Download Associated Conditions cont.

Hypothermia / Hyperthermia and
Rhabdomyolysis
大林慈濟醫院 SICU
范文林 醫師
2009.07.05
Outline
• Introduction about hypothermia and
hyperthermia
• Rhabdomyolysis: Etiology, pathophysiology,
clinical menifestations
• Mechanisms of ARF in rhabdomyolysis
• Diagnostic suggestions
• Therapeutic plans
1
Body temperature
• A balance between heat production and
heat dissipation
• Display a diurnal rhythmicity
• Hypothalamic thermoregulation
• Intact homeostatic response: fever
• Thermoregulatory failure: hypo-/hyperthermia
Hypothalamic temperature regulation
mechanisms
• peripheral nerves that reflect warm/cold
receptors
• temperature of the blood bathing
2
Events required for the induction of fever
Infection,microbial toxins
mediators of inflammation
immune reactions
Microbial toxins
Fever
Heat conservation
heat production
Cyclic
AMP
Monocytes,macrophages
endothelial cells,others
Elevated
thermoregulatory
set point
PGE2
Hypothalamic
endothelium
Pyrogenic cytokines
IL-1,IL-6,TNF,IFN
circulation
MDMA (toxin) + Overexercise
+Hot Environment
Rhabdomyolysis
Increased Sweating and
Increased body temperature
Central thermoregulatory
breakdown
Hyperpyrexia
Hyperthermia
DIC
Acute Renal Failure
Extreme fatigue
collapse
Convulsions
Brain Damage
Metabolic acidosis
(if prolonged)
Hyperkalemia
3
• Heat production:
increase cellular metabolism
striated muscle contraction
• Heat dissipation:
radiation
conduction
evaporation
convection
Hypothermia
• Hypothermia:
decreased heat production
increased heat loss
impaired thermoregulation
• Accidental or intentional
• Primary or secondary
• According to the degrees of hypothermia
4
rhabdomyolysis
5
After drop phenomenon!
Hyperthermia
• Heat related illnesses (Heat cramp,
exhaustion, stroke…)
• Malignant hyperthermia
• Neuroleptic malignant syndrome
• Hormonal hyperthermia
• Therapeutic hyperthermia
• Miscellaneous causes of hyperthermia
6
Hormonal hyperthermia
• Thyrotoxicosis
• Pheochromocytoma
• Adrenal insufficiency
• Hyperparathyroidism
• Hypoglycemia
Therapeutic hyperthermia
• Fever therapy
• Regional hyperthermia
• Whole-body hyperthermia
Lethal hyperthermia
• The most important causes of severe
hyperthermia (greater than 40ºC or 104ºF)
caused by failure of thermoregulation are:
– Heat stroke
– Neuroleptic malignant syndrome
– Malignant hyperthermia
7
Heat Stroke
• Core body temperature > 40.5ºC (105ºF)
with associated CNS dysfunction in the
setting of a large environmental heat load
that cannot be dissipated
• Complications include:
•
•
•
•
•
•
ARDS
DIC
Renal or hepatic failure
Hypoglycemia
Rhabdomyolysis
Seizures
Classic (nonexertional) heat stroke
• Affects individuals with underlying chronic medical
conditions that either impair thermoregulation or
prevent removal from a hot environment.
• Conditions include:
–
–
–
–
–
–
Cardiovascular disease
Neurologic or psychiatric disorders
Obesity
Anhidrosis
Extremes of age
Anticholinergic agents or diuretics
8
Exertional heat stroke
• Occurs in young, otherwise healthy individuals
engaged in heavy exercise during periods of high
ambient temperature and humidity
• Findings include cutaneous vasodilation,
tachypnea, rales due to noncardiogenic pulmonary
edema, excessive bleeding due to DIC, altered
mentation or seizures
• Labs: coagulopathy, ARF, elevated LFTs due to
acute hepatic necrosis, respiratory alkalosis, and a
leukocytosis as high as 30,000 to 40,000/mm3
• Heat stroke found an acute mortality rate of 21
percent
(Ann Intern Med 1998 Aug 1;129(3):173-81)
Heat related rhabdomyolysis
• Occurs in 25% of patients with exercised
induces heat stroke
– involves the individual’s ability to dissipate
heat. High cardiac output.
