Downloaded 194 times
Uploaded bySteve Mathieu
RRT
This document provides an overview of renal replacement therapies used in critical care settings. It discusses some of the key questions around when and how to use these therapies for acute kidney injury (AKI) patients. While there is no definitive evidence that answers all the questions, the literature suggests starting renal replacement therapy early according to RIFLE criteria and aiming for a minimum dose of 35 ml/kg/hr. Choice of therapy mode (intermittent vs continuous) may not be as important as ensuring adequate dosing. Further research is still needed to fully understand how to optimize outcomes for AKI patients requiring renal replacement therapy.
More Related Content
![Continuous rrt and its role in critically ill patients [autosaved]](https://cdn.slidesharecdn.com/ss_thumbnails/continuousrrtanditsroleincriticallyillpatientsautosaved-180707065857-thumbnail.jpg?width=640&height=640&fit=bounds)
RRT
- 1. Renal Replacement Therapies inCritical Care Rosie Kalsi Regional teaching October2014
- 2. Where are we- too many questions? • What therapy should we use? • When should we start it? • What are we trying to achieve? • How much therapy is enough? • When do we stop/switch? • Can we improve outcomes? Does the literature help us?
- 3.
- 4. Renal failure ofany cause Many physiologic derangements: • Homeostasis of water and electrolytes as the excretion of the daily metabolic load of fixed hydrogen ions is no longer possible. • Toxic end-products of nitrogen metabolism (urea, creatinine, uric acid, among others) accumulate in blood and tissue. • Endocrine organ dysfunction and failing production of erythropoietin and 1,25 dihydroxycholecalciferol (calcitriol).
- 5. Evaluating ARF Severity ofARF/AKI should not be estimated from measurements of blood urea or creatinine alone . Cockcroft & Gault equation or MDRD eGFR or reciprocal creatinine plots should not be used when the GFR is <30 mL/min or to determine the need for acute RRT.
- 6. AKI classification systems1: RIFLE Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the second International Consensus Conference of the Acute Dialysis Initiative (ADQI) group. Crit Care 2004; 8: R204–R212.
- 7. AKI classification systems2: AKIN Stage Creatinine criteria Urine output criteria 1 1.5 - 2 x baseline (or rise > 26.4 mmol/L) < 0.5 ml/kg/hour for > 6 hours 2 >2 - 3 x baseline < 0.5 ml/kg/hour for > 12 hours 3 > 3 x baseline (or > 354 mmol/L with acute rise > 44 mmol/L) < 0.3 ml/kg/hour for 24 hours or anuria for 12 hours Patients receiving RRT are Stage 3 regardless of creatinine or urine output Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
- 8. The ‘evolving’ evidencesays… • Early initiation of RRT and utilization of RIFLE criteria. Minimal dose 35ml/kg/hr (ie for 70kg person 2450ml/hr exchange)(1) • But results of RENAL and ATN suggest 25mg/kg/hr • Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int 2012;2(Suppl):S1-138. (1)Effects of different doses in CVVH on outcomes of ARF – C. Ronco M.D., R. Bellomo M.D. Lancet 2000; 356:26-30
- 9. Proposed Indications forRRT • Oliguria < 200ml/12 hours • Anuria < 50 ml/12 hours • Hyperkalaemia > 6.5 mmol/L • Severe acidaemia pH < 7.0 • Uraemia > 30 mmol/L • Uraemic complications (pericarditis, nausea, vomiting, poor appetite, hemorrhage, lethargy, malaise, somnolence, stupor, coma, delirium, asterixis, tremor, seizures) • Dysnatraemias > 155 or < 120 mmol/L • Hyper/(hypo)thermia • Drug overdose with dialysable drug • Refractory hypertension Lameire, N et al. Lancet 2005; 365: 417-430
- 10. “Non-renal” indications • Substanceswith higher degrees of protein binding and is sometimes substances with very long plasma half-lives. • In general, the size of the molecule and the degree of protein binding determines the degree to which the substance can be removed (smaller, nonprotein bound substances are easiest to remove). • Techniques such as sorbent hemoperfusion may also be used. • These substances include drugs, poisons, contrast agents, and cytokines.
