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Acute Renal Failure in Surgical Patients by sammyc2007

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									   Acute Renal Failure in
     Surgical Patients
Division of Critical Care Nephrology
     Department of Nephrology
  Chang Gung Memorial Hospital
        腎臟科系 加護腎臟科
            Approach to Patients with ARF
Basic patient data
History taking
Physical examination
Laboratory studies
Renal Imaging
Kidney biopsy
Impression: Acute Renal Failure (Syndrome Diagnosis)
              Oliguria, or Non-oliguria
              Pre-renal ARF or Renal ARF or Post-renal ARF
              Underlying disease
Plan: 1) Diagnostic plans
      2) Therapeutic plans
      3) Patient’s education
                    Steps involved in renal function

1) Blood from the                                        4) Final
renal arteries is                                        tubular
delivered to the                                         fluid -
glomeruli                                                Urine -
                                                         the kidney,
2) Glomeruli
                                                         into the
form an ultra-
filtrate which
flows into the
                                                         bladder and
renal tubules
                                                         excreted via
                    3) Tubules reabsorb/secrete solute   the
                    and water from ultrafiltrate         urethra
                   Acute Renal Failure

Pre Renal Causes         Intrinsic causes        Post Renal Causes

 Tubular                Interstitial          Acute
 necrosis                nephritis       glomerulonephritis
                        (10% of cases)         (5% of cases)

 Ischemia           Toxins
 (50% of cases)    (35% of cases)
    Causes of renal hypoperfusion associated with
            ARF (Prerenal azotemia) (I)
1. Intravascular volume depletion (hypovolemia)
   Major trauma, burns, crush syndrome, hemorrhage, dehydration
   GI fluid loss: vomiting, surgical drainage, diarrhea
   Renal fluid loss: diuretics, osmotic diuresis, adrenal insufficiency
   Sequestration of fluid in extravascular space: pancreatitis, peritonitis,
2. Decreased cardiac output (low cardiac output)
   Severe congestive heart failure or low cardiac output syndrome:
   myocardial failure, valvular or pericardial disease, including arrhythmias
   and tamponade
   Pulmonary hypertension, massive pulmonary embolism
   Positive pressure mechanical ventilation
   Causes of renal hypoperfusion associated with
           ARF (Prerenal azotemia) (II)
3. Increased renal /systemic vascular resistance ratio
  Systemic vasodilatation: sepsis, antihypertensive agents, afterload
   reducers, anesthesia, anaphylaxis
   Renal vasoconstriction: hypercalcemia, norepinephrine, epinephrine,
   cyclosporin, amphotericin B
   Liver cirrhosis with ascites
4. Increased blood viscosity (hyperviscosity syndrome)
   Multiple myeloma, macroglobulinemia, polycythemia
5. Renal hypoperfusion with impairment of renal autoregulatory responses
  Cyclooxygenase inhibitors, angiotensin-converting enzyme inhibitors
         Renal causes of acute renal failure
          (Intrinsic acute renal failure) (I)
1. Acute tubular necrosis
   Ischemia: as for prerenal azotemia, obstetrical complication
  (abruptio plancentae, postpartum hemorrhage)
   Nephrotoxic damage: contrast media, antibiotics (e.g.
  aminoglycosides, amphotericin B), cyclosporine, chemotherapeutic
   agents( e.g. cisplatin), organic solvents (e.g. ethylene glycol),
   heavy mental, snake venom, mushrooms
   Pigment nephropathy: myoglobin, hemoglobin
   Tumor-specific syndrome: plasma cell dyscrasia, tumor lysis
             Renal causes of acute renal failure
             (Intrinsic acute renal failure) (II)
2. Disease of glomeruli or renal microvasculature
   Glomerulonephritis and vasculitis
   Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura,
   disseminated intravascular coagulation, toxemia of pregnancy,
   accelerated hypertension, radiation nephritis, scleroderma, systemic
   lupus erythematosus
3. Interstitial nephritis
   Allergic: antibiotics (e.g. beta-lactams, sulfonamides, trimethoprime,
             rifampicin), cyclooxygenase inhibitors, diuretics, captopril
   Infection: bacterial (e.g. acute pyelonephritis, leptospirosis), viral (e.g. CMV),
   Infiltration: lymphoma, leukemia, sarcoidosis
         Renal causes of acute renal failure
         (Intrinsic acute renal failure) (III)
4. Renovascular obstruction
   Renal artery: artherosclerosis, embolism, thrombosis, dissecting
   Renal vein: thrombosis, compression
5. Intratubular deposition and obstruction
    myeloma proteins, uric acid, oxalate, acyclovir, methotrexate
 Postrenal causes of acute renal failure
1. Obstruction of ureters
      Tumor: cervix, prostate, endometriosis, metastatic cancer
      Periureteral fibrosis (retroperitoneal fibrosis)
      Accidental ureteral ligation during operation
      Stone, blood clots, pyogenic debris, papillary necrosis
2. Bladder neck obstruction
   Neurogenic bladder, bladder carcinoma, prostate hyperplasia, calculi
3. Urethral obstruction
   Stricture, phimosis, congenital valve, tumor, trauma
                        Ischemic Acute Renal Failure
                    Intravascular volume depletion and hypotension
               Gastrointestinal, renal, dermal losses, hemorrhage, shock