– Classic heat stroke
• heat is transferred to the body from the enviroment
– Exertional heat stroke
• heat generated in the body due to extreme
strenuous activities. ie firefighter, military
9
Neuroleptic malignant syndrome
• Idiosyncratic reaction to antipsychotic
agents.
• Mechanism is depend on decreased level
of dopamine.
• Features of NMS: FEVER (Fever,
Encephalopathy, Vitals unstable, Elevated
enzymes, Rigidity of muscles).
• Treatment is generally supportive.
Malignant Hyperthermia
F. Wappler, 2001 European Academy of Anaesthesiology. European Journal of Anaesthesiology, 18, 632-635
•
•
AD inherited disorder of the skeletal muscle cells
Pathophysiology:
– Ca released from the SR at an abnormally high rate through
ryanodine receptor (on chromosome 19q13.1)
– Sustained hypermetabolic state
• Excess lactate production, high ATP consumption, elevated O2 consumption,
increased CO2 production and elevated heat production
10
Malignant Hyperthermia
•
•
•
•
•
Rapid rise in end tidal CO2: most valuable early sign of impending MH
Generalized muscle rigidity
Masseter muscle rigidity
Hyperthermia
Unexplained tachycardia: hypoxia, hypercarbia, pain, inadequate anesthesia,
•
•
•
•
•
•
•
Tachypnea
Rhabdomyolysis
Acidosis
Myoglobinuria
Elevated CK: MI, surgical trauma, intramuscular injections, myopathy. >20,000 U in MH
Hyperkalemia
Others: cyanosis, hypoxemia
cocaine toxicity
Malignant Hyperthermia
• Diagnosis:
– In vitro contracture test: abnormal elevated
contracture of MHS skeletal muscle after caffeine and
halothane exposure (caffeine
caffeine and halothane contracture
test）
test）
– Muscle biopsy: skeletal muscle tissues >500mg,
invasive
– Genetic screening:
– Clinical presentation: not a definitive diagnosis
• Triggering anesthetic agents:
– Halothane, isoflurane, enflurane, sevoflurane,
desflurane, SCC (Anectin)
11
Management of established MH
General resuscitative measures
Reversal of the primary disorder with dantrolene
•
•
•
•
•
•
•
•
•
•
•
Call for help
The trigger agent is discontinued
100% O2 is given
Manually hyperventilated
Surgery should be aborted
Dantrolene 1mg/kg is given, and then 1-2.5 mg/kg every
10 min until MH under control ( max. dose of 10 mg/kg)
Measure core temperature
Fluid resuscitation, maintain adequate urine output
The patient is cooled aggressively
Cardiac arrhythmias are treated as appropriate
Correct electrolyte imbalances and acidosis
Consequences of hyperthermia
• Increased metabolic rate & O2
consumption
• Hyperdynamic status
• Neurologic effect
• Metabolic abnormalities
• Hematologic abnormalities
• Rhabdomyolysis, ARF
• MODS
12
Diagnostic evaluation
• Get a rectal temperature; check vital signs
• CXR,EKG,Labs: CBC, coagulation studies,
creatine kinase, electrolyte, myoglobinuria
• Myoglobinuria should be suspected in a
patient who has a brown urine supernatant
that is heme-positive, and clear plasma.
• Toxicologic screening
• Head CT and lumbar puncture if CNS
etiologies were suspected
Diagnostic evaluation
• Diagnosis confirmed by in vitro muscle
contracture test with halothane or caffeine
• However, this test is expensive, not widely
available, and frequently not covered by
insurance.
