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BASICS OF HEMODIALYSIS & CRRT
ALL INDIA INSTITUTE OF MEDICAL SCIENCES , JODHPUR
ANAESTHESIOLOGY AND CRITICAL CARE
PRESENTER : DR NAVIN VINCENT
GUIDE : DR PALLAVI
MODERATOR : DR TANVI
INTRODUCTION
 Acute renal failure, also known as acute kidney injury (AKI), is defined as an
abrupt (within 48 hours) reduction in kidney function.
The AKI network defines the reduction in kidney function as the presence of any
one of the following
• 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)
 The initial management of AKI involves treating the underlying
cause, stopping nephrotoxic drugs and ensuring that the patient is
euvolaemic with an adequate mean arterial blood pressure
 RRT is the cornerstone for further management
INDICATIONS FOR RRT
1. ACUTE KIDNEY INJURY (AKI) WITH:
• Fluid overload (refractory to diuretics)
• Hyperkalemia (K+ > 6.5)
• Severe metabolic acidosis (pH < 7.1)
• Rapidly climbing urea/creatinine (or urea > 30mmol.l-1)
• Symptomatic uraemia: encephalopathy, pericarditis, bleeding,
nausea, pruritus
• Oliguria/anuria.
2. OVERDOSE WITH A DIALYZABLE DRUG OR TOXIN
 Drugs are cleared by RRT if they are water-soluble and not highly
protein-bound.
3. SEVERE SEPSIS
 Haemofiltration to remove inflammatory mediators in patients
with severe sepsis/septic shock
 Small studies (with 25 subjects or less) have suggested that high
volume haemofiltration (40-85ml.kg-1.hr-1) may reduce
vasopressor requirements and possibly improve survival in
patients with septic shock
 Irrespective of whether they have an AKI
TYPES OF RRT IN USE IN CRITICAL CARE
1. Intermittent haemodialysis (IHD)
2. Continuous renal replacement therapies (CRRT)
1. Continuous venovenous haemofiltration (CVVH)
2. Continuous venovenous haemodialysis (CVVHD)
3. Continuous venovenous haemodiafiltration (CVVHDF)
4. Slow continuous ultrafiltration (SCUF)
5. Continuous arteriovenous haemofiltration (CAVHD)
3. Hybrid therapies e.g. Sustained low-efficiency dialysis (SLED)
 The functional differences between the techniques :
• The mechanism of solute removal (Filtration versus
• The duration of the treatment (Continuous versus
MECHANISM OF SOLUTE REMOVAL: FILTRATION
(CONVECTION)VERSUS DIALYSIS (DIFFUSION)
HAEMOFILTRATION
 Blood pumped through an extracorporeal system that incorporates a
semi-permeable membrane.
 The hydrostatic pressure that is created on the blood-side of the filter
drives plasma water across the filterultrafiltration.
 Molecules that are small enough to pass through the membrane
(<50,000 Daltons) are dragged across the membrane with the water by
the process of convection.
 The filtered fluid (ultrafiltrate) is discarded and a replacement fluid is
added in an adjustable fashion according to the desired fluid balance.
Haemodialysis
 Blood being pumped through an extracorporeal system that incorporates
a 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.
 Bicarbonate moves from dialysate to blood whereas urea and potassium
move from blood to dialysate.
 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
Haemodiafiltration
 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 ultrafiltration
 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
DURATION OF TREATMENT
INTERMITTENT HAEMODIALYSIS
 Dialysing with higher flow rates than CRRT for defined periods
of time.
 A typical regime is 3-5 hours of dialysis 3 times a week.
 The high flow rates and rapid fall in plasma osmolality mean that
it is only suitable for patients who are cardiovascularly stable.
 Basis of long term RRT for chronic renal failure
CRRT
 Better fluid management
 Creates less haemodynamic disturbance
 More expensive than IHD
 requires continuous , rather than intermittent coagulation
 Superior to IHD in sepsis, cardiovascular instability or head
injury
Sustained low efficiency dialysis
 Hybrid therapy
 Combine the logistic and cost advantages of IHD with the
relative cardiovascular stability of CRRT.
