Pseudocholinesterase Deficiency

Report
Pseudocholinesterase
Deficiency
Etiology and considerations
Angela Hepler
RN, BS Biology, SRNA
Allegheny Valley Hospital School of
Anesthesia
Objectives
• 1. Review physiology, diagnosis, prevalence,
and effects of pseudocholinesterase deficiency
• 2. Address the management implications and
contraindications which result
• 3. Discuss alternative therapy choices
Case Study
• 64 year old male undergoing craniotomy listing
Succinylcholine as an “allergy”
• The patient has a diagnosis of pseudocholinesterase
deficiency, secondary to a muscle biopsy
• H&P reveals hypertension, CAD, and hyperlipidemia
Concerns
Craniotomies often involve:
• Remifentanil, Propofol, and 0.5 MAC of volatile agent
• Succinylcholine for induction, no long term paralytics
• Antihypertensives on emergence, sometimes including
Esmolol
Succinylcholine is contraindicated, but can we still use
Remifentanil and Esmolol?
A&P Review
• The Motor Neuron Body resides within the Grey Matter of
the spinal chord
• Axon terminates within the target muscle Myofibrils
• Endplate
• Neuromuscular Synapse
• Propagation of the impulse:
• Releases Acetylcholine (Ach) into the synaptic cleft
• Engages Nicotinicm receptors on the distal neuron
• Depolarizes and contracts the innervated muscle
Motor neuron
Motor end
plate
Tb
Succinylcholine
• First used in 1951
• Chemically similar to 2 Acetylcholine (Ach) molecules
• Depolarizing neuromuscular blockade
• A competitive antagonist of Ach
• Short term paralysis, limited by pseudocholinesterase
metabolism
Acetylcholine and Succinylcholine
Acetylcholine
Succinylcholine
Indications for Succinylcholine
• Rapid Sequence Induction (RSI)
• Electroshock Therapy (ECT)
• Motor evoked potential (MEP) monitoring
• Any situation where brief paralysis is desirable
Pseudocholinesterase
• Located on Chromosome 3
• Also known as:
Acetylcholine Acyl Hydrolase
Butyrylcholinesterase (BChE)
• Primary metabolic pathway for
Succinylcholine
H
,
Pseudocholinesterase
• Present in all tissues except RBCs
• Represents 0.01% of total body protein
• Results in Ester hydrolysis of:
Succinylcholine, Mivacurium, Ester LA, Heroin, and Cocaine
• Unknown physiological use
Pseudocholinesterase
• Normal levels range from 3,000- 6,600 IU/L
• Lab testing is available for direct quantification
• Reportedly ≥ 80% of patients presenting with symptoms
will have atypical pseudocholinesterase present
Pseudocholinesterase inhibitors
• Onset of symptoms usually occurs when 75%
suppression of the wild type is present
• Can occur with as little as 50% depression, depending on
comorbidities and coexisting conditions
Pseudocholinesterase inhibitors
• Each can decrease the effectiveness of normal BChE:
• Advancing Age
• Renal failure
• Malnutrition
• Hepatic failure
• Pregnancy
HELLP -Induced Deficiency
• Case study:
• Primigravida at 29 wk gestation, presented with
abdominal pain
• Day 1-2: medically managed, tocolytics administered
• Day 3: Rapid elevation in LFT’s and deterioration,
decision made  C-Section
Departure from “the norm”…..
HELLP-Induced Deficiency
• Case study (cont.):
• Plt count 125,000/µL- Spinal and Epidural deferred
• GETA, intraoperatively stable, no long term paralysis
• End of surgery: No response to TOF stimulus
•  ICU, extubated 3 hours post section
• Pseudocholinesterase levels ~ 2,200 IU/L
• Spontaneous return to normal levels as LFT’s
returned to baseline on POD 16
Other Cholinesterase inhibitors
• Organophosphates- permanent
• Carbamates – temporary (our reversal agents)
• Various medications:
some antidepressants, antibiotics, and chemotherapeutics
echothiophate, LAs, cocaine and heroin
• Malignancies
• Burns
• Cardiopulmonary Bypass
Comorbidities with multifaceted deficiency
• Case Study:
• 54 year old female
• 5’4”, 156 kg
• OSA
• Recent prolonged exposure to pesticides
Presenting with Cellulitis of the Abdomen; for I&D
Comorbidities with multifaceted deficiency
• Case Study:
• No TOF response post Succinylcholine
• Remained intubated x 12 hours
• Post op Pseudocholinesterase level: 552 IU/L
• 6 months post: ~ 700 IU/L: Undiagnosed homozygous
deficiency
Atypical Pseudocholinesterase
• Results from a mutation of the BCHE gene
All atypical varieties are autosomal recessive:
• Heterozygous patients: minimal prolongation of paralysis
• Homozygous: variable paralysis, from 1-4 hours or more
• More prevalent among:
• Inuit / Native Alaskans
• Persian descendants/Jewish communities
• Specific Hindu populations
The Genetics Of It All
N
d
N
N
NN
Nd
N
NN
NN
dd
Nd
d
Nd
Nd
N- normal genetic coding (wild type allele)
d- heterozygous, atypical BCHE (carrier)
- homozygous, atypical BCHE
Pseudocholinesterase Variants
• Up to 98% of individuals are homozygous
for normal pseudocholinesterase
• 4 major varieties, with 65 variants known
Pseudocholinesterase Deficiency types
1. K variant
•
Minimal effects alone, but often present in
conjunction with other variants
•
Slight prolongation of apnea
•
Most prevalent variant (1.5% population)
Pseudocholinesterase Deficiency types
2. Dibucaine resistant/ Atypical
•
First subtype identified
•
Paralysis can last up to 2 hours
•
Affects 0.01-0.03%
Pseudocholinesterase Deficiency types
•
Dibucaine Number
•
A qualitative test of enzyme activity
•
Dibucaine (Nupercaine) attenuates normal enzyme
action, but the atypical type is unaffected
•
Normal: 80 (80% attenuation of BChE)
•
Heterozygous: 40-60 (reduced attenuation)
•
Homozygous: 20 or less (only slight attenuation
noted)
Pseudocholinesterase Deficiency types
(cont.)