• Genetic testing for the more than 40 known
mutations of the SKM ryanodine receptor (RyR1)
can be used in conjunction with the in vitro
muscle contracture test
13
Management
• Ensure ABCs, initiate rapid cooling, treat
complications
• Assessing volume status and determining the
need for fluid resuscitation
• Alpha-adrenergic agonists should be avoided.
• Continuous core temperature monitoring with a
rectal or esophageal probe
• In the case of NMS or malignant hyperthermia,
the presumed causative agent must be
discontinued immediately
Cooling measures
– Naked patient is sprayed with a mist of lukewarm water
while air is circulated with large fans. Shivering may be
suppressed
– Immersing the patient in ice water is the most effective
method of rapid cooling but complicates monitoring and
access
– Applying ice packs to the axillae, neck, and groin is
effective, but is poorly tolerated in the awake patient
– Cold peritoneal lavage, cold oxygen, cold gastric lavage,
cooling blankets, and cold intravenous fluids may be
helpful adjuncts.
– There is no role for antipyretic agents, since the
underlying mechanism does not involve a change in the
hypothalamic set-point
– Alcohol sponge bath should be avoided
14
A case at ER
15-year-old boy, generally well before Monday,
Alternating split squat jump at school,
no significant symptoms were noted then.
C.C.: tea-colored urine, bilateral leg pain, muscle
weakness and lower back pain since Tuesday.
U/A: brown and cloudy, OB 4+, RBC 11-20;
Blood: GOT 1326, GPT 153, CK 12700,BUN 16,
AC sugar 105, Cr 0.8, amylase 65, K 5.8
Rhabdomyolysis
Rhabdo = striated
Myo = muscle
Lysis = breakdown
• A large variety of diseases, trauma, toxic insults to
skeletal muscle, damage to the integrity of sarcolemma
• Clinical syndrome in which contents of injured muscles
cells leak into circulation and results in electrolyte
abnormalities, acidosis, clotting disorders, hypovolemia,
ARF
15
1. Axon
2. Neuromuscular junction
3. Muscle fiber
4. Myofibril
16
Etiology of rhabdomyolysis
• Physical causes
‧Trauma and compression
‧ traffic or working accidents
‧ disasters
‧ torture
‧ abuse
‧ long-term confinement to
the same position
‧ Occlusion or hypoperfusion of
the muscular vessels
‧ thrombosis
‧ embolism
‧ vessel clamping
‧ shock
‧ Electrical current
‧Strainful exercise of muscles
‧ exercise
‧ epilepsy
‧ psychiatric agitation
‧ delirium tremens
‧ tetanus
‧ amphetamine overdose
‧ecstasy
‧status asthmaticus
‧ Temperature-related
‧exercise
‧high ambient temperatures
‧ sepsis
‧ neuroleptic malignant syndrome
‧ malignant hyperthermia
‧ high-voltage electrical injury
‧ lightning
‧ cardioversion
Critical care (2005) 9:158-169
17
Nonphysical causes
‧Metabolic myopathies
‧ McArdle disease
‧ mitochondrial respiratory chain
enzyme dificiencies
‧ carnitine palmitoyl transferase
dificiency
‧ myoadenylate deaminase deficiency
‧ phosphofructokinase deficiency
‧ Drugs and toxins
‧ regular and illegal drugs
‧ toxins
‧ snake and insect venoms
‧ Polymyositis/dermatomyositis
‧ Endocrinologic causes
‧ Hyper/hypothyroidism
‧Infections
‧ local infection with muscular
invasion(pyomyositis)
‧ metastatic infection(sepsis)
‧ systemic effects
‧ toxic shock syndrome
‧ Legionella
‧ influenza
‧ HIV
‧ herpes viruses
‧ coxsakievirus
‧ Electrolyte abnormalities
‧hypokalemia
‧hypocalcemia
‧hypophosphatemia
‧hyponatremia
‧hypernatremia
‧hyperosmotic conditions
‧ DKS, NKHS
Critical care (2005) 9:158-169
Associated Conditions
•
Direct Muscle Injury
– Crush injuries, deep burns, electrical injuries, acute necrotizing myopothy of
certain cancers, assaults with prolonged and vicious beating/repetitive
blows
•
Excessive Physical Exertion
– Results in state in which ATP production can’t keep up with demand →
exhaustion of cellular energy supplies & disruption of muscle cell membrane
– Protracted tonic-clonic seizures, psychotic hyperactivity (mania or druginduced psychosis)
•
Muscle Ischemia
– Interference with O2 delivery to cells and therefore limiting production of
ATP
– Generalized ischemia from shock & hypotension, carbon monoxide
poisoning, profound systemic hypoxemia, localized compression leading to
skeletal muscle ischemia, tissue compression d/t immobilization of muscle,
intoxicated/comatose down for long periods, immobilization from acute SCI,
compartment syndrome, arterial/venous occlusions
18
Associated Conditions cont.
