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As neuromuscular blockade agents have come back into vogue, let’s talk about the big picture. When we understand the repercussions of this intervention, we will paralyze with fear.
Episode Transcription
Kali Dayton 0:00
Oh, neuromuscular blockade agents, such a hot topic right now. I approach it with trepidation, and passion. Let’s start with the foundation upon which to build this conversation. Let’s make sure we all understand an important term critical illness poly neuro myopathy. Critical Illness polyneuropathy is a term that captures two separate diseases. Critical Illness poly neuropathy, which is when motor and sensory nerve fibers are damaged and lead to the degeneration of skeletal muscle.
And then critical illness myopathy is when there is direct damage to the myostatin causing muscle necrosis. The difference between polyneuropathy and myopathy can only be distinguished by EMG and muscle biopsy. From the bedside, they just look weak. So when those two are combined, or they both happen, critical illness Paulie neuro my apathy is associated with severe weakness, reduced or absent limb reflexes, and marked muscle wasting, critical critical illness. polyneuropathy is associated with longer time on the ventilator and in the hospital, higher hospital costs and less discharges home. It makes sense, right?
You are likely seeing this on a replay with COVID survivors. One study from Italy showed that the mean rehabilitation state time was 76 days, and even after that survivors with new chronic illness polyneuropathy suffered from difficulties in health status. It seems that once nerves are damaged, recovery is more difficult and less feasible.
One study showed that 88% of survivors with critical illness, my apathy, were recovered one year after discharge, but only 55% of those with critical illness. Paulie neuro myopathy, were recovered one year after discharge. 36% still needed assistance with their daily routine. This significantly impacts quality of life. So why am I bringing this up before discussing paralytics critical illness polyneuropathy is strongly associated with paralytics neuromuscular blockade agents or en bas. Yet, it is really difficult to give neuromuscular blockade agents. All of the credit for critical illness weakness myopically or Paulina, Polly neuroma apathy. There are usually confounding factors such as steroid use, septic shock, and immobility, occurring at the same time as when these agents are given.
Yet I would suggest that there is enough evidence to have suspicion or a healthy respect for the strong possibility that prolonged neuromuscular blockade agents put patients at risk for critical illness, poly neuro myopathy. When patients already have risk factors for critical illness polyneuropathy, such as sepsis and steroid use, then we should be even more cautious when considering adding an additional risk factor.
This should be part of our big discussion as we weigh risks versus benefits prior to deciding to give pushes or start a continuous infusion of neuromuscular blockade agents. Let’s look back at the history of MBAs. They used to use nm bas for asthma exacerbations in addition to high dose steroids, which as I mentioned, are a big risk factor for my apathy. And I found that it did not go well. So that practice for asthma exacerbations is out. neuromuscular blockade agents have been a topic of controversy since the diagnosis of ARDS was developed.
They use it a ton with ARDS patients because it improved and eased oxygenation for that moment. But after further investigation, it was realized that they did not improve mortality. Some studies show that it may improve the 21 to 28 day mortality, but not at 90 days. Hopefully that makes sense. If you’ve listened to the dozens of episodes painting the picture of why muscular atrophy and neuropathy increase mortality.
One study showed right patients are too weak to breathe on their own. So they are traped pegged and said to ELPAC during those 28 days, but hey, they’re alive. Now they have risks of hospital acquired infections and complications during the next few months and l tak that will eventually kill them. So yet their 21 to 28 day mortality was improved. But overall mortality was not. The outcomes were essentially the same, just with more suffering.
One study showed that neuromuscular blockade agents may increase in hospital mortality, again that 21 to 28 day window, but not 90 days, but that the benefit was lost after 48 hours. This is likely due to the benefit being lost to the damage that is incurred when these infusions last for longer than 48 hours. Their use continues to vary according to provider perspective, culture and training. In 2016, the pedal network conducted the row study to re evaluate the use of early mass neuromuscular blockade agents, and ARDS. They evaluated 1006 patients with ARDS. Half the group was separated into the control group, which discouraged the use of paralytics. And the intervention group received neuromuscular blockade agents for two days.
The study was stopped for futility as more patients died in a paralytic group. And we have found to have less mobility and more cardiovascular events, which makes sense when we understand the effect immobility and muscular atrophy have on the cardiovascular system. So even the trial was stopped because it was shown to be harmful to give neuromuscular blockade agents. S CCN published updated parameters in 2016.
