Geng Li; Jingping Wang

Case Report

Austin J Anesthesia and Analgesia. 2014;2(4): 1022.

Residual Muscle Weakness after Succinylcholine Infusion: Clinical Presentation, Diagnosis and Treatment

Geng Li and Jingping Wang*

Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School, USA

*Corresponding author: Jingping Wang, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.

Received: February 24, 2014; Accepted: April 04, 2014; Published: April 10, 2014

Abstract

Here we report 2 cases of succinylcholine infusion for short surgical procedures, complicated by clinical presentation of upper airway obstruction in the immediate postoperative period, likely due to residual muscle weakness. In both cases, patients were extubated in OR. The presentation of residual muscle weakness in PACU was supported either with oxygen supplement via nasal cannula or with CPAP. No reintubation was needed. Lab work showed decreased pseudocholinesterase level in one of the patients. Literature review does not support an absolute number of total succinylcholine dosage or total administration time of succinylcholine infusion as a reliable predictor of progression into phase II block. Lab test of pseudocholinesterase function is not routinely performed. Therefore it is prudent to apply neuromuscular monitoring during succinylcholine infusion even when the surgery is considered a short procedure.

Keywords: Succinylcholine infusion; Pseudocholinesterase activity; Phase II neuromuscular block; Train-of-four nerve stimulation

Background

Succinylcholine is the only depolarizing neuromuscular block agent that possesses the unique features of a rapid onset of effect and an ultra short duration of action. Continuous succinylcholine infusion is commonly used in most of laparoscopic cholecystectomy cases performed by a single surgeon at our institution. Administration of 1mg⁄kg of succinylcholine results in complete suppression of neuromuscular activity in approximately 60 seconds, and it takes 9-13 minutes to recover 90% muscle strength in patients with normal pseudocholinesterase activity (also known as plasma cholinesterase or butyrylcholinesterase) [1,2]. Here we present 2 cases of succinylcholine infusion with postoperative complaints consistent with prolonged residual muscle weakness.

Case Presentation

Case 1: 35yo ASAI female, without significant past medical history but mild asthma and allergy to augmentin, presented for umbilical hernia repair. She was 60 inches in height and 50kg in weight. She was induced with 150mcg Fentanyl, 100mg Propofol and 80mg Succinylcholine and intubated smoothly. 6 minutes after initial dose of Succinylcholine, Succinylcholine infusion was started at 100mcg⁄kg⁄min. The infusion was stopped at the end of surgery with total infusion time of 16min. The patient was able to follow commands and establish spontaneous breathing with RR 15-20⁄min and tidal volume reaching 300ml before extubation, which was about 7 minutes after succinylcholine infusion was stopped. She was sent to post–anesthetic recovery unit (PACU) where she soon complained of difficulty in swallowing. She has maintained normal SpO2 level through the course with no complaints of difficulty in breathing. Her symptoms resolved spontaneously and she was able to be discharged home directly from PACU the same day. Her pseudocholinesterase level was found to be within normal limits.

Case 2: 35yo ASAII male presented for ileostomy closure. He has past medical history significant for rhabdomyosarcoma of the psoas s⁄p radiation therapy and recent rectal cancer s⁄p low–anterior resection with diverting ileostomy. He was 69 inches in height and 60kg in weight. He was induced with 150mcg Fentanyl, 150mg Propofol and 100mg Succinylcholine and intubated smoothly. 12 minutes after intubation, Succinylcholine infusion was started at 100mcg⁄kg⁄min and was titrated up to 140mcg⁄kg⁄min till the end. 3 boluses of total 100mg succinylcholine were given intraoperatively to achieve adequate surgical muscle relaxation. The total Succinylcholine infusion time was 70min. His emergence was complicated by residual muscle weakness as shown by low tidal volume during pressure support ventilation. He adequately followed command and was extubated about 30min after succinylcholine infusion had stopped. He was observed in OR with SpO2 99–100% throughout. After he was brought to PACU, he complained of difficulty breathing although his SpO2 level never reached below 90%. CPAP was initiated and his symptoms resolved. No reintubation was needed. His pseudocholinesterase level was found to be low at 2485 with normal range of 3100–6500.