 Solute and fluid removal are slower than ihd, but faster than
crrt
PERITONEAL DIALYSIS
WHICH FORM OF RRT SHOULD WE
USE?
1. What we want to remove from the plasma
2. The patient`s cardiovascular status
3. The availability of resources
4. The clinician`s experience
5. Other specific clinical considerations
1. What we want to remove from the plasma
Other specific clinical considerations
 Convective modes of RRT may be beneficial if the patient has
septic shock
 CRRT feeding regimes by improving fluid management
 CRRT better cerebral perfusion in patients with an acute brain
injury or fulminant hepatic failure
OPTIMAL FLOW RATES / DOSE OF RRT
 Flow rate refers to the ultrafiltrate produced by the filtration process as well as any effluent
dialysis flow
 Marker of solute clearance so it can simplistically be thought of as the dose of RRT
Two recent randomised controlled trials have concluded that there is no benefit to
increasing the flow rate from 20 to 35ml.Kg.-1hr-1:
 The randomised evaluation of normal versus augmented level of renal replacement therapy in
ICU (RENAL) study randomised 1400 critically ill patients with AKI
 The acute renal failure trial network (ATN) study compared intensive or less-intensive dosing
strategies for patients undergoing CRRT (35ml.Kg.-1hr-1 versus 20ml.Kg.-1hr-1), IHD (daily
versus alternate days) and SLED. The recovery of renal function and the mortality at 60 days
were the same in both arms of the trial but there were more hypotensive episodes in the
intensive group
Vascular access
Types of AVF
Extracorporeal circuits
Anticoagulation
 All modes of RRT that utilise an extracorporeal circuit will activate
coagulation pathways leads to premature clotting off of a filter
 Clot formation will reduce filter performance
 If a filter clots off completely the blood contained in the circuit is lost
 Clot formation in the filter will trigger the transmembrane pressure
alarm
 Clot in the venous catheter will trigger the access pressure alarm
 Kinking of the catheter or a collapsing vein can also be responsible
for triggering the access pressure alarm.
Non-pharmacological measures
 Ensuring the patient has an adequate central venous
pressure
 Optimising vascular access
 Adding a proportion of the replacement fluid to the patients
blood before it passes through the haemofilter (this is
predilution)
Guidelines published in 2009 by Intensive Care
Society suggest that anticoagulation is NOT
required
when:
 There is a already a degree of coagulopathy
o INR > 2-2.5
o APTT > 60 seconds
o platelet count < 60 x 103.mm-3
 There is a high risk of bleeding
 The patient is receiving activated protein C.
Anticoagulation should be considered in all other situations
and the aim is to anticoagulate the filter and not the patient
Unfractionated heparin (UFH) [5-30kDa]
 Most commonly used anticoagulant
 40-70 iu.Kg-1 bolus followed by a pre-filter infusion at 5-10
IU.Kg.-1hr-1.
 Most cost effective anticoagulant
 Fully reversible with protamine
 APTT should be monitored to avoid excessive anti-
coagulation
Low molecular weight heparins (LMWH)
[4.5-6kDa]
 Dependant on renal elimination
 Dosing needs to be guided by anti-factor xa levels (aiming
for 0.25-0.35 iu.Ml-1)
 Half life of lmwhs is longer than for UFH (2-6 hrs versus
1.5-3hrs)
 Effect can only be partially reversed with protamine
Prostaglandins
 Prostaglandins (prostacyclin or prostaglandin E2) inhibit platelet function
 Either be used on their own or in combination with heparin for
synergistic effect
 Short half life (several minutes)  administered as an infusion (2.5 – 10
ng.Kg-1.Min-1)
 Anticoagulant effect stops within 2 hours of discontinuing the infusion
 Useful alternative to heparin in patients at high risk of bleeding.
