Let’s consider the following case:
A 92-year-old, 74 kg woman with a history of type 2 diabetes, chronic kidney disease, gastroesophageal reflux disease, hypertension, depression, hypothyroidism, and stroke, presents to the emergency department (ED) after a mechanical fall. She undergoes a bimalleolar ankle fracture repair. At the end of the surgery, the patient has a train of four of 3 out of 4 and rocuronium-induced neuromuscular blockade is reversed with neostigmine 3 mg and glycopyrrolate 0.4 mg. The patient demonstrated 5-second sustained tetany after reversal and was extubated 22 minutes later.
The patient was admitted to the post-anesthesia care unit (PACU) and placed on 6 liters/minute of oxygen via simple mask. Oxygen saturation was 97%, respiratory rate was 19, and heart rate was 115 (atrial fibrillation). The patient’s level of consciousness was documented as obtunded. Shortly after arrival the patient became apneic with oxygen saturation dropping to 88%. An oropharyngeal airway was placed with bag mask ventilation. Two doses of naloxone were given with no return of spontaneous ventilation. The patient was re-intubated. After discussing the patient’s condition, sugammadex was administered. Per nursing notes, the patient’s “condition improved dramatically: alert, strong, and following commands.” The patient was subsequently extubated in the PACU and admitted to the observation unit, a higher level of care than anticipated. The patient was discharged on postoperative day 3.
On postoperative day 7, the patient presented to the ED with chest pain and a cough. She was re-admitted, underwent a cardiac work-up and due to an elevated white blood cell count, exacerbated chest pain with coughing. Radiographic imaging was consistent with pneumonia and she was started on empiric antibiotics.
What can we learn from this case?
First, among the myriad of causes of hypoxemia in the postoperative period, there is one that is largely preventable: residual neuromuscular blockade (rNMB). This occurs when residual effects of intraoperatively administered neuromuscular blockers mechanistically cause impaired contraction of ventilatory muscles, dysfunction of the pharyngeal muscles, and blunting of the hypoxic ventilatory response. Depending on the depth of residual block and patient specific risk factors, rNMB can lead to pulmonary complications such as upper airway obstruction, pulmonary aspiration, atelectasis, and pneumonia.1,2 While some hypoxemic events may be temporized in the postanesthesia care unit (PACU) with interventions such as supplemental oxygen, placement of a nasopharyngeal airway, and attentive care, some patients will proceed to decompensate and ultimately experience a critical respiratory event (CRE) in the PACU. CREs are commonly defined as a major, unanticipated ventilation issues inclusive of hypoxemia (hemoglobin oxygen saturation < 90%), hypoventilation (respiratory rate < 8 breaths/minute or arterial carbon dioxide > 50 mmHg), upper-airway obstruction that requires a physical intervention (e.g., bag-mask ventilation, insertion of an oropharyngeal/nasal airway, tracheal intubation) and/or pharmacologic intervention (opioid reversal, neuromuscular blockade reversal).3
To reverse muscle paralysis used during general anesthesia, we have two pharmacologic options: neostigmine and sugammadex. While neostigmine has traditionally been used as the agent of choice, recent evidence tells us that despite its use along with qualitative neuromuscular monitoring, 40-65% of surgical patients still have residual neuromuscular blockade at tracheal extubation.4,5 These residual effects persist on admission to the PACU as supported by several studies including a recent systematic review of observational studies indicating a median incidence of 30%.6 In a recent systematic review and meta-analysis of 20 randomized controlled trials, the incidence of rNMB at PACU entry was 0.3% among those treated with sugammadex and 42.5% among those treated with neostigmine.7
In the immediate postoperative phase, patients with rNMB have higher rates of critical respiratory events compared to those without rNMB.6,8 These events are associated with an increase in healthcare resource utilization such as longer PACU lengths of stay and intensive care or observation unit admissions.9 Clinically, evidence supports that rNMB is a cause of oxygen desaturations, airway obstruction, reintubations, and postoperative pneumonia. Research evaluating the link between neuromuscular blockade reversal strategies and the development of clinically significant postoperative pulmonary complications is emerging. In the STRONGER study, sugammadex was associated with an overall 30% reduction in the risk of postoperative pulmonary complications.10 Although not all endpoints reached clinical significance, in a small randomized trial of 200 elderly patients, sugammadex, when compared to neostigmine, was associated with a 40% reduction in rNMB, 13 minute reduction in PACU length of stay, 7% reduction in postoperative pulmonary complications, and a 10% reduction in 30-day hospital readmission rate.11 Larger studies are needed to further evaluate these endpoints on patients at greatest risk for pulmonary complications.
