Pseudocholinesterase (also known as plasma cholinesterase or butyrylcholinesterase) deficiency has both genetic and acquired etiologies. One condition that can drastically affect the levels of serum pseudocholinesterase is malnutrition. We present the case of a patient who had a complicated course after a bariatric surgery procedure and then went on to subsequently develop a malnutrition-induced pseudocholinesterase deficiency resulting in prolonged neuromuscular blockade.
The patient reviewed this manuscript and gave written consent for its publication.
An obese (body mass index 32 kg/m2) 63-year-old woman with a complicated medical and surgical history was admitted to the hospital with altered mental status. Approximately a year before admission, she underwent gastric sleeve resection at an outside hospital that was complicated by a staple-line leak requiring an esophageal stent, gastrocutaneous fistulas, abdominal wall abscesses, and severe malnutrition. In addition, she had a history of right ureterolithiasis with hydronephrosis requiring percutaneous nephrostomy tube placement and multiple prior admissions for urosepsis.
Upon presentation to the hospital, she was found to have an elevated white blood cell count and C-reactive protein, a urinalysis suggestive of urinary tract infection, and abdominal imaging that demonstrated fluid collections near the existing esophageal stent and spleen for which she was started on broad-spectrum antibiotics. The esophageal stent was removed on hospital day 4, because it was no longer controlling the leak and she was continuing to have significant nausea and poor diet tolerance. On hospital day 7, she underwent upper endoscopy with placement of a postpyloric nasojejunal feeding tube. During that same procedure, she also underwent cystoscopy, stone extraction, and right ureteral stent placement.
Before the induction of anesthesia on hospital day 7, she was premedicated with ondansetron (4 mg), midazolam (1 mg), and fentanyl (100 μg). After adequate preoxygenation, general anesthesia was induced with propofol (120 mg) and rocuronium (50 mg). Desflurane (4–5%) was used as a maintenance anesthetic. The operative procedures lasted for approximately 3 hours, and the patient was reversed with neostigmine (5 mg) and glycopyrrolate (1.2 mg).
After the procedure, she remained somewhat sleepy in the operating room, and so she was transferred to the recovery room with the endotracheal tube in place. Notably, she had not received any additional neuromuscular-blocking agent or narcotic aside from that which was given during induction. Before extubation, she was spontaneously breathing with tidal volumes of 400 mL (on pressure support), was nodding her head to questions, and was gripping with both hands. Within 5 to 10 minutes after extubation, she developed increased work of breathing, had poor inspiratory effort, and had her oxygen saturations dropped to 90%. Thereafter, she required bag–mask ventilation to maintain her oxygen saturations at that same level. She remained responsive during this time, but it was determined that she needed reintubation to control her airway. After administering propofol (70 mg) and succinylcholine (80 mg), she was intubated and then transferred to the surgical intensive care unit. On examination, she was found to be hypothermic (92°F), but her blood pressure, heart rate, and oxygenation were within normal limits. In addition, she was found to have a prolonged neuromuscular blockade on physical examination with flaccid extremities with absent deep tendon reflexes. However, she was able to blink her eyes and slightly nod her head to questions. Using a twitch monitor, her ulnar and posterior tibial twitches were absent bilaterally. Facial twitches were 1 out of 4 and weak bilaterally.
Initial laboratory evaluation revealed significant electrolyte abnormalities including hypokalemia (2.2 mmol/L), hypophosphatemia (1.6 mg/dL), and hypomagnesemia (1.1 mg/dL). Also of note were markedly decreased albumin (1.2 g/dL) and prealbumin (11 mg/dL) levels. Liver function tests and random cortisol and thyroid-stimulating hormone levels were within normal limits. Computed tomography scans of the head and cervical spine were negative for any acute pathology.
Over the next few hours in the intensive care unit, her motor function gradually improved. In addition, with aggressive rewarming and electrolyte repletion, her temperature and laboratory values returned to normal levels. She was successfully extubated the next day. Twenty-four hours after her episode of prolonged neuromuscular blockade, her total pseudocholinesterase level was found to be 232 U/L (reference range: 2900–7100 U/L) and her dibucaine number was 71% (normal range: 70%–80%).
After approximately 1 month of aggressive nutritional support with tube feeds and total parenteral nutrition, her parameters greatly improved. Her albumin rose to 3.0 g/dL and her prealbumin increased to 23 mg/dL. Furthermore, a similar trend was seen in her total pseudocholinesterase level, which increased to 1445 U/L. Her dibucaine number at that time was 76%.
