Download Rhabdomyolysis in the Perioperative Period

Rhabdomyolysis In The
Perioperative Period
Henry Rosenberg, MD
Director, Department of Medical
Education and Clinical Research
Saint Barnabas Medical Center
Livingston, NJ
President of MHAUS
Professor of Anesthesiology
Mount Sinai School of Medicine
Goals And Objectives
• Discuss pathophysiology of
rhabdomyolysis
• Describe the clinical implications of rhabdo
• Discuss the differential diagnosis of
perioperative rhabdo
Myoglobin And
Myoglobinemia / Myoglobinuria
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Heme protein of 15,500mol weight
Found in muscles of vertebrates
Oxygen store/transfer
Necessary for oxygen consumption /
contraction / membrane integrity
muscle
Myoglobin Appears Following
Muscle Membrane Destruction
• Many etiologies of muscle membrane
destruction
• 26,000 cases of rhabdo each year in US
Rapid Test For Myoglobin
• Urine dipstick for hemoglobin then
check for RBCs -- sensitivity 80%
• Urine dipstick for myoglobin -sensitivity 20%
• CK over 10,000
Pathophysiology Of Rhabdo
• Energy supply not adequate to maintain membrane integrity
because of low ATP
– Increased demand — MH hyperthermia, exercise, seizures
– Decreased production – Ischemia, metabolic disturbances,
glycogen storage disease, propofol infusion
• Direct membrane destruction
– Toxins, e.g .infection
– Drugs
– Disease,eg. dystrophies
Factors Leading To
Rhabdomyolysıs
ABNORMAL MUSCLE METABOLISM
• Myopathies, e.g. glycogen storage disease, CPTdeficiency
MAXIMAL FUEL EXHAUSTION
• Exercise, especially in heat environments
• Seizures
• Contractures secondary to drugs
TRAUMA/ISCHEMIA
• Crush injuries
• Surgery
• Compression
Manifestations Of Rhabdomyolysis
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Brown or cola colored urine, heme pos, without RBC’S
Myoglobinemia
Myoglobinuria
Elevated creatine kinase
Elevated LDH;Decreased Ca++2 Incr P04
Renal failure –
~50% of patients with rhabdo develop ARF
• Causes 5-25% of ARF
Pattern Of Myoglobin Release
• Myoglobin appears within minutes or hours of
injury
• Myoglobin is cleared by the kidney rapidly
• Creatine kinase appears after several hours
• Peak CK is 14-20 hours after injury
• Brown urine appears when CK over ~10,000
• Hyperkalemia often associated
Complications Associated With
Myoglobinuria
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Renal Failure
Muscle Swelling and Edema
Compartment Syndrome
Hyperkalemia, hypocalcemia
History Of Periop Rhabdo
• 1960s-70s rhabdo associated with succ
• Ryan found that 40% of children receiving succ
develop myoglobinemia •Greater CK release
with succ and inhalation agents
1970s:Recognition of MH as cause of rhabdo
• 1980s:Recognition of occult myopathy and
rhabdo
• Drugs and rhabdo
• Surgical causes of rhabdo
Succinylcholine And
Myoglobin Release
Ryan, Kagen and Hyman, 1971
Myoglobin Release in 1/30 Adults, 17/40 Children
Tammisto, 1966; Innes, 1973; Plotz, 1982
Succinylcholine, Especially with Halothane
Associated with CK Release, Myoglobinemia
(Occasionally 40fold Increase)
Noguchi, 1993
Thiopental, Propofol Reduces Myoglobin Release
InnesR and Stromme J, BJA(1973)45.185.