•
Temperature Extremes
– Excessive Cold → ↓ muscle perfusion, ischemia; freezing causes cellular
destruction
– Excessive Heat → destroys cells & ↑ metabolic demands (every degree ↑
temp = ↑ metabolic demand by ~ 10%) & if body can’t keep up with ↑
requirement, cellular hypoxia → anaerobic environment
– Malignant hyperthermia, neuroleptic malignant syndrome (d/t psychotropic
medications)
•
Electrolyte & Serum Osmolality Abnormalities
– Chronic hypokalemia → significant total body loss of K+ disrupts Na+ K+
pump → cell membrane failure, leak of toxic intracellular contents from
muscle cells
– Overuse of diuretics or cathartic drugs, hyperemesis gravidarum, some
drugs (amphotericin B), hyperglycemic hyperosmolar nonketotic coma
Associated Conditions cont.
•
Infections
– Pneumococcal & Staphylococcus aureus sepsis, salmonella & listeria
infections, gas gangrene, NF
– Can destroy large quantities of muscle tissue through generation of toxins or
direct bacterial invasion
•
Drugs, Toxins, Venoms
– Ethanol → depresses CNS and leads to ↑ periods of immobility; alcohol also
has toxic effects on myocytes with binge drinking
– Drugs that mimic or stimulate SNS (cocaine, methamphetamines, ecstasy,
pseudoephedrine, excessive caffeine)
– Chemicals & toxic plants
– Snake venoms, multiple stings by wasps, bees, hornets
– Pharmaceutical agents – benzodiazepines, corticosteroids, narcotics,
immunosuppressants, antibiotics, antidepressants, antipsychotics
19
Associated Conditions cont.
•
Endocrinologic Disorders
– Either wasting or hypermetabolic conditions
– K+ wasting → diabetic ketoacidosis, hyperosmolar nonketotic coma,
hyperaldosteronism
– Na+ depletion → Addison disease
– ↑ sympathetic stimulation & metabolic demands beyond sustainability →
thyroid storm & pheochromocyoma
•
Genetic & Autoimmune Disorders
– Carbohydrate & lipid metabolism; muscular dystrophies, autoimmune
disorders such as polymyositis & dermatomyositis
Pathophysiology of rhabdomyolysis
•A clinical and biochemical syndrome
•The final common pathway is a disturbance
in myocyte calcium homeostasis
20
21
22
23
Pathophysiology of Myolysis
•Changes in Cellular Metabolism
•Reperfusion Injury
•Compartment Syndrome
J Am Soc Nephrol 2000;11:1553-1561
N Eng J Med 1990
Pathophysiology of Myolysis (1)
Changes in Cellular Metabolism
• Stretching of muscle cells
– Increases sacroplasmic influx of sodium, chloride and
water
– Cell swelling and autodestruction
– Large free calcium ions trigger persistent contraction
then cell death
• Calcium activates phosphalipid A2 (vasoactive)
• Invasion by activated neutrophils →release
proteases and free radicals
24
Pathophysiology of Myolysis (2)
Reperfusion Injury
• Most of the damage is not inflicted during
the period of ischemia, but after the blood
flow is restored
• Leukocytes migrate into damaged tissue
after reperfusion started
• Free radical starts when oxygen is amply
Pathophysiology of Myolysis (3)
Compartment Syndrome
• Striated muscle contained within rigid
compartments ischemic change
• Intracompartmental pressure rises as muscle
cells swells
• Compartment pressure > 30mmHg produce
clinically significant muscle ischemia
• Timing of faciotomy :
– In nonhypotensive > 50mmHg
– Between 30 and 50 mmHg show no tendency to
decrease after a maximum of 6 hr
25
Pathophysiology of Rhabdo.
