CRUSH INJURY

AND
RHABDOMYOLYSIS
Trauma and Critical Care Symposium
Penrose-St. Francis Trauma Center
Colorado Springs May 2, 2013
Darren Malinoski, MD
Associate Professor of Surgery
Oregon Health & Science University

ROADMAP
General definitions
History
Pathophysiology of muscle injury
Pathophysiology of renal injury
Diagnosis
Treatment strategies
Thresholds for treatment
Natural disasters
Research at LAC/USC and OHSU

RHABDOMYOLYSIS

(Rhabdo): striped muscle dissolution.

Etiologies
Release of cellular contents into the circulation
How to measure/quantify
Treatment?

MYOGLOBIN

An oxygen-binding protein found within skeletal

muscle that contains a single heme prosthetic
group with an iron atom at the center that serves
as the oxygen-binding site. Higher affinity for
oxygen than hemoglobin which facilitates
delivery to muscle.

CREATINE KINASE

CK: intramuscular enzyme that catalyzes the

formation of ATP:
CK

ADP + creatine phosphate ATP + creatine

Several isoenzymes: CK-MM (striated muscle),
CK-MB (cardiac), CK-BB (brain)
Normal plasma range 45-397 IU/L; plasma level
of CK is proportional to degree of rhabdo

COMPARTMENT SYNDROME

Refers to the local manifestations of

neuromuscular ischemia because of
increased pressure within the osteofascial
compartments.

Signs and symptoms

Diagnosis
Fluid sequestration

CRUSH SYNDROME

The systemic manifestations of muscle injury after

direct trauma or ischemia-reperfusion injury.
Commonly found in victims of earthquakes who have
been caught under the rubble of collapsed buildings.

SIGNS AND SYMPTOMS:

Tense, edematous, painful muscles
Dark tea-colored urine
Shock
Acidosis
Acute renal failure

RENAL IMPACT

Acute Renal Failure (ARF): a decline in

renal function severe enough to require
some form of renal replacement therapy.
Many definitions
Mortality ranges from 5-50% when renal
failure follows crush injury

HISTORY OF
RHABDOMYOLYSIS
1880s: first reported in the German Literature
1911: Meyer-Betz described a clinical
syndrome consisting of dark brown urine,
muscle pain, and weakness
1941: Bywaters and Beall report 4 cases of
crush syndrome during the bombing of
London during WWII. They recognized the
association between swollen extremities,
hypovolemia, vaso-constriction, and eventual
oliguria / renal failure.

CAUSES OF
RHABDOMYOLYSIS
Alcohol intoxication, immobility, compression
Positioning during surgery
Seizure disorders
Medications: steroids, paralytics
Toxins: alcohol, cocaine, insect bites, reptiles

Costa Rican jumping viper venom

Genetic Disorders
Infection: bacterial and viral
Trauma: Crush injury / Vascular Occlusion

PATHOPHYSIOLOGY OF
MUSCLE INJURY
Immediate cell disruption
Direct pressure on muscles

Stretch-activated channels opened Ca++ influx

Ischemia/Anaerobic metabolism
Loss of cellular membrane integrity

Vascular compromise
Prolonged compression vs. vascular injury
Histologic changes at 2 hours
Necrosis at 6-8 hours

ISCHEMIA-REPERFUSION
INJURY

Occurs when patients are extricated from collapsed

buildings or when vascular flow is re-established:

Swelling of affected extremities / Compartment Syndrome

Hypovolemia / Shock
Free Radical formation
Lipid Peroxidation cell lysis
Toxin release: lactic acidosis, aciduria, myoglobinemia, CK,
and thromboplastin (can DIC)
Electrolyte abnormalities: K, Phos, Ca

-Malinoski, Slater, Mullins. Crit Care Clin, 2004.

PATHOPHYSIOLOGY OF
RENAL INJURY
Hypovolemia and Shock
Myoglobinuria: when plasma concentration
exceeds 0.5-1.5 mg/dL, myoglobin filtered
into urine.