Decreased effective                                              Large vessel renal vascular disease:
intravascular volume: CHF,                                       Renal artery thrombosis or embolism,
cirrhosis, nephrosis, peritonitis                                operative arterial cross clamping, renal
                                                                 artery stenosis
  Medications: ACE                   or localized reduction in
  inhibitors, NSAIDS,                    renal blood flow
  radiocontrast agents,                                            Small vessel renal vascular disease:
  Ampho B, Cyclosporin                                             Atheroembolism, vasculitis, malignant
                                                                   hypertension, hypercalcemia,
                                                                   transplant rejection
              Hepatorenal syndrome

                                      Acute Renal Failure
               Pathophysiology of
              acute tubular necrosis
1. Initiation phase                   3.Diuretic phase
   * Tubular epithelial cell injury      * Restoration of tubular epithelial
   * Vasoconstriction                      cell integrit
2. Maintenance phase                  4.Recovery phase
   * Tubular obstruction
                                         * Vasodilatation
   * Passive back leakage of
                                         * Nephron recruitment
   * Decreased renal blood flow
   * Decreased ultrafiltration
   * Impairment of medullary
        Pathophysiology of Intrinsic ARF
Afferent and efferent
arteriolar vaso-

                                  Tubular cell necrosis or
        Obstruction from intra    swelling
        luminal cellular debris
            Clinical risk factors for
         aminoglycoside nephrotoxicity
Factors not readily modifiable clinically
Age, Sex, Obesity, Preexisting liver disease, Preexisting chronic
renal insufficiency, Renal hypoperfusion, Sepsis
Factors potentially modifiable clinically
Daily drug dose, drug interval, duration of therapy
Specific aminoglycoside, Volume depletion
Hypokalemia, Hypomagnesemia
Metabolic acidosis
Concurrent drug therapy: Amphotericin B, Cephalothin,
Vancomycin, Cisplatin, Furosemide, Calcium channel blockers,
Radiocontrast agents
 Risk factors for NSAID-induced acute
               renal failure
Decreased effective arterial blood volume
Congestive heart failure, cirrhosis, nephrotic
syndrome, sepsis, hemorrhage, diuretic therapy,
postoperative patients with third space fluid, volume
Normal or increased effective arterial blood volume
Chronic renal failure, glomerulonephritis, elderly,
contrast-induced nephropathy, obstructive uropathy,
cyclosporin A
       Effects of NSAIDS and ACE inhibitors on
            glomerular hydrostatic pressure
Prostaglandins cause
afferent vasodilation                Locally produced AII causes
                                     efferent vasoconstriction