- 11. Acute Kidney Injuryin the ICU • AKI is common: 3-35%* of admissions • AKI is associated with increased mortality • “Minor” rises in Cr associated with worse outcome • AKI developing after ICU admission (late) is associated with worse outcome than AKI at admission (APACHE underestimates ROD) • AKI requiring RRT occurs in about 4-5% of ICU admissions and is associated with worst mortality risk ** * Brivet, FG et al. Crit Care Med 1996; 24: 192-198 ** Metnitz, PG et al. Crit Care Med 2002; 30: 2051-2058
- 12. Mortality by AKISeverity (1) Clermont, G et al. Kidney International 2002; 62: 986-996
- 13. Mortality by AKISeverity (2) Bagshaw, S et al. Am J Kidney Dis 2006; 48: 402-409
- 14. CRRT Treatment Goals •The concept behind CRRT is to dialyse patients in a more physiologic way, slowly, over 24 hours, just like the kidney • Tolerated well by hemodynamically unstable patients • Maintain fluid, electrolyte, acid/base balance • Prevent further damage to kidney tissue • Promote healing and total renal recovery • Allow other supportive measures; nutritional support
- 15. Determinants of Outcome •Initiation of Therapy – Ronco Study (2000) – Gettings Study (2000) – ADQI Consensus Initiative - Rifle Criteria (2004) • Dose – Ronco Study (2000) – Kellum Meta-Analysis (2002) – Saudan Study (2006) – RENAL and ATN studies (2007) – IVOIRE (2013)
- 16. RRT for AcuteRenal Failure • Newer evidence from RENAL and ATN trials suggest no difference between higher therapy CRRT dose and better outcome • There is no definitive evidence for superiority of one therapy over another, and wide practice variation exists • Accepted indications for RTT vary • No definitive evidence on timing of RRT
- 17. Therapy Dose inCVVH 25 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr Ronco, C et al. Lancet 2000; 355: 26-30
- 18. ATN (2007) large numbers mixed RRT 20vs 35ml/kg/hr 60 days
- 19. RENAL (2007) Large numbers 20vs 40ml/kg/hr CVVHDF 90 days
- 20. Outcome with IRRTvs CRRT (1) • Trial quality low: many non- randomized • Therapy dosing variable • Illness severity variable or details missing • Small numbers • Uncontrolled technique, membrane • Definitive trial would require 660 patients in each arm! • Unvalidated instrument for sensitivity analysis Kellum, J et al. Intensive Care Med 2002; 28: 29-37 “there is insufficient evidence to establish whether CRRT is associated with improved survival in critically ill patients with ARF when compared with IRRT”
- 21. Outcome with IRRTvs CRRT (2) Tonelli, M et al. Am J Kidney Dis 2002; 40: 875-885 • No mortality difference between therapies • No renal recovery difference between therapies • Unselected patient populations • Majority of studies were unpublished
- 22. Outcome with IRRTvs CRRT (3) Vinsonneau, S et al. Lancet 2006; 368: 379-385
- 23. Outcome with highvs low dose CRRT (1) Min Jun et al. Intensities of Renal Replacement Therapy in Acute Kidney Injury: A Systematic Review and Meta- Analysis. Clin J Am Soc Nephrol. Jun 2010; 5(6): 956–963.
- 24. Outcome with highvs low dose CRRT (2)
- 25. Implications of theavailable data ARF is not an innocent bystander in ICU We must ensure adequate dosing of RRT Choice of RRT mode may not be critical Septic ARF may be a different beast We must strive to avert acute renal failure
- 26. The Ideal RenalReplacement Therapy • Allows control of intra/extravascular volume • Corrects acid-base disturbances • Corrects uraemia & effectively clears “toxins” • Promotes renal recovery • Improves survival • Is free of complications • Clears drugs effectively (?)
