Neostigmine is a polar acetylcholinesterase inhibitor (does NOT cross the blood-brain barrier) that is routinely used to reverse non-depolarizing neuromuscular blocking agents (NMBA) like rocuronium, vecuronium, and cisatracurium. These NMBAs are competitive inhibitors at the nicotinic acetylcholine receptor (AChR). Neostigmine prevents the degradation of acetylcholine (ACh) allowing more of this substrate to be available to bind its receptor (AchR) to overcome the competitive inhibition of the aforementioned NMBAs.
This surplus of ACh can also work on muscarinic acetylcholine receptors causing things like bradycardia. This is why we use antimuscarinics like glycopyrrolate and atropine to mitigate this effect. I dose intravenous neostigmine based on the residual neuromuscular blockade on board as determined by a train-of-four peripheral nerve stimulator, but will not exceed 5 mg. In fact, too much neostigmine can lead to paradoxical muscle weakness defeating the purpose of reversing paralysis in the first place.
Another effect from excess ACh is an “overdrive” of the parasympathetic nervous system’s “rest and digest” function. For example, I’ve used small doses of neostigmine to help alleviate refractory constipation (after ruling out a true bowel obstruction) since neostigmine’s cholinergic effects have profound pro-motility effects. I’ve also used acetylcholinesterase inhibitors like neostigmine and pyridostigmine to treat patients with myasthenia gravis (MG). These medications allow more acetylcholine to be available to bind the few AchR that aren’t “attacked” by the antibodies inherent to MG’s pathophysiology.
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What is the physiological rationale for using neostigmine only if the patient has recovered spontaneous ventilation or in the case of using a NMB monitor a TOF above 0,7?
Even in patients who have recovered twitches on the TOF monitor, a significant percentage of their nicotinic receptors are still blocked. It’s important to show at least some semblance of recovery from neuromuscular blockade since neostigmine works by overwhelming competitive inhibition from the paralytic, and if the blockade is still too deep, it’s possible that reversal may be short-lived. Not sure what the specific evidence for this is, but it’s my understanding.