                                      Blocked by ACE
  Blocked by                          inhibitors
   Risk factors for development of
  radiocontrast agent-induced ARF
Age, renal insufficiency, diabetes mellitus, anemia,
proteinuria, abnormal liver function, volume
depletion, dehydration, hyperuricemia,
concomitant exposure to other nephrotoxins,
repeated exposure to radiocontrast, volume of
contrast, cardiovascular disease, hypertension,
renal transplantation
   Potential pathogenetic effects of
  radiocontrast agents on the kidney
Physiologic effects of an osmotic load:
Osmotic diuresis, vasopressin release, tubular
Intraluminal obstruction
Intrarenal vasoconstriction
Impaired microcirculation
Decreased systemic oxygenation
Direct tubular toxicity
Additional effects: allergic reactions, proteinuria
    Causes of Acute Renal Failure in 2216
Consecutive Medical and Surgical Admissions
Acute tubular necrosis:
      Hypovolaemia                       22
      Congestive cardiac failure         10
      Sepsis                             10
      Nephrotoxins                       25
      Postsurgical                       23
      Other                              12
Hepatorenal syndrome                     5
Obstruction                              3
Vasculitis                               2
Other/multifactorial/unknown             17
                                   Total 129(4.9% of admissions)
       Acute Renal Failure in Intensive Care Units
* High Mortality
* Mortality relates to severity of underlying condition
* Acute renal failure occurs as part of a complex of multiple organ
   failure caused by infection, sepsis, hypotension, hypovolemia and
   drug therapy
* Fluid overload causes pulmonary edema
* Increase in interstitial water with "leaky capillary" leading to
   impaired tissue perfusion
* Acid-base and electrolyte abnormalities
* Disseminated intravascular coagulation
* Toxic metabolites and drug accumulation
* Frequently hemodynamic unstable
* Required positive pressure ventilation
  Symptoms and signs of acute renal failure
1. Retention of nitrogenous waste products
    Nausea, vomiting, diarrhea, hiccough, foul taste, dry
    crusted mouth, itching, drowsiness, clouding of
    consciousness, neuropathy, pericarditis, GI bleeding, coma
2. Retention of salt and water
  Pulmonary edema, peripheral edema, ascites, pleural effusion
3. Retention of potassium
   Weakness, lassitude, paralysis, EKG changes with tenting T
   waves, widening of QRS complex, increased PR interval, sine
   wave pattern, cardiac arrest, VT
4. Retention of acid
  Kussmaul respiration, hyperreflexia, hypotension
Chronic history:
 Nocturia, polyuria, edema or hematuria
 Pruritus or other uremic symptoms (neuropathy)
 Underlying predisposing illness (e.g. hypertension, DM)
 Symptoms of anemia
Record of potential nephrotoxins (exogenous, endogenous)
History of fluid loss
 GI loss (vomiting, diarrhea, NG tubing, biliary drainage)
 Drainage of any fluid (third space)
 Renal (osmotic or non-osmotic diuresis, diuretic use)
 Skin (excessive sweating or burns)
Thirst, drynes of mucosa, oliguria
Fluid balance of I/O or weight loss/gain
               Physical examination
 Signs of volume depletion:
   Poor skin turgor – tenting of sternal skin when pinched
   Dry skin (axillary) and mucosa
   Decreased temperature of extremities
   Decreased intraocular pressure
   Postural signs: decreased BP (>10 mmHg), increased PR (>10/min)
   Body with and I/O records
Signs of volume excess:
  Gallop (S3), cardiomegaly
  Jugular vein distention
  Pulmonary congestion
  Liver congestion
  Peripheral edema; Third spacing (ascites, pleural effusion)
History and physical with special attention to
–   Last known serum creatinine
–   History of volume loss
–   Urine output
–   Changes in urine color
–   New medications
–   Over the counter medications
–   Presence of fever
–   Skin rash
–   Arthralgia
–   Radiocontrast studies
–   Preoperative and postoperative blood pressures
–   Intraoperative changes in blood pressures
           Urinary diagnostic indices
                                   Favor prerenal        Favors ATN

Urine osmolarity (mOsm/kg/H2O)             >500          <350
Urine sodium (mEq/L)                       < 20          >40
U/P creatinine ratio                       >40           <20
Renal failure index                        <1            >1
FE Na                                      < 1%          > 1%

Send blood and spot urine for BUN, Cr, Na, and osmolarity
Renal failure index: UNa / (U/P) Cr
Fraction excretion of sodium (FENa) = (U/P)Na / (U/P)Cr X 100%
       Blood tests in acute renal failure

•   Uric acid, creatine kinase or myoglobin levels
•   IgG, IgM, IgE, IgA
•   ANA, antids-DNA, C3, C4
•   ASLO
•   ANCA
•   anti-GBM Ab
•   Protein electrophoresis, immune electrophoresis
•   Peripheral blood smear
•    prostate-specific antigen
       Blood tests for suggestion of
          underlying disease (I)
• Elevated uric acid level: suggestive of malignancy or
  tumor lysis syndrome leading to uric acid crystals;
  also seen in prerenal acute renal failure
• Elevated creatine kinase or myoglobin levels:
• Elevated prostate-specific antigen: Prostate cancer
• Abnormal serum protein electrophoresis: Multiple
        Blood tests for suggestion of
           underlying disease (II)
• Low complement levels: Systemic lupus erythematosus,
  postinfectious glomerulonephritis, subacute bacterial
  endocarditis, shunt nephritis, cryoglobinemic GN,
• Positive antineutrophilic cytoplasmic antibody (ANCA):
  Small-vessel vasculitis (Wegener's granulomatosis or
  polyarteritis nodosa)
• Positive antinuclear antibody or antibody to double-
  stranded DNA: Systemic lupus erythematosus
         Blood tests for suggestion of
           underlying disease (III)
• Positive antibody to glomerular basement
  membraneGoodpasture's syndrome
• Positive antibodies to streptolysin O, streptokinase or
  yaluronidase: Poststreptococcal glomerulonephritis
• Schistocytes on peripheral smear, decreased haptoglobin
  level, elevated lactate dehydrogenase level or elevated
  serum bilirubin level: Hemolytic uremic syndrome or
  thrombotic thrombocytopenic purpura
• Low albumin level: Liver disease or nephrotic syndrome
              Renal Imaging
Renal sonography
Retrograde or antegrade pyelogram
Renal scan
CT scan
Renal angiography
Diagnosis of the Cause of Acute Renal Failure

