Conference Lectures

Renal replacement therapy in the ICU.
.Dr.LakshmiKumar,Amrita Institute of Medical Sciences,Kochi.
Renal replacement therapy (RRT) is a term that encompasses all supportive treatments for renal failure. It includes hemodialysis, peritoneal dialysis, hemofiltration and renal transplantation.The earliest form of renal replacement therapy that was introduced was dialysis.Dialysis is defined as the diffusion of molecules in solution across a semi permeable membrane along an electrochemical concentration gradient.
The indications for hemodialysis (HD)include the following:

  • Progressive uremic encephalopathy or neuropathy (asterixis, myoclonus, seizures)& uremic cardiomyopathy.
  • Fluid overload unresponsive to diuretics
  • Metabolic disturbances refractory to medical therapy (hyperkalemia, metabolic acidosis, hyper- or hypocalcemia, hyperphosphatemia)
  • Toxic overdose of a dialyzable drug.

The primary goal of hemodialysis is to restore the intracellular and extracellular fluid environment that is consistent with normal renal function.
In hemodialysis, blood is pumped through an extracorporeal system that incorporates a dialyzer. In the dialyzer, blood is separated from a crystalloid solution (dialysate) by a semi-permeable membrane. Solutes move across the membrane along their concentration gradient from one compartment to the other obeying Fick`s laws of diffusion. For example, bicarbonate moves from dialysate to blood whereas urea and potassium move from blood to dialysate. In order to maintain concentration gradients and therefore enhance the efficiency of the system the dialysate flows countercurrent to the flow of blood. When removal of water is required the pressure on the blood-side of the membrane has to be increased forcing water molecules to pass into the dialysate.
Adequacy of Dialysis: Precise standards and goals of dialysis adequacy are based on the clearance of urea, a byproduct of protein catabolism, which can bereadily and accurately measured. The volume ofdistribution of urea, which is neither lipophilic norhighly protein-bound, reflects total body water;consequently, urea is an attractive molecule forquantifying dialysis adequacy through mathematicalmodeling based on changing blood concentrations.
Solute concentration and molecular weight are the primary determinants of diffusion rates.
In additionto diffusion, solutes may pass through pores in the membrane by means of a
convective process driven by hydrostatic or osmotic pressure gradients  a processcalledultrafiltration.During ultrafiltration, there is no change in solute concentrations; its primary purpose is the removal of excess total body water.
The basic components of a dialyzer unit are a

  • Dialyzer (cellulose, substituted cellulose, synthetic noncellulose membranes)
  • Dialysis solution (dialysate – water must remain free of Al, Cu, chloramines, bacteria, and endotoxin)
  • Tubing for transport of blood and dialysis solution
  • Machine to power and mechanically monitor the procedure (includes air monitor, proportioning system, temperature sensor, urea sensor to calculate clearance).

Dialyser

 

Components

Hollow fibredialysers are preferred

Membrane biomaterials

 Synthetic membranes preferred owing to fewer blood membrane interactions

Membrane permeability

High flux membranes with larger pores allow removal of higher molecular weight solutes

Treatment time

 2 – 4 hours

Treatment flow rate

200- 400ml/min

Dialysis flow rate

Twice the blood flow rate to prevent intradialytic hypotension

Frequency of Hemodialysis in Chronic Kidney Disease:
Currently most patients with CKD are maintained on thrice weekly hemodialysis largely because of logistics and costs involved. More frequent dialysis is associated with better control of blood pressure and probably regression of the left ventricular hypertrophyand an improvement in quality of life indices.
Care for the patients who are receiving hemodialysis.


Variable

Goals

Dialysis dose

Urea kinetics model

Fluid balance

Individualised.Interdialytic weight gain should be lessthan 5% of IBW

Quality

Measure endotoxin and bacteria in the dialysate water

Anaemia

Target aHb of 10-12 gms%.Avoid high dose erythropoietin.

Vascular access

Monitoring.To establish  AV access rather than indwelling catheters

Bone & Mineral

Calcium levels between 8.4- 9.5 and a PO4 level between 3.5-5.5 mg/dl. Maintain PTH > twice normal value.

Blood Pressure

Optimum targets & strategies not well defined

LDL cholesterol

< 100 mg/dl

Quality of Life Indices.

Support from the medical social worker.

 Besides being the backbone of management of patients with chronic renal failure, Continuous Renal Replacement Therapy (CRRT) is usually performed in the following clinical situations.

  • Acute Kidney Injury (AKI)
  • Removal of dialyzable drugs and toxins.
  • Severe sepsis

Acute Kidney Injury (AKI) is defined as an abrupt (within 48 hours)reduction in kidney function. The diagnosis of an AKI is made when there is

  • An absolute increase in serum creatinine of ≥ 0.3 mg.dl-1 (≥ 26.4 mcmol.l-1)
  • A percentage increase in serum creatinine of ≥ 50% (1.5-fold from baseline).
  • A reduction in urine output (< 0.5 ml.kg-1 per hour for more than six hours).

It is estimated that a third of patients in the critical care setting have an AKI and approximately 5%will require renal replacement therapy (RRT) The hospital mortality in patients with an AKI requiringRRT is as high as 60%.
Removal of Drugs and Toxins:
Drugs that are removed by RRT are lithium,methanol,ethylene glycol,salicylates,barbiturates, metformin, aminoglycosides, metronidazole, carbapenams, cephalosporins and most penicillins.
Severe Sepsis: There has been a revival of interest in the role of hemofiltration in the removal of inflammatory mediators in severe sepsis and septic shock.

Types of Renal Replacement Therapies

  • IHD: Intermittent Hemodialysis(both in AKI & CKD)
  • Continuous Renal Replacement Therapies.
      • Continuous VenoVenous Hemofiltration (CVVH)
      • Continuous Venovenous Hemodiafiltration(CVVHDF).
      • Slow Continuous Ultrafiltration(SCUF)
      • Continuous Arteriovenous Hemofiltration (CAVHD)
  • Hybrid procedures: Sustained low efficiency dialysis.(SLED)

The major difference between dialysis and filtration is the mechanism for solute removal, diffusion versus filtration.
Haemodiafiltration, as its name suggests, is a combination of filtration and dialysis. It has the benefits of both techniques but to a lesser extent than when the individual techniques are used on their own.There is no evidence to suggest that CVVDF has a survival benefit when compared to CVVH but may be a useful way of increasing clearance of small solutes.
Slow continuous ultrafiltrationis used when the only requirement is water removal. Effectively, it is CVVH with a low filtration rate. It can remove up to 6 litres of fluid a day but solute removal is minimal.
CRRT involves filtering and/or dialyzing on a continuous basis. It allows better fluid management and creates less hemodynamic disturbance, but it is more expensive than IHD and requires continuous rather than intermittent coagulation.
SLED is an example of a hybrid therapy which aims to combine the logistic and cost advantages of IHD with the relative cardiovascular stability of CRRT. Treatments are intermittent but usually daily and with longer session durations than conventional IHD. Solute and fluid removal are slower than IHD, but faster than CRRT.

Factors that dictate the choice of RRT for any patient.

  • Type of toxin or molecule to be removed

 

Molecule to be removed

Size

Examples

Preferred RRT

Small molecules or electrolytes

< 500 daltons

Urea,creatinine, K, H, lithium

Dialysis or filtration

Middle molecules

500 - 5000

Large drugs like vancomycin

Filtration better than dialysis

Low molecular weight proteins

5000- 50000

Cytokines , complement

Filtration

Water

18

 

Filtration better than Dialysis

  • Cardiovascular stability.  Any patient with impaired hemodynamic stability may withstand CRRT better than HD.
  • Resources & Availability: CRRT is more expensive and time consuming and decision towards its use based upon the individual situation.
  • CRRT may improve feeding regimes by improving fluid management.
  • CRRT is reported to reduce cerebral edema associated with fulminant hepatic failure and in acute brain injury.
  • Convective modes of CRRT are reported to be beneficial in septic shock.

