Fentanyl-induced rigidity is typically reported in association with high doses of fentanyl (generally > 17 mcg/kg) [8]. However, it is also known to occur even with small boluses of 100 mcg fentanyl [1]. Considering that naloxone administration immediately relieved the muscle rigidity in our patient, it is reasonable to infer that his muscle rigidity was opioid-induced.

Opioid-induced rigidity, especially during anesthetic induction, is usually characterized by episodic breath-holding spells, tense abdominal muscles, a firmly locked jaw, and stiff extremities. Hypoxia and hypertension can also be observed during these episodes [6]. In the present case, opioid-induced rigidity upon anesthesia emergence was apparent after the administration of sugammadex sodium. Unlike typical opioid-induced rigidity, the patient’s spontaneous breathing was preserved; this made it difficult to differentiate between anesthetic emergence agitation and opioid-induced rigidity at that time. Breath-holding spells caused by opioid-induced rigidity are a manifestation of prolonged chest wall skeletal muscle contraction, which leads to decreased chest wall compliance and thus ineffective assisted and spontaneous ventilation. Even bag-valve-mask ventilation can be difficult because of high resistance [6]. These breath-holding spells caused by opioid-induced rigidity are also considered to be a result of upper airway obstruction due to glottic closure [9, 10]. From this perspective, respiration is possible if the trachea is secured by an intratracheal tube. However, in our patient, spontaneous breathing was preserved even after tracheal extubation; however, he developed tense abdominal muscles, a firmly locked jaw, and stiff extremities, and these symptoms were immediately reversed by naloxone administration.

In general, the trigger of opioid-induced rigidity is the rapid administration of a large amount of fentanyl. In our case, we administered a relatively large amount of fentanyl before the operation, but rocuronium was administered soon after fentanyl administration. Therefore, even if opioid-induced rigidity had developed, it could have been masked by the muscle relaxant effect and gone unrecognized. The opioid-induced rigidity observed at anesthesia emergence in this case manifested with sugammadex sodium administration. Our case illustrates that sustained opioid-induced rigidity, which may be masked by rocuronium, can manifest as reversal of muscular relaxation.

Roy and Fortier [4] reported a case of opioid-induced rigidity at the time of anesthesia emergence. Their patient received intermittent administration of fentanyl to a total of 0.5 mg, and termination of spontaneous breathing was thought to be largely responsible for glottic closure [4]. Even though we administered a larger amount of fentanyl than in their case, spontaneous breathing was preserved even after tracheal extubation. In our patient, the effect site concentration of fentanyl before naloxone administration was estimated to be 1.46 ng/mL using the Shafer model in the Tivatrainer simulation program (Version 8, Build 5) (Gutta B.V., EuroSIVA, Amsterdam, The Netherlands). Although the estimated effect site concentration of fentanyl provided an acceptable level of postoperative analgesia [11], rigidity may still occur even at low doses. Therefore, it may be prudent to refrain from administering potentially excessive opioids.

Roy and Fortier [4] speculated that the concurrent use of venlafaxine, which affects norepinephrine and serotonin levels, may have contributed to the rigidity in their patient. In our patient, remimazolam, an ultrashort-acting benzodiazepine [12], was administered in conjunction with propofol. Benzodiazepines are known to alleviate opioid-induced rigidity, and their antagonist flumazenil can counteract this beneficial effect [13]. Therefore, the rapid reversal of remimazolam by flumazenil might have played a role in the opioid-induced rigidity observed in our case.

In our patient, rigidity became apparent after the reversal of the muscle relaxant and was difficult to distinguish from agitation at that time. Nevertheless, oxygenation and ventilation were maintained, and flumazenil was administered with the expectation of further recovery of consciousness. Considering that rigidity can be accelerated by the administration of flumazenil, clinicians should refrain from routinely administering flumazenil. Most cases of opioid-induced muscle rigidity present with ventilatory failure due to glottic closure; therefore, our patient should have been extubated after he was fully awake, and naloxone should have been administered if rigidity was suspected before extubation.

Caution is needed because opioid-induced rigidity may occur even when spontaneous breathing is maintained. Fortunately, even after our patient’s trachea was extubated, his condition did not become critical because the glottis was not closed. However, considering that most cases of opioid-induced muscle rigidity involve glottic closure, our patient should have been extubated after resolution of the muscle rigidity by naloxone.

Both remifentanil and fentanyl can cause rigidity. Although our patient’s effect site concentration of remifentanil was very low when we observed the rigidity, a rapid decrease in the remifentanil concentration from a high level can cause withdrawal symptoms. Instead of administering relatively large doses of opioids, we should have initially used regional analgesic techniques to achieve opioid-sparing anesthesia [14]. Peripheral nerve block may help reduce opioid consumption and potentially avoid opioid-related complications.

Loss of subcortical inhibitory activity may be a common mechanism involved in the neuroexcitation characteristic of opioid-induced rigidity [4]. In the present case, the patient had a history of cerebral infarction and chronic subdural hematoma, and preoperative magnetic resonance imaging indicated chronic ischemic changes in the substantia alba. These comorbidities might have been involved in the development of opioid-induced rigidity. Our patient may have been exhibiting signs indicative of a risk of opioid-induced rigidity, but this is only speculation at this stage.

Considering his comorbidities, our patient might have also been at high risk of postoperative cognitive decline, and we should have performed intraoperative electroencephalographic monitoring. Additionally, considering his postoperative cognitive function, peripheral nerve blocks should have been used to reduce opioid consumption [15].

In summary, we experienced a case of atypical opioid-induced rigidity in which spontaneous breathing was preserved. The opioid-induced rigidity upon emergence from anesthesia was apparent after sugammadex sodium administration, and it was reversed by naloxone administration. Even as the simulated effect site concentration of fentanyl decreases during anesthesia emergence, opioid-induced rigidity may still occur. We consider that the rapid remimazolam reversal by flumazenil might have contributed to the rigidity in this case.