p seudocholinesterase deficiency
DESCRIPTION
P seudocholinesterase 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 - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/1.jpg)
Pseudocholinesterase Deficiency
Etiology and considerations
Angela HeplerRN, BS Biology, SRNA
Allegheny Valley Hospital School of Anesthesia
![Page 2: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/2.jpg)
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
![Page 3: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/3.jpg)
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
![Page 4: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/4.jpg)
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?
![Page 5: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/5.jpg)
![Page 6: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/6.jpg)
![Page 7: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/7.jpg)
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
![Page 8: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/8.jpg)
![Page 9: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/9.jpg)
![Page 10: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/10.jpg)
Motor end plate
Tb
Motor neuron
![Page 11: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/11.jpg)
![Page 12: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/12.jpg)
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
![Page 13: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/13.jpg)
Acetylcholine and Succinylcholine
Acetylcholine Succinylcholine
![Page 14: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/14.jpg)
![Page 15: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/15.jpg)
Indications for Succinylcholine
• Rapid Sequence Induction (RSI)
• Electroshock Therapy (ECT)
• Motor evoked potential (MEP) monitoring
• Any situation where brief paralysis is desirable
![Page 16: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/16.jpg)
Pseudocholinesterase
• Also known as: Acetylcholine Acyl Hydrolase Butyrylcholinesterase (BChE)
• Primary metabolic pathway for Succinylcholine
• Located on Chromosome 3
![Page 17: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/17.jpg)
H
![Page 18: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/18.jpg)
,
![Page 19: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/19.jpg)
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
![Page 20: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/20.jpg)
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
![Page 21: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/21.jpg)
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
![Page 22: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/22.jpg)
Pseudocholinesterase inhibitors• Each can decrease the effectiveness of normal BChE:
• Advancing Age
• Renal failure
• Malnutrition
• Hepatic failure
• Pregnancy
![Page 23: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/23.jpg)
![Page 24: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/24.jpg)
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
![Page 25: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/25.jpg)
Departure from “the norm”…..
![Page 26: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/26.jpg)
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
![Page 27: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/27.jpg)
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
![Page 28: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/28.jpg)
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
![Page 29: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/29.jpg)
![Page 30: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/30.jpg)
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
![Page 31: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/31.jpg)
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
![Page 32: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/32.jpg)
N
d
N- normal genetic coding (wild type allele)d- heterozygous, atypical BCHE (carrier) - homozygous, atypical BCHE
N d
NN Nd
Nd
N N
NN NN
Nd Nddd
The Genetics Of It All
![Page 33: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/33.jpg)
Pseudocholinesterase Variants
• Up to 98% of individuals are homozygous for normal pseudocholinesterase
• 4 major varieties, with 65 variants known
![Page 34: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/34.jpg)
![Page 35: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/35.jpg)
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)
![Page 36: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/36.jpg)
Pseudocholinesterase Deficiency types
2. Dibucaine resistant/ Atypical
• First subtype identified
• Paralysis can last up to 2 hours
• Affects 0.01-0.03%
![Page 37: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/37.jpg)
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)
![Page 38: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/38.jpg)
Pseudocholinesterase Deficiency types (cont.)
• 3. Silent variant
oHomozygous results in complete lack of pseudocholinesterase
oAll metabolism by alternative methods
oRelatively rare (0.008-0.01%)
oParalysis can last 3-4 hours
![Page 39: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/39.jpg)
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
![Page 40: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/40.jpg)
Treatment…….
![Page 41: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/41.jpg)
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
![Page 42: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/42.jpg)
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?
![Page 43: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/43.jpg)
What about our Case Study?
![Page 44: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/44.jpg)
What about our Case Study?
• Remifentanil- metabolized by nonspecific plasma esterases
• Esmolol- metabolized by RBC esterases
Both are unaffected by BChE deficiency
![Page 45: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/45.jpg)
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
![Page 46: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/46.jpg)
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
![Page 47: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/47.jpg)
Questions?
![Page 48: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/48.jpg)
References• Soliday, Conley, Henker. “Pseudocholinesterase deficiency: A Comprehensive
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_Page06.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 blockade as a result of malnutrition-induced pseudocholinesterase deficiency." 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.
![Page 49: P seudocholinesterase Deficiency](https://reader036.vdocument.in/reader036/viewer/2022062316/568166ff550346895ddb642d/html5/thumbnails/49.jpg)
References• Lurati, A. R. "Organophosphate exposure with pseudocholinesterase
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.