 

Vascular Access in HD/CRRT.
Vascular access in hemodialysis can be of 4 types

  • Dialysis Catheters
  •  Cuffed Tunneled dialysis catheters(permcath)
  • AV fistula
  • AV graft

The most commonly used site for access is the jugular vein.


Site

Advantages

Disadvantages

IJV

Straight access

Swings in flow associated with respiration

Subclavian

Least association with infection.
Most comfortable for the patient

Swings in flow as above can occur.
Subclavian vein stenosis if catheter indwelling for a long time.
Risks of pnuemothorax

Femoral

Ease of access

Infection rates high

Permcaths  can be safely used for patients on long-term dialysis if the fistula is not working. Fistulas and grafts carry the risks for infection, thrombosis and aneurysmal dilatations.
Anticoagulation duringHD & CRRT.

Heparins are presently the most commonly used anticoagulants worldwide for CRRT. They are widely available and can be easily monitored, but disadvantages include risks of hemorrhage, heparin resistance, and heparin-induced thrombocytopenia (HIT). Because of the potential side effects of heparin, alternative methods of anticoagulation have been investigated, including regional heparin/protamine, low molecular weight heparins, heparinoids, thrombin antagonists (hirudin and argatroban), regional citrate, and platelet inhibiting agents (prostacyclin and nafamostat).

Anticoagulation during IHD.(Heparin UFH- commonly used)

 

Indication

Dosage

Target

UFH

Normal bleeding risk

LD:50IU/kg
MD:500-1500IU/hr

ACT: 80% above baseline

UFH

Increased bleeding risk

LD:10 – 25 IU/Kg
MD:250-500 IU/h

40% above baseline

Very low

Very high bleeding risk or ongoing active bleeding

Rinse with 5000- 20000U Heparin, flush with 0.502.0 L saline

No change in baseline. Use flows above 250 ml/min

LMWH

? advantageous in reducing long term complications with heparins

 

Need monitoring factor  antiXa levels

UFH: Unfractionated Heparin    ACT;Activated Clotting Time
LD: Loading dose
MD: Maintenance dose
Complications of RRT:
These are common to all forms of RRT and include  access related issues like sepsis, thrombosis anticoagulation related like heparin induced thrombocytopenia. Other problems include hemodynamic instability, electrolyte imbalances and rarely air embolism.
Conclusion;
The provision of renal replacement therapies occur over several clinical scenarios from ambulatory surgery, trauma and in the critically ill. There are two forms of RRT, those based on diffusion (dialysis) and those based on convection.(filtration). The choice of a particular technique is based upon the indications of dialysis an and the facilities at a particular centre. The intensity of RRT has not been shown to make a significant improvement in outcomes of AKI and in CKD outcomes long term have not been shown to be significantly better although ther  are improvements in the control of hypertension and left ventricular size. A prospective ongoing study will evaluate the 28 day mortality benefits of   high volume CVVHF in septic patients with acute kidney injury.
There have been advances in the choice of anticoagulation for the dialysis and some centers have documented safety with use of regional anticoagulation with citrate in adults. Although replacing filtration and waste elimination functions of the kidney, endocrine and metabolic functions are not and recent technology has moved to the developmentof the renal assist device (RAD), which allows the culture of human renal tubular cells on a hollow membrane technology and will provide glutathione and normal vitamin D metabolism in the recipient.While investigations are underway for documenting the safety and feasibility of this in human more research is underway  in creating an artificial kidney and this would be the  most promising invention of the future.

References

  • Dr. Andrew Baker & Dr. Richmond Green. Renal Replacement Therapy in Critical Care.Tutorial 194, 30th Aug 2010.
  • Geoffrey Fleming. Renal Replacement Therapy Review.Past,present and the future.Organogenesis 7:1, 2-12; January/February/March 2011.
  • Karl-Georg Fischer. Essentials of Anticoagulation in Hemodialysis. Hemodialysis International 2007; 11:178–189.
  • The Renal Replacement Therapy Study Investigators. Intensity of Continuous Renal Replacement Therapy in Critically Ill patientsEngl J Med 361;17.October 22, 2009.