Cast formation/tubular obstruction *

Free radical formation and lipid peroxidation *
Vaso-constrictor formation: PAF, endothelins
*intensified by acidic urine

Myoglobin cast formation in renal tubules

Myoglobin cast formation in renal tubules

DIAGNOSIS
History
PEX
Labs:

Serum: CK, myoglobin

Urine: inspection, dipstick, myoglobin
Is general screening necessary?

TREATMENT
Prevention of Muscle Injury
Fasciotomy
Amputation
Prevention of Renal Injury
Dialysis

PREVENTION OF MUSCLE
INJURY

Prompt restoration of blood flow

Delivery of intravenous fluid is the FIRST priority

Extricate victims from rubble NEXT
Reduce fractures and splint extremities
Repair vascular injuries

TREATMENT OF MUSCLE
INJURY

Fasciotomy
Controversies: indications and timing
compartment pressure >30-50mmHg
P <30 mmHg (diastolic minus compartment)

Amputation

if limb salvage is not possible

if the patient will die from intractable
hyperkalemia, acidosis, or infection

White, et al. Elevated Intramuscular Compartment

Pressures Do Not Influence Outcome after Tibial
Fracture. JOT, 2003.

Hypothesis: Absolute intramuscular pressure

measurements are non-specific and lead to
unnecessary fasciotomies
Prospective analysis of 210 patients with tibial
fractures
Continuous compartment pressure (CP)
Fasciotomy for P >30 mmHg or clinical Dx
109 pts either had Dx of compartment syndrome or
elevated compartment pressures for less than 6 hrs.
101 patients remained with CP > 30 mmHg

White, et al. Elevated Intramuscular Compartment

Pressures Do Not Influence Outcome after Tibial
Fracture. JOT, 2003.

101 pts with elevated CP and normal P

41 patients: CP > 30 mmHg (30 to >70)
60 pts: CP < 30 mmHg
None developed compartment syndrome
None required fasciotomy
No significant difference in outcome:

Sensory function, Muscle power, Peak torque,

Functional indices of recovery

TO CUT or NOT TO CUT

Irreversible muscle damage after 6-8 hours

Sheridan, et al. J Bone Joint Surg Am 1976

Only 8% of pts with fasciotomy after 12 hours
had restoration of normal function
46% infection, 21% amputation

Bradley. Surg Gynecol Obstet. 1973

Meta-analysis: 80% of pts with paralysis had
unsatisfactory outcomes

TO CUT or NOT TO CUT

Matsuoka, et al. J Trauma. 2002

Increased disability in pts who underwent fasciotomy
>12 hours after injury (47% vs 16%)

Seddon. J Bone Joint Surg Br. 1956

Spontaneous recovery of muscle function up to 3
months after injury
Recommends delayed fasciotomy and release of
ischemic contractures to maximize outcome

Better and Finkelstein condemn delayed

fasciotomy due to risk of overwhelming infection

FASCIOTOMY

Two incisions
Lateral incision:
Anterior compartment
Lateral / Peroneal compartment

Medial incision:
Posterior compartments

One incision
Lateral: all four compartments

LATERAL INCISION: anterior and lateral compartments

Delayed Primary Closure of fasciotomy wound.

Split Thickness Skin Graft to close fasciotomy wound

after several weeks.

PREVENTION OF RENAL
INJURY
Goal is to prevent rise in serum Cr and the
need for renal replacement therapy.
Treatment of shock and hypovolemia

Restoration of adequate intravascular volume

6-12 L of saline in first 24hrs is recommended
Urine flow rate of 100-200cc/hr is ideal
Correction of underlying cause of shock

Measure serial CK levels in high-risk patients

Treatment threshold 5000-30,000 U/L

PREVENTION OF RENAL
INJURY
Alkalinization of urine with NaHCO3- (K+)
Mannitol
Dopamine, acetazolamide, and Lasix
Experimental therapies:

Deferoxamine
PAF-receptor blockade
Bosentan endothelin receptor blockade
Anti-oxidants

Mannitol

Mannitol
Sodium Bicarbonate

Better OS, Stein JH. Early Management of Shock and

Prophylaxis of Acute Renal Failure in Traumatic
Rhabdomyolysis. New England Journal of Medicine 1990;
322 (12): 825-829

