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Emily Silverman: This is The Nocturnists, Uncertainty in Medicine.

[bells ringing]

[alarm ringing]

Emily: Today we're looking at time.

[music]

Dr. JP: The 14-year-old girl lay pale and lifeless on the stretcher. A plastic breathing tube jutted out of her mouth and at the head of the bed, the intern squeezed oxygen into her lungs. The medic said they found her down in the bathroom without a pulse. The resident pushed on her chest, doing compressions, her ribs crunched with a nauseating sound of broken bones grinding against each other. When I asked the parents what happened, her dad stared at me, glassy eyed, mute from shock, while the mother screamed incoherently, so loudly I almost couldn't hear my own thoughts.

The medic handed me a can of silver spray paint. He said the patient had locked herself in the bathroom 30 minutes ago. Dad broke down the door, finding her with a spray can in one hand and a paper bag in the other. She collapsed to the ground instantly in cardiac arrest. The diagnosis was immediately clear, sudden sniffing death. The result of sniffing, huffing, bagging, chroming, or otherwise misusing inhalants. In contrast to most cases of cardiac arrest in the ER, the uncertainty wasn't in the cause, but in the treatment. Give epinephrine or don't give epinephrine?

Inhalants affect the heart. In the myocardium, cells are supposed to be synchronized, conducting nerve impulses and squeezing to pump the blood in an organized fashion. Inhalant exposure causes disorganization. This is the first insult. If a second insult occurs, the primed myocardium might suddenly conduct abnormal impulses in a disorganized fashion, resulting in sudden death. What's the source of the second insult? An adrenaline or epinephrine spike. How does that occur? Well, one way is terror or fear causing a fight-or-flight response. For example, being caught by a parent or by the police.

The standard of care for treatment in cardiac arrest? Epinephrine. The second insult in sudden sniffing death? Epinephrine. I faced a choice to withhold a potentially heart restarting drug or to give more of the exact same substance that put her into cardiac arrest. Did I want to withhold the drug? No. Not just that, but not giving epi could be considered legally and ethically wrong. On the other hand, did I want to expose her to more? Also no. Uncertainty is common in medicine.

It's an everyday occurrence, and normally, I discuss the options with the patient or the parents, explain the risks and benefits, then engage in shared decision making. With this patient, there was no time for discussion, and the parents weren't in a position to help. Standing at the bedside, I ran the risks and benefits on a continuous loop through my brain, hoping desperately to come up with the right answer. I considered pitfalls, possibilities, pros and cons. Each time I arrived at the same answer, I didn't know what to do. At the end of the two minutes, the nurse held up a syringe of epinephrine waiting for me to say yes.

My heart raced, my breathing sounded loud, my palms were wet, but despite this, I had to pretend to be calm and collected. The parents and the team looked at me expectantly. I had to answer. I wished I'd read the medical literature more recently. Wished I had the 2,000 page toxicology textbook, Bible, Goldfrank’s in my pocket. Wished I could call my mentors. I hoped her heart would restart on its own so I didn't have to make the decision. A colleague stood next to me, another ER doctor. As I turned to ask his opinion, he said, "I'm glad you're here since you're the toxicologist and you know what to do."

I was the expert, but I didn't know what to do. Had I never learned it, or did I not remember it? I took a deep breath, "No. No, epi." The nurse and the entire team looked at me surprised. I decided to hedge my bets, hold off on epi at least for a few minutes and try a different approach. Instead, I called for esmolol, a beta blocker. Essentially the opposite of epinephrine. We continued CPR and electrical shocks, and miraculously, after four minutes, she got a pulse back. I'd like to be able to tell you what made her heart restart.

Truth is, I have no idea. Was it holding the epi, giving the beta blocker, giving the shocks, or just plain luck? After she was stabilized and transferred to the ICU, I scoured the medical literature to see if I'd made the right decision or not. The verdict, unknown. It was recommended to avoid epinephrine when possible. Whatever that means.

[music]

Emily: Uncertainty is something we all live with, but how we experience it, how we move through it, can look very different. One theme that's emerged again and again as we've made this series is the subject of time. Compare, for example, the ICU doctor's split second decision with a crashing patient with the slow burning uncertainty of living with a chronic illness. Both are steeped in uncertainty, but they feel wildly different, because time doesn't move in a straight line when we're uncertain. It can stretch out endlessly or vanish in a blink.