They noted that evidence for neuromuscular blockade agents was insufficient to really set firm guidelines. So they created what they called, quote, 10 week recommendations. Among those, they gave the green light to use an MBAs for P F ratio of less than 150 and essentially said, and might as well give a brief trial for some severe hypoxemia and respiratory acidosis, too. There has been no mention anywhere of instantly paralyzing patients with lower ventilator settings with unknown PF ratios for weeks.
That is not evidence based. Remember to the impact that sedation has on muscles, propofol and medazepam have direct and adverse impacts on diaphragm function. propofol disrupts sodium channels caused insulin resistance increases vasopressor use and doses delirium and obviously leads to absolute muscle disuse. medazepam are said as a benzodiazepine is one of the worst culprits of delirium, post ICU PTSD and post ICU dementia. In addition to its impact on the muscles.
Each sedation has agent including ketamine and barbiturates seem to affect the muscles in a different way, by impacting neurotransmitters, and muscle function. How much higher are the doses and combination of these medications when we are getting paralytics? We must take the cost of each medication into consideration. And episodes 63. Six through 65, you’re on low interest shared with us the inflammatory response that is triggered by muscular atrophy. To summarize, muscular atrophy leads to or at least contributes to multi organ failure.
If our COVID patients are getting worse because of an inflammatory response, shouldn’t we be implementing practices that avoid further inflammation and to be avoiding sedation, immobility and paralytics that worsen inflammation at all costs? I know people are going to jump in and say okay, but what about our patients that drop into the 70s with any slight deviance from the mental it or, or the twist of a finger?
Absolutely. I feel that when lung compliance and oxygen consumption hit that point of impasse options are extremely limited. We are hitting that threshold and an unprecedented volume of patients. Right now in the COVID pandemic. Even the awakened walking ICU will throw out the Hail Mary and paralyzed patients at that point. And they have had survivors, the big difference is likely that they have been walking patients up until that point, even on high ventilator settings of a peep of 18 or 20 and 100% that we’re still oxygenating with movement.
And this a briefly paralyzed them. Anecdotally, Dr. Kenneth Hurwitz on Episode 44, was paralyzed for 48 hours, deeply sedated for a little a little bit longer. And then he was back on his feet as soon as he could oxygenate with movement. Brian Carter and Episode 15, was also walking out a peep of 20 100% until he couldn’t oxygenate with movement, and needed to be paralyzed for 48 hours, and was then right back on his feet. So this episode, and the next are not to say that paralytics should never be in our practice.
Yet, like sedatives, we need to really understand the big picture of them, so that we can appropriately triage their use. There is concern that neuromuscular blockade agents are sneaking into our casual or prompt use, meaning patients are being paralyzed arbitrarily for increasing but not max, ventilator settings, or even just to shut the ventilator up. I have heard too many stories like the following.
New Nurse 11:58
So so often in the ICU, our “go to” is sedation or paralytics. And I am a new grad nurse. And so I don’t know what I don’t know. And so I have to rely on the people around me, including the nurses, the RTs, the entire team. And I’m trying to do best for my patient. And so I collaborate a lot just to try to get a better idea of how to best treat my patient.
So I have one experience that happened fairly recently off orientation. So I was still very new, still getting an idea for things. And it was a night shift. And so I was really trying to get a collaborative collaboration for this one particular patient. He was invented, he was COVID. And he was relatively awake from my ICU. He was not on sedation, but he wasn’t able to really fully respond to me, but he could sit up he was fighting the restraints, because that’s also a norm in my ICU for Vinda patients is basically automatic restraints, you know, he was double stacking his breaths, for the most part like all night, he but is he was holding us out.
And so I was not sedating him. I was not adding to sedation, I was not doing anything to make him quote, vent compliant. And I had this one respiratory therapist who was all night she was telling me that he needs to be paralyzed. He needs the PRN vac you have to he’s uncomfortable. Look at him. You have to sedate him, you have to paralyze him. And she wouldn’t stop. And she knows that I was a new grad. And there was something in me though, and I just I didn’t want to do it. He he was holding a saturation.