  Q 1: Is the renal failure really acute?
        Measurement of renal size
  Q2: Is urinary obstruction a possibility?
        Renal imaging to detect obstruction
        Relief of obstruction
  Q3: Are glomerulonephritis, interstitial nephritis, vasculitis,
      or other rarities possible?
  Q 4: Is an acute renal vascular event possible?
 Non-specialist Management of Acute Renal
 (Stevens PE et al. Q J Med 2001; 94: 533-540.)
• Key assessments to distinguish prerenal, renal, and postrenal ARF.
These including assessment of fluid status, urinalysis, and renal tract
• In total, 81/288 had all three of these key assessments,
100/288 had 2/3, 75/288 had only one, and 32/288 did not
have any.
* Long-term outcome at 36 months : 36(44%) of the 81 receiving all
three key assessments were still alive, compared with 27/100(27%)
receiving two key assessments, 14/75(19%) receiving only one, and
5/32(16%) who had none (p=0.001).
Management of acute renal failure
 1. Prevention
 2. Etiology treatment
 3. Prevention additional injury
 4. Establish diuresis
 5. Treatment of complication
 6. Conservative measurement
 7. Renal replacement therapy
Basic Medical and Nursing Care to Prevent
the Development of Acute Renal Failure

* Recording of fluid input and output
* Daily weighing
* Postural measurement of blood pressure
* Measurement of plasma urea, creatinine,
  and electrolyte concentrations
       Drug Therapy to Prevent ARF:
          Does Anything Work ?
•   Optimal volume status
•   Low dose dopamine
•   Mannitol and loop diuretics
•   Atrial natriuretic peptide (ANP)
         Volume expansion for
     prevention/attenuation of ARF

• Nephrotoxin exposure    • Crystaluric states
  Cisplatin,                Uric acid
  Radiographic contrast     Acyclovir
  material                  Methotrexat
  Amphertericin B           Sulfonamides
• Pigmenturia states      • Ischemic state
   Hemoglobinuria           Shock
  Myoglobinuria             Major surgery
                            Severe trauma
          Influence of Dopamine
         on Normal Renal Function
* Increase renal blood flow ( RBF)
   dose -response relationship:
1. 0.5 ~ 3 ug/kg/min: intrarenal vasodilation through DA-1
   subclass of dopamine receptor
2. 3 ~10 ug/kg/min: increased cardiac index through cardiac
   B1 adrenoreceptors
3. 5 ~ 20 ug/kg/min: apha1 adrenoreceptor, systemic
* Increase GFR
* Natriuresis
* Diuresis
          Low-Dose Dopamine in ARF
Source                  Type of study     Efficacy
Lindner 1983            Established ARF      yes
Graziani et al 1983     Established ARF      yes
Lumlertgul et al 1989   Established ARF      No
Weisberg et al 1993     Prophylaxis ARF      No
Duke et al 1994         Established ARF      No
Myles et al 1993        Prophylaxis          No
Wagner and Daul 1993    Prophylaxis          No
Baldwin et al 1994      prophylaxis          No
Chertow et al 1996      Established ARF      No
Perdue et al 1998       Prophylaxis          No
Ichai et al 2000        Established ARF      No
 Low-dose dopamine in patients with early renal
 dysfunction: a placebo-control randomized trial
                ( Lancet 2000; 356:22139-43)

• Multicentre, randomized, double-blind, placebo-controlled study
(328 pt; 23 ICUs, dopamine 2 ug/kg/min)
• Australian and New Zealand Intensive Care Society (ANZICS)
Clinical Trial Group
• Peak Cr, Increase Cr, ICUs stay, Hospital stay, RRT
• Conclusion: Administration of low-dose dopamine by continuous
intravenous infusion to critically ill patients at risk of renal failure
does not confer clinically significant protection from renal dysfunction
                   A Meta-analysis of
                   Dopamine in ARF
• Data Synthesis: a total of 58 studies (n = 2149).
• Outcome data reported in 24 studies (n = 1019) and 17 were
  randomized clinical trials (n = 854).
• Dopamine did not prevent
   – mortality (relative risk, 0.90 [0.44–1.83];p = .92),
   – onset of ARF (relative risk, 0.81 [0.55–1.19];p = .34),
   – need for dialysis (relative risk, 0.83 [0.55–1.24];p = .42).
• There was sufficient statistical power to exclude any large (>50%)
  effect of dopamine on the risk of acute renal failure or need for
• (Use of dopamine in acute renal failure. Crit Care Med 2001, Vol 29:1526)
              A Meta-analysis of
              Dopamine in ARF

