The Purge

by Howard Greller

 

 

 

An absurdists’ take on whole bowel irrigation

Throw out your conceited opinions, for it is impossible for a person to begin to learn what he thinks he already knows.

– Epictetus, Discourses, 2.17.1

A consensus means that everyone agrees to say collectively what no one believes individually.

– Abba Eban, Israeli diplomat

Introduction

There are few topics more controversial in Medical Toxicology than gastrointestinal decontamination. This is the Yankees vs Red Sox (well, actually that’s an easy one). No, it’s The Dress. Ask a bunch of toxicologists about decontamination and you’ll get many, many opinions (Juurlink 2000 PMID 10981955). There’s no question why the topic is controversial. The question is why I would risk my sanity to tackle it?

Following through on Dan’s excellent post last week, a question arose in the comments and on Twitter. Would a toxicologist recommend whole bowel irrigation (WBI) for a large bupropion overdose?

Our scenario

A 32 year-old male presents 2 hours after an intentional ingestion of 90 tabs of 300 mg bupropion XL. His vitals: BP 136/67 mmHg; HR 110 bpm; RR 22/min; O2 95% RA. His EKG shows sinus tachycardia (148 beats/min), a QTc of 549 msec, and a QRS of 110 msec. During the initial evaluation he has multiple generalized tonic-clonic seizures and is intubated. Do you treat him with WBI?

First principles

There are a few things that we will have to agree upon before we tackle whole bowel irrigation.

1. We are going to be talking about orally ingested, mostly pharmaceutical, toxins. We’re not going to talk about caustics. We’re not going to discuss radiation or inhalation or envenomation or any other “-tion” other than “ingestion”.
2. We accept that there will always be uncertainty. It is baked into every single poisoning we encounter. We don’t know if we can rely on the history. We don’t know who will and who won’t decompensate. We don’t know or have clear markers (in most instances) that will predict future events. We rely on the history (flawed as it is), physical exam and focused diagnostic studies to define a clinical picture and to inform our interventions.
3. The pharmacokinetic journey of orally ingested toxins leads to their toxicity. The map looks like this (grossly oversimplified thanks to clipart) . . .

The initial and most important step in that journey is absorption. If you can decrease absorption, you can prevent or decrease toxicity.

This is the fundamental underpinning of GI decontamination. Prevention of absorption. How you do it, whether you can do it safely and effectively, and more importantly, does it matter, is where the debate arises.

Two holes, one tube

The human body is a donut. Admittedly it would be a long, stretched donut. More akin to a miles-long eclair with the least popular filling ever . . . but I digress. The GI tract, however convoluted and complex, is a tube that is contiguous with the external world. Once a poison enters the tube, you have a few options to prevent or limit its absorption. Either you get it out (gastric emptying), chaperone it so that it doesn’t touch anything during the journey (activated charcoal), or push it through quickly (whole bowel irrigation). We’re going to focus here on number 3 (ironic it isn’t number 2. . . ) Seems simple, right? What’s all the fuss and bother about?

The Impossibility of Incontrovertability

Scientists, and distillers, love proof. Does whole bowel irrigation save lives? This post could stop here if I could answer that. However, GI decontamination is the overlapping part of the Venn diagram of art and science. It is an extremely difficult area to study, for many reasons. There are enrollment issues. How do you ethically ask suicidal, sick and/or altered patients to participate in an experiment? There are confounding issues. Poisoning is markedly heterogeneous. You can’t control for every kind of poisoning or the combinations of poisons, or the particular physiology of the person exposed. Every overdose is a unique disaster. There are numbers issues. Fortunately, the outcome in which we are most interested, mortality, is rare. Overall poisoning mortality ranges from 0.08 – 4.2% (Cheung 2018 PMID 29628190, Gunnell 2004 PMID 14734371, Lee 2008 PMID 18182104, Schaper 2006 PMID 17098590). Additionally, many bad outcomes (e.g. anoxia, aspiration, rhabdo, etc.) occur before patients are under our care. To determine if whole bowel irrigation, or any form of decontamination for that matter, saves lives would require a cardiology-sized trial. It will never happen.

