J Oral Maxillofac Surg61:845-847, 2003

Heterozygous PseudocholinesteraseDeficiency: A Case Report and Review of

the LiteratureAnthony Maiorana, DDS,* and Robert B. Roach, Jr, DDS†

Pseudocholinesterase (plasma cholinesterase) isproduced in the liver and metabolizes mivacurium,succinylcholine, and ester local anesthetics. Theduration of blockade with mivacurium or succinyl-choline may be prolonged if there is a reducedquantity or quality of pseudocholinesterase. A re-duction may be seen in liver disease, malignancies,pregnancy, collagen vascular disease, malnutrition,and hypothyroidism. Qualitative effects can be mea-sured with the use of dibucaine. Dibucaine is anamide local anesthetic agent that inhibits normalplasma cholinesterase activity by 80% and atypicalenzyme by 20%.1,2 The “dibucaine number” reflectsthe ability to metabolize mivacurium or succinyl-choline and not the quantity of circulating enzymein the plasma. The following is a case report of ahealthy ASA 1 woman who stated she had no med-ical problems. She underwent her first experienceof general anesthesia for a 30-minute dentoalveolarprocedure and unexpectedly met extubation re-quirements 5 hours later due to a pseudocholines-terase deficiency.

Report of a Case

A 19-year-old Hispanic woman, weighing 61 kg, wasscheduled for extraction of maxillary third molars, man-dibular third molars, and nonrestorable maxillary leftsecond premolar while under general anesthesia in theoral and maxillofacial surgery suite. Induction of anesthe-sia was achieved with 3 mg of midazolam, 50 �g offentanyl, and 150 mg of propofol. Muscular relaxationwas achieved before intubation with 14 mg of mivacu-rium. Isoflurane was used as the general anesthetic inha-lation agent. The dentoalveolar surgery was uneventful.After the surgery, the inhalation agent was discontinued

and the patient received 100% oxygen. It was noted thatemergence seemed to be prolonged after 10 minutes. Allvital signs were stable, showing no signs of tachycardiaor hypertension. Oxygen saturation remained 100%. Af-ter an additional 10 minutes, there was suspicion of aplasma cholinesterase deficiency. Peripheral nerve stim-ulator produced zero twitches. The anesthesia servicewas consulted, confirming a prolonged neuromuscularparalysis, and agreement with our diagnosis of a plasmacholinesterase deficiency. Two milligrams of Versed (mi-dazolam; Baxter Healthcare Corporation, Deerfield, IL)was administered intravenously for its sedation and am-nestic effects. The patient was transferred to the inten-sive care unit for observation and ventilator support.

Received from the Oral and Maxillofacial Surgery Residency Pro-

gram, Madigan Army Medical Center, Fort Lewis, WA.

*Third Year Resident.

†Assistant Program Director.

Address correspondence and reprint requests to Dr Maiorana:

Oral and Maxillofacial Surgery, Madigan Army Medical Center, Attn:

MCDS-NI-D, Tacoma, WA 98431; e-mail: maiorana@hotmail.com

© 2003 American Association of Oral and Maxillofacial Surgeons

0278-2391/03/6107-0018$30.00/0

doi:10.1016/S078-2391(03)00163-0

Table 1. PATIENT LABORATORY INQUIRY

Pseudo cholinersterase(normal range)

799 IU/L(3,200 to6,600 IU/L)

Dibucaine number 48% InhibitedNormal homozygote 73% to 90%Heterozygote 54% to 70%Atypical homozygote 16% to 28%

Table 2. GENOTYPES AND PHENOTYPES FOUND ATLOCUS E1

UU: Usual, no prolonged apneaUA: Heterozygote, occasionally has prolonged apneaAA: Homozygote (rare), always has prolonged apneaUS: Usual/silent, occasionally has prolonged apneaSS: Silent (rare), always has prolonged apnea

AS:

Indicates patient will always have prolongedparalysis following the use of succinylcholine ormivacurium

FF:

Very rare, indicates patient will have prolongedparalysis following the use of succinylcholine ormivacurium

FS:

Rare, indicates patient will have prolongedparalysis following the use of succinylcholine ormivacurium

AF:

Rare, indicates patient will have prolongedparalysis following the use of succinylcholine ormivacurium

UF:

Rare, indicates patient may rarely haveprolonged paralysis following the use ofsuccinylcholine or mivacurium

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Four hours later, spontaneous muscle twitching wasnoted. Five hours from the initial use of mivacurium, thepatient had regained sufficient motor function to meetextubation requirements. Blood samples were drawn andsent to confirm a plasma cholinesterase deficiency. Thepatient was transferred to a hospital ward for the eveningand discharged the next day. Patient blood tests reportedthe results given in Table 1.

