The beast in the belly – mystifying and deadly gastrointestinal disease in a hospital emergency room
Sherwin B. Nuland
NOT LONG AGO A 24-YEAR-OLD woman named Grace Lopat(*) registered for assignment as a substitute teacher in the elementary school system of a small town outside New Haven, Connecticut. Although Grace walks nowadays with a barely perceptible shuffle, in all other ways she presents the perfect image of vibrant good health. It comes as no surprise, for example, to learn that she placed third in a county beauty pageant a few years ago. Even forewarned with the knowledge that since the age of eight she has required twice-daily insulin injections to control her diabetes, anyone meeting Grace would have good reason to see in her the personification of that idealized image of a past generation’s sketchers and artists, the American Girl. Certainly it is a great deal easier to think of her as a wholesome, smiling beauty contestant than it is to imagine her mottled and swollen, in a delirium of fever and near death, being rapidly wheeled toward an operating room one spring afternoon four years ago. She had been assessed a Class 5 risk for anesthesia, in the opinion of every physician who saw her. To this day, she’s not sure whether to credit her survival to the flabbergasting marvels of modern scientific medicine ro the spiritual intervention of her long-dead father, and even a few of her doctors sometimes wonder. Either way, it took a miracle to save her life.
The American Society of Anesthesiologists describes a person in Class 5 as “a moribund patient who is not expected to survive without operation.” No one, doctor or otherwise, seeing Grace Lopat just before those preoperative moments had reason to dispute that description, and most observers would have projected her survival period to be hours rather than days. I was her surgeon, and I’ve now had four years to think about it. I’m absolutely convinced that I have never taken a sicker patient to the operating room, even if I include in my recollections those few who didn’t leave it alive.
THE REASON FOR GRACE’S SURVIVAL IS NO easier to pin down than is the origin of her sudden catastrophic illness. Although our clinical team was later able to trace the details of the process that made her so sick, we’re still puzzled by the “why” of it. We know the culprit but have no idea how it managed to get as far as it did as fast as it did. Even the instructions we gave Grace after her recovery were based on guesswork: she was told never to eat pork again. The injunction had no scientific basis. In fact, it was nothing more than a kind of clinical rabbit’s foot that none of us were willing to throw away, probably because it was the only piece of advice we could think of. Grace never shared our concerns; I recently discovered that she eats pork whenever she can.
Actually, the amount of pig meat consumed by our patient in the days before the onset of her illness was not enough to indict it. She’d had a Chinese dinner about 40 hours before her first symptoms, and it included pork fried rice and spareribs. Other than that, she has no recollection of having eaten anything at all different from her usual fare.
Grace’s medical saga began in May, on the Monday of finalexam week at the state university where she was completing her sophomore year as an education major. She had just taken the performance exam for a dance course in which she’d been enrolled that semester. It was about three o’clock in the afternoon, and she was walking across the campus, feeling pleased with how well she’d done and thinking about the coming series of finals.
“All of a sudden, I was on the ground–I couldn’t imagine how I got there. I got up quickly because of course there were a thousand people around the campus, and I was thinking, ‘Dear God, I hope no one saw me fall.’ I looked around and there were no stones, no sticks, no cracks in the sidewalk–there was absolutely nothing that I could possible have tripped on. It was like my legs gave out, and I thought it must have been because I’d just danced for an hour. My roommates said later that I was such an idiot I must have tripped over my own two feet.”
On the following morning Grace awoke feeling sick.
“I was vomiting, I was running to the bathroom with diarrhea, and I was sweating. I thought, ‘Oh great, I caught some kind of a grippe, some kind of a flu. I went back to bed, but I kept going in and out of it. Finally, my roommates began to get worried because there had been several times in the past when I got dehydrated and had to go to the hospital because my diabetes went out of control. But when I tested my sugar, it wasn’t any higher than usual.
“Finally, the girls started to get scared. They called my mother at work, and she took me home. I drank lots of diet ginger ale the rest of the day and used suppositories to stop the vomiting. That whole night i was dizzy and throwing up, and drinking water and vomiting again. By early the next morning, my abdomen was aching and I couldn’t feel my arms and legs. I tried flapping my arms around and I still couldn’t feel them. No matter how weak I’d been in the past, nothing like that ever happened before. I was in hysterics–it was like a nightmare.”