Today, we hear stories from clinicians and patients reflecting on uncertainty across different time scales. When does time ease uncertainty? When does it augment uncertainty? How do time and uncertainty shape each other?

Tricia Tunstall: In August 2016, my husband and I had a lovely vacation in Scotland, and we spent a lot of time hiking in hills. On the last day, I twisted my ankle in the mud. Mud is a very big feature in Scottish hiking. I felt some pain right beneath the inner ankle bone of my left foot. So when I came back to the States, I saw an orthopedist who ordered an MRI and said I had a slight ankle sprain. He said, "Ice, rest, elevation, it'll get better." It didn't get better. The pain blew up. It got so bad I could hardly walk.

I went back to the orthopedist, who saw me for less than a minute, and then said, "Oh, you have CRPS, chronic regional pain syndrome. This is a really bad thing, and there's no cure for it. You'll have to see a pain management doctor." By December of that year, I had seen four pain management specialists, each for less than five minutes, and two said I absolutely didn't have CRPS, two said I absolutely did. They prescribed pills, they prescribed shots. One gave me a series of lumbar injections for which he completely put me out. One gave me lumbar injections for which he gave me no anesthetic at all.

Meanwhile, the ankle pain kept getting worse. Some friends suggested that I see their "wizard orthopedist," who said I had a completely ruptured deltoid ligament and prescribed a boot. On my follow up visit six weeks later, he did another X-ray and lo and behold, pronounced that deltoid ligament was fixed. I said, "What about my pain?" He said, "Well, you know, I'm seeing now that you have a tibial contusion. Look, you have a hole in your bone." He told me I had to be non-weight bearing for another six weeks. In the seven years since then, as my pain continued, I saw dozens of doctors. Every one of them had an immediate diagnosis and an immediate prescription.

Among those diagnoses, I can kind of rattle them off. Peripheral neuropathy, tendinitis, tenosynovitis, autoimmune disease, tarsal tunnel syndrome, os trigonum, sciatica, arthritic spinal spurs, stress factor, gait irregularity, nerve damage, arthritic spinal spurs, os trigonum, and spinal curvature was in there, too. Among my treatments were acupuncture, nerve pain pills, ketamine cream, diclofenac cream, spinal steroid injection, ankle steroid injection, electric stim, oral prednisone, orthotics, physical therapy, extra strength Tylenol three times a day, ankle aqua therapy, supplements, TENS units, lidocaine patches, oh, and also ankle surgery.

Dutifully, I did all those things. Not any of them helped my pain at all, and the surgery made it worse. No surprise there. Seven and a half years later, I am still in constant pain. I still can't really wear shoes, because any shoe that has even the slightest heel, or it presses on the spot right under my inner ankle, where my pain is, makes the pain shoot up. It's clogs and sandals for me, for the duration, I guess. There are worse things. I am grateful to say that my average pain level now is down quite a bit from where it was at its worst. Over the last two or three years, I've gradually regained the ability to walk for as long as 30 or 40 minutes at a time, and to swim regularly.

The reason for these improvements isn't anything medical science gave me. It's just things that I've figured out on my own. Like walking a very little bit at a time, and then increasing the walking bit by bit, and applying ice, and also doing lots of work on the inner game of living with pain. During my years long medical quest, here's what I learned about the medical profession. Most doctors are very uncomfortable with uncertainty. Almost every one of the doctors I saw gave me a cursory exam and a snap diagnosis and prescription. They did not ask many questions, they didn't take time to reflect.

One after the other of these guys was visibly uncomfortable when I mentioned conflicting diagnoses from other doctors. They would usually say, "No, that's not right." I will never forget one orthopedist who, when I didn't improve on the basis of his diagnosis and treatment, said to me, "You know, patients like you are really unsatisfying for doctors." There was one doctor in that whole parade, a wonderful podiatrist, who had long, thoughtful examinations and discussions with me, and when he finally gave me his diagnosis, which was tarsal tunnel syndrome, he added, "I think so, but I'm not sure." I'll never forget those words, because they were so rare. Such doctors do exist. We just need a whole lot more of them.

[music]

Emily: When we heard Tricia's story, we were struck by how well it illustrated the cost of time scarcity in clinical medicine. When patient visits are squeezed into the smallest unit of time possible, medicine starts to feel more like a conveyor belt than an opportunity for care. We wanted to talk to someone who could shed light on what it looks like to partner with time, not to fight against it, and who faces some of the most uncertain cases in medicine. So we called up Sarah Goglin.