What do we do then? We must make decisions based on an approach that emphasizes an understanding of basic principles rather than solid evidence. We must extrapolate from case literature, the few (flawed) trials that exist, animal models, an understanding of physiology, and dare I say it, common sense. Common sense has to play a role where the data falls short. So yes, I am advocating for a treatment without a proven benefit. record scratch. WHAT DO YOU MEAN? YOU ARE EXPERIMENTING ON PEOPLE! WHO RAISED YOU?!?! THINK OF THE CHILDREN!?!?

The Rules of De-Con Game

So now that we’ve set the board, a few rules I follow before deciding upon whole bowel irrigation.

First, we are worried about the toxin. The exposure is bad, and not doing something will lead to morbidity or mortality. If someone ingests a Costco-sized barrel of Skittles™, we’re not going to get the hose.

Second, you have to be able to get at the thing that you are worried about. If the drug is somewhere inaccessible through the tools that you have, then there is no need to go after it.

Third, you don’t have another option. There isn’t an effective antidote, there isn’t an effective alternative therapy, supportive care falls short, and you don’t think thoughts and prayers will be enough.

Fourth, the risk of the toxin outweighs the risk of what you do. Primum non nocere.

Finally, most decontamination procedures are resource monsters. This is a team sport. If you don’t have help, focus on the fundamentals first.

The Purge

So, back to our Illbutrin case. For this situation, I would endorse a little charcoal and lotta WBI. For those of you who weren’t sure, this is a whole bowel. (it was there)

Whole bowel irrigation is exactly what it sounds like. It is the bulk flow of a non-absorbable, osmotically inactive liquid (polyethylene glycol + balanced electrolyte solution, or PEG-ELS) that, when performed effectively, clears the GI tract in a few hours (Goldman 1982 PMID: 7056467). It has been used safely in children, adults and pregnant women (Lo 2012 PMID:22578074, Clifton 2002 PMID: 12066009, Turk 1993 PMID: 8249269, Van Ameyde 1989 PMID: 2929685).

WBI has been evaluated in both experimental models and actual toxic ingestions (e.g. iron, sustained-release theophylline, sustained-release verapamil, fenfluramine, zinc, lead, arsenic trioxide, arsenical herbicides, mercuric oxide, strontium, potassium chloride, clonidine, venlafaxine, ingested fentanyl patches, etc.) It is recommended for poisons that don’t bind to charcoal (e.g. metals and ions – iron, lead, lithium, zinc, etc.), drugs that have sustained or modified release preparations such as lithium, theophylline and verapamil, and drugs with a slow absorptive phase and the potential for high morbidity (lithium again), and for the recovery of packets from gastrointestinal drug smuggling (i.e. body packers). (Beckley 2009 PMID: 19865578, Bretaudeau 2013 PMID: 23566313, Buckley 1993 PMID: 8450791, Burkhart 1992 PMID: 1416325, Goldfrank’s Toxicologic Emergencies 10th Ed, A2: Antidotes in Depth, Janss 1990 PMID: 2399454, Kirshenbaum 1989 PMID: 2673619, Kumar 2009 PubMed:19606091, Kumar 2011 PubMed:21306417, Lapatto-Reiniluoto 2001 PMID: 11557913, Ly 2004 PMID: 14747807, Smith 1991 PMID: 2024795, Tennenbein 1997 PMID: 9482429, Traub 2003 PMID: 14695412)

In our case, bupropion is a sustained release preparation with the potential for high morbidity (perhaps already manifest). Think about that. This very toxic drug is slowly moving through our patient’s very long GI track while being absorbed and adding to the toxicity. It’s in there, and we can help get it out.

A rejection of therapeutic nihilism

Why, you would ask, would you subject this patient to a procedure without definitive benefit, and associated with potential risks including aspiration, intestinal obstruction and bowel ischemia (Gutierrez 1996, PMID:19099287, Wax 1995 PMID:8523502, Fauville 1995 PMID:22969229, Cumpston 2010 PMID:18614321)?

The case reports that describe these complications all suffer from the same flaw. You can’t distinguish the toxicity of the drug they were trying to manage from the therapy that they associate with the outcome. Additionally, one has to remember that this is not a “Set it and Forget it” therapy. Any advanced treatment has risks and needs close monitoring. If the patient doesn’t tolerate the therapy, or has a complication, you stop. This follows for anything that we do, from dialysis to n-acetylcysteine.