Anne Lopat, Grace’s mother, has been teaching elementary school for more than 20 years. After her husband, Bill, died suddenly of a coronary when her only child was ten, Anne became not only the small family’s sole breadwinner but Grace’s entire support system. After Grace’s juvenile diabetes was diagnosed in 1978, Anne took it on herself to learn all she could about the disease, and to become something of an expert in the various ways it manifested itself in Grace. Her job wasn’t always easy. Like most diabetic kids, Grace had a way of breaking the rules, and it sometimes took all of Anne’s accumulated diabetic wisdom to extricate her child from the consequences. Occasionally her efforts failed, and it would then be necessary to rush the dehydrated girl down to the Yale-New Haven Hospital emergency room. Over the years, actual admission had been necessary seven times, always to treat acidosis, the rapid buildup of metabolic products in the blood of diabetics, which can lead to air hunger, coma, and finally, if not reversed, death. The last admission had been only six weeks earlier.
But knowledgeable as Anne was about the way Grace’s diabetes behaved, on that May morning she found herself facing an entirely new symptom. “When she woke me at about 5:30 and said she couldn’t feel her arms or legs, I knew I had to get her down to the hospital right away. While I was helping her to the car, she told me she couldn’t even feel her feet touching the ground.”
There was no prolonged wait in the emergency room when the Lopats signed in at 6:19. As Grace recently told me, “Generally, you can come in holding your head in your hands and they tell you to wait. But when you’re a diabetic, they take you right away.”
Blood samples were drawn and intravenous fluids were started without delay. About an hour and a half after her arrival, Grace was told that her test results seemed reasonably satisfactory. But she couldn’t be reassured, and she began to feel herself become increasingly panicky. Soon she was shouting.
“Nothing felt right. At that point, the doctors and nurses were changing shifts, and no one was paying any attention to this screaming person. I was yelling, ‘Won’t someone listen to me? There’s something wrong!’ My abdomen really, really hurt, like it was a tight, tight muscle spasm and everything was all squeezed together. That frightened me, but I tried to blame it on the 24 hours of vomiting. But what really scared me was that I had no body perception. I didn’t feel like I was there. It was that same spacey feeling I’ve had when I’ve had a tooth filled and been given gas. It’s like I have no body at all.
“My mother kept to me all the time, trying to calm me down because I was yelling and thrashing around. And then she asked me if I knew I was going to the bathroom–I didn’t. Then I heard her yell, ‘My God, it’s blood!’ and she began calling out, ‘Nurse, Nurse!’ The nurse came right away, and after that my only perception was dribs and drabs of the faces of the doctors and nurses around me.”
In fact, Grace’s blood tests had not been normal at all. The most striking abnormalities were a markedly elevated white blood cell count of 28,500 per cubic milliliter (the normal level is about 5,000 to 10,000) and what is called a shift to the left, which refers to a large increase in the number of mature and immature granulocytes, cells that increase in number when an acute infection must be fought off. At 654 milligrams per deciliter, the blood sugar was elevated to some seven times its normal value, and a moderate degree of acidosis was present. The entire picture was characteristic of the abnormalities that rapidly appear when a diabetic develops serious infection. Once the proper cultures had been taken, the emergency room physicians started Grace on several intravenous antibiotics.
The most unusual aspect of the blood studies was the extremely high white cell count, which was approximately twice what might be expected in the ordinary kind of infection. But far more worrisome than the laboratory results was Grace’s appearance. She was throwing herself around the gurney and shouting for help without seeming to be completely aware of what she was doing or that she had just passed half a pint of bloody stool. The skin of her entire body had become mottled, with great purple-gray blotches appearing everywhere, separated from one another by small patches of stark whiteness. Her body temperature was a full degree below normal and her blood pressure was beginning to fall.
The entire sequence of events added up to the clinical picture of sepsis, a massive bloodstream infection that leads rapidly to inadequacy of the circulation, often followed by organ failure and then death.