Discussion

Residual muscle weakness in PACU unfortunately has remained common. Despite the efforts to limit the degree of residual paralysis with pharmacological reversal of non–depolarizing NMBDs, still up to 33–64% of patients manifest inadequate neuromuscular recovery on arrival to PACU [3,4]. In addition, factors that could contribute to prolonged neuromuscular blockade by succinylcholine [5,6] (Table 1) should not be overlooked. Situations such as pseudocholinesterase deficiency, succinylcholine–induced phase II block should be considered [7,8] (Table 2).

Table 1: Factors contributing to prolong blockade by succinylcholine.



  
    I. Reduced plasma cholinesterase activity 
  
  
    1) Decreased levels of the enzyme
  
  
    Extremes of age (newborn, old age)
  
  
    Disease states (hepatic disease, uremia, malnutrition, plasmapheresis,    cancer, burns et al.)
  
  
    Pregnancy
  
  
    2) Inhibited activity of the enzyme
  
  
    Irreversible (echothiophate)
  
  
    Reversible (edrophonium, neostigmine, pyridostigmine)
  
  
    Medications (contraceptives, metoclopramide, monoamine oxidase    inhibitor, esmolol, pancuronium et al.)
  
  
    II. Genetic variant (atypical plasma cholinesterase)



Table 1:  Factors contributing to prolong blockade by succinylcholine.

Table 2: Differentials for prolonged muscle weakness after succinylcholine administration.



  
     
       
       
      1. pseudo- cholinesterase    deficiency
       
     
      1-1.decreased enzyme activity
     
      1-1-1. Inhibition
    medications such as    contraceptives, metoclopramide, neostigmine et al.
  
  
    1-1-2. genetic variant
    heterozygous;
      homozygous;
  
  
    1-2.decreased enzyme level
    extremes of ages (newborn or    the eldly);
      Disease states (hepatic dx,    uremia et al.);
      pregnancy; et al.
  
  
    2. phase II neuromuscular block
      The development of phase II block of succinylcholine was defined as the    fourth twitch (T4) in a train-of-four (TOF) response (4 twitches in 2s with    2Hz frequency and 0.2ms length) becomes less than 50% of the height of the first    twitch (T1) in the same train (T4/T1 < 50%) (14-15).



Table 2:  Differentials for prolonged muscle weakness after succinylcholine administration.

Pseudocholinesterase deficiency

Pseudocholinesterase is synthesized by the liver and exists in plasma. It breaks down Succinylcholine to inactive metabolites. There is little or no pseudocholinesterase at the neuromuscular junction, therefore succinylcholine is metabolized only when it is in the circulation – before it reaches and after it diffuses away from the neuromuscular junction (NMJ). Pseudocholinesterase is very efficient in hydrolyzing succinylcholine and only 10% of administered succinylcholine ever reaches the NMJ [9]. The duration of succinylcholine action however can be prolonged by decreased activity of geno typically normal enzyme or by the presence of genetic variant of the enzyme [4].

In our cases, the lab results of the 1^st patient showed normal pseudocholinesterase level and normal dubicaine number, indicating both normal pseudocholinesterase quantity and quality [10]. However the lab results of the 2^nd patient did show decreased pseudocholinesterase level (though dubicaine number is unavailable), which indicated decreased enzyme quantity. We inferred from the lab test that decreased pseudocholinesterase function may account for residual muscle weakness after discontinuing succinylcholine infusion in the 2^nd patient.