- 27. Intermittent Therapies -PROS (Relatively) Inexpensive Flexible timing allows for mobility/transport Rapid correction of fluid overload Rapid removal of dialyzable drugs Rapid correction of acidosis & electrolyte abnormality Minimises anticoagulant exposure
- 28. Intermittent Therapies -CONS Hypotension 30-60% Cerebral oedema Limited therapy duration Renal injury & ischaemia Gut/coronary ischaemia
- 29. Intradialytic Hypotension: RiskFactors • LVH with diastolic dysfunction or LV systolic dysfunction / CHF • Valvular heart disease • Pericardial disease • Poor nutritional status / hypoalbuminaemia • Uraemic neuropathy or autonomic dysfunction • Severe anaemia • High volume ultrafiltration requirements • Predialysis SBP of <100 mm Hg • Age 65 years + • Pressor requirement
- 30. Managing Intra-dialytic Hypotension •Dialysate temperature modelling • Low temperature dialysate • Dialysate sodium profiling • Hypertonic Na at start decreasing to 135 by end • Prevents plasma volume decrease • Midodrine if not on pressors • UF profiling • Colloid/crystalloid boluses • Sertraline (longer term HD) 2005 National Kidney Foundation K/DOQI GUIDELINES
- 31. Continuous Therapies -PROS Haemodynamic stability => ?? better renal recovery Stable and predictable volume control Stable and predictable control of chemistry Stable intracranial pressure Disease modification by cytokine removal (CVVH)?
- 32. Continuous Therapies -CONS Anticoagulation requirements Higher potential for filter clotting Expense – fluids etc. Immobility & Transport issues Increased bleeding risk High heparin exposure
- 33. Comparison of IHDand CVVH John, S & Eckardt K-U. Seminars in Dialysis 2006; 19: 455-464
- 34.
- 35. Continuous Renal Replacement Therapy(CRRT) ““Any extracorporeal blood purification therapy intended to substitute for impaired renal function over an extended period of time and applied for or aimed at being applied for 24 hours/day.” Bellomo R., Ronco C., Mehta R, Nomenclature for Continuous Renal Replacement Therapies, AJKD, Vol 28, No. 5, Suppl 3, Nov 1996
- 36. Anatomy of aHaemofilter • 4 External ports – blood and dialysis fluid • Potting material – support structure • Hollow fibers – Semi-permeable membrane • Outer casing
- 37. Semi-permeable Membranes • Semi-permeablemembranes are the basis of all blood purification therapies. • They allow water and some solutes to pass through the membrane, while cellular components and other solutes remain behind. • The water and solutes that pass through the membrane are called ultrafiltrate. • The membrane and its housing are referred to as the filter.
- 38. RRT Molecular TransportMechanisms • Ultrafiltration • Diffusion • Convection • Adsorption Fluid Transport Solute Transport }
- 39. Ultrafiltration • Ultrafiltration isthe passage of fluid through a membrane under a pressure gradient. • Pressures that drive ultrafiltration can be positive, that is the pressure pushes fluid through the filter. • They can also be negative, there may be suction applied that pulls the fluid to the other side of the filter. • Also osmotic pressure from non-permeable solutes. • The rate of UF will depend upon the pressures applied to the filter and on the rate at which the blood passes through the filter. • Higher pressures and faster flows increase the rate of ultrafiltration. • Lower pressures and slower flows decrease the rate of ultrafiltration.
- 40. Blood Out Blood Intowaste (to patient) (From patient) HIGH PRESSLOW PRESS Fluid Volume Reduction Ultrafiltration
- 41. Diffusion • Diffusion isthe movement of a solute across a membrane via a concentration gradient. • For diffusion to occur, another fluid must flow on the opposite side of the semi-permeable membrane. In blood purification this fluid is called dialysate. • Solutes always diffuse across a membrane from an area of higher concentration to an area of lower concentration until equilibration.
- 42. Haemodialysis: Diffusion Dialysate In DialysateOut (to waste) Blood Out Blood In (to patient) (from patient) HIGH CONCLOW CONC
- 43. Convection • Convection isthe movement of solutes through a membrane by the force of water (“solvent drag”). • Convection is able to move very large molecules if the flow of fluid through the membrane is fast enough. • In CRRT this property is maximized by using replacement fluids. • Replacement fluids are crystalloid fluids administered at a fast rate just before or just after the blood enters the filter.