Discussion

The genetics of pseudocholinesterase was firstdescribed3 by Bourne in 1952 and Frobet in 1953.The studies of cholinesterase revealed that 4 auto-somal allelic genes at locus E1 control the synthesisof variants of pseudocholinesterase. The four geno-types are E1

u (usual), E1a (atypical), E1

f (fluoride re-sistant), and E1

s (silent, not producing activity ofcholinesterase). The combination of these 4 allelescan give any one of 10 different genotypes at locusE1 (Table 2).

Kalow and Genest4 illustrated that prolonged ap-nea following succinylcholine could be due to aninherited abnormal serum cholinesterase concen-tration, which was more resistant to inhibition bydibucaine than the normal enzyme. This dibucaineconcept can identify the 10 phenotypes in Ta-ble 2.3-6

Mivacurium is a short-acting, nondepolarizingneuromuscular blocker hydrolyzed by pseudocho-linesterase. A typical adult intubation dose is 0.2 to0.25 mg/kg. Onset is 1.0 to 1.5 minutes with aduration of 15 to 20 minutes. This a very attractivemuscle relaxant for use in short oral and maxillofa-cial procedures because a reversal agent is notnecessary.7

The patient received 0.23 mg/kg of mivacurium,and her only preoperative medication was birth con-trol pills. A patient taking metoclopramide (Reglan;A.H. Robins Company, Richmond, VA) for gastro-

esophageal reflux disease has been shown to inhibitpseudocholinesterase by as much as 70%.

A presurgical bHCG level of the patient was neg-ative, but it has been shown that pregnancy de-creases pseudocholinesterase levels by only 25% to30%. A quantitative decrease in this nature prolongsclinical effects by only a matter of minutes.2

After this procedure, the patient learned that hermother had also had a very long “wake-up” periodafter surgery; unfortunately, she had never sharedthat information with her children. The patientnow wears a Medic Alert bracelet and has sincereceived general anesthesia 2 additional times with-out an abnormal response, simply by avoiding mi-vacurium and succinylcholine. The guidelines givenin Table 3 are recommended for the proper man-agement of patients with a suspected pseudocho-linesterase deficiency.

An oral and maxillofacial surgery procedure maybe the first encounter with general anesthesia forthe undiagnosed patient. A prolonged “wake-upperiod” with sustained muscular paralysis and pos-sible unexplained tachycardia should alert the sur-geon to a possible pseudocholinesterase deficiency.The paralyzed yet conscious patient is capable ofrecall and requires reassurance. The surgeon shouldconsider sedative and amnesic pharmacotherapy ifa pseudocholinesterase deficiency is suspected.

References1. Stoelting RK, Miller RD: Basics of Anesthesia (ed 3). New York,

NY, Churchill Livingstone, 19942. Ravindran RS, Cummins DF, Pantazis KL, et al: Unusual aspects

of low levels of pseudocholinesterase in a pregnant patient.Anesth Analg 61:953, 1982

3. Hanel HK, Viby-Mogensen J, Schaffalitzky de Muckadell OB:Serum cholinesterase variants in the danish population. ActaAnesth Scand 22:505, 1978

4. Kalow W, Genest K: A method for the detection of atypicalforms of human serum cholinesterase. Determination of dibu-caine numbers. Can J Biochem 35:339, 1957

Table 3. PROPER MANAGEMENT OF PATIENT WITH PSEUDOCHOLINESTERASE DEFICIENCY

Blood testa. Wait at least 3 days after exposure before testing.b. Wait at least 8 weeks after blood transfusion before testing.9

c. Request pseudocholinesterase genotyping.d. Ensure that the anesthesiologist/anesthetist receives a copy of the report as well as the patient.

Consultation with patient and spousea. Record history of prolonged apnea, including type of surgery, date of surgery, location, anesthetic drugs used, andduration of intensive care unit ventilation.b. Construct a family tree recording the names of the patient’s parents, siblings, and children and the nature of theanesthetic problems.c. Discuss the ramifications of both homozygous and heterozygous test results for future anesthetics.d. Testing is advisable for siblings of a homozygous patient.e. Recommend a Medic Alert bracelet after a positive test result.

846 PSEUDOCHOLINESTERASE DEFICIENCY

5. Viby-Mogensen J: Succinylcholine neuromuscular blockade insubjects heterozygous for abnormal plasma cholinesterase. An-esthesiology 55:231, 1981

6. Viby-Mogensen J: Correlation of succinylcholine durationof action with plasma cholinesterase activity in subjectswith genotypically normal enzyme. Anesthesiology 53:517,1980

7. Rosenberg MK, Lebenbom-Mansour M: Markedly prolongedparalysis after mivacurium in a patient apparently heterozy-

gous for the atypical and usual pseudocholinesterase allelesby conventional biochemical testing. Anesth Analg 84:457,1997

8. Cerf C, Mesguish M, Gabriel I, et al: Screening patients withprolonged neuromuscular blockade after succinylcholine andmivacurium. Anesth Analg 94:461, 2002

9. Lovely MJ, Patteson SK, Beuerlein FJ, et al: Perioperative bloodtransfusion may conceal atypical pseudocholinesterase. AnesthAnalg 70:326, 1990

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