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					THE CRUSH SYNDROME:
A nephrological overview


             F. Fevzi Ersoy
  Professor of Medicine and Nephrology,
    Akdeniz University Medical School
                Antalya
     Definition of acute renal injury/Acute renal failure:
      Renal functional deterioration within 48 hours:



• Serum Cr         ≥ 0.3 mg/dl increase
                  or
• Serum Cr         ≥ % 50 increase (1.5Xbasal)
                  or
• Decrease in urinary volume:
  (Urinary volume <0.5 ml/kg/hour for 6 hours or longer)
           GFR Criteria                           Urine volume criteria

           Scr increase x 1.5 or                  UrinVol < 0.5
           GFR decrease > % 25
Risk                                              ml/kg/hour               High
                                                  x 6 hour                 sensitivity

                 Scr increase x 2 or           UrinVol < 0.5
  Injury         GFR decrease > % 50           ml/kg/hour
                                               x 12 hour
                    Scr increase x 3 or
                    GFR decrease > % 75        UrinVol < 0.3
                    or                         ml/kg/hour
       Failure      Scre≥4 mg/dl
                                               x 24 hours or
                    Acute increase≥0.5 mg/dl
                                               anuriaX12 hours



                           Permenant failure = Total loss of renal
             Loss          function > 4 weeks
                                                                      High
                                    ESRD>3 months
                                                                      specificity
                  ESRD
    Timeline in Acute Tubuler Necrosis
       Induced Acute Renal Failure
                                                                        kreatinin
Sürekli diyaliz                                                          mol/L
   tedavisi

      Üre hacmi
        L/gün




                                                                     time / days

     1. Renal               2. Oliguria/Anuria     3. Poliüria   4.Renal recovery
 injury(minutes-            total loss of renal   (1-2 weeks)     (A few months)
      days)                      function
                             (Up to 6 weeks)
 Zöllner, Innere Medizin, modified
 ACUTE TUBULAR
 NECROSIS
                      ATN
                              ISCHEMIC
                             HEMORRHAGES
 NEPHROTOXIC                 HYPOVOLEMIA
     ATN                     HYPOTENSION

RADYOCONTRAST USE            CARDIAC ARREST

NEPHROTOXIC DRUGS
MYOGLOBINE
HEMOGLOBINE
                       CRUSH SYNDROME !
ETHYLEN GLYCOL ETC.
 BACKGROUND



 ETIOLOGY of RHABDOMYOLYSIS

   Non-traumatic                              Traumatic
• Metabolic myopathies                  • Traffic or working accidents
• Drugs and toxins                      • Prolonged immobilization
• Infections                            • Vessel clamping
• Electrolyte abnormalities             • Strainful exercise of muscles
                                        • Electrical current
• Endocrine disorders
                                        • Hyperthermia
• Polymyositis, dermatomyositis
                                        •    Disasters

    Brumback et al. Pediatr Clin N Am 1992      Vanholder et al. JASN 2000
         “CRUSH” SYNDROME

• Hypovolemic shock + hyperpotasemia +
renal failure + infections + heart failure +
muscle trauma + muscle edema etc.. =
CRUSH SYNDROME.
• Occurs 2-5 % of overall trauma cases.
• If an apartment building crashes 80% of
the inhabitants die, 40% of the rest develop
CRUSH SYNDROME.
BACKGROUND

                  TERMINOLOGY - I

Crush: injury due to pressure between opposing elements
   Crush syndrome: systemic manifestations
   caused by rhabdomyolysis as a result of crush

                                    MEDICAL
                                    • Hypovolemic shock
                                    • ARF
       SURGICAL
                                    • Hyperkalemia
       • Local findings of trauma
       • Compartment syndrome       • Heart failure
                                    • Respiratory failure
A complex clinical picture!         • Infections
BACKGROUND

  PATHOGENESIS of TRAUMATIC RHABDOMYOLYSIS
       Pressure-induced increase in capillary permeability
          muscle cell edema (compartment syndrome)
       Impaired muscle perfusion / reperfusion injury

     TRIGGERING EVENT: Increase in cytosolic Ca++


        Activation of intracellular proteolytic enzymes


                  RHABDOMYOLYSIS
Better OS, Stein JH. NEJM, 1990; Zager
Kidney Int, 1996                                Zager. Kidney Int 1996
   I. DETERIORATION IN RENAL PERFUSION
                                                 IV. OTHER
   A.HYPOVOLEMIA, HYPOTENSION                     FACTORS
   (COMPARTMENT BSYNDROME) NO                REPERFUSION
   B. INCREASE IN VASOCONSTRICTOR CYTOKINES
                                              FREE RADICALS
   AII, CATECHOLAMINES, AVP, NO
                                              DIC
                                              Na-K-ATP’ase 
                                              CYTOSOLIC Ca 

                       RABDOMYOLYSIS
                                              III. INTRATUBULAR
                                                 OBSTRUCTION
 II. DIRECT TOXIC EFFECT OF
  MYOGLOBINE ON TUBULAR                       MYOGLOBIN
          EPITHELIA                           CASTS
DIRECT EFFECT IS NOT OF
                                              HEMATINE
PRIMARY IMPORTANCE,
DEHYDRATATION AND                             CRYSTALS
ACIDOSIS AUGMENTS DIRECT                      URIC ACID
TOXIC EFFECT.                                 CRYSTALS
   GLOBAL SEISMIC HAZARD MAP




EARTHQUAKES: A WORLWIDE PROBLEM
AREAS IN RED SHOW 1. DEGREE RISK
   OF SEVERE EARTHQUAKES !
North Anatolian Fault
     17 Ağustos 1999
        Saat: 03:01
    Kandilli İstasyonu
Vertikal amplitüd kayıtları
MARMARA EARTHQUAKE


  • Death toll: 17,480

  • Injured: 43,953
   80% die instantly                  Crush syndrome
   10% minor injuries
                                  2nd most frequent cause of deaths
   10% major injuries              (following direct effect of trauma)


“R E N A L D I S A S T E R”
Ron et al. Arch Intern Med 1984                          Ukai. Ren Fail 199
RENAL DISASTER !
 CRUSH SYNDROME


             In earthquakes:
   (following the direct effect of trauma)
IS THE MOST FREQUENT CAUSE OF DEATH!
BACKGROUND



    The Marmara                The Hanshin-Awaji
     Earthquake                (Kobe) Earthquake

Pts. with renal prob.: 639     Pts. with ARF:      202
Pts. requiring Dx.: 477        Pts. requiring Dx.: 123


 The largest “renal disaster” documented so far !

Sever et al. Kidney Int 2001             Oda et al. J Trauma 199
   CLINICAL FINDINGS IN CS


     MEDICAL                   SURGICAL
(Crush syndrome            (Travma ile ilgili)
and complications comp.)
                            • Compartment syndrome
                            • Thorax trauma
 • Hypovolemıc shock
 • Acute renal failure      • Abdominal trauma
 • Hyperpotasemia           • Other traumas
                            (Skull , spine, pelvis)
 • Heart failure
 • Pulmonary failure
 • Infections
• Death/injured ratio in earthquakes is:  1/3

    • Not all trauma cases develope rhabdomyolysis !
     •   Not all rhabdomyolysis cases developes crush syndrome
     •   (30-50%) !
     •   Not all crush syndome cases develope acute renal failure
         2 -5 % of overall trauma cases
           developes crush syndrome

                    Marmara Earthquake:
                     1.5% (639/43,953)
  CLINICAL FINDINGS ON ADMISSION

   MEAN BLOOD PRESSURE
   Died: 88 ± 21 mmHg              (p=0.004)
   Survived: 95 ±17 mm Hg

   Urıne volume in first 24hs
   • Died: 563 ± 965               (p=0.017)
   • Survived: 761 ± 1131 ml/gün

    Mean body temperature
    • Died: 37.5 ± 1.0°C           (p=0.027)
    • Survived: 37.1 ± 0.7°C

Hypotensive, oliguric and hypertermic patients
   pose a greater probability for death and
    therefore should be followed closely!
CLINICAL FINDINGS IN THE DISASTER FIELD



         • Crush syndrome may
     develope even in lightly injured
                 victims




      Check urine volume and color!
              TRAUMA PATTERN ON ADMISSION
No. of traumatized      Thoracic   69                                         Trauma (+)              Trauma (-)
   extremities                                                                                                        p<0.00
    1        274        Abdominal 41                     40                                   p<0.00                  01
                                                                                              01




                                        Mortality rate
                                                         35
    2        205
                        Skull      32




                                                                                                               36,6
                                                         30
                                                                  P=0.




