Reversal of Partial Neuromuscular Block and the Ventilatory Response to Hypoxia

Abstract

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background The ventilatory response to hypoxia is a life-saving chemoreflex originating at the carotid bodies that is impaired by nondepolarizing neuromuscular blocking agents. This study evaluated the effect of three strategies for reversal of a partial neuromuscular block on ventilatory control in 34 healthy male volunteers on the chemoreflex. The hypothesis was that the hypoxic ventilatory response is fully restored following the return to a train-of-four ratio of 1. Methods In this single-center, experimental, randomized, controlled trial, ventilatory responses to 5-min hypoxia (oxygen saturation, 80 ± 2%) and ventilation at hyperoxic isohypercapnia (end-tidal carbon dioxide concentration, 55 mmHg) were obtained at baseline, during rocuronium-induced partial neuromuscular block (train-of-four ratio of 0.7 measured at the adductor pollicis muscle by electromyography), and following reversal until the train-of-four ratio reached unity with placebo (n = 12), 1 mg neostigmine/0.5 mg atropine (n = 11), or 2 mg/kg sugammadex (n = 11). Results This study confirmed that low-dose rocuronium reduced the ventilatory response to hypoxia from 0.55 ± 0.22 (baseline) to 0.31 ± 0.21 l · min−1 · %−1 (train-of-four ratio, 0.7; P < 0.001). Following full reversal as measured at the thumb, there was persistent residual blunting of the hypoxic ventilatory response (0.45 ± 0.16 l · min−1 · %−1; train-of-four ratio, 1.0; P < 0.001). Treatment effect was not significant (analysis of covariance, P = 0.299) with chemoreflex impairment in 5 (45%) subjects following sugammadex reversal, in 7 subjects (64%) following neostigmine reversal, and in 10 subjects (83%) after spontaneous reversal to a train-of-four ratio of 1. Conclusions Despite full reversal of partial neuromuscular block at the thumb, impairment of the peripheral chemoreflex may persist at train-of-four ratios greater than 0.9 following reversal with neostigmine and sugammadex or spontaneous recovery of the neuromuscular block.

Cholinergic Chemotransmission and Anesthetic Drug Effects at the Carotid Bodies

“…By showing that the response to hypercapnia was not significantly affected, it was hypothesized that muscle relaxants exerted these effects within the peripheral chemoreflex loop at the peripheral chemoreceptors. Similar observations have been made recently for the more commonly used muscle relaxant rocuronium [9]. Together, these studies show that a shallow neuromuscular block (e.g., train-of-four muscle twitch response ratio of 70 to 90%, see ref [26].…”

“…However, as cholinergic transmission is primarily involved in modulatory effects in the chemoreflex loop, the exact effect of muscle relaxants on the type 1 cell and chemotransduction process is not known. One example that supports the hypothesis that muscle relaxants interfere with cholinergic chemotransmission is that, following administration of rocuronium, the AHVR is depressed, an effect that is just partly related to the reduction in muscle strength [9].…”

“…Unfortunately, incidences of residual NMB in clinical practice are substantial [41,46,47], and these episodes often remain undetected by healthcare personnel as patients commonly do not display symptoms of evident muscle weakness. In addition, recent observations by Broens et al suggest that, even after full recovery of the muscle relaxation (as measured at the thumb by relaxation monitoring with a train-of-four muscle twitch response ratio of 100%), the peripheral chemoreflex remains depressed in a significant subset of subjects [9]. This suggests that a large proportion of patients remains at risk for hypoxia, even when the muscle relaxation has fully worn off according to clinical monitors.…”

“…Peripheral control of breathing is mediated through the carotid bodies, which are sensitive to derangements in arterial oxygen, carbon dioxide and glucose levels [6]. Especially muscle relaxants and intravenous and inhalational anesthetics depress peripheral chemosensitivity [1,4,5,[7][8][9]. Attenuated peripheral chemosensitivity following surgery, when the patient is just off artificial ventilation, may precipitate adverse respiratory events in the postoperative period.…”

Is less really more? A critical appraisal of a POPULAR study reanalysis

“…Additional data are available to support return of the TOF ratio to unity. Broens and colleagues 14 recently reported that 'Despite full reversal of partial neuromuscular block at the thumb, impairment of the peripheral chemoreflex may persist at train-of-four ratios greater than 0.9 following reversal with neostigmine and sugammadex [sic] or spontaneous recovery of the neuromuscular block.' This study was performed in healthy volunteers (with no premedication or sedation), and neuromuscular monitoring included electromyography, a technique that is devoid of the inverse fade phenomenon (TOF ratios >1.0 that require normalisation) that plagues acceleromyography.…”