 The main side effect is vasodilation  reduction in hypoxic pulmonary
vasoconstriction leading to hypoxemia.
 They are expensive and so are only used as second line therapy
Regional citrate anticoagulation
 Effective therapy especially when there is an increased risk of
bleeding
 Sodium citrate is infused into the circuit pre-filter which chelates
calcium and inhibits clot formation
 The calcium citrate complex is freely filtered so a calcium infusion is
required post-filter
Limited by the metabolic derangements that it can cause:
 Hypocalcaemia,
 Hypomagnesaemia
 Hypernatraemia
 Metabolic alkalosis
Filters
 Biocompatibility the degree to which the membrane will
activate the patient`s inflammatory and coagulation pathways.
The greater the biocompatibility of a membrane the less
activation it will cause
 Flux the permeability of the filter. High flux membranes are
hydrophobic and may have more or larger pores allowing more
water and solute to move across the membrane
 Thickness thinner membranes allow greater movement of solute
by diffusion and also favour convective movement
 Adsorption The ability of larger solutes to adhere to the surface of
the membrane. A highly adsorptive membrane offers the potential
benefit of adsorbing mid sized molecules including inflammatory
mediators but only until it is saturated with them (usually after the
first few hours).
 Surface area The surface area of the membrane determines the
available area for diffusion and ultrafiltration
 Filters are either cellulose-based or synthetic
 Synthetic filters polysulphone and polyamide are more
biocompatible and are higher-flux membranes  more suitable for
CRRT
 Most filters used for CRRT are synthetic, high-flux membranes with
a surface area of 0.6–1.2m2 and a pore size allowing the passage
Replacement fluid
1. Bicarbonate
2. Acetate
3. Lactate
4. Citrate
Bicarbonate
 More physiological anion
 More reliable buffering capacity
 Instability
 Ca & mg precipitated as carbonate when sterilized with buffer
 Apparent predilection to bacterial growth
Lactate
 Stable and cheaper
 Buffering capacity depends on the conversion of lactate into
bicarbonate
 Contraindications: impaired liver function ,lactic acidosis
 Replacement fluid can be added pre- or post-filter
 Replacement fluid pre-filter  lowers the haematocrit of the blood 
reduces the likelihood of the filter clotting
 Downside is that pre-dilution reduces solute clearance and a
compensatory increase in flow rates should be considered
Pharmacokinetics while on RRT
 Most reliable guide to dosing is by measuring drug levels but not feasible
 Referring to the drug manufacturer’s recommendations
Factors that affect the pharmacokinetics while on RRT :
 Protein binding
 Size of drug molecule
 Mode of RRT
 Timing of RRT
 Dose of RRT
 Membrane permeability
 Patient’s residual GFR
Prescription of RRT
A typical prescription for a 75kg patient requiring CRRT for an AKI would be as follows
Anticoagulation:
· Unfractionated Heparin: 5,000 IU bolus followed by a pre-filter infusion at 500 IU.hr.-1
 Aim to anticoagulate filter but ensure APTT<2
Fluid balance over 24 hours:
· Aim for an even balance if the patient is euvolaemic
· Aim for the appropriate negative balance if the patient is fluid overloaded
(<1500ml/24hrs
 Type of Replacement fluid/Dialysate:
· Use solutions without potassium if serum potassium is high but switch to
potassium containing solutions as serum potassium normalises.
 Use a bicarbonate-based buffer rather than a lactate-based buffer if there
are concerns about lactate metabolism or if serum lactate>8mmol.l.
