamic parameters, there was no difference in splanchnic perfusion or markers of tissue hypoxia.

In terms of clinical outcomes, including mortality and renal recovery, Mehta et al performed the first RCT comparing continuous and intermittent therapies, published in 2001 [24]. The multi-centered trial randomised 166 patients and, surprisingly found an increase in ICU and hospital mortality associated with continuous therapy. Review of baseline characteristics showed that despite randomisation, those in the continuous group had a significantly higher burden of disease sufficient enough to negate the trial outcomes. However, the trial uncovered an important obstacle for planning future studies, an obstacle that has not always been overcome. One of the inclusion criteria for this trial was a MAP >70mmHG with or without inotropic support.­ Of the 208 patients excluded from the trial, 20% were excluded because they failed to achieve this criterion. An additional 20% were excluded at the discretion of the admitting ICU physician or nephrologist for undisclosed medical reasons.

This potential source of bias was overcome in trials by Augustine et al in 2004, and Uehlinger et al in 2005, with no patients being excluded due to haemodynamic compromise [25,26]. ­Neither trial showed any difference in ICU or hospital mortality though Augustine et al showed a significant drop in MAP associated with IHD. Uehlinger  failed to show any difference in haemodynamic parameters as did Gasparovic et al in a trial published in 2003 [27]Vinsonneau et al published similar findings of a RCT in 2006, with no significant difference in 60-day mortality, renal recovery, and haemodynamic compromise (again) between CRRT and IHD [28]. ­They did report an increase in hypothermia associated with continuous therapy.­ Most recently, Lins et al performed a large multi-centre RCT involving 316 patients who were randomised to IHD or CVVH [29].­ 650 patients were eligible for randomisation, though a significant proportion (344/650) were excluded.­ Of the 344 excluded, 124 were excluded for medical reasons, the most common being haemodynamic compromise or coagulopathy.­ This study also showed no difference in ICU survival, hospital survival or renal recovery.

A Cochrane review published in 2008 that included all but the most recent trial by Lins et al concluded “RRT modality does not appear to influence important patient outcomes, and therefore the preference for CRRT over IRRT in such patients does not appear justified in the light of available evidence” [30].­ There is however sufficient evidence to suggest that IRRT may be detrimental to haemodynamics.­ Though this has not been found in all studies; many trials excluded those with haemodynamic compromise, and if it was not part of the exclusion criteria, and patients were often excluded at the discretion of the physicians.­ The KDIGO guideline acknowledges this issue, and recommends that the two modalities should be seen as complementary therapies, but that CRRT should be the modality of choice in haemodynamically unstable patients.

The KDIGO guideline (2012) suggests:

  • Use continuous and intermittent RRT as complementary therapies in AKI patients. (Not Graded)
  • We suggest using CRRT, rather than standard intermittent RRT, for haemodynamically unstable patients. (2B)
  • We suggest using CRRT, rather than intermittent RRT, for AKI patients with acute brain injury or other causes of increased intracranial pressure or generalized brain edema. (2B)

Since publication of the KDIGO guideline, some evidence has emerged that among AKI survivors, initial treatment with IRRT might be associated with higher rates of dialysis dependence than CRRT [31].­ However, most data stem from retrospective studies and more research in this area is needed.­


RRT dose in critically ill patients

Clearance

Clearance of a given solute describes the volume of blood that will be left 100% solute free after it passes through the filter – be it during haemodialysis, haemodiafiltration, or haemofiltration.­ It is measured in mls/min.­

CVVH clearance

CVVH relies entirely on convection, and the clearance of any given molecule is largely dependent on the size of that molecule compared to the membrane pore size. ­Small molecules move across the membrane unhindered whilst larger molecules will be more restricted. ­The ease at which a molecule crosses the membrane is termed the Sieving Coefficient.­ The clearance (K) in ml/min is a product of the sieving coefficient (SC) and the Ultrafiltration rate (Qf) in ml/min.­

K=Qf x SC

In those molecules with a SC of 1, such as urea, clearance is equal to UF rate.­ In CVVH, this represents the volume of ‘waste’ exiting the filter, or the effluent flow.­ The dose of CVVH is therefore the effluent flow rate in ml/hr, or ml/kg/hr when standardized to weight.