The 2^nd patient has a complicated medical history including a long history of cancer. The presence of chronic malignancy increases the likelihood of pseudocholinesterase abnormality, including both quality and quantity, not to mention the possibility of genetic variant of pseudocholinesterase [5,6]. The detection of decreased pseudocholinesterase level may warrant further lab test such as dubicaine number or genetic test for pseudocholinesterase. That information will help direct the choice of NMBD or other medications which also require pseudocholinesterase for metabolism during future surgeries or medical treatment.

Phase II block of succinylcholine

Residual muscle weakness can take place following succinylcholine infusion even in patients with normal pseudocholinesterase level and activity (Table 2).

The nerve stimulation pattern after succinylcholine administration is defined as phase I block. It presents with no fade response to repeated or prolonged nerve stimulation. In contrast, phase II block is characterized by the occurrence of fade, a gradual diminution of evoked response during prolonged or repeated nerve stimulation [11].

Based on the studies of both Ramsey and Brandom (Table 3) the development of phase II block of succinylcholine was defined as the fourth twitch (T4) in a train–of–four (TOF) response (4 twitches in 2s with 2Hz frequency and 0.2ms length) becomes less than 50% of the height of the first twitch (T1) in the same train (T4⁄T1 < 50%) [12,13]. In general the likelihood to produce phase II neuromuscular block increases with larger total dosage over longer infusion time of succinylcholine,[13,14] clinical studies are consistent in supporting that none of parameters, the total dosage, duration of infusion or infusion rate, are reliable predictors for the onset of phase II block [12,13,15,16]. They further showed that due to individual variabilityin sensitivity to development of phase II block, it is not feasible to define a narrow dose range where transition from phase I to phase II block would occur [12,15]. In our cases, the time interval between succinylcholine discontinuation and endotracheal extubation in the 1st patient was about 7min, which could be just enough to regain adequate neuromuscular function in the context of normal pseudocholinesterase activity [1,2]. On the other hand, the time interval between succinlycholine discontinuation and extubation in the 2^nd patient was about 30min, which was significantly prolonged. It indicated that the 2^nd patient may have prolonged neuromuscular block resulting from phase II block of succinylcholine [1,17].

Table 3: Literature review.



  
    Studies
    Sample Number
    Total Infusion Time of Succinylcholine (min)
    Total Infusion Time of Phase I block (min)
    Infusion Rate of Succinylcholine
      (ug/kg/min)
    Incidence of
      Phase II Block
    Incidence that the Time of recovery from Phase II block is comparable    to that from Phase I block
  
  
    Total Infusion Time of Phase II block (min)
  
  
    Ramsey's [14]
      (1980)
    32
    187 +/- 15
      (86 - 365)
    111 +/- 9* (86 � 155)
    86 +/- 5
      (32-175)
    3/4
      (24 out of 32)
    50%
  
  
    187 +/- 15 *(87 � 365)
  
  
    Brandom's [15]
      (1989)
    16
    55.1 +/- 7.0
      (14 - 111)
    N/A
    88.6 +/- 10.4
      (40 � 165)
    3/16
      (3 out of 16)
    N/A
  
  
    Chen's [16]
      (1993)
    15
    50.74 +/- 18.06
      (28 - 93)
    48.50 +/- 8.08
    83.5 +/- 21.4
      (45 � 117)
    1/3
      (5 out of 15)
    100%
  
  
    51.86 +/- 29.87



Table 3:  Literature review.

In our cases, we did not apply acceleromyography to measure TOF or its fade ratios in PACU for the concerns of uncomfortable sensation initiated by electrical nerve stimulation in an awake patient; hence we cannot tell whether either of the patients had actually gone into phase II block.

Both Ramsey and Chen showed that patients with phase II block of succinylcholine can recover adequate neuromuscular function spontaneously and the time taken to recover was not statistically different from the time taken to recover from phase I block of succinylcholine [12,15].

