Residual neuromuscular blockade

There are two pharmacological subtypes of neuromuscular blockers: depolarizing and non-depolarizing. Succinylcholine (suxamethonium) is a nicotinic acetylcholine receptor agonist that produces depolarizing blockade, but is rapidly metabolized by pseudocholinesterase. In individuals with normal activity of pseudocholinesterase, the duration of action of succinylcholine is limited to 3 to 5 minutes. The rapid onset and rapid offset are the major clinical advantages of the medication and the reason it is in clinical use. However, in individuals with pseudocholinesterase deficiency, the duration of neuromuscular blockade is extended. Deficiencies of pseudocholinesterase may be quantitative or qualitative, and inherited or acquired.

Pseudocholinesterase has no identified biological function besides the metabolism of a few pharmaceuticals, so individuals with an inherited lack of normal enzymatic function are phenotypically normal and often cannot be identified preoperatively. After exposure to succinylcholine, paralysis is prolonged. Over 65 genetic mutations have been identified as producing abnormal or deficient pseudocholinesterase.^[1] Depending upon the mutation and whether the individual is homozygous or heterozygous for the gene encoding for the defective enzyme, the duration of action of succinylcholine may be extended by several minutes to several hours. The most severe inherited enzymatic deficiency is the silent variant. The incidence of the homozygous silent variant mutation is estimated to be between 1 in 40,000^[2] and 1 in 100,000^[3] among individuals of European descent and produces clinical paralysis of 4 to 8 hours after exposure to succinylcholine.^[2] Among the ethnic Vysya of India the incidence climbs to 1 in 24.^[3] It is not possible to acutely identify the cause of prolonged paralysis from succinylcholine, so affected patients need to be monitored for return of neuromuscular function. Analysis of pseudocholinesterase activity is best deferred until the interfering effect of succinylcholine has dissipated.^[2] Many of the variants of abnormal pseudocholinesterase produce paralysis of 1 to 2 hours’ duration when challenged with succinylcholine, so if more than 2 hours has elapsed since administration the individual likely possesses a severe mutation. Acquired deficiencies in serum pseudocholinesterase may be observed in liver disease, renal insufficiency, malnutrition, pregnancy, malignancy, and leprosy,^[3] although the increased duration of action of succinylcholine is rarely clinically significant with these disorders. Deficient pseudocholinesterase activity may also be acquired from the concurrent administration of other pharmaceuticals. The most clinically significant is administration of competitive cholinesterase inhibitors including neostigmine, physostigmine, or pyridostigmine. These medications are typically administered at the conclusion of surgery for reversal of non-depolarizing neuromuscular blockade. If succinylcholine is administered as part of emergency airway management of failed extubation, prolonged paralysis may result. A number of other medications also prolong the action of succinylcholine through pseudocholinesterase inhibition, but the effects are generally short-lived and rarely of clinical significance (Table 43.1).

Non-depolarizing neuromuscular blocker duration of action is variable and dependent upon the particular pharmaceutical administered. Typically, spontaneous recovery from an intubating dose of a non-depolarizer occurs within 2 hours. There are many factors that can affect the duration of non-depolarizing neuromuscular blockade, including interference from other pharmaceuticals, hepatic or renal insufficiency, electrolyte disturbances, hypothermia, acidosis, and pre-existing pathology at the neuromuscular junction.

Recovery from neuromuscular blockade is evaluated by utilizing a twitch monitor to determine a train-of-four (TOF) ratio. The TOF ratio is defined as four successive electrical stimulations each occurring every half second. The response to the fourth stimulus is compared with the response to the first stimulus. A ratio of 0.9 signifies that pharyngeal function has been restored; if pharyngeal function is not restored there may be an increased risk of upper airway obstruction upon extubation. Of note, diaphragmatic function returns before pharyngeal function does. Therefore, adequate tidal volumes during spontaneous ventilation are not sufficient for extubation. At the end of an anesthetic the trachea is extubated, but only when the effects of the neuromuscular blockade have been terminated. The termination of neuromuscular blockade is facilitated by spontaneous recovery (metabolism by the body) or by pharmacological antagonism (reversal). Reversal is achieved by using an cholin esterase inhibitor such as neostigmine. Residual neuromuscular blockade is a common complication in the PACU with approximately 40% of patients exhibiting TOF ratios <0.9.^[4]

Management: Significant residual neuromuscular blockade may require intubation and mechanical ventilation, both to ensure adequacy of oxygenation and ventilation, and for airway protection.^[5] When a patient presents to the PACU intubated with residual neuromuscular blockade, assess TOF ratio and evaluate need for sedation. Clinically weak patients requiring mechanical ventilation should be sedated. Neuromuscular blockade is terrifying for the awake patient, and anxiolysis and amnesia should be supplied. Once the TOF ratio is >0.9 one can assume that pharyngeal tone has been restored and extubation can be performed.^[6] If TOF monitoring is not available, assessment of adequate clinical strength for extubation may be achieved with a 5 second head lift.^[7]

Negative pressure pulmonary edema

Negative pressure pulmonary edema is a type of non-cardiogenic pulmonary edema. Any type of airway obstruction can lead to negative pressure pulmonary edema, but the most common cause of precipitating obstruction is laryngospasm.^[8] The underlying cause of the pulmonary edema is thought to be the creation of a large pressure gradient across the pulmonary capillary wall. The creation of a large negative intrathoracic pressure against an obstruction draws fluid from the interstitial space/capillaries and into the alveoli.^[9] The process is also mediated by a disruption of the alveolar capillary membrane secondary to this large negative pressure. This phenomenon is observed in 1 of every 1,000 general surgeries.^[10]

Management: This will lead to pulmonary edema and potentially hypoxia. Intubation and mechanical ventilation is reserved for only the most severely affected individuals and is rarely necessary. Management is supportive care. The pathophysiology is a transudative process, not volume overload, so the role of diuretics in management is controversial.^[11] Some advocate diuresis for affected patients, but the evidence of benefit is anecdotal and limited to case reports. Spontaneous recovery is also common. Severely affected patients requiring mechanical ventilation will most likely require only short-term support and may benefit from brief sedation.