CVVHDF Clearance

In CVVHDF, clearance is achieved by both convection and diffusion.­ The convective clearance is calculated exactly as described above.­ However, the additional clearance obtained by diffusion depends on the movement of solute down a concentration gradient from blood into the dialysate.­ CVVHDF utilises very slow dialysate flow rates (1000ml-1200mlL/hr compared with 500ml/min in IHD) such that a state of equilibrium is rapidly reached between blood and dialysate.­ Accordingly, the dialysate exiting the filter will have the same concentration of small solutes (such as urea), as the blood exiting the filter; therefore the ‘diffusive clearance’ is equal to the dialysate flow rate.­ The total clearance achieved during CVVHDF is the sum of the ultrafiltration rate in ml/min and the dialysate flow rate in ml/min, which is the total effluent flow of waste leaving the filter.­ Again, the dose is described in ml/kg/hr when standardised for weight.

CVVHD Clearance

In CVVHD dialysate flow rates are low, and equilibrium is reached rapidly between solutes in blood and in the dialysate.­ Thus, clearance is equal to dialysate flow rate.­ Effectively, this again represents the effluent flow rate, which will also take into account the potential convective clearance achieved by any amount of ultrafiltration.

­

Key Points:­

  1. In CVVH, the clearance of urea in ml/hr is equal to the effluent flow rate of ultrafiltration in ml/hr.
  2. In CVVHD and CVVHDF, the clearance of urea in ml/min is equal to total effluent flow rate which is the sum of ultrafiltration rate in ml/hr and the dialysate flow rate in ml/hr.
  3. The dose of both CVVH and CVVHDF is standardised according to weight as the effluent flow rate in ml/kg/hr.

RRT dose in critically ill patients

The optimal dose of RRT has been subject to much debate for many years and continues to be so.­ The controversy exists because of the conflicting evidence, with earlier studies tending to show a benefit with higher intensity RRT; whereas the more recent studies tending to show no added benefit with higher doses of ­RRT. ­When reflecting on the evidence it becomes apparent that the studies are not directly comparable, having used different modalities of RRT, compared different doses of RRT, and involving different populations of patients. ­Ronco et al in 2000 compared 3 levels of post dilutional CVVH - 25ml/kg/hr, 35 ml/kg.hr and 45 ml/kg/hr - in patients with an AKI on the ICU, the majority of which were surgical patients [32]. They reported better survival and renal recovery in the high intensity groups (35ml/kg/hr and 45ml/kg/hr).­ In contrast, ­Bouman et al in 2002 compared CVVH at 48ml/kg/hr to 25ml/kg/hr in largely cardiothoracic patients with no difference in outcome [14].

­Schiff et al in 2002 compared daily IHD with alternate day IHD (Total weekly Kt/V 8.4 vs 4.2) in patients whose primary cause of AKI was hypotension and found a benefit to high intensity RRT [33]. This group specifically excluded patients with significant haemodynamic compromise whereas Bouman et al specifically targeted patients who were haemodynamically maintained on inotropes, and required ventilation. ­In 2006, Saudan et al compared 25ml/kg/hr of CVVH to 45ml/kg/hr of CVVHDF and reported a benefit in both mortality and renal recovery in the high dose CVVHDF arm compared to the low dose group [34]. Tolwani et al in 2008 randomised 200 patients to either high intensity CVVHDF (35ml/kg/hr) or low intensity CVVHDF (20ml/kg/hr) and found no significant difference [35]. The patient population in this trial included those with septic shock and cardiogenic shock.