Hypothesis: Shock occurs only after

extrication, when compressed extremities are
released, resulting in ischemia-reperfusion
injury
1979: 7 men with rhabdo due to building
collapse who did not receive IV fluid for at
least 6 hours; all 7 developed ARF
1982: 7 men with traumatic rhabdo who
received IV fluid before extrication and forced
mannitol-alkaline diuresis within 2 hours of
extrication; none developed ARF

TREATMENT THRESHOLD

SERUM CREATINE
KINASE LEVELS

$15
1-2 hour turnaround
Elimination T1/2: 42 hrs
More prevalent in the
literature - >3000 pts
Peak levels of 5000 to
75,000 risk ARD
All pts with increased
CK levels have positive
urine dipstick**

URINE OR SERUM
MYOGLOBIN LEVELS

$97
1-3 day turnaround
Elimination T1/2: 12 hrs
Studies with small
numbers - <300 pts
Most studies use urine
levels which are affected
by renal function

DIALYSIS

Risk factors for developing ARF:

CK level >20,000
Delay in diagnosis or treatment
Extent of injury
Dehydration
Preexisting renal disease
Advanced age
Administration of nephrotoxic agents

Normalization of Hyperkalemia is the main

priority.
Need for dialysis is temporary in most cases

EARTHQUAKES AND
RHABDOMYOLYSIS

1988: Armenian Republic of Soviet Union

100,000 injured, 15,254 extricated from rubble,
crush injury third most common injury but
leading cause of death, 323 patients required
hemodialysis, poorly organized disaster
response

1991: Limon, Costa Rica

Crush injury was the leading cause of injury
and death

EARTHQUAKES AND
RHABDOMYOLYSIS

1995: Kobe, Japan

41,000 injured, 5000 died, 54% of victims with
crush injury developed ARF and 13% died

1999: Marmara, Turkey

Renal Disaster Relief Task Force created in
1995 after Armenian earthquake
462 patients underwent dialysis, with <19%
mortality rate (this was a dramatic
improvement in the delivery of treatment and
survival)

Oda et al. Analysis of 372 Patients with Crush

Syndrome Caused by the Hanshin-Awaji Earthquake.
Journal of Trauma 1997; 42: 470-476

Retrospective review of 6107 charts at 95

hospitals; 372 patients with crush syndrome
ARF= Cr > 2.5; 200 (54%) ARF, 123 (33%)
required dialysis
Many patients had a delay until treatment, either
due to transportation problems or failure to
accurately diagnose crush injury.
Risk factors for ARF: <6 L fluid / day, delay until
treatment, and CK >75,000
50 patients died (13.4%); causes of death within 5
days of the earthquake were mainly hyperkalemia
and hypovolemia.

Oda et al. Analysis of 372 Patients with Crush

Syndrome Caused by the Hanshin-Awaji Earthquake.
Journal of Trauma 1997; 42: 470-476

*black = hypovolemia, diagonal stripe = hyperkalemia,

horizontal stripe = other form of shock, vertical stripe =
multiple organ failure, open = other causes

Oda et al. Analysis of 372 Patients with Crush

Syndrome Caused by the Hanshin-Awaji Earthquake.
Journal of Trauma 1997; 42: 470-476

***9% had trunk involvement; extremities do not

need to be involved to develop rhabdomyolysis.

Trauma patient with crush injury to the flank

CT scan of same patient.

RECENT PUBLICATIONS
AND UNPUBLISHED DATA
FROM USC/LAC AND OHSU

RHABDOMYOLYSIS
AT OHSU

Treatment Protocol in 1992

Mannitol and Bicarbonate infusions
Treatment threshold = CK >10,000 U/L

Interim Analysis 1997

Threshold raised to 20,000 U/L
Urine myoglobin levels abandoned

Second Analysis 2002

CK > 20,000 U/L = risk factor for dialysis

CK > 10,000 U/L = risk factor for AKI/death

2000 trauma ICU admissions

85% elevated CK
18% CK > 5000 U/L 19% vs 8% ARD
Bicarbonate and Mannitol no sig difference
Trend in CK >30,000 U/L group
Limitations

A FORCED ALKALINE DIURESIS

DECREASES THE INCIDENCE OF ACUTE
RENAL DYSFUNCTION IN PATIENTS
WITH TRAUMATIC RHABDOMYOLYSIS
Malinoski, Slater, Schreiber, Mullins
Oregon Health & Sciences University

OBJECTIVE
To determine if the increase in
the treatment threshold from
CK 10,000 to 20,000 U/L
would lead to an increase in
ARD.