Sarah Goglin: My name is Sarah Goglin, I am a rheumatologist at UCSF.

Emily: Sarah is a beloved physician and was one of my favorite teachers in residency.

Sarah: I would say broadly, we take care of patients who have autoimmune diseases and/or inflammatory conditions.

Emily: Lupus, rheumatoid arthritis, vasculitis. Rheumatology is full of ambiguous conditions whose presentations can be very time-dependent. Some of these diseases might take years to officially declare themselves with definitive symptoms, while others will inexplicably improve or burn themselves out. Sarah says, because the pathophysiology of these diseases is so time-dependent, her approach to working with them has to be, too.

Sarah: I mean, we use time all of the time.

Emily: Take one of her current patients.

Sarah: One of the patients that has perplexed me now for going on three years is a middle-aged gentleman who first started to have severe eye inflammation about eight years ago.

Emily: When Sarah first started seeing him, he was already five years into his symptoms and had seen countless doctors. He came to Sarah because though she doesn't talk

about it much, she happens to be a world expert in vasculitis, a type of inflammatory disease that affects the blood vessels. At the time, he carried a diagnosis of sarcoidosis, which

made sense. It's a disease that can cause eye inflammation. Then something weird happened.

Sarah: This was back almost three years ago now. He then was found to have this kind of very unusual infiltrative process along the large blood vessels in his chest, his abdomen, as well as around the coronary arteries affecting the heart.

Emily: This is not something you typically see in sarcoidosis. So Sarah called in some backup.

Sarah: He has now seen me, a hematologist at UCSF, he's seen one of our cardiologists who specializes in inflammatory cardiac diseases, the ophthalmologist, and in spite of seeing that group of highly specialized people, lots of diagnostic testing, he still does not have a clear diagnosis. Luckily, his main organ threatening issue, that eye inflammation, is under control, but we still don't know what's wrong with him.

Emily: This is what I mean about rheumatology. It's full of diagnostic puzzles. Sarah says at least half of her patients don't even carry an official diagnosis. In those cases, she has to chart a path forward without the certainty that traditional diagnostic frameworks can provide.

Sarah: One thing that I was trained to do is to avoid the need to impose a diagnostic label on someone, just to make ourselves feel better. It's tempting, we want answers as clinicians, patients want answers, but I think we get into trouble if we anchor prematurely on a diagnosis that we are really not confident in.

Emily: So what she does instead, is make a list of all the things she does know.

Sarah: Okay, they have low platelets. I'm going to approach that as I would in a patient with lupus, who has low platelets, but I also remind myself that I'm not making a diagnosis of lupus, so that I remember to revisit the diagnosis and how we're approaching treatment if things are not going as expected or as hoped.

Emily: Like in the case of this patient with eye inflammation, they're not doing anything right now beyond waiting, making sure nothing changes, and staying in the uncertainty.

Sarah: He, initially when I started seeing him, seem to have, understandably, a lot of anxiety around this, but now he and I both have kind of gotten to a point where I don't want to

call it complacent, because I don't think that's the goal here, but at least acceptance for the time being.

Emily: There's a critical difference, Sarah says, between clinically indicated waiting and laziness. The difference is staying with the uncertainty. Staying alert, attentive, responsive as new information presents itself. It's not just diagnostic uncertainty that Sarah faces. Even when she can make a clear diagnosis, figuring out the effective treatment can be just as convoluted, if not more so. Take one of her rheumatoid arthritis patients. The diagnosis was easy, but then the patient didn't respond to the first-line treatment, or the second-line, or the third-line. So Sarah had to just keep trying things.

Sarah: We don't have a way of assessing, what is the specific medication that will work for an individual patient? So, it's kind of like a roulette wheel, how we pick it. We will try a therapy, in her case, for four months at a time. It doesn't really help very much, and then we move on to the next thing. She has been on medication after medication after medication. Essentially, we've exhausted all current options. I think, for me, these types of cases can be very defeating, because I know what her disease is, and I know what the options are, and I also know that at this point, I don't have anything else I can offer her. That's challenging for me.