•Goldman: Cecil Medicine 23rd ed
26
Pathophysiology of Rhabdo.
•Goldman: Cecil Medicine 23rd ed
Pathophysiology of Rhabdo.
Trauma or
physical injury
Toxin and drugs
Excessive activity
Hypoxia
Metabolic
Skeletal muscle cell
destruction
Electrolyte
disturbance
Infection
K, P, uric acid,
myoglobulin,
creatinine, creatine
kinase, lactic and
other organic acid,
Na, Cl, Ca, Water
Intracellular
Extracellular
American Family Physician (2002) 65:907-912
27
Clinical manifestations
•
•
•
•
Local features: muscular symptoms/signs
Systemic features: general disturbances
Complications
Classic triad: muscle pain, weakness, dark urine
American Family Physician (2002) 65:907-912
28
American Family Physician (2002) 65:907-912
ARF in rhabdomyolysis
• Incidence: 8-30%
• Associated with higher mortality and morbidity
compared to those patients who have
rhabdomyolysis without ARF
The journal of trauma (2004) 56:1191-1196
29
Hospital Physician (2008) Jan 25-31
PATHOGENESIS OF
RHABDOMYOLYSIS-INDUCED
RENAL FAILURE
1.Tubular necrosis initiated by free-radical
mediated lipid peroxidation
2.Renal vasoconstriction by several mechanisms
3.Tubular obstruction due to binding of free
myoglobin to Tamm-Horsfall protein and
hyperuricemia
• Compounded by hypovolaemia and aciduria
30
1.Tubular necrosis initiated by freeradical mediated lipid peroxidation
• This involves redox cycling between two oxidation
states of myoglobin haem: Fe3+ (ferric) and Fe4+
(ferryl)
• Ferryl (Fe4+) myoglobin can initiate lipid
peroxidation
• Its formation requires the presence of lipid
hydroperoxides (LOOH)
• Ferryl (Fe4+) myoglobin reacts with lipids (LH) and
.
lipid hydroperoxides (LOOH) to form lipid alkyl (L )
.