The evidence by 2006 was therefore conflicting; despite numerous relatively large RCTs. In 2008, a large multicentre RCT involving 1124 patients - The VA/NIH Acute Renal Failure Trial Network (ATN) Study – was published [36].­ This was a large pragmatic multi-centre RCT which compared high dose RRT (CVVHDF at 35ml/kg/hr and/or 6 times weekly IHD/SLED) with lose dose RRT­ (CVVHDF at 20ml/kg/hr and/or thrice-weekly IHD/SLED). The study protocol dictated that those with haemodynamic compromise received CVVHDF and those who were more stable commenced IHD/SLED. The protocol allowed a switch in modality according to haemodynamic stability, though patients were to remain in the allocated intensity arms. This study represents a pragmatic comparison between low and high intensity strategies as utilised in the US hospitals involved in the trial.­ It was not a direct comparison between high and low intensity CVVH, or high and low intensity CVVHDF, or indeed high and low intensity IHD/SLED.­ Nevertheless it showed no difference in mortality, duration of RRT or rate of renal recovery between the two strategies. ­

A second large multi-centre RCT was conducted in Australia and New Zealand and also published in 2008, the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) study [37].­ This study randomised patients to receive either 40ml/kg/hr or 25ml/kg/hr of post-dilution CVVHDF. 1508 patients across 35 ICUs were randomised between December 2005 and November 2008,.­ Like the ATN study, this study failed to show a difference in outcome between the two groups, with 90-day mortality being 44.7% in both groups.­ At 90 days, 6.8% of survivors in the high intensity arm were RTT dependent compared to 4.4% of the standard arm.

Table 1: RCT comparing lower and higher intensities of RRT­

Author Year MC-RCT Low Intensity Arm High Intensity Arm Benefit with high dose RRT

Ronco [32]

2000 No 25ml/kg CVVH 35 & 45ml/kg CVVH Yes
Bouman [14] 2002 No 25ml/kg CVVH 48ml/kg CVVH No
Schiff [33] 2002 No

Kt/V 4.2 IHD

Kt/V 8.4 IHD

Yes
Saudan [34] 2006 No 25ml/kg CVVH 45ml/kg CVVHDF Yes
Tolwani [35] 2008 No 20ml/kg CVVHDF 35ml/kg CVVHDF No

ATN [36]

2008 Yes 20ml/kg CVVHD or 3 x weekly IHD/SLED 35ml/kg CVVHD or 6 x weekly IHD/SLED No
Hannover [38] 2009 No SLED Urea 20-25 mmol/L SLED Urea <15mmol/L No
RENAL [37] 2009 Yes

25ml/kg CVVHDF

40ml/kg CVVHDF No
Zhang [39] 2011 No

50ml/kg CVVH

85ml/kg CVVH

No
IVOIRE [40] 2013 Yes

35ml/kg CVVH

70ml/kg CVVH

No

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

­

There are notable differences between these studies, but there is no convincing evidence that high intensity therapy is associated with better outcomes,.­ ‘High intensity’ uniformly refers to a prescribed dose >25ml/kg/hr, most commonly 35-45ml/kg/hr. ­Two more resent trials by Zhang et al in 2011 and the IVOIRE study of 2013 both studied the benefit of very high volume haemofiltration in critically ill patients with AKI [39,40]. Neither study showed a benefit with very high volume hemofiltration. In addition, both studies highlighted the fact that increasing the does of RRT is not without its complications.­ High volume CRRT was associated with increased losses of electrolytes and antibiotics resulting in higher electrolyte replacement rates and subtherapeutic antibiotic levels.