He was he wasn’t technocratic, his blood pressure was fine. He was just awake. And even though that wasn’t the norm, there was like something inside of me that told me that it was okay that he was this patient was appropriate that I didn’t need to do anything. I didn’t need to make an intervention at that time. And but she would not get off of me. And all night she was basically criticizing me to my face for not doing what she was asking me to do. And just we got a parallelism. We’ve got a parallelism.
And I refused. And by the end of the night, I had myself convinced that I didn’t know what I was doing that I was a bad nurse that I was doing the wrong thing because I didn’t have any evidence or experience to back up my decision, even though I felt like it was right. I couldn’t come back at her and say no, this is this is what I’m doing. I’m not doing that. And this is why so I just kind of held the course and I just kind of took took it from her all night basically when the new respiratory therapist came on shift. It’s a little bit of an overlap with the nurses schedule. She He increased his pressure pressure control. And he stopped over breathing.
He just wanted to take a little bit bigger breath than we were allowing him. He wanted to have a little bit of more of that control. And as soon as she did that, he was fine. And I felt so good about not paralyzing her. But I still my whole new grad brain, still doubted myself. And so I called my preceptor and I told him the situation. And he talked me through it, he had ABCDE reasons why we, I shouldn’t have paralyzed that patient in that moment. And the long term effects in the end, it can lead to this syndrome.
And you know, all the reasons, and I just, I felt so good in that moment that I didn’t want to paralyze him and over sedate him. But that’s the culture, isn’t it, that they’re moving around, they must be uncomfortable, they’re double stacking their breaths, let’s sedate them, instead of you know, and that the newer story therapist that came on, I just, I appreciated her so much for not just taking that plan and going with it, but instead trying something new, and basically, you know, allowing that patient to be comfortable on event.
And then that patient was excavated a day later and transferred into the ICU and which isn’t pretty rare. And I just I am glad to be a part of that. And I learned a lot from that and not just the just, you know, reason to sedate and paralyzed by learned that, you know, there is this culture of oversaturation and over paralyzing and that a goat. It’s just the go to and it doesn’t need to be that gut feeling, I think is what made me resonate so much with your presentation, because I knew it already. I already knew it for some reason.
And yet, here’s this entire culture telling me that I’m almost wrong. And then to hear it from you that no, we don’t have to sedate we don’t have to paralyze we don’t have to do these things. It just kind of is like vindicating, and it’s like empowering almost especially as a new grad who, like I said, I didn’t know what I didn’t know. So I couldn’t back myself up. But now I can.
Kali Dayton 17:19
Recently, I was in a meeting to help formulate general guidelines for ventilator management with experts among respiratory therapists, registered nurses and intensivist. I expressed my concerns about the gap in care and the problems in our culture with the following scenarios that were described to me by listeners.
One of the the respiratory therapists asked for sedation vacation to win the ventilator, or try spontaneous breathing trial, but was met with resistance by the nurse to the respiratory therapist asked for a better mode for ventilator synchronization, but the alarm is instead fixed with a paralytic three. The nurse asks the respiratory therapist to help the patient’s ventilator alarms. But the respiratory therapist barely looks at the ventilator and tells the nurse to give the paralytic to the patient.
The RN doesn’t know what to do with the alarms, but they find the turn off with more sedation or paralytic for the nurse is trying to lighten sedation and even has success and helping the patient be awake and calm on the ventilator. When the ABP or MD comes into the room and demands, sedation be resumed. Because the patient needs to quote five orders are put in for sedation and PRN paralytics. With the rationale listed as quote, to keep quiet overnight.
As I relayed these scenarios, I saw almost every head nodding, then some smiles, and even some laughs I love that we can all commiserate together and appreciate that we are fighting a lot of the same battles. Yet these problems are not just personality quirks and funny riffs between disciplines. This is not an office episode. These are human lives that are suffering because of our failure to utilize all our tools to customize care.
They also seemed to question why sedation and paralysis was coming into the discussion on ventilator management. I was shocked that even among people far more experienced and educated than I am. That I started crazy for mentioning that sedation impacts ventilator management, and ventilator management impacts sedation practices.
Next episode, we will be with a ventilator master Dr. Siuba, the Zenintensivist, to talk more about that. Ultimately, respiratory therapists and pulmonologist have so much expertise and can really tame and whisper the ventilator. Please Before we just crank up sedation or run to the paralytics, please, please pull in the experts to really evaluate the root cause of those alarms and assess the needs of the patient.