On the presumption that the bloody stool and abdominal pain might be clues to finding the infected site from which bacteria were being hurled into the circulation, the resident physicians sought consultation with Suzanne Lagarde, a gastroenterologist on the hospital staff. When they phoned the patient’s physician, Murray Brodoff, to tell him their plan, he said he would also contact a surgeon, on the chance that some remediable intra-abdominal event might be the cause of his patient’s strange symptoms. I was draping a middle-aged man for a hernia repair when Brodoff’s message reached me. Because I was decked out in sterile regalia, the nurse held the phone to my ear, and Brodoff described what he had been told. I was committed to the operation about to begin, so I had the nurse page the resident on my surgical service, and I delayed the operation just long enough to ask him to go directly to the intensive care unit, to which Grace had by then been transferred.
Sue Lagarde is a slight, bespectacled woman in her late thirties whose stylish good taste in clothes seems pleasantly incongruous with her studious face. She is a skilled clinician, and so enthusiastic about her work that she approaches diagnosis with a certain cheerful ebullience, manifested most directly by a rapid verbal delivery in which the words tumble out so closely on one another that she seems always on the verge of stuttering. When Lagarde examined Grace, she saw a young woman with what she called a hysterical personality throwing herself around the intensive care unit bed, complaining loudly and sometimes incoherently of diffuse body pain. The girl’s skin was cold and broken out with the blotchiness doctors call livedo reticularis. Although she shouted bitterly and above all about belly pain, there was no abdominal tenderness and only a mild degree of distension at the time of Lagarde’s examination.
Of all the confusing, indeterminate findings, the most disquieting was the acidosis–it was worsening in spite of vigorous treatment. Whatever the obscure nature of the disease process might prove to be, it was obvious to Lagarde that she was dealing with a desperately ill young woman whose condition was deteriorating rapidly. The situation was not only dire, it defied diagnosis. Lagarde recommended what she called a fishing expedition, including a CT scan and a neurological consultation to help point out the proper diagnostic direction. Unless some sense could be made of Grace’s bewildering set of symptoms, she would soon reach a point beyond retrieval.
BY THAT TIME I WAS COMPLETING THE hernia repair. As soon as the dressing was applied, I paged the surgical resident. He responded in less than a minute and assured me that the young woman had “no surgical problem.” His examination of her abdomen, he said, was without findings that might suggest the need for operation. “She’s a hysterical kid,” he said, “and whatever she’s got is medical, not surgical. You don’t have to see her.” He went on to describe Grace’s bizarre behavior, her blotchy skin, and the laboratory findings. It was clear that he was a bit irritated at being asked to consult on a patient who so obviously didn’t need to be seen by a surgeon.
I stopped by the waiting room to have a few words with my patient’s wife, and then headed up to the medical intensive care unit (or the MICU, as such places are acronymically and universally called by those who work in them). One of the nurses quickly briefed me on Grace’s condition; though it had already been very bad when Lagarde examined her a short time earlier, it was now worsening rapidly. Despite the attempted clinical detachment of the nurse’s description, it was obvious that she was upset, even distraught. The best intensive care nurses never do become inured to the daily tragedies they witness, and helplessness in the face of imminent catastrophe, especially when it involves a patient not much younger than oneself, is unbearable even for the most stoic of professional personnel.
After our brief discussion, I sat down with Grace’s chart to run a quick eye over the lab reports and the previous medical and nursing notes. As I scanned the three pages of neurology consultation, my eye caught the word hysterical, this time used to explain the arm and leg symptoms, which fit into no clinical pattern that made sense. The overall impression of the neurologist was that the patient’s symptoms were the effects of diabetic acidosis. His final recommendation was: “Suggest close clinical observation. Consider L-S [lumbosacral] CT if symptoms persist.”
On the next page I found the surgical resident’s note, describing his findings. At the end, under Impression and Plan, he had written, “Benign abdomen in setting of acute neurological event and GI bleeding suggest vasculitis [underlining his] though sepsis possible … possibly meningococcus. No evidence for acute abdominal process.” There was a tone of finality in the note. Even the customary concluding words of the surgical consultation, “Will follow,” were absent. In their place was “Will speak with Dr. Nuland.”