Although higher doses of RRT do not translate into better outcomes, it is difficult to truly identify where exactly the lower limit of therapy should fall.­ Certainly, the majority of studies have used 25ml/kg/hr as the standard dose, though Tolwani found no difference in outcome when using 20ml/kg/hr as the standard dose. ­The measured delivered dose in the low intensity arm of this study was found to be as low as 17ml/kg/hr – without any deleterious effect. However, rarely, due to interruptions of CRRT for investigations or access/filter issues, does the delivered dose of CRRT match the prescribed dose.­ As such, to achieve any given delivered dose, one must anticipate disruptions to the therapy and prescribe a slightly higher dose.­ KDIGO acknowledge these difficulties with their recommendations as noted below.­

The Guidance (KDIGO 2012)

  • The dose of RRT to be delivered should be prescribed before starting each session of RRT. (Not Graded) We recommend frequent assessment of the actual delivered dose in order to adjust the prescription. (1B)
  • Provide RRT to achieve the goals of electrolyte, acid-base, solute, and fluid balance that will meet the patient’s needs. (Not Graded)
  • We recommend delivering a Kt/V of 3.9 per week when using intermittent or extended RRT in AKI. (1A)

­

We recommend delivering an effluent volume of 20–25ml/kg/h for CRRT in AKI (1A). This will usually require a higher prescription of effluent volume. (Not Graded)