- 44. to waste HIGH PRESSLOWPRESS Repl. Solution Haemofiltration: Convection Blood Out Blood In (to patient) (from patient)
- 45. Adsorption • Adsorption isthe removal of solutes from the blood because they cling to the membrane. • In blood purification. High levels of solute/molecule adsorption can cause filters to clog and become ineffective.
- 46. Adsorption • Molecular adherenceto the surface or interior of the membrane.
- 47. Molecular WeightsDaltons InflammatoryMediators (1,200-40,000) “small” “middle” “large”
- 48. Kinetic Modelling ofSolute Clearance CVVH (predilution) Daily IHD SLED Urea TAC (mg/ml) 40.3 64.6 43.4 Urea EKR (ml/min) 33.8 21.1 31.3 Inulin TAC (mg/L) 25.4 55.5 99.4 Inulin EKR (ml/min) 11.8 5.4 3.0 b2 microglobulin TAC (mg/L) 9.4 24.2 40.3 b2 microglobulin EKR (ml/min) 18.2 7.0 4.2 TAC = time-averaged concentration (from area under concentration-time curve) EKR = equivalent renal clearance Inulin represents middle molecule and b2 microglobulin large molecule. CVVH has marked effects on middle and large molecule clearance not seen with IHD/SLED SLED and CVVH have equivalent small molecule clearance Daily IHD has acceptable small molecule clearance Liao, Z et al. Artificial Organs 2003; 27: 802-807
- 49.
- 50. Uraemia Control Liao, Zet al. Artificial Organs 2003; 27: 802-807
- 51. Large molecule clearance Liao,Z et al. Artificial Organs 2003; 27: 802-807
- 52. Major Renal ReplacementTechniques Intermittent ContinuousHybrid IHD Intermittent haemodialysis IUF Isolated Ultrafiltration SLEDD Sustained (or slow) low efficiency daily dialysis SLEDD-F Sustained (or slow) low efficiency daily dialysis with filtration CVVH Continuous veno-venous haemofiltration CVVHD Continuous veno-venous haemodialysis CVVHDF Continuous veno-venous haemodiafiltration SCUF Slow continuous ultrafiltration
- 53. CRRT Modes ofTherapy • SCUF - Slow Continuous Ultrafiltration • CVVH - Continuous Veno-Venous Hemofiltration • CVVHD - Continuous Veno-Venous HemoDialysis • CVVHDF - Continuous Veno-Venous HemoDiaFiltration
- 54. Vascular Access andthe Extracorporeal Circuit • There are two options for vascular access for CRRT, venovenous and arteriovenous. • Venovenous access is by far the most commonly used in the modern ICU.
- 55. Electrolytes & pHBalance • Another primary goal for CRRT, specifically: – Sodium – Potassium – Calcium – Glucose – Phosphate – Bicarbonate or lactate buffer • Dialysate and replacement solutions are used in CRRT to attain this goal.
- 56. Dialysate Solutions • Dialysateis a crystalloid solution containing various amounts of electrolytes, glucose, buffers and other solutes. • Flows counter-current to blood flow between 600 – 1800mL/hour • Remains separated by a semi-permeable membrane • Drives diffusive transport – dependent on concentration gradient and flow rate • Facilitates removal of small solutes • Contains physiologic electrolyte levels • Components adjusted to meet patient needs
- 57. Replacement Solutions • Infuseddirectly into the blood at points along the blood pathway • Replacement fluids are used to increase the amount of convective solute removal in CRRT • Facilitates the removal of small middle and large solutes • Contains electrolytes at physiological levels • Important to understand that despite their name, Replacement fluids do not replace anything.
- 58. Effluent Flow Rate Effluent= Total Fluid Volume: • Patient Fluid Removal • Dialysate Flow • Replacement Flow • Pre-Blood Pump Flow
- 59. Anticoagulation & CRRT •Anticoagulation is needed as the clotting cascades are activated when the blood touches the non-endothelial surfaces of the tubing and filter. • CRRT can be run without anticoagulation
- 60. SCUF Slow Continuous Ultra-Filtration Primarytherapeutic goal: – Safe and effective management of fluid removal from the patient • No dialysate or replacement fluid is used • Primary indication is fluid overload without uremia or significant electrolyte imbalance. • Removes water from the bloodstream through ultrafiltration. • The amount of fluid in the effluent bag is the same as the amount removed from the patient. • Fluid removal rates are typically closer to 100-300 mL/hour.