CK Release In Children
Having Routine Surgery
Anesthesia
Pre-Op CK
20 Min.
Halo/succ
58
174
TPL (4 mg/kg)/succ
60
114
No succ
60
61
Myoglobin Release
Anesthesia
Pre-Op Mb
60 Min.
Halo/succ
19
2192
TPL (4 mg/kg)/succ
19
796
No succ
22
40
Hyperkalemic Cardiac Arrest During Anesthetics
In Infants And Children With Occult Myopathies
Number of Patients
25 (92 % Male)
Age Range
3 – 151 Months (Mean 45)
Mortality
40 %
DMD Diagnosed
7/8
Potassium Above 6
13 / 18
Succ Adm
60 %
Myopathy dxed
9 / 15
Previous anes
32 %
CK
118, 558 (2, 784-174,376)
Larach, Rosenberg, Gronert, Allen
Clinical Pediatrics 1997
Patients Predisposed To Myoglobinuria
Heat Stroke Victims
Status Epilepticus
Drug/Alcohol Abusers
Electrolyte Imbalance
Psychoactive Drugs, NMS
Infection
Cholesterol Lowering Agents
Major Trauma
Myopathies
MH Susceptibles
Larach, Rosenberg, Gronert, Allen
Clinical Pediatrics 1997
Pharmacologic Agents and Rhabdo
Drugs of Abuse
Pharmacologic Agents
Alcohol
Statins
Ephedra
Propofol
MDMA
Psychoactive Drugs
Cocaine
Haldol,SSRIs
Amphetamines
Steroids
Anabolic steroids
Succ
Colchicine
Zidurovine
Many others, sporadically
Case Report
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46 yo extreme body builder
124kg
Received succ and sevo for peripheral surgery
CK Post op 18,870, Creatinine 1.6
SGOT 448, SGPT 167
Drugs:
– Testosterone
– Fenofibrate, Zetia
• No history of MH
Statins and Anesthesia
• Few reports suggest a relation
• Incidence of rhabdo in patients on statins:
– High with fibrates: e.g. gemfibrizol and
lovastatin: 5%
• Most statins alone: ~`0. 2%
– increased with various CYP 3A4 inhibitors
– increased with age >65
• Should statins be discontinued prior to surgery?
Intrathecal Contrast
Injection of water soluble, ionic contrast agent into
CSF produces:
•Ascending tonic –clonic syndrome, seizures,
hyperthermia after 1-2 hr delay
•Loss consciousness, rhabdomyolysis
•Diagnostic feature: contrast in cerebral ventricles
on CT
•Treatment is supportive
Neuroleptic Malignant Syndrome
NMS is a potentially fatal, idiopathic
hypermetabolic response to a variety of
neuroleptics and dopamine receptor blocking
agents.
• Although peripheral manifestations include
rhabdomyolysis and rigidity, the
pathophysiologic changes occur in the CNS
• Treatment with dantrolene, benzodiazepines,
dopamine agonists have been effective
Principle Features of NMS
• Hypermetabolic response to potent neuroleptics and to
dopamine receptor blocking drugs
• Incidence 0.2% of those taking
neuroleptics/antipsychotics
• Onset may be gradual or slow
• Not inherited
• No animal model
• Responsive to a variety of drug treatments
Signs of NMS
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Leadpipe rigidity
Altered mental state
Hyperthermia
Rhabdomyolysis
Autonomic instability: tachycardia, hypo
/hypertension
Serotonin Syndrome
• Fever, acidosis, hypertension,
rhabdomyolysis,delirium, following use of drugs
that increase serotonin levels
• Increase release:
– Cocaine, Amphetamines, Meperidine, MDMA
• Decrease uptake:
– Tranylcypromine, Paroxetine, etc
Myopathies And Rhabdomyolysis
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Malignant Hyperthermia
Muscular Dystrophy and Dystrophinopathies
DMD, BMD, Myotonias
CPT-2 Deficiency
Disorders of Glycogen Metabolism
Myophosphorylase def (McArdle’s)
PFK, PGK other defects in Glycogenolysis
Mitochondrial Myopathies
Myopathies And Rhabdo
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Hypothyroid myopathy
Polymyositis
Denervated muscle
CCD
Myoadenylate Deeaminase Deficiency?
Other Disorders
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Trauma per se
Sepsis
Seizures (status)
Pheochromocytoma
Ischemia/reperfusion
New onset diabetes in adolescent
Patient Position As A
Cause Of Rhabdomyolysis
Lithotomy Position and Rhabdo
Compartment syndrome ,rhabdomyolyis and risk of acute
renal failure as a complications of the lithotomy position
Bocca G et al . J of Nephrology.2002:15:183-5
Risk factors:
• Obesity
• Duration > 4hrs
• Hypotension
• PVD
Gastric Bypass In The Morbidly Obese
• 1.4% of morbidly obese with laparascopic
bypass surgery
• Generally surgical times > 4hrs
Prone Position:
Vısceral Hypoperfusıon
And Rhabdomyolysıs
Ziser A., Friedhoff R.
Anesth Analg
1996; 82: 412 - 5
Rhabdomyolysis And Myonecrosis In A
Patient In The Lateral Decubitis Position
Mathes D., Assimos Dg.