You may argue that activated charcoal by itself does fine, so why would you add WBI? I think that charcoal does play a role here. However, for this ingestion, it’s hard to achieve the recommended 10:1 ratio of charcoal to drug. For our case, this would require 270 grams of charcoal, which is a lot. The studies that looked at charcoal versus WBI used volunteers ingesting either therapeutic doses of the study agent or non-toxic drugs. It’s hard to demonstrate a benefit when there won’t be a problem to begin with, which is what they concluded regarding WBI.

But, you say, WBI is hard and messy (well, technically, soft and messy). It is rarely done appropriately, with completion rates between 20-25% (Shih 2004 abstract, Bryant 2008 abstract), so why bother to try at all? Like Thomas Edison said, “there is no substitute for hard work.” This is less difficult than ECMO, prone ventilation, or the last bad airway you had.

This is a standard dose response curve. It can be applied to therapy and it can be applied to toxicity. Let’s assume that the Y-“response” axis represents morbidity or mortality. Any intervention that you can do that shifts the curve to the right, helps the patient. Where is our patient on the curve? How much have they absorbed and how much is left to absorb? We will never know in realtime. In fact, the kinetics of bupropion XL absorption therapeutically are not completely known. What we do know is based on information submitted to the FDA (heavily redacted) when the XL preparation was brought to market. In therapeutic dosing, peak concentrations are expected around 5 hours post ingestion for bupropion, and 8-16 hours post ingestion for the most concerning metabolite, hydroxybupropion. The elimination half-life is about 22 hours. More importantly (and frighteningly) we don’t understand the dissolution characteristics of the pill. So, we don’t know what the state of the medication is when we have an opportunity to intervene. In an in-vitro model of overdose, concentrations continued to rise up to 24 hours (Dr Morgan Riggan, personal communication). All of this is expected to be more clouded in an overdose when drug absorption is expected to be prolonged.

What are our other options for this case? We don’t have Illbutribind™ or gapjunctionipid (from the makers of Enditall™). So, if you could, would you reduce the exposure by half? What about by a third? A fifth? And so on. . . Like Abraham bargaining with God over the number of honest men in Sodom and Gomorrah, how many pills would you have to stop from being absorbed to spare this patient’s life? Can we take them from dead to mostly dead?

An approach

In my opinion, there is not a lot of risk, and the real potential for benefit. Follow the 7 P’s to bowel cleansing success:

1. Pick – the right patient, the right poison.
2. Phone – call your local toxicologist, or your regional poison center (1-800-222-1222). They’re nice folks who are there to help.
3. Physical – do an exam and ensure that the airway is protected and that the GI tract is clear for take off (no ileus or obstruction). Ongoing assessment for problems (e.g. vomiting, distention).
4. Prep – Grab your antiemetic of choice, along with your nursing allies. Roll up your sleeves, cuff your pants, insert and confirm your NG and rectal tubes. Position the patient upright (HOB 45°), left side slightly up.
5. Pump – find an enteral feeding pump. Depending on brand, see what the maximum flow rate is. If too slow, try the “flush” function (if accessible) or just hang your PEG in a gravity bag.
6. Push – right rate, right volume. 25 mL/kg/h for children and 1.5 to 2.0 L/h (20 to 30 mL/min) for adolescents and adults. Push it. Push it real good. If they vomit, half the rate for an hour, and if good, titrate back up.
7. Pan for (black) gold – check the effluent for recovered pills, fragments, sediment. Continue until what comes out looks similar to what goes in. For the situations in which I use WBI, I typically give charcoal before WBI. This also acts as a marker on the other end to show that something transited. But don’t mix them together like a cocktail, as that makes AC less effective (Atta-Politou 1998 PubMed: 9541057, Hoffman 1991 PubMed: 2051506, Kirschenbaum 1990 PMID:2221518, Makosiej 1993 PMID:8355315).

Conclusion

In the end, this is not a blanket recommendation for WBI. Absurdism attempts to describe the conflict between our desire to find value and meaning in life and our inability to find it. Rather than reject whole bowel irrigation outright because of flawed evidence, to follow therapeutic nihilism, I embrace the “absurd condition of human existence while also defiantly continuing to explore and search for meaning.”

So, in the end, would WBI make a difference in our case? I don’t know. What I do know is that it might, and that is enough for me to try.

Randy’s Donuts via Extra Medium Donut by Stas Ovsky