She's one of those patients where when I see her name on my schedule, I mean, she's lovely, but my heart sinks a little bit, because I know how that visit is going to go. I would say this type of uncertainty, I find a lot harder, honestly, than the diagnostic uncertainty.

Emily: When all said and done, the uncertainty of rheumatology, the way that you have to work with time, challenging as it is, is part of the reason Sarah got into the field to begin with.

Sarah: You have to be willing to wait. I enjoy that, I think, because of the ability to develop relationships with patients. That was a huge thing that drew me to medicine, was taking care of patients longitudinally. Just like there are people that would not be well suited for this, I am not well suited to go into the-- [laughs] through the intensive care unit and take care of people where you really need to make decisions in a matter of minutes. I will say that sometimes the challenges is the patients get frustrated and fed up with you and say, "What is wrong? Why can't you find the medication that's going to make me feel better?"

So, continuing to build that relationship and that therapeutic alliance with a patient, so that you don't lose them, they don't give up on you while you're going down this path together, is a really important piece of navigating that.

[music]

Emily: For our last story today, we learn how a new diagnosis can shape somebody's perception of the future. How do we build or plan a life when you're living on borrowed time? Here's Susy.

Susy Stirling: I'm cycling home, when I get the call. I'm going up a hill, not an uncommon occurrence in Sheffield, if you've ever been there. So I stop to respond. "You don't know me. I'm with your husband. He's had a fall in the park." Martin, my husband, is a 50-year-old doctor, a runner, recently completed a sub three marathon. I'm thinking ankle injury or, oh, I hope it's not knee. Tougher to rehabilitate as a runner. "He's not doing too well. An ambulance is on the way. He can't speak right now." What? My mind is racing as I drive to the park.

When I find him, he is pale, clammy, eyes closed. I hold his hand, find a pulse at his wrist. Racing, weak. I wonder if he's about to arrest. He looks like he's a person holding on to life by the thinnest of threads.

Martin Billington: I could feel my heart pounding in my chest, and I remember strangely looking up at these amazing old oak trees. It was autumn, so they were beginning to turn color. I sort of remember noticing them and thinking, is this the last view I'm going to have?

Susy: Remarkably, and to a huge relief all round, he reverts to sinus rhythm, but it takes an alarming 45 minutes, which seems a lifetime. The Martin I recognize returns. Making witty banter with the paramedics. My journey into medical uncertainty has begun. Did that just happen? It seem so serious, but it can't be. Look at him now. He's taken to the hospital. I follow. Various tests, waiting. No one can confirm or deny anything. Pain, distress, exasperated relative, exhausted staff, the lights of the emergency department are always the same. At some point, this afternoon becomes this evening.

Martin: Initially, I was just relieved that whatever had happened was over. Even though there was this unknownness, I still felt safe in the hospital.

Susy: A week in, no one knows yet what's wrong. How will we stop this occurring again? What if he arrests? Why is it happening? After many tests, including the predictable ones and the unpleasant extra ones, pieces of his heart were removed for scrutiny under a microscope. More scans in another tertiary center. The diagnosis is one of exclusion.

Martin: I think it was a couple of weeks, sort of ruling things out. Then my cardiologist said, "We think the most likely thing is sarcoid of the heart." No, I never heard of sarcoid of the heart. It's so unusual. He did say, at one stage, he said, "Yes, we don't have many people with this. In fact, in our region, I think you're the only one." He did use the phrase, "I'm afraid you've become rare and interesting," which is what nobody wants to become in the medical world. That was quite mixed, I suppose.

That, "Okay, we know what's going on now," but that doesn't sound like the answer I wanted to hear. One of the things he said was, "Don't google it, because there's so little data, and a lot of it is post mortem data and horrible case histories of people dying suddenly."

Susy: How do we construct a life between an anecdote in a post mortem series? A neurologist and a neuroendocrinologist are added to the cardiologist, respiratory physician and hematologist. Who will explain to us how to pick up the pieces of life again and feel confident to live it?

Martin: At the start, it was kind of 100% medical anxiety. Like, "What can I do physically?" I can really remember, really early on, I think I'm out of the hospital going for a walk with Susy, and Sheffield is blessed with beautiful countryside very nearby. I remember saying, "Actually, I think I just want to walk along the road, because I don't want to walk on a path where an ambulance can't get to me." That's how scared I was, still.