References

  1. Chertow GM et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005; 16(11): 3365-70
  2. Fang Y, Ding X, Zhong Y, Zou J, Teng J, Tang Y, Lin J, Lin P: Acute kidney injury in a Chinese hospitalized population. Blood Purif 30: 120–126, 2010
  3. Lafrance JP, Miller DR: Defining acute kidney injury in database studies: The effects of varying the baseline kidney function assessment period and considering CKD status. Am J Kidney Dis 56: 651–660, 2010
  4. Lafrance JP, Miller DR: Acute kidney injury associates with in- creased long-term mortality. J Am Soc Nephrol 21: 345–352, 2010
  5. Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C: An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med 34: 1913–1917, 2006
  6. Correlation between the AKI classification and outcome.­ Marlies Ostermann, Rene Chang and The Riyadh ICU Program Users Group.­ Critical Care 2008, 12:R144
  7. Chertow GM, Christiansen CL, Cleary PD, Munro C, Lazarus JM. Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Archives of Internal Medicine 1995;155 (14):1505–11.
  8. Barton IK, Hilton PJ, Taub NA, Warburton FG, Swan AV, Dwight J, et al.Acute renal failure treated by haemofiltration: factors affecting outcome. Quarterly Journal of Medicine 1993;86(2): 81–90.
  9. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 294: 813– 818, 2005
  10. Vesconi S, Cruz DN, Fumagalli R, Kindgen-Milles D, Monti G, Marinho A, Mariano F, Formica M, Marchesi M, René R, Livigni S, Ronco C, DOse REsponse Multicentre International collaborative Initiative (DO-RE-MI Study Group): Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury.­ Crit Care 2009, 13:R57
  11. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA: Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury. J Crit Care 2009, 24:129-140.
  12. Shiao CC, Wu VC, Li WY, et al. Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery. Crit Care 2009; 13: R171.
  13. Liu KD, Himmelfarb J, Paganini E, et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2006; 1: 915–919.
  14. Bouman CS, Oudemans-van Straaten HM, Tijssen JG, Zandstra DF, Kesecioglu J: Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial. Crit Care Med 2002, 30:2205-2211.
  15. Sugahara S, Suzuki H. Early start on continuous hemodialysis therapy improves survival rate in patients with acute renal failure following coronary bypass surgery. Hemodial Int 2004; 8: 320–325
  16. Karvellas CJ, Farhat MR, Sajjad I et al. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care 2011; 15: R72
  17. Ostermann M, Dickie H, Barrett NA. Renal replacement therapy in critically ill patients with acute kidney injury–when to start.­ Nephrol Dial Transplant 2012; 27: 2242–2248
  18. Kramer P, Wigger W et al.­ Arteriovenous haemofiltration:­ A new and simple method for treatment of overhydrated patients resistant to diuretics.­ Klin Wochenschr 1977; 55: 1127
  19. Kramer R Kaufhold, G, Gr6hne HJ et al (1980) Management of anuric intensive care patients with arteriovenous hemofiltration. Int J Artif Organs 3:225-230
  20. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 294: 813– 818, 2005
  21. J. J. Gatward, G. J. Gibbon, G. Wrathall and A. Padkin.­ Renal replacement therapy for acute renal failure: a survey of practice in adult intensive care units in the United Kingdom.­ Anaesthesia (2008); 63: 959–966
  22. Misset B, Timsit JF, Chevret S, Renaud B, Tamion F, Carlet J:­ A randomized cross-over comparison of the hemodynamic response to intermittent hemodialysis and continuous hemofiltration in ICU patients with acute renal failure.­ Intensive Care Med (1996)­ 22:742-746
  23. John, S.; Griesbach, D.; Baumgartel, M.; Weihprecht, H.; Schmieder, R.E.; Geiger, H. Effects of continuous hemofiltration vs. intermittent hemodialysis on systemic hemodynamics and splanchnic regional perfusion in septic shock patients: a prospective, randomized clinical trial. Nephrology Dialysis Transplantation 2001, 16 (2), 320–327.
  24. Mehta RL, McDonald B, Gabbai FB et al. A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int 2001; 60: 1154–1163
  25. 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: 1000–07.
  26. Uehlinger DE, Jakob SM, Ferrari P et al. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Nephrol Dial Transplant 2005; 20: 1630–37.
  27. Vladimir Gasparovic ́ , Ina Filipovic ́-Grcic ́ , Marijan Merkler, Zoran Pisl.­ Continuous Renal Replacement Therapy (CRRT) or Intermittent Hemodialysis (IHD)—What Is the Procedure of Choice in Critically Ill Patients?­ RENAL FAILURE
Vol. 25, No. 5, pp. 855–862, 2003
  28. Vinsonneau C, Camus C, Comber A et al. for the Hemodiafe Study Group. Continuous venovenous haemofiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet 2006; 368: 379–385
  29. Lins RL, Elseviers MM, Van der Niepen P, et al. Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial. Nephrol Dial Transplant 2009; 24: 512–518.
  30. Rabindranath K, Adams J, Macleod AM, et al. Intermittent versus continuous renal replacement therapy for acute renal failure in adults. Cochrane Database Syst Rev 2008: CD003773.
  31. Schneider AG, Bellomo R, Bagshaw SM et al (2013) Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: a systematic review and meta-analysis. Intensive Care Med 39:987–997
  32. Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G:­ Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000, 356:26-30.
  33. Schiffl H, Lang SM, Fischer R: Daily hemodialysis and the outcome of acute renal failure. N Engl J Med 346: 305–310, 2002
  34. Saudan P, Niederberger M, De Seigneux S, Romand J, Pugin J, Perneger T, Martin PY: Adding a dialysis dose to continuous hemofil- tration increases survival in patients with acute renal failure. Kidney Int 70: 1312–1317, 2006
  35. Tolwani AJ, Campbell RC, Stofan BS, Lai KR, Oster RA, Wille KM. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol 2008; 19:1233-8.
  36. The VA/NIH Acute Renal Failure Trial Network: Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008, 359:7-20.
  37. RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S: Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009, 361:1627-1638.
  38. Faulhaber-Walter R, Hafer C, Jahr N, et al. The Hannover Dialysis Outcome study: comparison of standard versus intensified extended dialysis for treatment of patients with acute kidney injury in the intensive care unit. Nephrol Dial Transplant 2009; 24: 2179–2186.
  39. Zhang P, Yang Y, Lv R, Zhang Y, Xiea W, Chen J: Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial.­ Nephrol Dial Transplant (2012) 27: 967–973
  40. Joannes-Boyau O, Honoré PM, Perez P, et al. High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med 2013;39:1535-46