Pseudocholinesterase Deficiency

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Transcript Pseudocholinesterase Deficiency

Etiology and considerations
Angela Hepler
RN, BS Biology, SRNA
Allegheny Valley Hospital School of
• 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
Craniotomies often involve:
• Remifentanil, Propofol, and 0.5 MAC of volatile agent
• Succinylcholine for induction, no long term paralytics
• Antihypertensives on emergence, sometimes including
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
• 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
Acetylcholine and Succinylcholine
Indications for Succinylcholine
• Rapid Sequence Induction (RSI)
• Electroshock Therapy (ECT)
• Motor evoked potential (MEP) monitoring
• Any situation where brief paralysis is desirable
• Located on Chromosome 3
• Also known as:
Acetylcholine Acyl Hydrolase
Butyrylcholinesterase (BChE)
• Primary metabolic pathway for
• 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
• 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
• 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
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- 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
Pseudocholinesterase Deficiency types
• 3. Silent variant
o Homozygous results in complete lack of
o All metabolism by alternative methods
o Relatively rare (0.008-0.01%)
o Paralysis can last 3-4 hours
Pseudocholinesterase Deficiency types
• 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
• 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
• Plant-derived recombinant pseudocholinesterase?
What about our Case Study?
What about our Case Study?
• Remifentanil- metabolized by nonspecific plasma
• 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
• 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
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