However at the same time, Ramsey also showed in their study that about 50% of the patients who developed phase II block did not recover adequate neuromuscular function within 30 mins (defined as T1 less than 95% of Tcontrol and T4⁄T1 less than 60%) [12]. The residual phase II block was then antagonized promptly upon the administration of anticholinesterase – edrophonium and neostigmine [12]. They pointed out that neither the dose nor the duration of succinylcholine infusion serves as a reliable predictor for spontaneous recovery from phase II block or the need for antagonism of residual phase II block [12].

Tachyphylaxis to succinylcholine

Tachyphylaxis to succinylcholine was defined as a 20% or greater increase in rate of infusion in order to maintain 80 to 90% twitch depression [12,17]. In the 2^nd case, the patient's succinylcholine infusion rate was increased from 100mcg⁄kg⁄min to 140mcg⁄kg⁄min, in addition to 3 extra boluses of succinylcholine, in order to achieve surgical relaxation. The mechanisms underlying tachyphylaxis during succinylcholine infusion have remained unclear. The possible explanations are either enzyme (pseudocholineasterase) induction leading to increased metabolism of succinylcholine or a change in receptor sensitivity to succinylcholine with time. However there is no solid evidence to support the correlation of tachyphylaxis with occurrence of phase II block [12,17].

Managing residual muscle weakness in extubated patients in PACU

Airway Support: Postoperative observation and care of any residual muscle weakness is necessary. As the diaphragm muscle recovers from neuromuscular blockade sooner than pharyngeal muscles, the most common manifestation of muscle weakness from residual neuromuscular blockade turns out to be upper airway obstruction in extubated patients in PACU. Efforts to open the airwayby noninvasive measures should be executed before resorting to reintubation of the trachea as most cases of residual muscle weakness are transient and reversible. Jaw thrust and CPAP (5 to 15cm H2O) is often sufficient enough to tent the upper airway open. That is usually enough airway support in patients who are able to make purposeful efforts to breathe and whose pain is under good control [18–20].

Pharmacological support: The use of anticholinesterase should be prudent. There have been concerns of anticholinesterase use during or after the use of depolarizing NMBD (succinylcholine) because of the thought that in the presence of succinylcholine, administration of anticholinesterase would inhibit pseudocholinesterase, which hydrolyzes succinylcholine. Thus this would lead to prolongation instead of antagonism of neuromuscular block by succinylcholine [21].

Both Ramsey and Brandom demonstrated the use of anticholinesterase in cases of phase II block, without worsening neuromuscular blockade [12,13]. Of note, anticholinesterase (edrophonium or neostigmine) was only applied when the first twitch (T1) recovered to 76% of control strength (Tc) and T4⁄T1 to 48% that was about 31 +⁄− 5 min after succinylcholine infusion had stopped in Ramsey's study [13]. While Brandom's study did not indicate the time interval between the application of anticholinesterase and discontinuation of succinylcholine infusion, anticholinesterase was only administered in 2 of their 3 cases of phase II block (at the application of neostigmine, T1⁄Tc was at 94% and 87% respectively, while T4⁄T1 was at 55% and 52% respectively) [13].

They reasoned that when anticholinesterase is given at 20min or longer after succinylcholine infusion has been discontinued, the circulating levels of succinylcholine should be negligible, therefore the concern of prolongation of succinylcholine block would be inconsequential [12,21].

Conclusion

More recent evidence supports that the development of phase II block with continuous succinylcholine infusion during balanced anesthesia is a gradual process [12,15]. Literature review does not support an absolute number of total succinylcholine dosage or total administration time of succinylcholine infusion as a reliable predictor of progression into phase II block. Lab test of pseudocholinesterase function is not routinely performed. Therefore it is prudent to apply neuromuscular monitoring (such as acceleromyography with trainof– four nerve stimulation) during succinylcholine infusion even when the surgery is considered a short procedure [7,8].

References

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Citation: Li G, Wang J. Residual Muscle Weakness after Succinylcholine Infusion: Clinical Presentation, Diagnosis and Treatment. Austin J Anesthesia and Analgesia. 2014;2(4): 1022. ISSN: 2381-893X

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