The differential diagnosis for postoperative apnea includes the following:

This patient showed clear signs of residual neuromuscular weakness upon arrival in the PACU. TOF stimulation at the ulnar nerve showed a TOFC of only 2 at the adductor pollicis (thumb). A provisional diagnosis of residual nondepolarizing block was made and the patient received neostigmine 0.05 mg per kg plus an appropriate dose of glycopyrrolate (0.01 mg per kg). Seven minutes later, the TOFC was 4 with no evidence of fade on palpation of the thumb, and all signs of residual block had abated.

Although facial nerve stimulation is widely used by clinicians to judge the adequacy of block and recovery, this practice can be very misleading. At a time when the TOFC at the orbicularis oculi or corrugator supercilii muscles shows good recovery from nondepolarizing block, the response at the hand may be almost nonexistent. Thus, facial nerve stimulation may give the clinician a false sense of security about the adequacy of neuromuscular recovery at the end of a case.

Similarly, in the intubated patient breathing spontaneously, a normal tidal volume and maintenance of an acceptable PCO₂ do not necessarily indicate adequate neuromuscular recovery. The diaphragm is the first muscle to recover from nondepolarizing block and requires significantly higher plasma levels of relaxants to maintain paralysis. The muscles which protect the upper airway are far more sensitive to nondepolarizing relaxants. Thus, a patient who may be able to maintain adequate respiratory exchange while intubated may experience complete airway obstruction when extubated.

The easiest possibility to exclude is residual neuromuscular block. In the given patient, stimulation of the ulnar nerve with a PNS resulted in no response of the muscles of the hand. Hence, the diagnosis of a prolonged response to succinylcholine was established. Extreme prolongation in succinylcholine’s duration of effect is usually a manifestation of an atypical genotype. Following a 1.0 mg per kg dose of succinylcholine, in patients homozygous for the most common atypical butyrylcholinesterase (BChE) genotypes, apnea generally lasts upward of an hour, and it may take as much as 3 hours for adequate respiratory efforts to return. However, the duration of apnea is highly dependent on the BChE variant in question and may be shorter or longer than the figures just cited.

Traditionally, identification of the human BChE variant has been performed by biochemical analysis. These tests, which have been used for decades, consist of the measurement of plasma cholinesterase activity with different substrates and of testing the degree of inhibition of this activity with a well-known inhibitor, such as dibucaine, fluoride, or R02-0683. These tests have identified multiple genes that can reside at the same allelic site, such as the atypical, silent, fluoride-resistant, J, K, H, and Newfoundland variants. However, biochemical testing often leads to equivocal results. More recently, molecular biologic techniques have been applied to identifying a patient’s exact genotype.

Once the diagnosis of an atypical response to succinylcholine is ascertained, treatment is entirely supportive and symptomatic. Since the duration of residual block is hard to predict, the patient should remain intubated, artificially ventilated, and sedated. Only after a strong, sustained response to indirect tetanic stimulation at the wrist can be demonstrated should sedation be terminated and an attempt made to wean the patient off controlled ventilation. Patients recovering from prolonged succinylcholine induced block usually exhibit a “dual” or “phase II” block during recovery (fade on repetitive stimulation). While neostigmine or edrophonium can under certain circumstances antagonize this block, this approach is risky when dealing with prolonged succinylcholine apnea. If significant plasma levels of succinylcholine are still present, the administration of an acetylcholinesterase may be counterproductive.

The patient should obviously be informed that she had a prolonged episode of muscular weakness and that the presumptive cause was an atypical reaction to succinylcholine. The patient should be urged to have this diagnosis confirmed and she should be directed to an appropriate laboratory. If an atypical genotype is confirmed, she should encourage her family members to be tested as well. Finally, the patient should be assured that this diagnosis has no adverse health consequences but that in the future when surgery is planned, her anesthesiologist needs to be informed of this diagnosis.