Exchange rate/treatment dose:
· 1500ml.hr.-1 (75kg x 20ml.kg.-1hr-1)
COMPLICATIONS
 Complications related to the HD catheter
 DDS
 Haemodynamic instability
 Air emboli
 Platelet consumption
 Blood loss
 Electrolyte imbalances
 Hypothermia
 Effects of anticoagulation
Basics of Hemodialysis & CRRT
Basics of Hemodialysis & CRRT

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Basics of Hemodialysis & CRRT

  • 1. BASICS OF HEMODIALYSIS & CRRT ALL INDIA INSTITUTE OF MEDICAL SCIENCES , JODHPUR ANAESTHESIOLOGY AND CRITICAL CARE PRESENTER : DR NAVIN VINCENT GUIDE : DR PALLAVI MODERATOR : DR TANVI
  • 2. INTRODUCTION  Acute renal failure, also known as acute kidney injury (AKI), is defined as an abrupt (within 48 hours) reduction in kidney function. The AKI network defines the reduction in kidney function as the presence of any one of the following • 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)
  • 3.
  • 4.  The initial management of AKI involves treating the underlying cause, stopping nephrotoxic drugs and ensuring that the patient is euvolaemic with an adequate mean arterial blood pressure  RRT is the cornerstone for further management
  • 5. INDICATIONS FOR RRT 1. ACUTE KIDNEY INJURY (AKI) WITH: • Fluid overload (refractory to diuretics) • Hyperkalemia (K+ > 6.5) • Severe metabolic acidosis (pH < 7.1) • Rapidly climbing urea/creatinine (or urea > 30mmol.l-1) • Symptomatic uraemia: encephalopathy, pericarditis, bleeding, nausea, pruritus • Oliguria/anuria.
  • 6. 2. OVERDOSE WITH A DIALYZABLE DRUG OR TOXIN  Drugs are cleared by RRT if they are water-soluble and not highly protein-bound.
  • 7. 3. SEVERE SEPSIS  Haemofiltration to remove inflammatory mediators in patients with severe sepsis/septic shock  Small studies (with 25 subjects or less) have suggested that high volume haemofiltration (40-85ml.kg-1.hr-1) may reduce vasopressor requirements and possibly improve survival in patients with septic shock  Irrespective of whether they have an AKI
  • 8. TYPES OF RRT IN USE IN CRITICAL CARE 1. Intermittent haemodialysis (IHD) 2. Continuous renal replacement therapies (CRRT) 1. Continuous venovenous haemofiltration (CVVH) 2. Continuous venovenous haemodialysis (CVVHD) 3. Continuous venovenous haemodiafiltration (CVVHDF) 4. Slow continuous ultrafiltration (SCUF) 5. Continuous arteriovenous haemofiltration (CAVHD) 3. Hybrid therapies e.g. Sustained low-efficiency dialysis (SLED)
  • 9.  The functional differences between the techniques : • The mechanism of solute removal (Filtration versus • The duration of the treatment (Continuous versus
  • 10. MECHANISM OF SOLUTE REMOVAL: FILTRATION (CONVECTION)VERSUS DIALYSIS (DIFFUSION) HAEMOFILTRATION  Blood pumped through an extracorporeal system that incorporates a semi-permeable membrane.  The hydrostatic pressure that is created on the blood-side of the filter drives plasma water across the filterultrafiltration.  Molecules that are small enough to pass through the membrane (<50,000 Daltons) are dragged across the membrane with the water by the process of convection.  The filtered fluid (ultrafiltrate) is discarded and a replacement fluid is added in an adjustable fashion according to the desired fluid balance.
  • 11. Haemodialysis  Blood being pumped through an extracorporeal system that incorporates a 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.  Bicarbonate moves from dialysate to blood whereas urea and potassium move from blood to dialysate.  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
  • 12.
  • 13.
  • 14. Haemodiafiltration  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.
  • 15. Slow continuous ultrafiltration  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
  • 16. DURATION OF TREATMENT INTERMITTENT HAEMODIALYSIS  Dialysing with higher flow rates than CRRT for defined periods of time.  A typical regime is 3-5 hours of dialysis 3 times a week.  The high flow rates and rapid fall in plasma osmolality mean that it is only suitable for patients who are cardiovascularly stable.  Basis of long term RRT for chronic renal failure
  • 17. CRRT  Better fluid management  Creates less haemodynamic disturbance  More expensive than IHD  requires continuous , rather than intermittent coagulation  Superior to IHD in sepsis, cardiovascular instability or head injury
  • 18.