                                             (%)
    3         26                                         25




                                                                                       31,9
                                                                  19
    4         7         Multiple   54                    20
                                                         15




                                                                       18,9
             790
                                                         10




                                                                                                                       13,7
  Global




                                                                                               13,2
                        Others     51




                                                                14,3
                                                          5
                                                          0
Multivariate analysis for mortality risk:                     Extremity Thoracic trauma Abdominal
• Thoracic (p=0.001, RR=2.8)                                   trauma                    trauma

• Abdominal (p<0.0014, RR=3.8)

           Victims with thoracic / abdominal trauma
      should be referred from the field as soon as possible

Sever et al. NDT 2002
 Most important rule in renal triage:

• Rescued patients should be checked for
  their urinary output with or without using
  Foley catheters, cases with dark and low
  volume of urine pose a greater risk for
  developing acute renal failure and should be
  transferred to larger medical centers with
  nephrology departments.
CLINICAL FINDINGS


   TRAUMA PATTERN – RISK OF CRUSH SYNDROME


         Even mildly injured victims carry
           the risk of crush syndrome



         Discharged patients should frequently check
                  the color of their urine !

  Sever et al. NDT 2002
   Laboratory findings in CS

Laboratory:
Dark brown granular
or tubuli epithel
containing cellular
casts,
         Laboratory Findings at Admission


             Parameter          Mean      S.D.
       Creatinine (mg/dl)        3.9       2.3
       CK (U/L)                58.205    77.889
       Potassium (mEq/L)         5.4       1.3
       Phosphorus (mg/dl)        5.2       1.8
       Albumin (g/dl)            2.6       0.7
       Haematocrit (%)          35.0       9.3
       Platelets (/mm3)        183.975   134.012
       Corr. calcium (mg/dl)     8.8       0.9

Sever et al. NDT 2002
LABORATORY FINDINGS ON ADMISSION
Hct:          Died: (%32.3 ± 9.8)                           (p=0.028)
              Survived:%35.5 ± 9.1

Platelets:   Died: 143.344 ± 80.383 /mm3
             Survived: 192.557 ± 141.398 /mm3
                                                            (p<0.001

Calcium:     Died:8.5 ± 1.1 mg/dl                           (p=0.039)
             Survived:8.9 ± 0.9 mg/dl

Albumine:    Died:2.3 ± 0.7 mg/dl                           (p=0.003)
             Survived:2.6 ± 0.7 mg/dl

Potassium: Died:6.0 ± 1.7 mEq/L
                                                            (p=0.001)
           Survived:5.3 ± 1.2 mEq/L

Close follow up is crucial for the patients with
low hct, platelets, calcium, albumine and high potassium!
         HYPERKALEMIA-DEATH RELATIONSHIP
        IN EARTHQUAKE-RELATED DEATH CASES


   Hyperkalemia                                arrythmias         DEATH

                 Hypocalcemia                        arrythmias

        “Most frequent cause of earthquake related deaths is
                                    direct effect of trauma.”
                On the other hand most rescued patients die
                                   because of hyperkalemia.

Collins, 1991; Better, 1993; Noji, 1992; Oda, 1997
CLINICAL FINDINGS

                                    THE MARMARA EARTHQUAKE –
                                   SERUM POTASSIUM ON ADMISSION
                                          Mean: 5.3 ± 1.3 ( 2.4 – 13.3) mmol/L
                      140

                      120
                                                                                             Cum. No. Potassium
                      100
                                                                                             of the pts. (mmol/L)
    No. of patients




                       80

                       60                                                                       22      < 3.5
                       40                                                                      116       >=6.5
                       20
                                                                                                70      >=7.0
                        0
                            <3,5   3,5-4,4 4,5-5,4 5,5-6,4 6,5-7,4 7,5-7,9 8,0-8,4   >=8,5      6       >=8.5
                                         Serum Potassium (mmol/L)



 Many patients died at the disaster field or within the first
hours of admission to hospitals due to fatal hyperkalemia!
Sever et al. Clin Nephrol 2003
CLINICAL FINDINGS




                     ECG should be taken
          as soon as possible at admission to hospitals
Sever et al. Clin Nephrol 2003
 MEDICAL INTERVENTIONS AT THE DISASTER FIELD – I -
  • Rescued victims who are seemingly well, can get worse
    or even die as soon as extrication

                                               RESCUE
                                               DEATH


                                    • Severe metabolic acidosis
                                    • Fatal hyperkalemia


• Rescue teams must include health care providers
Noji. Crit Care Clin 1992
HYPERPOTASEMIA DURING HOSPITAL STAY

 40 PATIENTS ADMITTED AFTER FIRST WEEK
     In 8 pts.         K > 6.5 mEq/L
     In 4 pts.         K > 7.5 mEq/L
     In 3 pts          K > 8 mEq/L
Especially in heavily traumatized, male patients:

 •Serum K should be checked 3-4 times daily!
 •Extensive care for low potassium diet !
 •Drugs with potential risk for inducing
  hyperkalemia should be limited !
        TREATMENT IN THE DISASTER FIELD
        / RISK of HYPERKALEMIA

    • Many victims lost their lives due to hyperkalemia
      Need for empirical treatment for hyperkalemia


            • Some patients were hypokalemic!