• Conclusions: The use of low-dose dopamine for the
  treatment or prevention of acute renal failure cannot
  be justified on the basis of available evidence and
  should be eliminated from routine clinical use.
  Potentially Deleterious Effect of Dopamine
• Local extravasation of dopamine may provoke distal ischemia
  and gangrene
• Dopamine can depression respiratory drive and may increase
  cardiac output and myocardial oxygen consumption, even at
  “ renal-dose” and trigger tachyarrhythmias and myocardial
• Dopamine may induce or exacerbate hypovolemia and
  prerenal ARF through its natriuretic effect and trigger
  hypokalemia and hypophosphatemia
• Hastened gut ischemia in a porcine model of hemorrhagic
  shock due to shunting of blood away from the bowel mucosa
                      Furosemide in ARF
Study                Nature of ARF        Change in        Change in
                                          Renal function   Mortality

Hans et al 1990       Prophylaxis, contrast       No            No
Solomon et al 1994          Contrast              No            No
Nuutinen et al 1978 (P)     Surgery               No            No
Cantarovich et al 1971(p)   Established ARF       Yes           No
Cantarovich et al 1973(p)   Established ARF       No            No
Kleinknecht et al 1976 (R) Established ARF        No            No
Brown et al 1981 (P)        Posttrauma, surgery   No            No
Loop diuretics in the management of acute renal
 failure: a prospective, double-blind, placebo-
          controlled, randomized study
    ( Shilliday IR et. al:Nephrol Dial Transpl 1997; 12:2592)

 • Furosemide 3 mg/kg q6h (92 patients)
 • Renal recovery, need for dialysis, death: no
 significantly different
 * The use of loop diuretics in oliguric patients with
 ARF can result in a diuresis. There is no evidence
 that these drugs can alter outcome
                           Mannitol in ARF
Study                Nature of ARF                   Change in
                                             Renal function    Mortality

Gubern at al 1988 (P) Prophylaxis, surgery          No             No
Baird et al 1963 (R)        Surgery                 No             No
Beall 1963 (P)              Surgery                 No             No
Berman et al 1964 (P)       Surgery                 No             No
Old et al 1980 (R)          Contrast                No             No
Anto et al 1981(R)          Contrast                No             No
Weisberg et al 1994 (P)     Contrast                No             No
Van Valenberg 1987 (P)      Transplant              Yes            No
     Complication of mannitol
* Volume depletion and Hypernatremia
* Volume expansion, hyponatremia, hyperkalemia,
  metabolic acidosis
* Induction of renal failure
  High mannitol concentration >1050 mg/dl
  Osmolar gap > 60-75 mosm/kg
      Atrial Natriuretic Factor in Oliguric ARF
1. 222 patients with oliguric ARF
2. Mulitcenter, randomized, double-blind, placebo-controlled
3. 24 hour infusion of ANP (anaritide, 0.2 ug/kg/min)
4. Dialysis-free survival rate 21% ANP, 15% placebo(p=0.22)
5. D14, 64% ANP, 77% placebo undergone dialysis (p= 0.054)
6. No statistically significantly beneficial effect of ANP in dialysis-
   free survival or reduction in dialysis in patients with oliguric ARF
7. Mortality rate (D60): ANP 60%, placebo 56%
8. Decreased blood pressure in ANP group (p<0.001)
            ( Julia Lewis et al, AJKD, Vol 36, No 4, 2000)
           Etiology Treatment

•   Stop nephrotoxic drugs
•   Correct postrenal factor
•   Correct prerenal factor
•   Treat underlying sepsis and etiologies
    Prevention of Additional Injury

•   Avoid iodinated radiocontrast medium
•   Avoid NSAIDs
•   Avoid nephrotoxic agents
•   Adjusted drug dosage and interval
  Common Drugs Used with Caution in Acutely
    Ill Patients or Those with Renal Failure
Aminoglycosides          e.g. gentamicin
Amphotericin B
Cephaloridine, cephalothin
Non-steroidal anti-inflammatory agents
Angiotensin-converting enzyme (ACE) inhibitors
Electrocardiographic manifestations of hyperkalaemia