and lipid peroxyl (LOO ) radicals
• These radicals damage to phospholipid membranes
& cause progressive tubular damage
2. Renal vasoconstriction occurs
due to
• Reduced circulating blood volume
(hypovolaemia)
• Activation of the sympathetic nervous system
and renin-angiotensin system
• Scavenging of the vasodilator, nitric oxide (NO),
by myoglobin
• 15-F2t isoprostane and 15-E2t isoprostane are
potent vasoconstrictors
31
3.Tubular obstruction occurs due to
formation of tubular casts
• Formed by binding of free myoglobin to TammHorsfall protein (Uromodulin), most abundant
renal glycoprotein
Tubular obstruction occurs due to urate crystal
deposition (local inflammation)
Figure 1. Pathophysiology of acute renal failure in rhabdomyolysis
VANHOLDER, R. et al. J Am Soc Nephrol 2000;11:1553-1561
32
INJURY or EXCESSIVE MUSCLE STRAIN
compromise of capillary blood flow
PATHOPHYSIOLOGY
OF
RHABDOMYOLYSIS
MUSCLE FIBRE INJURY
CELL MEMBRANE BREAKDOWN
Physically - crushing, tearing, burning, pounding, poisoning, dissolving
Functionally - ↓ O2 needed for ATP prod which fuels Na+ K+ pump → anaerobic conditions break down
pump which helps maintain cell membrane
EXTRACELLULAR TO INTRACELLULAR MOVEMENT
Influx Na+ & H2O follows → cells swell & leave vasculature hypovolemic → hemodynamic instability
Cl - & Ca++ → hypocalcemia & calcium deposition into skeletal muscle and renal tissues
MOVEMENT OUT OF INJURED MYOCYTES
K+ moves from intracellular high [ ] into serum which normally has low [ ] and lethal hyperkalemia can rapidly
develop → risk for cardiotoxic effects & dysrhythmias aggrivated by coexistence of hypocalcemia &
hypovolemia
Phosphate → hyperphosphatemia which potentiates hypocalcemia (more Ca++ driven from serum into damaged
muscle & kidney tissue) - remember inverse relationship
Lactic Acid & Organic Acids → metabolic acidosis & aciduria
Purines (released from disintegrating myocytes are metabolized into uric acid & leade to hyperuricemia) →
nephrotoxic because damage renal tubules on contact
Myoglobin (dark red protein giving muscle red-brown color & O2 carrying molecule that supplies O2 to
myocytes → nephrotoxic (accumulates in renal tubules) in patients with oliguria & aciduria
→ lysis of 100g skeletal muscle = myoglobinuria
→ lysis of 200g skeletal muscle = notice change in urine color
thromboplastin (clot-promoting agent) & tissue plasminogen (thrombocyte substance) → ↑ risk DIC
CK (↑ serum total CK) → no toxic effects but ↑ plasma levels marker of ↑ muscle membrane permeability &
grossly high values indicate rhabdomyolysis (no other condition causes such high levels of CK increase)
NECROSIS,OBSTRUCTION OF RENAL TUBULES
ARF → ↑ mortality risk
Main drugs responsible for rhabdomyolysis,
together with the mechanism causing ARF
J Am Soc Nephrol 2000;11:1553-1561
Agent
Alcohol
Amphetamine
Amphotericin B
Antimalarials
Carbon Monoxide
CNS depressants
Cocaine
Colchicine
Corticosteroids
Diuretics
Ecstasy
Fibrates
HMG-CoA reductase
inhibitors
Heroin
Isoniazid
Laxatives
Licorice
Narcotics
Phencyclidine(PCP)
Zidovudine
Compression
+
+
Myotoxicity Hypokalemia
Other
+
+
Hypophosphatemia
Agitation
+
+
Energy deficiency, hypoxia
+
Hyerthermia, agitation
+
+
+
Agitation
+
+
+
+
+
+
+
+
+
Agitation, seizures
+
33
Diagnostic suggestions
•
•
•
•
•
•
History
Physical exam.