  • 19. Sustained low efficiency dialysis  Hybrid therapy  Combine the logistic and cost advantages of IHD with the relative cardiovascular stability of CRRT.  Solute and fluid removal are slower than ihd, but faster than crrt
  • 21.
  • 22.
  • 23.
  • 24. WHICH FORM OF RRT SHOULD WE USE? 1. What we want to remove from the plasma 2. The patient`s cardiovascular status 3. The availability of resources 4. The clinician`s experience 5. Other specific clinical considerations
  • 25. 1. What we want to remove from the plasma
  • 26. Other specific clinical considerations  Convective modes of RRT may be beneficial if the patient has septic shock  CRRT feeding regimes by improving fluid management  CRRT better cerebral perfusion in patients with an acute brain injury or fulminant hepatic failure
  • 27. OPTIMAL FLOW RATES / DOSE OF RRT  Flow rate refers to the ultrafiltrate produced by the filtration process as well as any effluent dialysis flow  Marker of solute clearance so it can simplistically be thought of as the dose of RRT Two recent randomised controlled trials have concluded that there is no benefit to increasing the flow rate from 20 to 35ml.Kg.-1hr-1:  The randomised evaluation of normal versus augmented level of renal replacement therapy in ICU (RENAL) study randomised 1400 critically ill patients with AKI  The acute renal failure trial network (ATN) study compared intensive or less-intensive dosing strategies for patients undergoing CRRT (35ml.Kg.-1hr-1 versus 20ml.Kg.-1hr-1), IHD (daily versus alternate days) and SLED. The recovery of renal function and the mortality at 60 days were the same in both arms of the trial but there were more hypotensive episodes in the intensive group
  • 31.
  • 32.
  • 33. Anticoagulation  All modes of RRT that utilise an extracorporeal circuit will activate coagulation pathways leads to premature clotting off of a filter  Clot formation will reduce filter performance  If a filter clots off completely the blood contained in the circuit is lost  Clot formation in the filter will trigger the transmembrane pressure alarm  Clot in the venous catheter will trigger the access pressure alarm  Kinking of the catheter or a collapsing vein can also be responsible for triggering the access pressure alarm.
  • 34. Non-pharmacological measures  Ensuring the patient has an adequate central venous pressure  Optimising vascular access  Adding a proportion of the replacement fluid to the patients blood before it passes through the haemofilter (this is predilution)
  • 35. Guidelines published in 2009 by Intensive Care Society suggest that anticoagulation is NOT required when:  There is a already a degree of coagulopathy o INR > 2-2.5 o APTT > 60 seconds o platelet count < 60 x 103.mm-3  There is a high risk of bleeding  The patient is receiving activated protein C. Anticoagulation should be considered in all other situations and the aim is to anticoagulate the filter and not the patient
  • 36. Unfractionated heparin (UFH) [5-30kDa]  Most commonly used anticoagulant  40-70 iu.Kg-1 bolus followed by a pre-filter infusion at 5-10 IU.Kg.-1hr-1.  Most cost effective anticoagulant  Fully reversible with protamine  APTT should be monitored to avoid excessive anti- coagulation
  • 37. Low molecular weight heparins (LMWH) [4.5-6kDa]  Dependant on renal elimination  Dosing needs to be guided by anti-factor xa levels (aiming for 0.25-0.35 iu.Ml-1)  Half life of lmwhs is longer than for UFH (2-6 hrs versus 1.5-3hrs)  Effect can only be partially reversed with protamine
  • 38. Prostaglandins  Prostaglandins (prostacyclin or prostaglandin E2) inhibit platelet function  Either be used on their own or in combination with heparin for synergistic effect  Short half life (several minutes)  administered as an infusion (2.5 – 10 ng.Kg-1.Min-1)  Anticoagulant effect stops within 2 hours of discontinuing the infusion  Useful alternative to heparin in patients at high risk of bleeding.  The main side effect is vasodilation  reduction in hypoxic pulmonary vasoconstriction leading to hypoxemia.  They are expensive and so are only used as second line therapy