Pseudocholinesterase is an enzyme that is synthesized in the liver, released into the plasma, and subsequently located in many tissues of the human body.1 It is notably absent in erythrocytes, as this is predominantly a site of action of the closely related enzyme acetylcholinesterase.2 Although the exact scope of pseudocholinesterase’s function is debated, it is clear that it plays a key role in the hydrolysis of choline esters. Deficiencies in pseudocholinesterase enzyme activity often manifest in the form of apnea or prolonged neuromuscular blockade after administering anesthesia. The etiologies of such deficiencies can have genetic and/or acquired explanations, some of which include liver disease, malnutrition, malignancy, or severe burns.1
Pseudocholinesterase deficiency is often recognized only after administration of a neuromuscular-blocking agent. Succinylcholine is a commonly used depolarizing neuromuscular blocker with a rapid onset of action. In addition, under normal conditions, succinylcholine also has a short duration of action because of the ability of pseudocholinesterase to quickly and efficiently hydrolyze the molecule. The vast majority of a standard dose of intravenously delivered succinylcholine will be hydrolyzed by pseudocholinesterase within a minute of administration.3 This markedly reduces the quantity of succinylcholine that reaches the nerve endplate. Thereafter, the number of receptors occupied at the nerve endplate and the rate at which succinylcholine diffuses away from them determine the rate of recovery from paralysis.4 Recovery time is on the order of 9 minutes (first train-of-four twitch [T1] to 90%) after administering a 1-mg/kg IV dose of succinylcholine.5
Patients who have undergone bariatric surgery are at risk for developing both macronutrient and micronutrient deficiencies.6 Any bariatric procedure predisposes a patient to such deficiencies, and the potential for malnutrition increases with the degree of intestinal exclusion or excision.7 Our patient had a complicated course after her sleeve gastrectomy and developed severe malnutrition. During one of her many readmissions, she was administered succinylcholine as part of an emergent airway procedure. Despite having previously received this drug without any adverse effects, she developed a prolonged neuromuscular blockade in this instance. At the time of this event, her albumin level was 1.2 g/dL (reference range: 3.3–4.9 g/dL) and her pseudocholinesterase level was 232 U/L (reference range: 2900–7100 U/L). Prior studies have demonstrated a link between malnutrition and deficiencies in pseudocholinesterase levels. For instance, a study analyzing undernourished German men found that they had decreased levels of pseudocholinesterase, which dramatically improved when these men were given a calorically rich diet.8 Similar to the trend found in this study, our patient had a 6-fold increase in her pseudocholinesterase level after aggressive nutritional supplementation. In addition, pseudocholinesterase enzyme assays have previously been used to gauge prognosis in children clinically diagnosed with malnutrition. Here, over 80% of the children found to have a nutritional deficiency were also found to have an abnormal level of serum pseudocholinesterase.9 Furthermore, patients with anorexia nervosa have been shown to have decreases in pseudocholinesterase levels that are associated with their poor nutritional states.10 In addition, one case report has demonstrated a prolonged neuromuscular blockade in a malnourished patient who received mivacurium during the course of an operative procedure.11 Similar to our patient, this individual had previously been exposed to the neuromuscular-blocking agent with no deleterious effects. Subsequent serum studies revealed a decreased level of pseudocholinesterase, which resulted from a poor nutritional state.
There is a clear, inverse relationship between pseudocholinesterase activity and the time to 100% twitch recovery after succinylcholine administration (Figure). Viby-Mogensen5 reported that patients with genotypically normal pseudocholinesterase levels as low as 150 to 200 U/L only had moderately prolonged neuromuscular blockade with the maximal time to 100% twitch recovery being 22 minutes (after receiving a standard dose of succinylcholine). Our patient’s neuromuscular blockade of a few hours was prolonged when compared with what would be considered “normal” for her level of serum cholinesterase. This observation can be at least partially explained by the fact that she received neostigmine shortly before receiving succinylcholine for an emergent reintubation. Neostigmine can prolong the neuromuscular blockade of succinylcholine, but it often only accounts for an additional 20 to 30 minutes of neuromuscular blockade.12 Although the low levels of pseudocholinesterase were paramount in causing her prolonged neuromuscular blockade, it was likely further exacerbated by a recent dose of neostigmine, hypothermia, and electrolyte abnormalities.
Although there are known genetic causes for pseudocholinesterase deficiency, it is unlikely that there was any inherited component to this patient’s disease. For one, she had multiple previous exposures to succinylcholine with no deleterious effects. Second, her dibucaine number does not suggest any genetic component of disease. Dibucaine is a local anesthetic, which inhibits normal pseudocholinesterase to a much greater degree than the abnormal variant of the enzyme, and the dibucaine number is a measure of the degree of inhibition of pseudocholinesterase obtained with dibucaine. Kalow and Genest13 reported 3 types of individuals: the typical (normal homozygote) with a dibucaine number >70%, the intermediate (heterozygote) with a value between 40% and 70%, and the atypical individual (atypical homozygote) with a dibucaine number <20%. Our patient had a dibucaine number of 71% to 76%, which is suggestive of a normal pseudocholinesterase enzyme.
This case report illustrates how a patient with profound malnutrition after complications from bariatric surgery later developed a prolonged neuromuscular blockade after the administration of succinylcholine. With supportive cares, she made an uneventful recovery and was able to be weaned from the ventilator by the next day. Her pseudocholinesterase levels were very low at the time of the prolonged blockade (one-tenth of the lower limit of normal), but after nutritional supplementation for the next month, there was a drastic improvement. This patient’s course demonstrates how severe malnutrition can result in an acquired pseudocholinesterase deficiency. Like many individuals at risk for malnutrition, patients undergoing bariatric surgery should be closely followed to ensure optimum nutritional status. Anesthesia and critical care practitioners must always consider the diagnosis of malnutrition-induced pseudocholinesterase deficiency as a possible etiology in those patients who have a poor nutritional state and experience an unexpected episode of apnea or prolonged neuromuscular blockade.
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