Laboratory studies
Histologic studies
Imaging studies: CT, MRI, bone scan
Procedures: measure compartment
pressures
Laboratory findings
• CK levels: most sensitive
Rises within 12 hours of the onset
Peaks in 1–3 days, and declines 3–5 days
5000 U/l or greater is related to renal failure
• Myoglobin in serum or urine
The early phases
Filtered by the kidney, plasma > 1.5 mg/dl→ appear in urine
Red–brown color to urine, >100 mg/dl
short half-life (2–3 hours)
Metabolized by liver
Critical care medicine(2002) 30:2212-2215
34
Heme pigment found in myoglobin (MW: 16700)
Hemoglobin -- transports O2 from lungs to
cells
Myoglobin -- stores O2 in cells
35
Causes of reddish-brown discoloration of the
urine
•
Myoglobinuria
‧rhabdomyolysis
‧ traumatic
‧ nontraumatic
•
Hemoglobinuria
‧ hemolysis
‧ mechanical damage
‧ immunologic damage
‧ structural fragility of RBC
‧ microangiopathy
•
Hematuria
‧renal causes
‧postrenal causes
•
External factors
‧ red beets
‧ drugs
‧ vitamin B12
‧ rifampin
‧ phenytoin
‧ metablites
‧ bilirubin
‧ porphyrin
36
Characteristics of urine and plasma in the different
conditions that may cause red discoloration of the urine
Characteristic
Red discoloration
Plasma
Positive benzidine
dipstick
Presence of
erythrocytes by
urine microscopy
Elevated CK
concentration in the
blood
Rhabdomyolysis
Hemolysis
Hematuria
-
+
-
+
+
+
-
-
+
+
-
-
An exam. reveals tender or
damaged skeletal muscles
•
•
•
•
•
CPK is commonly very high
Serum potassium may be high
Serum myoglobin test is positive
Urine myoglobin test is positive
Urinalysis may reveal casts and be
positive for hemoglobin without evidence
of RBCs
37
After suspecting rhabdomyolysis on the basis
of dark urine, perform the following test
1.Urine Dipstick: If positive for blood but no RBCs seen on
microscopic examination, myoglobinuria is very likely
(sensitivity > 80%).
2.CK: If the CK is > ~ 5,000 IU/L, then myoglobinuria is
likely.
3.Send specimen for myoglobin levels in blood and urine.
4.If any of the above tests are positive, check electrolytes,
BUN, Creatinine, and CK every 12 hours.
American Family Physician (2002) 65:907-912
38
39
Therapeutic plans
• The primary therapeutic goal is to prevent the
predisposing factors
• Initial stabilization
• Aggressive fluid resuscitation
• Preserve renal function
Diuretic therapy
Alkalinization of urine
Dialysis
• Free radical scavengers ?
• Correction of electrolyte disturbances
• Supportive therapy: DIC, compartment syndrome
Intensive care medicine (2001) 27:803-811
Renal failure (2001) 23:183-191
The journal of trauma (2004) 56:1191-1196
Critical care (2005) 9:158-169
Hospital Physician (2008) Jan 25-31
40
Hospital Physician (2008) Jan 25-31
41
Management
Hydration: with isotonic fluid, saline 1-2L/hr(Grade IB)
keep 200-300ml/hr urine output till CK begin to decrease.
Fluid administration strategy in patients with
impending or ongoing traumatic rhabdomyolysis
• Find a vein in arm or leg even if the patient is still trapped
• Administer fluid as early as possible: start with 1 L before
extrication
• Preferable fluid combination (for 2 L)
‧1 L of isotonic saline
‧1 L of glucose 5%+ 100 mmol bicarbonate
• Administer at least 3 to 6 L/d (in emergencies when supervision is
not guaranteed) or up to 10 L/d or more if continuous supervision
is available
• Add 10 ml of mannitol per hour if urine output is greater than 20
ml/h
42
Management
• Forced diuresis: Mannitol minimizes intratubular heme
pigment deposition, free-radical scavenger, reduces
blood viscosity, renal vasodilator
Evaluate plasma osm Q4-6H, osmolal gap↑
>55mosm/kg => stop Mannitol
• Loop diuretics (furosemide, bumetanide and torsemide)
– Increase tubular flow
– Decrease the risk of precipitation of myoglobin
– Simultaneously acidifying urine and increase calcium losses
Management
• Alkalinization of the urine> pH
6.5(Grade 2B): bicarbonate(75mmol in 11.5L saline), may worsen the degree of
hypocalcemia
• Volume expansion with saline alone
prevented progression to renal failure and
that the addition of mannitol and
bicarbonate had no additional benefit
J Trauma 2004;56:1191-1196
Crit Care Clin 2004;20:171-192
43
Management
• Role of free-radical scavengers and
antioxidants:
• Experimental models: reduced ischemia
reperfusion injury
• Mannitol
• Pentoxyphylline: improve microvascular blood
flow, neutrophil adhesion↓ cytokine release↓
• Allopurinol
– Reduces the production of uric acid
– Acts as a free radical scavenger
• Vitamin E, C…
Extracorporeal Blood Purification
• Who requires dialysis:
– acute renal failure, severe hyperkalemia and acidosis
• Fluid overload is a rare indication
• Hemodialysis advantages
– Provides efficient removal of solutes
– Creates the possibility without anticoagulants
– Provides the opportunity to treat severe patients per
day on the same dialysis post
44
Extracorporeal Blood Purification
• Continuous renal replacement therapies:
– Allows for the gradual removal of solutes and slow
correction of fluid
– Disadvantages: need anticoagulation
• Peritoneal dialysis
– Difficult in patients with abdominal trauma
– Insufficient for the removal of K+ and other
metabolites
• Plasma exchange: no demonstrated benefit!