- 61. SCUF • High fluxmembranes • Up to 24 hrs per day • Objective VOLUME control • Not suitable for solute clearance • Blood flow 50-200 ml/min • UF rate 2-8 ml/min
- 62. SCUF Slow Continuous UltraFiltration Effluent Pump Infusionor Anticoagulant Blood Pump PBP Pump Effluent Access Return
- 63. CVVH Continuous VV Hemofiltration •Primary Therapeutic Goal: - Removal of small, middle and large sized solutes - Safe fluid volume management • Blood is run through the filter with a replacement fluid added either before or after the filter. • No dialysate is used. • Extremely effective method of solute removal and is indicated for uremia or severe pH or electrolyte imbalance with or without fluid overload. • Removes solutes via convection, and is particularly good at removal of large molecules. • Ideal in severe renal impairment combined with a need to maintain or increase fluid volume status. • The amount of fluid in the effluent bag is equal to the amount of fluid removed from the patient plus the volume of replacement fluids administered.
- 64. CA/VVH • Extended durationup to weeks • High flux membranes • Mainly convective clearance • UF > volume control amount • Excess UF replaced • Replacement pre- or post-filter • Blood flow 50-200 ml/min • UF rate 10-60 ml/min
- 65. CVVH Continuous VV Hemofiltration Effluent Pump Blood Pump Effluent Access Return Replacement Pump1 Replacement Pump 2 Replacement 1Replacement 2 Infusion or Anticoagulant PBP Pump
- 66. Pre-Dilution Replacement Solution •Decreases risk of clotting • Higher UF capabilities • Decreases Hct Hemofilter Effluent Pump Blood Pump PBP Pump Effluent Access Return Replacement Pump Replacement Fluid Infusion or Anticoagulant
- 67. Post-Dilution Replacement Solution •Consider lowering replacement rates (filtration %) • Higher BFR (filtration %) • Higher anticoagulation • More efficient clearance (>15%) Hemofilter Effluent Pump Blood Pump Effluent Access Return Replacement Pump Replacement Fluid Replacement Pump Replacement Fluid PBP Pump Infusion or Anticoagulant
- 68. CVVHD Continuous VV HemoDialysis •Primary therapeutic goal: – Small solute removal by diffusion – Safe fluid volume management • Dialysate is run on the opposite side of the filter, no replacement fluid is used. • Similar to traditional hemodialysis, and is effective for removal of small to medium sized molecules. • Solute removal due to diffusion • Dialysate can be tailored to promote diffusion of specific molecules. • CVVHD can be configured to allow a positive or zero fluid balance, it is more difficult than with CVVH because the rate of solute removal is dependent upon the rate of fluid removal from the patient. • The amount of fluid in the effluent bag is equal to the amount of fluid removed from the patient plus the dialysate.
- 69. CA/VVHD • Mid/high fluxmembranes • Extended period up to weeks • Diffusive solute clearance • Countercurrent dialysate • UF for volume control • Blood flow 50-200 ml/min • UF rate 1-8 ml/min • Dialysate flow 15-60 ml/min
- 70.
- 71. CVVHDF Continuous VV HemoDiaFiltration •Primary therapeutic goal: – Solute removal by diffusion and convection – Safe fluid volume management – Efficient removal of small, middle and large molecules • Dialysate and replacement fluid either before or after the filter. • Combines the benefits of diffusion and convection for solute removal. • The amount of fluid in the effluent bag equals the fluid removed from the patient plus the dialysate and the replacement fluid.
- 72. CVVHDF • High fluxmembranes • Extended period up to weeks • Diffusive & convective solute clearance • Countercurrent dialysate • UF exceeds volume control • Replacement fluid as required • Blood flow 50-200 ml/min • UF rate 10-60 ml/min • Dialysate flow 15-30 ml/min • Replacement 10-30 ml/min
- 73.