The “Awake and Walking ICU” is estimating that they are paralyzing less than 10% of their COVID patients and their high acuity COVID ICU. I suspect that that is a mix between their deep hesitation to paralyze without hitting that threshold that I’ve described, and their practices that are likely preventing patients from becoming that ill.
The “Awake and Walking ICU” is part of a multi hospital system, but stands almost alone and the practices and etiology. As with any hospital system, there is unfortunate politics and variation and practices throughout the system. When statistics such as a difference and 98% discharge home rate from the awakened walking ICU, and 46% discharge home rate from a different neighboring hospital in the same system with the same diagnosis and the same Apache scores. The argument is repeatedly made, quote, well, your patients are not that sick, unquote. Despite clarifying that the Apache score is for us and the data collection to make the comparison.
To that I have to clarify, the awake and walking ICU is a medical surgical ICU and a tertiary and referral hospital. It receives failing patients from many states, there is a bone marrow transplant unit and a detox unit in the hospital that often sends their patients to this unit. septic shock detox multi organ failure graft versus host and ARDS, are among their expertise and frequent diagnoses.
These patients have significantly better outcomes, but not because they are less sick than most other ICU patients. It is easy to demonstrate in the literature that their practices of avoiding sedation and prompt mobility lead to decreased mortality decreased time on the ventilator decreased time in the ICU decreased tricky ostomies decrease infection decreased readmissions and increases and rates of ambulation at transfer from the ICU and discharges home.
They prevent severe levels of acuity and multi organ and functional failure because of their sedation, or lack thereof, and mobility practices. Please understand that and episode 58 Louie’s nurse practitioner and then awake and walking ICU, shared her horror at how her own uncle was treated in a different COVID unit when he was paralyzed. For weeks.
She reported that paralysis is still very rare in the wake and walk in ICU. After almost 40 years of critical care experience. She could not fathom why or how her uncle was left paralyzed and rotting in bed for weeks. Considering the severe repercussions of neuromuscular blockade agents, sedation and immobility, Louise feels that the treatment her uncle received was a main contributor to his demise. Listen, as far as I can find, there is no evidence to support the early routine use of neuromuscular blockade agents and adult areas of any severity.
The evidence can still be swayed to allow for 48 hours for those that have actually hit the wall of desperately needing minimization of oxygen consumption and impossible lung compliance. Until we have hit those thresholds, we have to stop and reconsider applying possible lethal interventions that will increase mortality. I continue to plead with the ICU community to reconsider automatically starting deep sedation after every intubation.
Please keep your patients awake, free of delirium and mobile until they can no longer oxygenate with movement, or have other extreme exceptions such as inter cranial hypertension, active seizures, and such. Please go back and listen to this podcast from the beginning. A big mission of this podcast is to customize and optimize care, as I am combating the culture of automatically sedating every patient on a ventilator. I also recognize that there are always exceptions and circumstances in which sedation and paralytics aren’t necessary.
We can best way our risks versus benefits and define necessity when we understand the cost of these interventions. Stay tuned for the next episode as we dive into ventilator management to help decrease the temptation per station and nmba use. I understand that our ICU community is under incredible stress. I address us with great respect for teams doing their best as well as a sense of obligation to discuss the research during these pivotal times. Thank you for caring so deeply and tenderly for your patients. Even during this time of trauma and exhaustion.
Hang in there, Louise. Elizabeth said on the Facebook discussion group you can’t unknow what you know, I recognize the perspective that this information brings can feel like a big responsibility. Be patient with the revolution, keep fighting for evidence based and humane practices. You are making a difference. If you want to join in on the conversation, leave a voicemail at 801-784-0472 or reach out to me on Twitter.
Transcribed by https://otter.ai
References
Critical Illness Polyneuromyopathy:
<Dodson, Barbara A. MD; Kelly, Brian J. MD; Braswell, Leon M. BS; Cohen, Neal H. MD FCCM Changes in acetylcholine receptor number in muscle from critically ill patients receiving muscle relaxants, Critical Care Medicine: May 1995 – Volume 23 – Issue 5 – p 815-821
Nicola Doherty, Colin D. Steen,. Critical illness polyneuromyopathy (CIPNM); rehabilitation during critical illness. Therapeutic options in nursing to promote recovery: A review of the literature, Intensive and Critical Care Nursing, Volume 26, Issue 6, 2010, Pages 353-362, ISSN 0964-3397, https://doi.org/10.1016/j.iccn.2010.08.008.