Electrocardiographic changes , as serum potassium rises the
following changes occur progressively:

* Tenting of the T wave
* Reduction in size of P waves, increase in PR interval, widening
of QRS complex
* Disappearance of P wave, further widening of QRS complex
* Irregular 'sinusnoidal' waveform
               Treatment of Hyperkalemia

1. Intravenous calcium (10 ml of 10% calcium gluconate, over 60 s,
repeated until ECG improves)
2. Intravenous insulin and glucose
3. Intravenous sodium bicarbonate
4. Cation exchange resins, e.g. sodium or calcium polystyrene
sulphonate (15 g by mouth 6-hourly or 15-30 g per rectum 6-hourly)
5. Intravenous salbutamol (0.5 mg over 15 min) or nebulized
salbutamol (10 or 20 mg) can reduce plasma potassium
concentration by a mean of about 1 mmol/l over 30 to 60 min
6. Haemodialysis/filtration
        Therapeutic Options for Bleeding in ARF
Therapy              Mechanism                       Dose/Duration
1. Dialysis          Removal of acquired             3-4X/Week
                     platelet inhibitors
                     Not universally effective
2. Correction        Improved platelet rheology      Hct >30%
   of anemia         Increased platelet ATP          EPO-30-50U/kg
                     Increased GPllbllla with EPO    3x/week
3. Estrogen          Decreased Nitric Oxide          0.6mg/kg IV qd x 5 d
                                                     50 mg/day oral
                                                     50-100 mcg transdermal
4. Cryoprecipitate   Increased large vWF multimers   10 bags immediately pre-
5. DDAVP             Increased large vWF multimers   0.3mcg/kg IV/SC q 8-12
                     From endothelium
                     Increased GPllbllla
                     Serotonin effect
  Conservative Mx in Management of ARF
• Fluid balance
• Careful monitoring of I/O and body weight
• Fluid restriction (usually less than 1 L/day in oliguric ARF)
• Total intake < urine output +extrarenal losses
• Electrolytes and acid -base balance
• Prevention and treat hyperkalemia
• Avoid hyponatremia
• Keep serum bicarbonate >15
• Minimized hyperphosphatemia
• Treat hypocalcemia only if symptomatic
• Uremia-nutrition
• Restriction protein but maintain caloric intake
• Carbohydrate at least 100gm/day to minimize ketosis and protein catabolism
• Drug:
Review all medication, Stop magnesium-containing medication
Adjusted dosage for renal failure, Readjust with improvement of GFR
      Systemic Complications of Fluid Resuscitation
* GI tract
          Fluid flux in stomach and intestine
          Gut edema and loss of protein
          Decreased motility, diarrhea
          Tissue hypoxia
* Heart
          Myocardial edema
          Decreased cardiac function
* Pulmonary edema
* Skin
          Poor wound healing
          Decreased tissue O2
* Central nervous system
          Cerebral edema
* Increased mortality
     Indications for Renal Replacement
       Therapy in Patients with ARF
• Prophylactic dialysis: BUN 80-100 mg/dl , creatinine 8-10
• Volume overloading with refractory to diuretics
• Pulmonary edema
• Hyperkalemia
• Severe metabolic acidosis
• Uremic symptoms: nausea, vomiting
• Uremic pericarditis
• Uremic bleeding tendency
• Uremic encephalopathy: coma, seizure
• Acute uric acid nephropathy
        Early vs Late
Initiation of Renal Support
               Renal Replacement Therapy for ARF
* When should dialysis be initiated? Usual practice
       based on extrapolation of strategy for ESRD
* Clinical evidence of uremia
       Diuretic resistant fluid
       CNS manifestation
       Pericarditis rub
       GI bleeding
*Biochemical evidence of solute and fluid retention
       BUN > 100 mg/dl
       Marked acidemia
               Acute Renal Failure in ICU

Initiation of Dialysis: Problems with usual practice

* Postpone dialysis as long as possible
* Encourages tendency to restrict nutrition to avoid solute
load and elevated BUN
* Promotes aggressive use of high dose combination diuretics
increasing chances for toxicity
* When dialysis is introduced a standard prescription is
usually offered based on prevailing local experiences
* No measures of dialysis delivered or adequacy
            Acute Renal Failure in ICU

                   Goals for treatment
Surgeon/Intensivist               Nephrologist
Maintain tissue O2 delivery       Fluid management
Increased cardiac output
Enhance ventilation
Maintain blood pressure           Solute control
Prevent hypermetabolism
Provide adequate nutrition
Treat primary process             Electrolyte balance
                                  Acid -Base balance
          Indication and Timing of Dialysis for ARF
            Renal Replacement v.s Renal Support
                  Renal replacement        Renal support
Purpose           Replace renal function   Support other
Timing            Based on level           Based on
of                biochemical markers      individual need