- 74. SLED(D) & SLED(D)-F: Hybrid therapy • Conventional dialysis equipment • Online dialysis fluid preparation • Excellent small molecule detoxification • Cardiovascular stability as good as CRRT • Reduced anticoagulation requirement • 11 hrs SLED comparable to 23 hrs CVVH • Decreased costs compared to CRRT • Phosphate supplementation required Fliser, T & Kielstein JT. Nature Clin Practice Neph 2006; 2: 32-39 Berbece, AN & Richardson, RMA. Kidney International 2006; 70: 963-968
- 75. Complications of CRRT •Bleeding • Hypothermia • Electrolyte Imbalances • Acid-Base Imbalances • Infection • Appropriate Dosing of Medications
- 76. CRRT, Haemodynamics &Outcome • 114 unstable (pressors or MAP < 60) patients • 55 stable (no pressors or MAP > 60) patients • Responders = 20% fall in NA requirement or 20% rise in MAP (without change in NA) • Overall responder mortality 30%, non-responder mortality 74.7% (p < 0.001) • In unstable patients responder mortality 30% vs non-responder mortality 87% (p < 0.001) • Haemodynamic improvement after 24 hours CRRT is a strong predictor of outcome Herrera-Gutierrez, ME et al. ASAIO Journal 2006; 52: 670-676
- 77. Common Antibiotics andCRRT These effects will be even more dramatic with HVHF Honore, PM et al. Int J Artif Organs 2006; 29: 649-659
- 78. Beyond renal replacement… RRTas blood purification therapy
- 79. Extracorporeal Blood PurificationTherapy (EBT) Intermittent Continuous TPE Therapeutic plasma exchange HVHF High volume haemofiltration UHVHF Ultra-high volume haemofiltration PHVHF Pulsed high volume haemofiltration CPFA Coupled plasma filtration and adsorption
- 80. Peak Concentration Hypothesis •Removes cytokines from blood compartment during pro-inflammatory phase of sepsis • Assumes blood cytokine level needs to fall • Assumes reduced “free” cytokine levels leads to decreased tissue effects and organ failure • Favours therapy such as HVHF, UHVHF, CPFA • But tissue/interstitial cytokine levels unknown Ronco, C & Bellomo, R. Artificial Organs 2003; 27: 792-801
- 81. Threshold Immunomodulation Hypothesis •More dynamic view of cytokine system • Mediators and pro-mediators removed from blood to alter tissue cytokine levels but blood level does not need to fall • ? pro-inflammatory processes halted when cytokines fall to “threshold” level • We don’t know when such a point is reached Honore, PM & Matson, JR. Critical Care Medicine 2004; 32: 896-897
- 82. Mediator Delivery Hypothesis •HVHF with high incoming fluid volumes (3-6 L/hour) increases lymph flow 20-40 times • “Drag” of mediators and cytokines with lymph • Pulls cytokines from tissues to blood for removal and tissue levels fall • High fluid exchange is key Di Carlo, JV & Alexander, SR. Int J Artif Organs 2005; 28: 777-786
- 83. High Volume Haemofiltration •May reduce unbound fraction of cytokines • Removes – endothelin-I (causes early pulm hypertension in sepsis) – endogenous cannabinoids (vasoplegic in sepsis) – myodepressant factor – PAI-I so may eventually reduce DIC • Reduces post-sepsis immunoparalysis (CARS) • Reduces inflammatory cell apoptosis • Human trials probably using too low a dose (40 ml/kg/hour vs 100+ ml/kg/hour in animals)
- 84. High-volume versus standard-volume haemofiltrationfor septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial Intensive Care Med. 2013 Sep;39(9):1535-46. No evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI
- 85. Towards Targeted Therapy Honore,PM et al. Int J Artif Organs 206; 29: 649-659 Non-septic ARF Septic ARF Cathecholamine resistant septic shock Daily IHD Daily SLEDD CVVHD/F ? dose CVVH > 35ml/kg/hour ? 50-70 ml/kg/hour CVVH @ 35ml/kg/hour Daily IHD? Daily SLEDD? HVHF 60-120 ml/kg/hour for 96 hours PHVHF 60-120 ml/kg/hour for 6-8 hours then CVVH > 35 ml/kg/hour EBT Cerebral oedema