  • 39. Regional citrate anticoagulation  Effective therapy especially when there is an increased risk of bleeding  Sodium citrate is infused into the circuit pre-filter which chelates calcium and inhibits clot formation  The calcium citrate complex is freely filtered so a calcium infusion is required post-filter Limited by the metabolic derangements that it can cause:  Hypocalcaemia,  Hypomagnesaemia  Hypernatraemia  Metabolic alkalosis
  • 40. Filters  Biocompatibility the degree to which the membrane will activate the patient`s inflammatory and coagulation pathways. The greater the biocompatibility of a membrane the less activation it will cause  Flux the permeability of the filter. High flux membranes are hydrophobic and may have more or larger pores allowing more water and solute to move across the membrane  Thickness thinner membranes allow greater movement of solute by diffusion and also favour convective movement
  • 41.  Adsorption The ability of larger solutes to adhere to the surface of the membrane. A highly adsorptive membrane offers the potential benefit of adsorbing mid sized molecules including inflammatory mediators but only until it is saturated with them (usually after the first few hours).  Surface area The surface area of the membrane determines the available area for diffusion and ultrafiltration  Filters are either cellulose-based or synthetic  Synthetic filters polysulphone and polyamide are more biocompatible and are higher-flux membranes  more suitable for CRRT  Most filters used for CRRT are synthetic, high-flux membranes with a surface area of 0.6–1.2m2 and a pore size allowing the passage
  • 42. Replacement fluid 1. Bicarbonate 2. Acetate 3. Lactate 4. Citrate
  • 43. Bicarbonate  More physiological anion  More reliable buffering capacity  Instability  Ca & mg precipitated as carbonate when sterilized with buffer  Apparent predilection to bacterial growth
  • 44. Lactate  Stable and cheaper  Buffering capacity depends on the conversion of lactate into bicarbonate  Contraindications: impaired liver function ,lactic acidosis  Replacement fluid can be added pre- or post-filter  Replacement fluid pre-filter  lowers the haematocrit of the blood  reduces the likelihood of the filter clotting  Downside is that pre-dilution reduces solute clearance and a compensatory increase in flow rates should be considered
  • 45. Pharmacokinetics while on RRT  Most reliable guide to dosing is by measuring drug levels but not feasible  Referring to the drug manufacturer’s recommendations Factors that affect the pharmacokinetics while on RRT :  Protein binding  Size of drug molecule  Mode of RRT  Timing of RRT  Dose of RRT  Membrane permeability  Patient’s residual GFR
  • 46. Prescription of RRT A typical prescription for a 75kg patient requiring CRRT for an AKI would be as follows Anticoagulation: · Unfractionated Heparin: 5,000 IU bolus followed by a pre-filter infusion at 500 IU.hr.-1  Aim to anticoagulate filter but ensure APTT<2 Fluid balance over 24 hours: · Aim for an even balance if the patient is euvolaemic · Aim for the appropriate negative balance if the patient is fluid overloaded (<1500ml/24hrs
  • 47.  Type of Replacement fluid/Dialysate: · Use solutions without potassium if serum potassium is high but switch to potassium containing solutions as serum potassium normalises.  Use a bicarbonate-based buffer rather than a lactate-based buffer if there are concerns about lactate metabolism or if serum lactate>8mmol.l. Exchange rate/treatment dose: · 1500ml.hr.-1 (75kg x 20ml.kg.-1hr-1)
  • 48.
  • 49.
  • 50. COMPLICATIONS  Complications related to the HD catheter  DDS  Haemodynamic instability  Air emboli  Platelet consumption  Blood loss  Electrolyte imbalances  Hypothermia  Effects of anticoagulation