                 Empirical treatment for

             Heavily traumatized, male victims !
Knochel. West J Med 1976                       Sever et al. NDT 2002
                                        AGE


   The Marmara earthquake: 31.714.7 (3.5 months – 90 years)
            30                   Inhabitants Crush syndrome
            25
            20
     (% )




            15
            10
            5
            0
                 0-9    10-19   20-29         30-39          40-49   50-59   60
                                        Age groups (years)

Sever et al. Kidney Int 2001
 • Uludağ Tıp Fak.: 18±5 s.   • Marmara Tıp Fak.: 35±13 s.
(Dönmez, 2001)                                     (İskit, 2001)
                                     TIME UNDER RUBBLE (Hours)
                                    300                                                                     100

                                                                                                            90
                                    250
                                                                                                            80




                                                                                                                  Kurtarılanların kümülatif yüzdesi
                                                                                                            70
      Yaralanan hastaların sayısı




                                    200
                                                                                                            60

                                    150                                                                     50

                                                                                                            40
                                    100
                                                                                                            30

                                                                                                            20
                                    50
                                                                                                            10

                                     0                                                                      0
                                          <1-4


                                                 5-8


                                                       9-12


                                                              13-16


                                                                      17-24


                                                                              25-36


                                                                                      37-48


                                                                                              49-72


                                                                                                      >72
                                                       Enkaz altında geçen süre (saat)



• Rescue operations within first 2 days are extremely important!
MEDICAL INTERVENTIONS AT THE DISASTER FIELD – I -

    EARLY
    FLUID
ADMINISTRATION
    IS OF
    VITAL
 IMPORTANCE !

   (1 L / hr
   saline)
                                 Better and Stein. NEJM 1990
MEDICAL INTERVENTIONS AT THE DISASTER FIELD – II


3. Check the amount of urine (Urination, Foley).

4. Fluid administration in case of hypovolemia; follow
urinary output.
5. If no urinary output, fluid output + 1000 -1500 ml.
6. Never use potassium containing fluids empirically
THERAPEUTIC INTERVENTIONS

 MEDICAL INTERVENTIONS AT THE DISASTER FIELD –III
     Marmara E.: Many patients (35/352=%10)
 were receiving K+ containing solutions at admission

      This was certainly a malpractice:


       Resulted in many patient deaths??

K+ containing solutions should NEVER be administered empirically !


     KADALEX             ISOLYTE             ISOLYTE-M
MEDICAL INTERVENTIONS AT THE DISASTER FIELD –IV-

 • After the rescue  Mannitol-alkaline solution
             {1000 cc %0.045 NaCl/5% Dextrose +
             4 amps NaHCO3 and 50 ml 20% Mannitol}

 • Adequate urine response  + mannitol

                                      8 - 12 L/day

 • Less aggressively (4 - 6 L/day) in disasters

  • CVP measurements

  Better and Stein. NEJM, 1990          Vanholder et al. Kidney Int. 2000
Compartment syndrome

 Compartment = space restricted
  by the rigid fasciae surrounding
  the muscles



 Increased pressure (>0-15 mmHg) in the compartments due to
  traumatic tissue swelling results in muscle injury and necrosis



Compartment syndrome = muscle tamponade)
A SECOND RISE IN CPK =
COMPARTMENT SYNDROME




               If hydrostatic pressure inside the compartment
               exceeds 40 mm Hg and remains there for more
               than 8 hours, fasciotomy is indicated.
  FASCIOTOMIES                       If necessary:
• Prefer staying supportive • Great care on wound care
• Objective criteria?
                                  • Regular dressing changes
 Culture in case of infection
• Debridment in infected wounds
 THERAPEUTIC INTERVENTIONS

       THE MARMARA
       EARTHQUAKE
         397 fasciotomies
          in 323 patients
               Fasc. (-)       Fasc. (+)
         -- 275 (%87)         243 (%75)
 SEPSIS
         + 41 (13%)            80 (25%)
   Total       316               323

              Survived       Died      Total
         -- 454 (87%)       64 (12%)   518
SEPSIS
         + 88 (72%)         33 (27%)   121
   Total      542              97      639

            (p<0.001)
Sever et al. Nephron 2002
            FLUID RESUSCITATION
         Mean fluid volume: 51091711 ml/day
  Died vs Survived: NS

Dialysis (+): 5407  1623ml/day
                                     (p=0.01)
Dialysis (-) : 3825  1539 ml/day
      In order to estimate the necessary
                 amount of fluid:



  CVP measurement as soon as possible
  OTHER MEDICAL TREATMENTS


Antibiotics: 347       Heparine:      82
Diuretics:    36       Other:         89


• Indications for broad spectrum antibiotics?

