Neurologic Examination Facilitated by Reversal of Rocuronium with Sugammadex

Abstract

Background: Patients with neurologic injuries often receive neuromuscular blocking agents to facilitate airway management. The urgent nature of intubation may result in paralytic administration prior to neurologic examination, delaying clinical assessment, prognostication, and surgical interventions. Objective: In October 2018, an institutional guideline was implemented to extend institutional sugammadex use to include patients with uncertain neurologic examinations with recent rocuronium administration. The guideline allowed for a dose range of 2 mg/kg to 16 mg/kg. The objective of this continuous quality improvement project was to describe the use of sugammadex after implementation of an institutional guideline. Methods: Patient records between October 2018 and March 2020 were reviewed for guideline adherence and outcomes. Information assessed included patient weight, injury mechanism, the dosage and timing of rocuronium and sugammadex administration, and neurologic examination findings. Descriptive statistics were used to assess outcomes. Results: During the study period, eleven patients received sugammadex to facilitate neurologic examinations. The most common dose of sugammadex was 4 mg/kg with a mean total dose of 498.4 ± 333.5 mg. The mean time between rocuronium and sugammadex administration was 73.9 ± 41 minutes. Most patients (72.7%) had definitive changes in neurologic examination after sugammadex administration. Five patients had neurosurgical interventions offered and performed, with 1 of the patients surviving. Conclusions: This case series suggests that sugammadex is useful for reversing rocuronium induced paralysis to facilitate neurologic examination needed to determine management strategies for patients with a neurologic injury.

Introduction

Neuromuscular blocking agents (NMBA) are often administered to patients suffering from a traumatic brain injury (TBI) or spontaneous neurologic injury to facilitate airway management. Unfortunately, the urgent nature of intubation can preclude completion of an accurate neurologic examination prior to administration of the NMBA. The duration of paralysis can impede clinician’s ability to make timely decisions about prognosis and potential management strategies including placement of external ventricular drain (EVD) systems or hematoma evacuation with craniectomy or craniotomy.

Historically, the only reversal agent available for reversal of NMBAs was neostigmine, which comes with several disadvantages including delayed or incomplete reversal, bradycardia, and nausea or vomiting.^1,2 Sugammadex was FDA approved in 2015 for the reversal of amino-steroid paralytic agents such as rocuronium and vecuronium. The medication is available in 200 mg ($138.50) and 500 mg ($253.70) vials. ³ Full dose rocuronium can be reversed with sugammadex at a dose of 16 mg/kg if urgent reversal is needed within ∼3 minutes, or a lower dose of 4 mg/kg can be considered if 0 to 2 twitches are present on train-of-four (TOF) monitoring.^4-6 Prior to 2018, the institution limited the use of sugammadex to the post-operative setting, failed intubations in the emergency department or intensive care units, or successful intubations of asthmatic patients with poor ventilation. In October 2018, the neurocritical care team at the institution developed a guideline for administering sugammadex to facilitate neurologic examination after a neurologic injury. This case series describes the use of sugammadex for neurologic examinations as a result of a quality improvement analysis after the implementation of a guideline.

Materials and Methods

A list of all adult patients admitted to an intensive care unit or the emergency department at a level 1 trauma center who received sugammadex orders for neurological examination from October 2018 to March 2020 was obtained. Patient records were reviewed for adherence to the guideline and outcomes following the implementation of the guideline. The criteria for use of sugammadex included the following: an uncertain neurologic examination prior to NMBA administration, a computed tomography (CT) head showing an emergent neurological injury, and it was deemed that an accurate post-intubation examination was urgently needed to determine if neurosurgical intervention was indicated. The institutional policy developed to facilitate neurologic examination allowed for alternative dosing depending on TOF assessment and/or time from NMBA administration.^4,7-9 If feasible, it was recommended that a TOF be obtained prior to sugammadex administration to guide dosing. de Boer et al found an average time to recovery after a rocuronium dose of 1.2 mg/kg to be 122 minutes. Based on these findings, the guideline suggested the use of sugammadex for patients who received rocuronium within the prior 2 hours. ⁴ An initial upfront dose of sugammadex without obtaining a TOF was allowed due to the variability in user capability outside the OR and the delay in obtaining equipment. Providers had the option to obtain a TOF if there remained any uncertainty after the initial sugammadex administration. Patient records were accessed to obtain the patient location, weight, mechanism of injury, documentation of NMBA (agent, time administered, and dose), documentation of sugammadex (time administered and dose), any record of TOF documented prior to sugammadex administration, recorded Glasgow Coma Scores (GCS), and confirmation that the indication was for neurologic examination and the outcomes after giving sugammadex. Patients without chart notes connecting sugammadex administration with neurologic status changes and/or clinical decisions were reviewed and ultimately categorized as cases where sugammadex did not clearly contribute to decision making. Descriptive statistics were used to assess outcomes. This research adhered to all ethical guidelines and, as a continuous quality improvement project, was exempt from Institutional Review Board assessment at this institution. Formal consent was not required for this study type.