I stood for a moment at the entrance to the glass-enclosed cubicle where Grace lay attached to electronic monitors, a nasal oxygen line, and a tangle of plastic intravenous tubing. As I observed her from the foot of the bed, I asked the nurse to pull the sheets away so that I might look at the patient’s entire body from that perspective. Even to me, a case-hardened veteran of other people’s affliction, the exposed sight was harrowing. The mottled object on the bed looked like a bloated corpse somehow preternaturally animated by the terror of yielding to eternal stillness. Its thrusting chest was straining up and down like a perverse bellows sucking air into itself, while the head and all four extremities were flinging about in a frenzy of attempted escape. In the glare of the brilliant MICU illumination, the skin looked almost eerie. Although I had been told of the livedo reticularis, I was unprepared to see the depth or extent of the large violaceous bursts, especially as they were so harshly revealed by the many foot-candles of piercing light. The pattern of blotch and pallor involved every visible inch of body and was much deeper in its purplishness than I had ever encountered, except on the freshly dead. The thing’s legs were quite swollen from the knees downward, and even its face had become puffy. Almost paradoxically, the swelling of the lids made the open, frightened eyes seem to bulge–very likely, the tissues behind them were also swollen.
The abdomen was so distended that it partially obscured my view of the heaving rib cage. In answer to my question, the nurse said that the abdominal girth had reached its grossly protuberant size over the previous two hours. When I stepped to the bedside and tapped on the belly in the diagnostic maneuver called percussion, the amphoric boomlet of resonance that filled the small cubicle had the pitch that might be produced by a felt hammer hitting a kettledrum. With good reason, clinicians call such a note tympanitic. Grace’s tympanitic abdomen told me that her intestines were blown up with gas, and the absence of gurgles when I listened through my stethoscope meant there was no peristalsis, no rhythmic contractions that normally push along the intestine’s contents. When I pressed down, as gently as I could, into the abdominal surface, the grimace on Grace’s puffy face let me know I was hurting her. She had stopped speaking some time earlier, but her bulging, uncomprehending eyes stared fearfully at me.
When an abdomen is expanded by a large volume of gas in a short period of time, it rises like an over-yeasted loaf of bread. Years ago clinicians used the word meteorism to refer to this rapid belly ballooning, which is encountered only in certain unusual circumstances. The word seems to be archaic these days–it is not to be found in my 1974 edition of Dorland’s Medical Dictionary, although, curiously, it does appear in my much more recent Webster’s Unabridged. Perhaps it has been preserved for literary use rather than clinical. In any event, I haven’t met a medical student in at least two decades who knows what it means.
What it means, almost always, is a belly with dead bowel in it. In my clinical experience, almost no other acute abdominal disease will raise the white count as high as intestine does when it is in the process of dying. A drastically risen white count in a patient with a drastically risen belly is a surgical call to action. Unless something is done quickly, the patient will not survive.
The presence of dead bowel furnished a logical explanation for Grace’s sepsis and also explained why all the vigorous measures being applied were not resulting in any improvement in her acidosis. As long as a major source of infection remains untreated, there is no way to stop the process of decline. Obviously, Grace needed an operation–soon.
As I was quickly writing my consultation note, Mike Bennick walked hurriedly into the MICU. Mike is an intense, fastpaced young gastroenterologist who had trained with Sue Lagarde and was now her associate in practice. He hadn’t seen Grace before, but Lagarde had described her condition to him. He instantly recognized how much had changed since his partner’s examination of a few hours earlier and concurred that immediate operation was mandatory. In that tone of euphemistic detachment that even the most caring doctors use in hospital charts, he wrote, “Emergent surgical intervention holds only valid option for this patient, whose risks for demise are severe.”
When he had completed his note, Bennick and I went out to speak to our patient’s mother. We found Anne Lopat standing with her two aunts and an uncle, just outside the door of the MICU. Bennick had recently treated Anne’s mother, and he knew that she would have confidence in his recommendations. He also knew that this very forthright woman, frightened though she was, would be impatient with explanations redolent of chart jargon, or with any hint of evasiveness. As I would increasingly come to appreciate during the next few weeks, she wanted the truth flat out, and Bennick now gave it to her as directly as possible, softening the harshness of his message by the gentle tone in which he delivered it: “Anne, Grace is dying, and we don’t know why. We have to look inside–it’s her only chance.”