• Dopamine use: Is it effective?
         Nonsteroidals: Indications?
         • Narcotics should be used liberally
          (pay attention to prevention of abuse in chaotic
                       disaster conditions)



               Gujarat Earthquake (India, 2001):

                       Epidural blocks


                  • Easy application
                  • Complications are rare
Trivedi. Lancet 2001
    INDICATIONS FOR DIALYSIS

• BUN 100 mg/dl, CREATININE 8 mg/dl
• Potassium >7 mEq/L
• Hyponatremia
• Blood pH < 7.1, sHCO3 <10 mEq/L
• Hypervolemia
• Uremic symptoms Pericarditis, uremic lethargy,
  nausea, vomiting.
• Clinical judgement is the most important
  criterium
               Selection of treatment modality in Acute
                             Renal Failure

                         Renal replacement threpies




 Peritoneal                      Intermittent           sürekli
  dialysis                          dialysis          hemodiyaliz
• Rarely used                                     • Hemofiltration
                               • Hemodialysis
• e.c. If no vascular access                        mostly.
• May be used more oftenly       mostly
                               • Isolated ARF     • Complicated case,
  in selected cases
                                                    multiorgan failure.
Hemodialysis Machines
     RENAL REPLACEMENT THERAPY
          INTERMITTENT HEMODIALYSIS

          Advantages:
          • High clearence rate
          • Possibility to dialyze without anticoagulation
          • Treating several patients at the same machine
          • Arterial cannulation is not required
            Disadvantages:
          • The procedure is complicated
          • Experienced health personnel is needed
          • Electricity and tap water are needed
          • Risk of dialysis disequilibrium syndrome

Collins Crit Care Clin 1991; Solez et al. Kidney Int 1993; Vanholder et al. NDT 2000
     RENAL REPLACEMENT THERAPY
          SLOW CONTINUOUS THERAPY

          Advantages:
          • Fluid balance can easily be maintained
          • No risk of dialysis disequilibrium syndrome
          • Can be rapidly set in the field
          • Opportunity to freely feed the patients
            Disadvantages:
          • Low clearence rate of uremic solutes and potassium
          • Experienced health personnel is needed
          • Electricity and large amount of fluids are needed
          • Need of continuous anticoagulation
          • Immobilization, decubitus
Collins. Crit Care Clin 1991; Solez et al. Kidney Int 1993; Vanholder et al. NDT 2000
   RENAL REPLACEMENT THERAPY
          PERITONEAL DIALYSIS

     Advantages:
     • System is very simple
     • No risk of dialysis disequilibrium syndrome
     • Vascular access is not required
     • Does not require electricity
       Disadvantages:
     • Low clearence rate of uremic solutes and potassium
     • Cannot be applied in abdominal trauma / heart failure
     • Large amount of fluids are needed
     • Unhygienic conditions in disasters may be problematic
Collins. Crit Care Clin 1991; Solez et al. Kidney Int 1993; Vanholder et al. NDT 2000
CLINICAL FINDINGS



                    CAUSES OF DEATH

     Sepsis: 30                           DIC + sepsis: 8
     Cardiac problems: 17                 Others: 8
     • Cardiopulmonary arrest: 9          • GIS bleeding: 2
     •   Congestive heart failure: 3      •   Intracranial hemorrhage: 2
     •   Cardiogenic shock: 2             •   Aspiration pneumonia: 1
     •   Acute myocardial infarction: 1   •   Hypovolemic shock: 1
     •   Arrhythmia: 1                    •   Intraoperative: 1
     •   Hemopericardium: 1               •   Hydrocephalia: 1
     Respiratory failure: 12              Unidentified: 22
 Erek et al. NDT 2002
    Total death toll in CS: 97


        MORTALITY RATE

 • General mortality: 15.2% (97/639)

• Dialized: 17.2% (82/477)        p=0.015
• Non-dialyzed: 9.3% (15/162)
               CONCLUSION–I

 • Rescue operation should continue for 5 days



• Even the slightly injured are prone to developing
  crush syndrome

• Empirical antihyperkalemia for especially male victims.
• EKG as the “first thing to do” on admission.
              CONCLUSION–II


• CVP measurement is reliable in the bginning and
also during the maintenance fluid treatment .

• Fasciotomy is a risk factor for septicemia,
should be done only if necessary.

• Patients from nearest location should be seen first!.


• “Disaster medicine training” for medical personel
continuously.
THANK YOU!

				
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