The most important findings of the present study were: firstly, both clinical duration and duration until 90% and 100% recovery are significantly prolonged in the group 80+. Secondly, compared to younger adults the onset of neuromuscular block is significantly slower in the group 80+. Moreover, a tendency toward deeper maximum levels of neuromuscular block could be observed in group 80+ (Table 2). Thus, a shift from rocuronium as a rapid onset, intermediate acting compound to a slower onset and long-acting compound can be observed in patients ≥ 80 years old.
The significance of an acceleromyographic TOF ratio of 0.9 as a criterion for sufficient neuromuscular recovery has been questioned by Capron et al., proposing recovery of the TOF ratio to 1.0 as benchmark when acceleromyography is used. Recent observations by Blobner et al. confirmed this limitation of an acceleromyographic TOF ratio of 0.9 for clinical decision-making. Hence, in the present study both parameters were assessed: a TOF ratio recovery to 0.9 facilitating comparison with data in the literature, and a TOF recovery to 1.0 indicating acceptable neuromuscular recovery when using acceleromyography. In the present study time course neuromuscular block was assessed with the TOFscan monitor. This AMG device has recently been approved for research purpose. This monitor does not need to be calibrated, as it operates with an alternative option to ensure a constant maximum stimulus, it measures the impedance of the skin directly (resistance) and as long as the resistance of the skin is within the measurement window, the stimulation of the nerve is assured with the user-selected electrical current. Moreover, according to the available evidence normalization of TOF values is not mandatory with this device. Thus, recovery parameters indicated in this study are raw TOF-ratios.
Murphy et al. reported a twice as high incidence of postoperative residual neuromuscular block in geriatric patients compared to younger patients, despite similar neuromuscular management. This increased incidence of residual paralysis in the elderly was associated with a higher incidence of hypoxic events, airway obstruction, and postoperative pulmonary complications. Moreover, even PACU and hospital length of stay was increased in the elderly. Hårdemark Cedborg et al. could report a profound negative impact of residual paralysis on airway integrity in elderly individuals, increasing the incidence of pharyngeal dysfunction from 37 to 71%, with impaired ability to protect the airway. Hence, elderly patients are prone to adverse pharyngeal effects of residual neuromuscular blockade and these effects may further increase the risk of postoperative pulmonary complications in this population segment. The present study gives new insights in neuromuscular block characteristics in the oldest old. Clinical duration and time needed to recover to a TOF-ratio of 90% and 100% of baseline are increased about approximatively 60% compared to the group 20–50. Thus, rocuronium shifts from an intermediate-acting compound to a long-acting compound in patients ≥ 80 years. Therefore, strategies to prevent residual paralysis in this patient population needs to be revised and the poor tolerance of even small degrees of residual paralysis in the elderly should be considered in the context.
Neuromuscular monitoring and pharmacological reversal are key elements in any strategy to prevent postoperative residual paralysis. Thilen et al. recently tested a protocol for the prevention of rocuronium-induced residual neuromuscular block based on qualitative monitoring and an optimized protocol for neostigmine-induced reversal. Timing and dosing of neostigmine were founded on best available evidence in their protocol.[20–22] Basically, a TOF count of 4 at the adductor pollicis was required before starting reversal with neostigmine, 40 μg/kg neostigmine were given at a TOF count of 4 with fade, and a delay of at least 10 min between neostigmine administration and extubation was respected.[20–22] Compared to the pre-protocol practice, the incidence of residual paralysis could be reduced from initially 58% to 35% of patients and severe residual paralysis corresponding to a TOF-ratio < 0.7 could be avoided with this protocol. However, small but clinically relevant degrees of residual paralysis corresponding to a TOF-ratio of 0.7—0.9 remained unchanged with this best practice protocol, suggesting that the association of qualitative monitoring and neostigmine-based reversal has limitations. Findings from Martinez-Ubieto et al. further confirmed this limitation of neostigmine. A lesser relative potency of neostigmine in the elderly further confirmed this assumption and emphasizes the need for age-appropriate reversal strategies for elderly patients. Of interest in this context, McDonagh et al. observed a rapid and complete reversal of rocuronium neuromuscular block in the elderly when sugammadex was given at a TOF count of 2. Sugammadex doses were similar to nonelderly adults although reversal was slightly slower in the elderly cohort: 2.2 min in patients < 65 years, 2.6 min in patients 65–74 years old and 3.6 min in patients ≥ 75 years.