Results

A total of thirteen patients had sugammadex ordered for neurological examination and eleven of these patients received sugammadex (Table 1). Two patients did not receive sugammadex due to return of reflexes prior to medication administration and were excluded. The mean age (±SD) was 53 ± 18.4 years old and the primary mechanism of injury was traumatic (81.8%). The mean dose of rocuronium administered was 102.7 ± 16 mg and the mean sugammadex dose administered was 498.4 ± 333.5 mg or most frequently 4 mg/kg. The mean time from rocuronium to administration of sugammadex was 73.9 ± 41 minutes. Only 2 patients had a TOF documented in the electronic medical record prior to administration of sugammadex, both with a TOF of 0 out of 4 (cases 2, 5). Nine patients had a definitive decision made about management strategy after receiving sugammadex. Eight of these patients had a change in neurologic examination and 1 patient had no change in examination (case 1). Of the patients with changing examinations, 4 patients had neurosurgical interventions offered, with 1 of the patients surviving (case 6). Of the 2 patients where sugammadex did not clearly contribute to the decision-making process, 1 patient was taken for emergent surgical intervention (case 11) and the other patient was transitioned to comfort care based on the family’s request (case 4). In total, 5 of the eleven patients received neurosurgical interventions (cases 2, 3, 6, 8, 11) and 2 of the eleven patients transitioned directly to comfort care measures based on the severity of injury and the family’s request (cases 4, 7). There were no adverse effects from sugammadex administration documented.

Table 1.

Characteristics and Outcomes of Patients.

Case #	Age and Sex	Weight (kg)	Mechanism of Injury	Rocuronium Dose (mg)	Rocuronium Dose (mg/kg)	Sugammadex Dose (mg/kg)	Time to Reversal Agent (min)	Glasgow Coma Scale (GCS) Response	Outcome
1	59 M	81.6	Traumatic	100	1.2	4	– a	3 -> 3	Devastating, non-survivable injury confirmed
2	48 F	86.5	Traumatic	100	1.2	4	77	3 -> 7	Right sided motor response, cough/gag reflex resulting in EVD placement
3	38 M	63.7	Traumatic	100	1.6	8	60	3 -> 4	Extensor posturing and possible illicit drugs masking examination so taken for EVD placement and hemispheric craniectomy
4	79 F	70.1	Traumatic	80	1.1	4	50	6 b	Family discussion resulted in transition to comfort care
5	24 F	106.6	Traumatic, resulting in occlusive stroke	150	1.4	4	184	3 -> 3	Opened eyes but no limb movement, did not qualify for alteplase
6	57 F	92.5	Spontaneous	100	1.1	16	44	3 -> 6	Neurology examination with positive gag and cough, withdrawal to pain, recommended neurosurgery consult for expanding intra-parenchymal hemorrhage, EVD placed; survived
7	74 F	92.9	Traumatic	100	1.1	4	78	3 -> 4	Family discussion resulted in transition to comfort care based on unlikelihood of return to full independence
8	27 M	92	Traumatic	100	1.1	4	68	3 -> 6	Patient moved all extremities and had cough. Emergently to OR for decompressive craniectomy and subgaleal drain
9	80 F	46	Spontaneous	100	2.2	16	39	3 -> 4	Cough/gag present but no purposeful movements, determined that craniotomy and EVD placement would not prevent likely mortality and were not pursued
10	45 M	75.6	Traumatic	100	1.3	4	– a	3 -> 4	Extensor posturing with unresponsive, non-reactive pupils, no surgical interventions offered after examination and CT head with tonsillar herniation
11	52 M	116	Traumatic	100	0.9	4	65	6 b	Emergent craniectomy and subdural hematoma evacuation

^aNo documentation of time.