Anesthesiology 1996; 84:727- 5
Major Surgery Per Se Does Not
Seem To Cause Significant Rhabdo
Malignant Hyperthermia And Rhabdo
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Frequently seen with MH
May appear early in the PACU
May appear >12 hours
May not be present at all
– Dose of agent
– Prompt recognition and rx
– Genotype
• May be the only sign of MH!!
Succ Induced MMR
• Always associated with rhabdo
• If CK >20,000 usually associated with
MHS or DMD
Rhabdomyolysis Post Anesthesia
• 48 yo male(109kg) for umbilical hernia repair.
• Anesthetic was propofol and 180mg succinylcholine,
followed by nitrous oxide-isoflurane-fentanyl.
• No problems intraoperatively. One hour case.
• Three days post op readmitted for myalgia,malaise,
vomiting
• BUN 56 mg/dl, CK 12,041
McKenny, K, Holman SJ. Anesthesiology 2002
Rhabdomyolysis Post Anesthesia
• Patient diuresed and renal function returned to
normal in fourteen days.
• Contracture to 3%halothane: 1.1g, 1.2g
• Contracture to 2mM caffeine: 0.5g, 1.0g
• No histologic abnormality. No RYR mutation
found
Similar case by
Harwood and Nelson,
Anesthesiology 1998
How Often Is Post Op Rhabdo
A Sign Of MH?
3 / 475 hospitalized patients with rhabdo at JHU
were found to have MHS(1993-2001)
Melli, G et al, Medicine 2005
A Variety Of Causes For Rhabdo
Reported To MH Hotline
• Source: MH hotline calls 1997-1999
• 77/554 calls were for rhabdo
– 26 thought to be MH
– 7 with MMR after succ
– ER and ICU :
• NMS, diabetic acidosis, heat stroke , trauma, sepsis, CP
bypass, direct pressure injury, hypoxic encephalopathy
• Renal failure -2
• Death: 6—MH, hyperkalemia, hypoxic encephalopathy,
sepsis, psychoactive drugs
Brandom, Rosenberg, A&A. S91,2001
Myoglobinuria In The PACU
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Is it myoglobin or hemoglobin?
Did the patient have a myopathy?
What drugs were used?
Succinylcholine, inhalation agents
What position and for how long?
Manifestation of malignant hyperthermia?
Intraoperative sepsis?
Evaluation Of Elevated
Ck / Rhabdomyolysis
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How high was the CK?
Is it in the range that is anticipated?
Was the CK elevated preoperatively?
What was the patient’s position?
Ischemia?
What medications was the patient taking?
Evaluation Of Elevated
Ck / Rhabdomyolysis
• Personal and family history of muscle disease/muscle
cramps?
• •Exercise related muscle problems?
• Neurologic exam with EMG
• Muscle biopsy
– Structural abnormalities
– Metabolic abnormalities
– Halothane/caffeine contracture test
Creatine Kinase Post Surgery
ALL SURGERY
N 135
Peak CK (Mean + SD)
722 + 266
Neck
35
460 + 145
Thoracic
30
1260 + 320
Abdominal
38
760 + 106
Genitourinary
22
842 + 220
Orthopedic
10
540 + 180
ALL MI
100
852 + 120
Roberts R Arch Int Med 1976
Rhabdomyolysis And MH
• Not present in all cases of MH
• Dark urine appearing in PACU or at end of long
case
• Dark urine in association with MH episode
• MMR is always associated with myoglobinuria
• Post op myoglobinuria as a sign of MH
Can Post Op Ck Be
Diagnostic For MH?
• Not usually
Creatine Kinase Alterations after Acute MH
and Common Surgical Procedures
Antognini, JF;Anesth Analg 81:1,1995
75% of MHS had CK in range of peak CK
occurring as a result of surgery only!
Additional Causes Of Rhabdo In ICU
• Disease state
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ICU myopathy
Sepsis
Ischemia
Hyperthermia per se
Status epilepticus
• Drugs
– Neuroleptics, esp haloperidol
– Propofol infusion
Treatment Of Rhabdomyolysıs
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Hydration and Diuresis
Alkalinization of the Urine
Check for Elevated Potassium
Follow CK
Determine the Etiology
Conclusions
• MH is only one of many causes of post op
rhabdo
• Rhabdo may occur from disease, drugs,
position, trauma
• Rhabdo may occur early or late
• A thorough history of previous disorders and
drugs is essential
• Of all anesthetic drugs succ is most often
implicated in rhabdo.
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