Acetylcholinesterase is a relatively specific enzyme that hydrolyzes acetylcholine (ACh) faster than it does other choline esters. It is found in red blood cells, the central nervous system, and at the neuromuscular junction. It is responsible for hydrolyzing and inactivating the ACh produced during normal neuromuscular transmission. It does not hydrolyze succinylcholine.

Serum cholinesterase, also called cholinesterase, pseudocholinesterase (PChE), butyrylcholinesterase (BChE), and nonspecific cholinesterase, hydrolyzes many choline esters, including
succinylcholine. It is found in many human tissues but not in the red blood cell. It is synthesized in the liver. Its physiologic function is unknown, but it may hydrolyze choline esters, such as propionylcholine and butyrylcholine, which may be formed by bacterial action in the gut and by the enzyme systems responsible for the formation of ACh.

The incidence of atypical cholinesterase activity varies with the population studied, but it is approximately 1 of 2,800 in the general population of the United States with a 1:1 male/female ratio.

The dibucaine number (DN) is the percentage of PChE enzyme activity that is inhibited by dibucaine. Together, the DN and the PChE enzyme activity results can help identify individuals at risk for prolonged paralysis following the administration of succinylcholine. Decreased PChE enzyme activity in conjunction with a DN less than 30 suggests high risk for prolonged paralysis. Normal to decreased PChE enzyme activity in conjunction with a DN 30 to 79 suggests variable risk. The relation between the DN and the duration of succinylcholine neuromuscular blockade is shown in Table 55.1.

Reduced PChE activity may be associated with the following:

These include liver disease, advanced age, malnutrition, pregnancy, burns, oral contraceptives, monoamine oxidase inhibitors, echothiophate, cytotoxic drugs, neoplastic disease, anticholinesterase drugs, tetrahydroaminacrine, hexafluorenium, and metoclopramide.

The most common untoward side effect seen after succinylcholine administration is muscle pain occurring in the first 24 to 48 hours postoperatively. Women and patients undergoing ambulatory surgery appear most susceptible to this phenomenon. The reported incidence of succinylcholine-induced myalgia is quite variable but probably occurs in 25% to 50% of patients. Discomfort is typically characterized as being similar to the muscle soreness that occurs after heavy or unusual exercise. It has been postulated that the etiology of the phenomenon is related to muscle damage caused by asynchronous contractions during the initial muscle depolarization that precedes paralysis. Defasciculating doses of nondepolarizing relaxants (10% of the ED₉₅) given 2 to 5 minutes prior to succinylcholine have been shown to reduce the incidence of myalgia by as much as 50%. Pretreatment with nonsteroidal antiinflammatory drugs has also been shown to reduce the incidence of muscle pain following succinylcholine administration.

Succinylcholine may also be associated with various cardiac dysrhythmias including bradycardia, tachycardia, and junctional and ventricular dysrhythmias. Stimulation of nicotinic receptors at sympathetic and parasympathetic ganglion and muscarinic receptors at the sinus node are believed to be involved in this phenomenon. Infants and children may be more likely to manifest clinically significant bradycardia following succinylcholine administration secondary to their relatively high degree of resting vagal tone as compared to adults. Pretreatment with atropine is effective in preventing succinylcholine-induced bradycardia and is recommended when succinylcholine is to be used in this patient population. Sinus bradycardia in adults is more commonly seen when a second dose of succinylcholine is given approximately 5 minutes after the first. Pretreatment with atropine can prevent this as well. Junctional rhythms following succinylcholine administration are also relatively common. The postulated mechanism of action is muscarinic stimulation of the sinus node that results in diminished sinus activity and the subsequent emergence of the atrioventricular node as the dominant pacemaker. Various mechanisms have been postulated to explain ventricular dysrhythmias that sometimes occur after succinylcholine administration including potassium release from skeletal muscle, succinylcholine mediated sensitivity to catecholamines, and profound sinus and atrioventricular node slowing.