• 3. Silent variant
o Homozygous results in complete lack of
pseudocholinesterase
o All metabolism by alternative methods
o Relatively rare (0.008-0.01%)
o Paralysis can last 3-4 hours
Pseudocholinesterase Deficiency types
(cont.)
• 4. Fluoride resistant
• Very rare (0.0007%)
• Effects similar to Dibucaine resistant variant
•
Fluoride number
• Quantitative test, similar to Dibucaine number test
• Normal Fluoride number: 55-65
Treatment…….
Treatment
• Supportive measures for unanticipated prolonged paralysis
• Known Congenital deficiency:
• Avoid Succinylcholine with known congenital deficiency
• Avoid Tetracaine, Chloroprocaine, and Procaine (OB patients)
• Consider NDMR in patients with potential for attenuated
pseudocholinesterase activity
• ALWAYS assess for return of muscle function (TOF) prior
to NDMR following Succinylcholine administration
Alternative Therapies
• RSI and ECT- Consider low dose Rocuronium,
Vecuronium or Cisatracurium
• MEP testing- consider Remifentanil for depressed
respiratory effort (cough) and/or higher volatile agent
concentrations
• Plant-derived recombinant pseudocholinesterase?
What about our Case Study?
What about our Case Study?
• Remifentanil- metabolized by nonspecific plasma
esterases
• Esmolol- metabolized by RBC esterases
Both are unaffected by BChE deficiency
What about our Case Study?
• Our plan of care:
• Intubated with minimal Rocuronium dosage, with
spontaneous recovery during positioning
• Baseline MEP’s then obtained
• Remifentanil, Propofol, and 0.5 MAC
• Nitroglycerin, Hydralazine, and Labetalol used on emergence
• Patient awake within 5-7 minutes of Remifentanil termination,
fully responsive with no respiratory depression
Summary
• Pseudocholinesterase (BChE) deficiency can be:
• 1. Drug, environment, or comorbidity induced (affecting quality)
• 2. Congenital (affecting quantity of true BChE)
• Heterozygous carriers -slightly prolonged paralysis
• Homozygous silent type -most prolonged paralysis
• Alternative therapies include intermediate acting paralytics,
volatile gases, and opioids
Questions?
References
• Soliday, Conley, Henker. “Pseudocholinesterase deficiency: A Comprehensive
•
•
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•
•
Review of Genetic, Acquired, and Drug Influences.” AANA Journal 2010: Vol. 78,
No. 4, p313-320.
http://stevegallik.org/sites/histologyolm.stevegallik.org/htm/HOLM_Chapter07_Page
06.html
Manullang, J., and T. D. Egan. "Remifentanil's effect is not prolonged in a patient
with pseudocholinesterase deficiency." Anesthesia and analgesia 89.2 (1999): 529.
Niazi, Ahtsham, Irene E. Leonard, and Breda O'Kelly. "Prolonged neuromuscular
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Journal of clinical anesthesia 16.1 (2004): 40-42.
Williams, Joseph, et al. "Pseudocholinesterase deficiency and electroconvulsive
therapy." The journal of ECT 23.3 (2007): 198-200.
Lang, John B., Susan A. Kunsman, and Michael T. Hartman. "Acquired
pseudocholinesterase deficiency." Current Anaesthesia & Critical Care 21.5 (2010):
297-298.
References
• Lurati, A. R. "Organophosphate exposure with pseudocholinesterase
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•
•
deficiency." Workplace health & safety 61.6 (2013): 243-245
Geyer, Brian C., et al. "Reversal of Succinylcholine Induced Apnea with an
Organophosphate Scavenging Recombinant Butyrylcholinesterase." Plos one
8.3 (2013): e59159.
Bryson, E. O., et al. "Prolonged succinylcholine action during
electroconvulsive therapy (ECT) after cytarabine, vincristine, and rituximab
chemotherapy." The journal of ECT 27.1 (2011): e42.
Sivak, Erica L., and Peter J. Davis. "Review of the efficacy and safety of
remifentanil for the prevention and treatment of pain during and after
procedures and surgery." Local and regional anesthesia 3 (2010): 35.
Cerf, C., Mesguish, M. et al. “Screening patients with prolonged
neuromuscular blockade after Succinylcholine and Mivacurium.” Anesthesia
& Analgesia 2002; 94:461-66.
Lurie, Samuel, Sadan, Oscar, et al. “Pseudocholinesterase deficiency
asociated with HELLP syndrome”. American Journal of Perinatology, 2004;
21:315-17.

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