Susy: A consultation about the future. Running? Oh, no, I don't think so. Short term? No. Medium term? No. Long term? We'll have to see.

Martin: Then, I suppose, just as you become less worried about dying soon, then the space for the existential, the luxury of the existential angst, comes in. Should I be working less? Doing other things? What interest should I be pursuing? How should I be living?

[music]

Susy: Fast forward again. The glacial melt water is crystal clear and freezing cold. My snorkel allows me to see deep below me. Shafts of sunlight cutting through turquoise water, light glinting on bright green seaweed. We're having a family holiday in Iceland. Then suddenly, I'm aware that Martin isn't with us. He's out the water, lying down with his legs lifted. Someone is trying to get his wetsuit off his chest. Oh, shit. What have we done? Was this too much?

Martin: I'd been a bit naughty in that you had to sign a sort of medical form saying you didn't have anything significant to allow you to do this. I thought, "If I write down what I've got here, they're not going to let me go." I kind of thought, "I think this is fine." Then, the woman who was our guide, she was helping me get out of my wetsuit and trying to see what I need. She said, "Is there something you need to tell me?" She was very switched on. I said, "Yes. Yes, I've got one of these devices, and I'm on some pills."

Susy: I'm now following a blue light ambulance tearing up the road between National Park and Reykjavik. We wanted to do something, see something, live a little. It seems so low risk. No exertion, no machinery or equipment. No speed. How could we have got it so wrong? Nervous voices from the back seat. "Will dad be okay?" "I hope so. I think so. He's in good hands. They'll look after him." I say all the things, but I'm not sure what I believe.

Martin: Yes, I think some bits of it are harder for her than they are for me. I think I knew at some level, this wasn't my heart. This was something else, and it was okay. Whereas I think she's just looking at me, not looking well, remembering that first day, and is understandably terrified again.

Susy: By the time we get there, he's sitting up in bed looking like himself again. How should we decide what to do? How to live? I'm reminded of the consultant conversation. Short term, no. Medium term, no. Long term, possibly. When does medium morph into long term? Oh, yes, I remember. There aren't any answers. There's only uncertainty. Making it up as you go along.

Martin: I suppose I didn't have a massive conversion experience, shall we say? Where my life flashed before me and made loads of big changes. I think it was just a long process over weeks and months, really, because there was a lot of unknowns still, even once we've made the diagnosis. Then I suppose just sort of slowly coming to terms with it, really.

Susy: Fast forward again. I'm in Sheffield in the local park. I'm waiting at the park run finish line. There they are. Martin crosses the line, hands aloft, triumphant, accompanied by one of our sons and our daughter and several of our good friends. Martin just completed his 100th park run.

Martin: I walk up and now run up that place quite often now, and there's a special bit to it. It's a bit where I didn't die here. I could have died here, but I didn't die here.

Susy: Have we made it to long term then? Go Martin.

[music]

Emily: Thanks for listening to The Nocturnists, Uncertainty in Medicine. Our core uncertainty team includes me, Emily Silverman, The Nocturnists Head of Story Development, Molly Rose-Williams, Producer and Editor, Sam Osborn, and our uncertainty correspondent, Alexa Miller of ArtsPractica. Our student producers are Clare Nimura and Selin Everett. Special

thanks to Maggie Jackson and Paul Han. Our executive producer is Ali Block. Our program director is Ashley Pettit. Our original theme music was composed by Asche & Spencer, andadditional music came from Blue Dot Sessions.

Artwork for Uncertainty in Medicine was created by Eleni Debo, who is represented by Folio illustration and animation agency. The Nocturnists, Uncertainty in Medicine, was made possible by generous support from the ABIM Foundation, the Gordon and Betty Moore Foundation, and the Josiah Macy Jr. Foundation. The Nocturnists title sponsor is the California Medical Association, a physician-led organization that works to keep the doctor-patient relationship at the heart of medicine. To learn more, visit cmadocs.org. The Nocturnists is also made possible by support from listeners like you.

In fact, we recently moved over to Substack, which makes it easier than ever to support our work directly. By joining us for a monthly or annual membership, you'll become an essential part of our creative community. If you enjoy the show, consider signing up today, at thenocturnists.substack.com. If you enjoyed this episode, please share with a friend or colleague, post on social media, and help others find us by giving us a rating and review in your favorite podcast app. I'm your host, Emily Silverman. See you next week.