What is the Pharmacists Role?
Pharmacists are well positioned to advocate for safe management of patients undergoing neuromuscular blockade and reversal. It is prudent for pharmacists to expand their knowledge on the management of neuromuscular blockade, intraoperative monitoring, and reversal so that they may effectively collaborate with anesthesia clinicians on each of these individual aspects. Pharmacists can also collaborate with nurses, medication safety officers, and re-admission teams to ensure familiarity with the clinical implications of rNMB. Due to more recent awareness of rNMB, it is not widely discussed in the perioperative nursing literature. As a result, PACU nurses often have variable depths of knowledge about rNMB. Efforts to educate, optimize, and help apply the information they receive during the OR to PACU handoff could help them respond more quickly and appropriately to a patient in respiratory distress. Unfortunately, not all CREs in the PACU will be avoided. Medication safety officers should be certain to broaden their perspective when reviewing PACU CREs. Pharmacists, often as a part of the medication safety team, can provide clinical insights and education to aid in differentiating opioid-induced respiratory depression from rNMB. Lastly, reducing hospital re-admissions is a key focus area for many institutions. Clinical re-admission review teams should scrutinize the management of neuromuscular blockade in any surgical patient readmitted with a postoperative pulmonary complication.
- Broens SJL, Boon M, Martini CH et al. Reversal of partial neuromuscular block and the ventilatory response to hypoxia: a randomized controlled trial in healthy volunteers. Anesthesiology. 2019; 131(3):467-76.
- Cammu G. Residual neuromuscular blockade and postoperative pulmonary complications: what does the recent evidence demonstrate? Curr Anesthesiol Rep. 2020: 1-6.
- Karcz M, Papadakos PJ. Respiratory complications in the postanesthesia care unit: a review of pathophysiological mechanisms. Can J Respir Ther. 2013; 49(4):21-9.
- Fortier LP, McKeen D, Turner K et al. The RECITE Study: A Canadian prospective, multicenter study of the incidence and severity of residual neuromuscular blockade. Anesth Analg. 2015; 121(2):366-72.
- Saager L, Maiese EM, Bash LD et al. Incidence, risk factors, and consequences of residual neuromuscular block in the United States: the prospective, observational, multicenter RECITE-US study. J Clin Anesth. 2019; 55:33-41.
- Raval AD, Anupindi VR, Ferrufino CP et al. Epidemiology and outcomes of residual neuromuscular blockade: a systematic review of observational studies. J Clin Anesth. 2020; 66:109962.
- Raval AD, Uyei J, Karabis A et al. Incidence of residual neuromuscular blockade and use of neuromuscular blocking agents with or without antagonists: a systematic review and meta-analysis of randomized controlled trials. J Clin Anesth. 2020; 64:109818.
- Murphy GS, Szokol JW, Marymont JH et al. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg. 2008; 107(1):130-7.
- Grabitz SD, Rajaratnam N, Chhagani K et al. The effects of postoperative residual neuromuscular blockade on hospital costs and intensive care unit admission: a population-based cohort study. Anesth Analg. 2019; 128(6):1129-36.
- Kheterpal S, Vaughn MT, Dubovoy TZ et al. Sugammadex versus neostigmine for reversal of neuromuscular blockade and postoperative pulmonary complications (STRONGER): a multicenter matched cohort analysis. Anesthesiology. 2020; 132(6):1371-81.
- Togioka BM, Yanez D, Aziz MF et al. Randomised controlled trial of sugammadex or neostigmine for reversal of neuromuscular block on the incidence of pulmonary complications in older adults undergoing prolonged surgery. Br J Anaesth. 2020; 124(5):553-61.