Succinylcholine may be contraindicated in many elderly patients because of comorbidities such as renal insufficiency with increased serum potassium levels or hemiplegia to name only a few. That's why rocuronium may be an interesting alternative for rapid sequence induction (RSI) in the elderly. In the present study, a tendency to deeper maximum level of neuromuscular block could be observed in the elderly (Table 2). However, the study was not primarily designed to detect differences in the depth of neuromuscular block. Moreover, the findings of the present study confirmed previous results reporting a slower onset of rocuronium 0.6 mg/kg in the elderly. In the light of these findings one may question whether rocuronium is still a useful compound for RSI in the elderly. In a cohort of elderly patients between 65–92 years Takagi et al. observed an onset time of 187 s after rocuronium 0.6 mg/kg and increasing the dose of rocuronium to 1 mg/kg decreased the onset time to 104 s. Unfortunately, their study design did not allow to draw conclusions on intubating conditions for RSI after rocuronium 1.0 mg/kg. The slower onset on rocuronium neuromuscular block observed in the study by Takagi et al. may be explained by findings from Shiraishi et al. reporting an inverse relationship between cardiac output and rocuronium onset time in the elderly. However, whether doses of rocuronium higher than 1 mg/kg will further decrease its onset time in the elderly is currently unknown, as is the question what level of neuromuscular block is really required in elderly patients to achieve good to excellent intubating conditions after 45–60 s.
Limits and Further Research
The new insights in neuromuscular block characteristics in patients ≥ 80 given in this study should incite future research addressing the question of safe management of RSI with rocuronium in the elderly. Especially the optimal rocuronium dose and the required level of neuromuscular block to achieve adequate intubating conditions within 45 to 60 s need to be determined. Moreover, as the present study was designed to assess the impact of increasing age on the pharmacodynamic properties of rocuronium, it does not allow detailed insights in the underlaying mechanisms. This has to be addressed in future studies. To this end patients ≥ 80 with hepatic and/or renal insufficiency should be compared with patients in the same age group but without these organ dysfunctions. In addition, different dosing strategies based on real body weight, ideal body weight, or lean body weight should be evaluated in patients ≥ 80 years, also. Finally, the findings of the present study are limited to an intravenous anesthesia background. Both parameters, duration and recovery of rocuronium may be significantly delayed during volatile anesthesia compared to TIVA, as volatile anesthesia may potentiate the effect of nondepolarizing neuromuscular blocking agents.
In conclusion, the present study observed a shift from rocuronium as a rapid onset and intermediate acting compound in the group of younger adults to a slower onset and long-acting compound patients ≥ 80 years old. Age-appropriate strategies for the management of neuromuscular blockade are required for the oldest old.
Assistance with the article: None
This work was supported by the Department of Anaesthesia, Critical Care & Perioperative Medicine and by the Department of Research and Innovation, CHRU Nancy, France, as well as the Department of Anesthesiology, CHU Brugmann, Brussels, Belgium.
Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Ethics approval and consent to participate
This paper adheres to the applicable Consolidated Standards of Reporting Trials guidelines and was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval for this study was provided by Comite de Protection des Personnes EST III, 10 September 2018, referral number 200, chairperson Pr Y. Martinet. All patients provided written informed consent.
Consent for publication
BMC Anesthesiol. 2021;21(225) © 2021 BioMed Central, Ltd.