1	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
2	GOALS AND OBJECTIVES
3	MYOGLOBIN AND MYOGLOBINEMIA/MYOGLOBINURIA
4	IMAGE: Molecule
5	IMAGE: Heme group
6	Myoglobin appears following muscle membrane destruction Many etiologies of muscle membrane destruction 26,000 cases of rhabdo each year in US
7	RAPID TEST FOR MYOGLOBIN Urine dipstick for hemoglobin then check for RBCs sensitivity 80% Urine dipstick for myoglobin sensitivity 20% CK over 10,000
8	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
9	FACTORS LEADING TO RHABDOMYOLYSIS
10	MANIFESTATIONS OF RHABDOMYOLYSIS
11	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
12	COMPLICATIONS ASSOCIATED WITH MYOGLOBINURIA
13	HISTORY OF PERIOP RHABDO
14	SUCCINYLCHOLINE AND MYOGLOBIN RELEASE
15	IMAGE: Rise in SCPK 24 hours post-operatively
16	CK RELEASE IN CHILDREN HAVING ROUTINE SURGERY
17	HYPERKALEMIC CARDIAC ARREST DURINGANESTHETICS IN INFANTS AND CHILDREN WITH OCCULT MYOPATHIES Larach, Rosenberg, Gronert, Allen Clinical Pediatrics 1997
18	Patients Predisposed to Myoglobinuria Heat Stroke Victims Drug/Alcohol Abusers Psychoactive Drugs, NMS Cholesterol Lowering Agents Myopathies Status epilepticus Electrolyte Imbalance Infection Major Trauma MH Susceptibles
19	Pharmacologic Agents and Rhabdo
20	Case Report
21	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?
22	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
23	Neurolept 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
24	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
25	Signs of NMS Lead pipe rigidity Altered mental state Hyperthermia Rhabdomyolysis Autonomic instability : tachycardia, hypo/hypertension
26	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
27	MYOPATHIES AND RHABDOMYOLYSIS
28	MYOPATHIES AND RHABDO
29	OTHER DISORDERS
30	Patient Position as a Cause of Rhabdomyolysis
31	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
32	IMAGE: exaggeraged lithotomy position
33	Gastric Bypass in the Morbidly Obese 1.4% of morbidly obese with laparascopic bypass surgery Generally surgical times>4hrs
34	PRONE POSITION : VISCERAL HYPOPERFUSION AND RHABDOMYOLYSIS
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36	Major Surgery Per Se does not seem to cause significant rhabdo
37	MALIGNANT HYPERTHERMIA AND RHABDO
38	SUCC INDUCED MMR Always associated with rhabdo If CK >20,000 usually associated with MHS or DMD
39	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
40	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
41	Similar case by Harwood and Nelson, Anesthesiology 1998
42	HOW OFTEN IS POST OP RHABDO A SIGN OF MH?? 3/475 hospitalised patients with rhabdo at JHU were found to have MHS(1993-2001) Melli, G et al, Medicine 2005
43	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
44	MYOGLOBINURIA IN THE PACU
45	EVALUATION OF ELEVATED CK/RHABDOMYOLYSIS
46	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
47	CREATINE KINASE POST SURGERY
48	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
49	CAN POST OP CK BE DIAGNOSTIC FOR MH?
50	Additional Causes of Rhabdo in ICU Disease state ICU myopathy Sepsis Ischemia Hyperthermia per se Status epilepticus Drugs Neuroleptics, esp haloperidol Propofol infusion
51	TREATMENT OF RHABDOMYOLYSIS
52	CONCLUSIONS
53	THANK YOU