Kelmenson, D. A., Held, N., Allen, R. R., Quan, D., Burnham, E. L., Clark, B. J., Ho, P. M., Kiser, T. H., Vandivier, R. W., & Moss, M. (2017). Outcomes of ICU Patients With a Discharge Diagnosis of Critical Illness Polyneuromyopathy: A Propensity-Matched Analysis. Critical care medicine, 45(12), 2055–2060. https://doi.org/10.1097/CCM.0000000000002763
Jennifer Confer, Pharm.D., BCPS, Janet Wolcott, Pharm.D., Robert Hayes, M.D., Critical illness polyneuromyopathy, American Journal of Health-System Pharmacy, Volume 69, Issue 14, 15 July 2012, Pages 1199–1205, https://doi.org/10.2146/ajhp110343
Intiso, D., Amoruso, L., Zarrelli, M., Pazienza, L., Basciani, M., Grimaldi, G., Iarossi, A. and Di Rienzo, F. (2011), Long-term functional outcome and health status of patients with critical illness polyneuromyopathy. Acta Neurologica Scandinavica, 123: 211-219. https://doi.org/10.1111/j.1600-0404.2010.01414.x
Koch, S., Wollersheim, T., Bierbrauer, J., Haas, K., Mörgeli, R., Deja, M., Spies, C.D., Spuler, S., Krebs, M. and Weber-Carstens, S. (2014), Long-term recovery In critical illness myopathy is complete, contrary to polyneuropathy. Muscle Nerve, 50: 431-436. https://doi.org/10.1002/mus.24175
Neuromuscular Blockade Agent Outcomes:
Suzanne Bennett, William E Hurford Respiratory Care Feb 2011, 56 (2) 168-180; DOI: 10.4187/respcare.01095
Puthucheary, Z., Rawal, J., Ratnayake, G., Harridge, S., Montgomery, H., & Hart, N. (2012). Neuromuscular blockade and skeletal muscle weakness in critically ill patients: time to rethink the evidence?. American journal of respiratory and critical care medicine, 185(9), 911–917. https://doi.org/10.1164/rccm.201107-1320OE
MacFarlane, I. A., & Rosenthal, F. D. (1977). Severe myopathy after status asthmaticus. Lancet (London, England), 2(8038), 615. https://doi.org/10.1016/s0140-6736(77)91471-4
Mefford, B., Donaldson, J. C., & Bissell, B. D. (2020). To Block or Not: Updates in Neuromuscular Blockade in Acute Respiratory Distress Syndrome. The Annals of pharmacotherapy, 54(9), 899–906. https://doi.org/10.1177/1060028020910132
Steingrub, J. S., Lagu, T., Rothberg, M. B., Nathanson, B. H., Raghunathan, K., & Lindenauer, P. K. (2014). Treatment with neuromuscular blocking agents and the risk of in-hospital mortality among mechanically ventilated patients with severe sepsis. Critical care medicine, 42(1), 90–96. https://doi.org/10.1097/CCM.0b013e31829eb7c9
https://www.nejm.org/doi/full/10.1056/nejmoa1901686
SCCM “10 Weak Recommendations”:
Murray, M. J., DeBlock, H., Erstad, B., Gray, A., Jacobi, J., Jordan, C., McGee, W., McManus, C., Meade, M., Nix, S., Patterson, A., Sands, M. K., Pino, R., Tescher, A., Arbour, R., Rochwerg, B., Murray, C. F., & Mehta, S. (2016). Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Critical care medicine, 44(11), 2079–2103. https://doi.org/10.1097/CCM.0000000000002027
Courcelle, R., Gaudry, S., Serck, N., Blonz, G., Lascarrou, J. B., Grimaldi, D., & on behalf the COVADIS study group (2020). Neuromuscular blocking agents (NMBA) for COVID-19 acute respiratory distress syndrome: a multicenter observational study. Critical care (London, England), 24(1), 446. https://doi.org/10.1186/s13054-020-03164-2
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