J Am Soc Nephrol 2001;11:1553-1561
Crit Care 2005;9:158-169
The justification of prophylactic
dialysis treatment
• Dialytic treatment is the pathogenetic
therapy by myoglobin removal
Renal failure (2001); 23: 183-191
• CVVH improves myoglobin clearance 10%
per day in pig model
• Clinical advantage has not yet been
conveyed
Intensive care medicine (2001);27:803-811
45
Is elevated serum CK level an indication for
renal replacement therapy in rhabdomyolysis?
• No, because:
For treatment:
1. CK itself is not harmful
2. If no other indication
For prevention of ARF:
1. Efficacy of preventive role of dialytic therapy
is not established
2. CK eliminates slower than myoglobin
3. No definite level of CK predict renal failure
5 times, >5000, >10000 ?J Trauma 2004;56:1191-1196
Hospital Physician (2008) Jan 25-31
46
Treatment Interventions
1. Prevention & early recognition are first steps
–
Muscle and renal cells fairly resilient
2. Minimizing amount of muscle damage
–
–
Limit ongoing release of intracellular contents
Extricate from trapped state, minimize immobilization, release
compartment syndrome, attempt to correct underlying cause
Treatment Interventions cont.
3. Enhancement of toxin clearance
– Restoring intravascular volume → isotonic crystalloids (up to 1.5L/hr)
– Inducing solute diuresis → mannitol (keep kidneys flushed & prevent
formation of casts in tubules) & diuretics (caution with Lasix as it can
acidify urine)
– Alkalinize urine (pH>6.5) → add sodium bicarbonate to IV
crystalloids to prevent dissociation of myoglobin to its nephrotoxic
metabolites
• Acetazolamide (carbonic anhydrase inhibitor) if arterial pH>7.45 after
bicarb treatment because it corrects metabolic alkalosis & ↑ urine pH
– Hemodyalysis when other treatment interventions fail
• management of oliguria, persistent electrolyte imbalance, resistant
metabolic acidosis (keep plasma pH 7.4-7.45), uremic encephalopathy
or fluid overload
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Treatment Interventions cont.
4. Supportive therapy
–
–
–
–
–
Ongoing monitoring of urine output (>300ml/hr until urine negative for
myoglobin)
Ongoing assessment for complications of disorder & therapy to
manage/correct disorder
Include psychosocial support for patient & family/support system
Invasive arterial & pulmonary artery pressure monitoring → accurately
assess volume status
Limit use of nephrotoxic antibiotics (aminoglycosides) & iodinated
radiocontrast medium
Take home message about
Rhabdo.
• Impairment of the production or use of ATP is
the basic cause
• Most useful laboratory findings are elevated
CK(> 5000U/L related to ARF), initial detection
of myglobulin
• Management: Aggressive hydration, diuresis,
urine alkalinzation, free-radical scavengers,
dialysis (as early as possible if need!)
• Do not treat hypocalcemia unless symptoms
developed
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Thanks for your attention!
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