Indications       Narrow                   Broad
for dialysis
Dialysis dose     Extrapolated             Targeted for
                  from ESRD                overall support
          Early vs Late Initiation of Renal Support

Year   Researcher    Threshold to initiate dialysis   outcome

1960   Teschan              BUN<200                   Positive
1961   Parsons              BUN 120-150               Positive
1971   Kleinknetch          BUN less than 105         Positive
1975   Conger               BUN less than 50          Positive
1999   Gettings             BUN less than 60          Positive
Outcome in Post-traumatic Acute Renal Failure when
CRRT is Applied Early vs Late

* Retrospective Experience in Baltimore, Maryland
100 trauma patients with ARF and treated with CRRT 1989-1997
* Early starters, BUN < 60; Late starters, BUN >60
* Both groups dialyzed equally intensely
* Both groups demographically identical
* Survival 40% (Early starters) vs 20% (Late starters)

            (Gettings LG et al. Int care Med 1999)
Proposed Criteria for the Initiation of Renal Replacement
Therapy in Adult Critically Ill Patients
Oliguria (urine output<200 ml/12 hr)
Anuria/extreme oliguria (urine output<50 ml/12 hr)
Hyperkalemia ([K+]>6.5 mmol/liter)
Severe academia (pH<7.1)
Azotemia ([urea]>30 mmol/liter)
Clinically significant organ (especially lung) edema
Uremic encephalopathy
Uremic pericarditis
Uremic neuropathy/myopathy
Severe dysnatremia ([Na]>160 or<115 mmol/liter)
Drug overdose with dialyzable toxin

                   ( KI 1998, R. Belloma and C. Ronco)
Methods for Renal Replacement Therapy
               in ARF

 • Intermittent hemodialysis
 • Peritoneal dialysis
 • Continuous renal replacement therapy:
                Comparison of CRRT versus IHD
                                  CRRT                IHD
* Hemodynamic stability    Stable            Unstable
* Fluid removal            Slow, gentle,     Rapid, harsh,
                            complete          incomplete
* Dialysis efficiency      Low efficiency,   High efficiecy,
                             long time        short time
* Anticoagulation          Frequently        0 heparin
                            necessary        possible
* Patient mobilization     Possible          Possible
* Specialty personnel      Perhaps           Definitely
* Drug dosing/delivery     Easier            Difficult
* Volume restriction       Minimal           Significant
Continuous v.s. Intermittent
   Critically Ill Patients
 with Acute Renal Failure
            Survival data of ACHD and CD patients
           according to illness severity: percentage of
             patients surviving hospital admission
                      ACHD,%          CD,%              Significance
Apache II
 < 19                 83 (5 of 6)     71.4 (5 of 7)       n.s.
 19-29                48 (40 of 80)   28.8 (15 of 52)     p<0.025
 >29                  21 (13 of 62)   20 (5 0f 25)        n.s.
Failing organs
 <3                   80 (32 of 40)   50 (6 of 12)        p<0.05
 3 or 4               30.5 (22 of 72) 26.5 (13 of 49)     n.s.
 4 or 5               20.3 (12 of 59) 22.7 (10 of 44)     n.s.
 >5                   18.2 (2 of 11)   25 (3 of 11)       n.s.

                 (Bellomo R. et al. Nephron 1995)
              Continuous v.s. Intermittent Therapy
                            in ARF
                       CRRT                IHD         P value

N                      84                  82
APACH II score         25.3                20.6        <0.001
ICU Mortality          59.5%               41.5%       0.02
Hospital Mortality     65.5%               47.6%       0.02
ICU length of stay     15.1 days           17.9 days   NS
Hospital length of stay 18.6 days          23.2 days   NS
Renal recovery          33.3%              36.6%       NS

           ( Mehta et al. J Am Soc Nephro 1996)
Continuous vs Intermittent Therapy in
        Acute Renal Failure