^bsugammadex administration not connected to decision making, GCS reported is initial reported GCS prior to interventions.

Discussion

The institutional policy developed to facilitate neurologic examination allowed for alternative dosing depending on TOF assessment and/or time from NMBA administration.^4,7-9 Despite a mean rocuronium dose of 1.3 mg/kg, lower dose sugammadex administration facilitated clinical decision making for most patients. Of those that received a lower dose strategy of 4 mg/kg (72.7% of patients), 5 of the 8 had a documented change in exam. This lower dosing is consistent with a recently published case report on the use of sugammadex to reverse rocuronium 1 hour after administration in a patient with end-stage renal disease and a TOF of 0 out of 4. ¹⁰ In addition to facilitating clinical decisions, the lower dosing strategy allowed for cost avoidance when compared to a moderate or high reversal dose strategy (eg, for a 70 kg patient using 200 mg vials, 4 mg/kg = $277, 8 mg/kg = $415.50, 16 mg/kg = $831).

Although rocuronium’s duration of action is expected to be 30-60 minutes, several reports of a longer duration of action have been documented.^10-12 The mean time between rocuronium and sugammadex administration was 73.9 ± 41 minutes, suggesting bedside clinicians believed these patients had a longer than expected paralysis. Higher weight-based rocuronium doses may have contributed to a longer duration of paralytic effect. ¹³ The previously established safety and reliability of sugammadex makes it an ideal agent when clinical assessment may be needed after administration of paralyzing agents. This quality improvement analysis provides information about potential dosing, timing of administration, and effectiveness of the use of sugammadex in the setting of reversing NMBA to facilitate neurologic examination. Although the retrospective design of this quality improvement project limits the ability to assess adverse events as a result of sugammadex administration, none were identified in review of clinical documentation. To the author’s knowledge, this case series and the recent case report by Curley and colleagues ¹⁰ are the first to report on the use of sugammadex in this patient population. In other settings, lower doses of sugammadex have been found to be adequate to reverse rocuronium. ¹⁴ However, in the operating room, the degree of neuromuscular blockade is measured by post-tetanic count (PTC) and TOF in a controlled setting, at regular intervals, and by personnel trained to perform the assessments. For reversal to facilitate examination, it may not always be practical to perform PTC/TOF monitoring and therefore the dose of NMBA and time from NMBA administration may be useful to determine initial dosing for sugammadex. Due to the time sensitive nature of completing exams in the emergency department, it was common practice to administer sugammadex without TOF. Therefore, it cannot be ruled out that the paralytic effect had subsided. However, clinicians were making decisions at bedside based on high suspicion that the paralytic effect could be contributing. Based on the findings of this case series, further study could explore the use of lower dosing strategies in a prospective manner.

Limitations

Limitations of this report include the small patient population and all patients receiving rocuronium for intubation. The institutional policy suggested TOF monitoring prior to sugammadex to assist with dosing determination, but 81.8% of patients did not have a TOF documented. Therefore, inadequate dosing could have been possible. However, the 2 patients with TOF monitoring had 0 out of 4 twitches and received 4 mg/kg of sugammadex. These 2 patients had a change in neurologic examination after sugammadex administration, which guided clinical decisions suggesting the lower dose strategy was adequate. If there was ongoing concern about an incomplete NMBA reversal, TOF monitoring was available for confirmation after sugammadex administration. No patients received multiple doses of sugammadex. The majority (72.7%) had a change in neurologic examination (change in GCS, return of reflexes) which was the outcome of interest. For the patients who did not have a change in neurologic examination reported (27.3%), 1 had no return of reflexes consistent with the devastating brain injury seen on imaging, 1 had no comment on the examination as the patient was made comfort care irrespective of sugammadex administration, and 1 went straight to the operating room for neurosurgical intervention.

Conclusion

This case series suggests that sugammadex is useful for reversing rocuronium induced paralysis to facilitate completion of a neurologic examination that is needed to determine management strategies for patients who suffered from a neurologic injury.