HYPOTHESIS:
A forced alkaline diuresis is
beneficial ONLY in patients
with a peak CK > 20,000 U/L.

Mannitol
Bicarbonate

METHODS
Retrospective review - 1/93 to 10/03
Selection criteria:

CPK >2000 U/L (normal 4-397)

No prior history of CRI or other cause of ARF

ARD = serum Cr >2.0 mg/dL

Protocol instituted for CPK >10K/20K U/L
Primary endpoint: ARD

STATISTICAL ANALYSIS

Univariate analysis
Parametric data: Pearson Chi-square, Fishers
exact, or independent samples T-test
Non-parametric: Mann-Whitney U

Multivariate analysis:
Logistic regression analysis
All variables with p<0.2 on univariate analysis
included

SPSS software utilized

CK levels checked in pts at risk for crush injury:

painful, swollen extremities; prolonged compression;
urine dipstick positive .

Protocol initiated when CK level >20,000 or

patient has dark urine

Urine output is monitored hourly

Additional mannitol boluses if needed
Titration of drips

Monitor urine pH (goal>6.5), ABG, serum

electrolytes, creatinine, and osmolarity
Consider acetazolamide for serum pH > 7.5

Volume status must be watched in elderly patients

and those with a history of heart disease
If oliguria persists after 2 hours, cessation of the
protocol is necessary and renal replacement
therapy should be initiated

RESULTS

N = 77

80
patients
77
included
CK <10K
21

CK 10-20K
6

3
excluded
CK 10-20K
16

CK >20K
34

Normal Cr = 16

Normal Cr = 3

Normal Cr = 14

Normal Cr = 20

ARD = 5

ARD = 3

ARD = 2

ARD = 14
ARF = 4

NO PROTOCOL

PROTOCOL*

*4 pts in CK > 20K did not receive protocol

Primary Endpoint = ARD

More common than ARF

Serum Cr > 2 mg/dL is a common definition of
renal failure in the literature
Associated with an increased risk of death
17% vs 51%, p<0.01
Veenstra, et al. Nephrol Dial Transplant 1994

9 deaths in our series:

Normal renal function (4%) vs ARD (33%)
p<0.001, Fishers exact

Prevalence of ARD in patients

with peak CK > 10,000 U/L
Prevalence of Acute Renal Dysfunction with or without the treamtent protocol

dichotomized peak
creatinine

0-2.0
2.1-max

Total

Count
% within protocol
Count
% within protocol
Count
% within protocol

protocol
no protocol yes protocol
3
34
30.0%
73.9%
7
12
70.0%
26.1%
10
46
100.0%
100.0%

Total
37
66.1%
19
33.9%
56
100.0%

p=0.022, Fishers Exact Test

**If Peak CK 2000-9999 vs > 10,000 U/L used,

OR = 9.8, p=0.013

PROTOCOL COMPLICATIONS

3 pt (3.9%) with reversible CHF

1 pt (1.3%) with pH=7.78

1 pt with abdominal compartment syndrome

after analysis completed

STUDY CONCLUSIONS

A peak CK > 20,000 U/L is a definite risk factor for

developing ARD.

A forced alkaline diuresis is protective in patients with

traumatic rhabdomyolysis.

Due to a trend towards increased renal dysfunction, we

recommend using a forced alkaline diuresis in patients
with peak CK >10,000 U/L.

UNFINISHED BUSINESS

TREATMENT OF MUSCLE INJURY

LATE FASCIOTOMIES

IDEAL TREATMENT FLUID

RANDOMIZED CONTROLLED TRIAL

Dont forget DVT prophylaxis

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