         Swartz et al. Am J Kidney Dis 1999
                Mortality in ARF: IHD vs CRRT
Investigator       Type     IHD          CRRT        p
                            No    Mort   No   Mort
Mehta 1991         Retro    24    85     18   72     ns
Kierdorf 1991      Retro    73    93     73   77     <0.05
Bellomo 1992       Retro    167   70     84   59     ns
Bellomo 1993       Retro    84    70     76   45     <0.01
Kruczynski 1993    Retro    23    82     12   33     <0.01
Simpson 1993       Pros     58    82     65   70     ns
Kierdorf 1994      Pros     47    65     48   60     ns
Mehta 1996         Pros     84    41.5   84   59.5   ns
Fang 1998          Retro    90    70     50   82     ns
Sandy 1998         Retro    40    60     39   71.4   ns
Mehta 2001         Random   82    47.6   84   65.5   <0.02
   Continuous versus intermittent renal replacement
              therapy: a meta-analysis
       (Kellum JA et al: Intensive Care Med 2001; Dec. 1159)
• MEDLINE search
• 13 studies (n=1400)
• No difference in mortality rate (RR 0.93, p=0.29)
• Adjusting for study quality and severity of illness, mortality was
lower in patients treated with CRRT (RR 0.72(0.60-0.87), p<0.01)
• Conclusion: Current evidence is insufficiency to draw strong
conclusions regarding the mode of replacement therapy for acute renal
failure in the critically ill. However, the life-saving potential with
CRRT suggested in our secondary analyses warrants further
investigation by a large, randomized trial.
             Applications for CRRT
    Renal Application vs Non-renal Application

Renal Application ( Renal replacement and Renal support)
* Acute renal failure ( specifically complicated ARF with multiple
  organ failure and cardiovascular failure)
* Oligouric ARF needs large amount of fluid or nutrition
* Acute renal failure with cerebral edema
* Acute renal failure with hypercatabolism
* An alternative to HD in the mass casualty situation
* Electrolytes and acid base disturbance
          Applications for CRRT
 Renal Application vs Non-renal Application
Non-renal Application
* Hepatic failure complicated with hepatic coma
* Congestive heart failure refractory to diuretics
* Overhydration during & after cardiac surgery ( CPB )
* Sepsis
* Life-threatening hyperthermia
* Lactic acidosis
* Cytokine removal: Acute respiratory distress syndrome
* Tumor lysis syndrome
* Crush injury
* Inborn errors of metabolism: maple syrup disease, urea cycle
  Vicious Circle Relating Cardiac Failure and
       Renal Failure and the Role of UF
Congestive Heart Failure: Cardiac output, Tissue perfusion,
Effective volume (    )

Neuro-humoral factors: Angiotensin II, Catecholamines,
Vasopressin, Aldosterone, Atrial natriuretic peptide, Arteriolar
vasoconstriction, Cytokines (    )

Functional Acute Renal Failure: Glomerular filtration (    ),
Na tubular reabsorption (    )

Oliguria, Natriuresis
Water-Salt retention
Ultrafiltration in Congestive Heart Failure
                              UF in CHF

Fluid overload
  correction               Clear mediators            Relief symptoms:
                                                    Edema, dyspnea, fatigue

SCUF, Indications
•Emergency procedure
-Severe and refractory heart failure with intractable edema
•Maintenance treatment
-Long term treatment in patients contraindicated to heart transplant
•Temporary treatment
-Patient waiting for heart transplant
                  Post Cardiac Surgery ARF
* Intra-operative support and post-operative problems
   a. Oxygenator membranes and cytokine generation
   b. Blood tubing and extraction of plasticizers (DEHP)
   c. Prolonged by-pass time and hemodynamic consequences
* Application of aggressive ultrafiltration in the cardiac support of
   children and outcome improvement
* Dialysis variants added to extracorporeal cardiac support system
   a. VAD and support
   b. ECMO and support
   c. IABP and support
    Liver-Assist Technologies and Applications
  Non-biological         Application
• Hemodialysis           Removal of low
                         molecular weight solutes
• Hemofiltration         Removal of low to middle
                         molecular weight solutes
• Sorption               Select removal of
                         hydrophobic and protein-
                         bound solute
• Plasma exchange        Removal of all plasma solutes
• Plasma fractionation   Select removal of protein-
                         bound or high molecular
                         weight solute
                CRRT in Liver Support
• Requirements for liver support
  Fluid regulation
  Acid-Base and electrolyte homeostasis
• Indications of CRRT support
  a. Combines renal and liver failure
  b. Liver transplant
  c. Mx of complications of decompensated liver disease
      1. Ascites
      2. Encephalopathy
          Prognostic factors in ARF
• Severity of renal dysfunction
• Magnitude of rise in serum creatinine concentration, Urinalysis,
• Presence of oliguria, Requirement for renal replacement therapy
• Duration of severe renal failure
• Underlying heath of the patient
• Age
• Presence, severity, and reversibility of underlying disease
• Clinical circumstances
• Cause of the renal failure
• Severity and reversibility of acute processes
• Number and type of other organ systems failed
• Development of sepsis and other complications

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