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