1. Pseudocholinesterase Deficiency
Etiology and considerations
Angela Hepler
RN, BS Biology, SRNA
Allegheny Valley Hospital School of Anesthesia

2. 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

3. 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
My interest in p.d. began during my neuro rotation at AGH, when I was presented with a….

4. 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?
Remifentanil suppresses the respiratory drive, reduces the cough reflex (important in pins!), is a great analgesic, and is short acting, which allows for neuro assessment immediately postop
Succinylcholine for induction as MEP’s and SSEP’s will be performed and long term paralysis is contraindicated

5. Time to tap into the biology nerd that lives in all of us (I happen to be mostly bio nerd….)

6. Time to tap into the biology nerd that lives in all of us (I happen to be mostly bio nerd….)

7. 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

8. Ventral= motor, Dorsal= sensory

9. Terminal neuromuscular junction
Channel is opened by Ach and Na channels are opened, propagating the impulse to the muscle

10. Motor neuron Tb Motor end plate MEP- motor end plate
Tb- terminal bouton/ synaptic knob- results in one singular chemical synapse to the adjoining myofibrils Tb

12. 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
Mimics Ach’s ability to open nicotinic m receptors, but due to the relative lack of Bche as compared to AchE, it maintains receptor activation until displacement and diffusion occur, usually w/in 3-10 minutes

13. Acetylcholine and Succinylcholine
Red- oxygen grey- CH1, CH2 or CH3) blue-nitrogen
Acetylcholine
Succinylcholine

15. Indications for Succinylcholine
Rapid Sequence Induction (RSI)
Electroshock Therapy (ECT)
Motor evoked potential (MEP) monitoring
Any situation where brief paralysis is desirable

16. Pseudocholinesterase
Located on Chromosome 3
Also known as:
Acetylcholine Acyl Hydrolase
Butyrylcholinesterase (BChE)
Primary metabolic pathway for Succinylcholine
PHASE 1 Hydrolysis of one of the single bonded O’s, resulting in a succinylmonocholine and a succinic acid molecule

17. H succinylcholine nicotinic m receptor, exerts its effects
Pseudocholinesterase enters, cleaving the succinylcholine at one of its terminal oxygens
Succinic acid is cleaved and released
Available hydrogen then bonds to the oxygen molecule, creating succinylmonocholine- inactive

18. ,

19. 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
Acetylcholinesterase are found on RBC membranes as well as tissues; pseudo produced in liver
Ester LA such as procaine, tetracaine, and chloroprocaine

20. 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

21. 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

22. Pseudocholinesterase inhibitors
Each can decrease the effectiveness of normal BChE:
Advancing Age
Renal failure
Malnutrition
Hepatic failure
Pregnancy
**Pregnancy- usu. not clinically significant, but may be w/ester LA’s!**
Hepatic- lack of synthesis
Renal- unknown MOA
Malnutrition- lack of protein synthesis

24. 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

25. Departure from “the norm”…..
Deviation from our standard spinal or epidural for c-section

26. 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

27. 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
Organophosphates- lice treatments, pesticides, chemical weapons like SARIN
Carbamates- our anticholinesterase reversal agents (neostigmine, physostigmine)
Antibiotic- clindamycin
Especially malignancies/disorders of the liver
Burns- usu not an issue, avoided after first hours due to hyperkalemia
CPB- dilutional reduction

28. 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

29. What we know about pesticides (anticholinesterases, make Ach too available. s/s of this)

30. 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
Possibly further complicated by organophosphate exposure

31. 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
Arva Vysya

32. The Genetics Of It All N N N NN Nd NN NN dd Nd Nd Nd N d
Any unknown pseudocholinesterase deficient patient will come from one of these two Punnett square genetic coding. As you can see, the risk for homozygous deficiency is only 1 in 8 even when one or more parents silently carry the gene. However, the risk of heterozygous deficiency is more than 50% if any parent is themselves heterozygous. This is why testing family members is so critical post discovery
N- normal genetic coding (wild type allele)
d- heterozygous, atypical BCHE (carrier)
- homozygous, atypical BCHE

33. Pseudocholinesterase Variants
Up to 98% of individuals are homozygous for normal pseudocholinesterase
4 major varieties, with 65 variants known
Some case studies report periods as long as 12 hours in patients with respiratory comorbidities

35. 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)

36. Pseudocholinesterase Deficiency types
2. Dibucaine resistant/ Atypical
First subtype identified
Paralysis can last up to 2 hours
Affects %

37. 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: (reduced attenuation)
Homozygous: 20 or less (only slight attenuation noted)
As opposed to direct serum BCHE levels
Interestingly, Dibucaine is an amide LA (does not affect deficient patients)

38. Pseudocholinesterase Deficiency types (cont.)
3. Silent variant
Homozygous results in complete lack of pseudocholinesterase
All metabolism by alternative methods
Relatively rare ( %)
Paralysis can last 3-4 hours

39. 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

40. Treatment…….

41. 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
Notify patients who exhibit prolonged effects and explain need for testing/further evaluation

42. 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?
Remember that Cisatracurium undergoes ester hydrolysis - dilutional or ↓ protein production may decrease metabolism
Plant derived pseudocholinesterases are used to reverse organophosphate ODs

43. What about our Case Study?

44. What about our Case Study?
Remifentanil- metabolized by nonspecific plasma esterases
Esmolol- metabolized by RBC esterases
Both are unaffected by BChE deficiency
Remifentanil- hydrolysis = loss of mu receptor effects

45. 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

46. 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

47. Questions?

48. References
Soliday, Conley, Henker. “Pseudocholinesterase deficiency: A Comprehensive Review of Genetic, Acquired, and Drug Influences.” AANA Journal 2010: Vol. 78, No. 4, p
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 blockade as a result of malnutrition-induced pseudocholinesterase deficiency." Journal of clinical anesthesia 16.1 (2004):
Williams, Joseph, et al. "Pseudocholinesterase deficiency and electroconvulsive therapy." The journal of ECT 23.3 (2007):
Lang, John B., Susan A. Kunsman, and Michael T. Hartman. "Acquired pseudocholinesterase deficiency." Current Anaesthesia & Critical Care 21.5 (2010):

49. References
Lurati, A. R. "Organophosphate exposure with pseudocholinesterase deficiency." Workplace health & safety 61.6 (2013):
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:
Lurie, Samuel, Sadan, Oscar, et al. “Pseudocholinesterase deficiency asociated with HELLP syndrome”. American Journal of Perinatology, 2004; 21: