Paralytics are not sedatives

“All subjects were responsive to questioning during the experiment, reported that they were completely aware and felt neither drowsy nor confused. The arithmetic questions were answered with 96% accuracy. Two subjects in the suxamethonium arm were not given memory tests, one because of ongoing difficulties with face-mask ventilation and a short duration of neuromuscular block, and the other because of an oversight. The memory stories were recalled with 94% accuracy. One subject could recall only two of the key facts (‘Something about a bush turkey on the tablelands’), reporting that they had been distracted at the time by an unpleasant sensation of secretions pooling in their pharynx.”

Stop, go back and read that again.

Paralytics are not sedatives. 

A too frequent situation I have encountered in my professional life has been the use of paralytics without sedation. Almost always it has been in a clinical environment where sedation using available agents could have made existing hypotension/hypoperfusion worse. *could have* in the sense that multimodal pathways and appropriate dosing could be used safely to targeted outcomes. 

We’ve all heard that these patients need sedation in didactic and experiential education. But I wasn’t prepared for the real-world environment where providers… well, I guess the were absent that day in class. While I understand the complexities of critical patient situations where sedation isn’t at the top of the problem list, that doesn’t equate to sedation being abandoned for paralysis alone.

Perhaps the misunderstanding arose from previous literature(1) where fully awake study subjects (3 of the study investigators themselves) were given paralytics alone and were assessed using the bispectral index (BIS). In these paralyzed subjects (with no sedation) demonstrated decreases in BIS levels to a minimal value of 64 and 57. BIS levels between 40 and 60 are thought to reflect a level of unconsciousness suitable for surgery and levels between 60 and 80 reflect sedation in which patients could respond purposefully to stimulus. The authors concluded that while paralytics decrease BIS and suggest some level of sedation, awareness in paralyzed patients cannot be fully excluded.

Despite letters to the editor questioning the conclusion, and highlighting the limitations of BIS and electromyographic monitoring, the questionable practice of paralysis without sedation continued. Why the possibility of sedation with paralytics alone was a consideration is confusing given pre-existing evidence demonstrated no change in the level of consciousness (including feelings of dyspnea in response to rising PCO2).(2-4)

The evidence we should all know

In 2015, a group of investigators attempted to resolve this issue by assessing whether the BIS decreases in awake volunteers in response to neuromuscular block alone using succinylcholine (suxamethonium) or rocuronium.(5) In other words, these healthy volunteers were given paralytics without sedation. 

The ten (N=10) patients in this study were all anesthetists (ie, themselves), between 29 and 52 years of age who had fasted for at least 6 hours prior to administration of study drugs. The study intervention was the administration of succinylcholine and rocuronium in non-sedated study subjects in a fully equipped OR on two separate occasions. The effect of the paralytic was assessed clinically by the movement of the subject’s left hand to command and electronically with the BIS-EMG parameter. Subjects were also followed up by personal interviews after the experiment to assess any negative psychological features relating to their participation.

To measure the BIS one electrode was placed on either side of the subject’s forehead: one BIS-xp electrode connected to a BIS Vista monitor and another to a BIS A2000 monitor. Additionally, a conventional 22-channel scalp EEG was also recorded. 

A baseline EEG with closed eyes was recorded for 3 min, and then the fun began. The ten (N=10) subjects were pre-oxygenated by face mask and were given succinylcholine 1.5 mg/kg IV. Once observed fasciculations ceased, the subjects were ventilated via a face mask to a target end-tidal Pco2 of 35 mm Hg, with tidal volumes of 7–10 ml/kg. 

Before the patients were paralyzed, their forearm was isolated using a padded cuff on the right upper arm inflated to 300 mm Hg. Now paralyzed subjects were assessed each minute and were asked to respond with their isolated forearm, using pre-arranged hand signals, to confirm conscious state, request any changes to ventilation, or indicate any distress, at which point anesthesia would be induced with a ‘rescue dose’ of propofol 2 mg/kg. If the subjects failed to respond, this was treated as loss of the integrity of the isolated forearm and the propofol was given. 

After this assessment and it was confirmed that the subject was comfortable, the subjects were asked a simple math problem every 2 minutes by which the answered with hand signals. Subjects were also told a brief story that contained five key facts that they had to later recite.

BIS, BIS-EMG, the signal quality index (SQI) and the suppression ratio (SR) data from these events were downloaded to a personal computer. Both BIS monitors were also video recorded

The study subjects repeated this experiment with rocuronium 0.7 mg/kg IV no sooner than 2 weeks later. The only difference in this arm of the study was that the subjects were paralyzed for as long as they were able to tolerate the discomfort from the inflated upper arm cuff or until they had difficulty communicating because of paraesthesia or muscle weakness. Once either of these endpoints was reached, rocuronium was reversed with sugammadex 3 mg/kg or 6 mg/kg depending on the time elapsed. 

In both sets of trials, BIS from both monitors decreased immediately after the onset of muscle relaxation and did not return to baseline levels until after clinical recovery from paralysis. 

Succinylcholine and rocuronium were administered to 10 subjects, but because of misadventures with BIS monitoring, so there were 12 trials conducted in the succinylcholine arm. In response to succinylcholine, BIS decreased within 15 seconds to values that were consistent with sedation arousable to a stimulus (BIS of 60-80). 

As stated by the authors at the top of this post, almost all of the study subjects were responsive to questioning during the experiment. They were also completely aware and felt neither drowsy nor confused while paralyzed. They answered the math questions with 96% accuracy. They also recalled the memory test (the story they were told) with 94% accuracy. We’ll forgive that one subject could recall only two of the key facts since they were distracted by the sensation of secretions pooling in their pharynx.

Thus despite BIS and other measures demonstrating “sedation,” the subjects were NOT sedated whatsoever. 

Let’s save our patients the unimaginable horror of being “sedated” with paralytics.

References to Paralytics are not sedatives

  1. Messner M, Beese U, Romstöck J, Dinkel M, Tschaikowsky K. The bispectral index declines during neuromuscular block in fully awake persons. Anesth Analg. 2003 Aug;97(2):488-91
  2. Smith SM Brown HO Toman JE Goodman LS . The lack of cerebral effects of d-tubocurarine. Anesthesiology1947; 8: 1–14
  3. Gandevia SC Killian K McKenzie DK et al.  Respiratory sensations, cardiovascular control, kinaesthesia and transcranial stimulation during paralysis in humans. J Physiol1993; 470: 85–107
  4. Banzett RB Lansing RW Brown R et al.  ‘Air hunger’ from increased pCO2 persists after complete neuromuscular block in humans. Respir Physiol1990; 81: 1–17
  5. Schuller PJ, Newell S, Strickland PA, Barry JJ. Response of bispectral index to neuromuscular block in awake volunteers. Br J Anaesth. 2015 Jul;115 Suppl 1:i95-i103.

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