DURING THE FEW SECONDS IT TOOK BENnick to speak and then to introduce me, I looked hard at my new patient’s mothe, trying to evaluate how she might respond to the details of what I would now have to spell out for her. Even when optimism is impossible, some measure of hope must be found, and it must be transmitted to those who will wait. In desperate circumstances, a surgeon speaking to a family facing the imminence of loss can usually point out that he has seen patients survive even though they were sicker than this one, but I couldn’t say that to Anne with any honesty. In the atmosphere of futility that surrounded Grace’s rapid decline, and the accumulating evidence of clinical helplessness, what was needed just at that point was some sense of equanimity, and perhaps even of control. I have children Grace’s age, and I knew what Anne, without saying it, was expecting of me. If I could do nothing else, I would at least cloak myself in the aura of calm assurance that is the surgeon’s armor against impending calamity.
Anne is a large woman, not only tall but roundly and firmly heavy. Even when she is distressed, there is stolidity and determination about her. She listened to me carefully, and her face revealed nothing. She kept her gaze fixed on me, and when she occasionally blinked, it was done very slowly, as though she were momentarily closing her eyes to keep her thoughts from being observed. She seemed by force of will to be separating herself from anxiety in order to focus her mind’s entire attention on each successive detail of what she was being told. In a way, each of those long blinks closed a distinct file on a package of newly processed information and sealed it into her hidden mental store. She never looked away, even when I concluded by telling her that the operation would kill her daughter if we were wrong–if no source of sepsis was found in Grace’s abdominal cavity. When she had heard me out, she simply nodded, and the slight downward motion of her head punctuated my final word with a full stop. Then she said, “Please operate right away.”
I called the OR and asked for the next available room. Within minutes an anesthesiologist was at Grace’s bedside, trying to determine whether she was already too far gone to tolerate his gases and drugs. The last paragraph of his scrawled consultation note summarized the pessimism we all felt: “Class 5. Critically ill, undergoing resuscitation–insulin, fluids, oxygen. Plan rapid sequence intubation. Patient has poor prognosis–heroic measure to attempt to save life.”
Fortunately, one of the hospital’s 18 ORs was about to open up, and the nurses quickly got it ready for us. Grace was having few lucid moments by then, but she clearly remembers the brief period when she was in the holding area just before being wheeled in for the surgery. She was still thrashing about and trying to find some comfortable position on the gurney.
“I wanted to be on my side because I thought that would relieve some of the pain. I was thinking, ‘I’m going to die–I’m 20 years old, and I’m going to die.’ A priest came and was praying. He was making the sign of the cross, and I thought, ‘Oh my God, this is the last rites’–that’s a sure sign that you’re on your way, you know. I began to say that to my mother, and she was crying–so were my uncle and my aunts, and they were trying to tell me I’d be okay, even though they were crying.
“I believe in the power of God, and I’ve always had some kind of relationship with my father even though he’s not here on Earth–I feel his presence all the time, and I know when he’s there. My uncle Ron passed away when I was five. I’ve always believed my father and my uncle Ron are in heaven. I’ve also always believed that someday when I die I’ll go to them, just like I believe that the smile on my father’s face when we found him dead was for my mother–I believe his parents greeted him in heaven. To me, that meant there’s something good out there, and that his parents came to him. So I was lying there, and I felt like my whole body was being pulled. You know, when you vacuum a rug and you put your hand over the open hose to be sure the suction’s working, and you feel that pull–it felt like my whole body was being pulled forward. I thought, ‘Here I come, this is it–I’m dying.’
“And then I saw my father and my uncle. They were just standing there, and I was thinking, ‘Okay, God, I’m dead.’ There weren’t lights–I think you have to go all the way to get the lights. Well, I really believe that either they came to me or I came to them, and my mother tells me I was saying, ‘Bill, Ron!’ Of course, I never called my father Bill and I never called my uncle Ron when they were alive, which makes me think things must be different in the afterlife. But I did say, ‘Bill, Ron,’ and my father put up his hand in front of him, and he said, ‘No, not yet.’ And I sat back. And then I looked up at my mother and I said, ‘I’m going to live,’ and those were the last words I said.”
True to their plan, the anesthesia team got Grace to sleep very rapidly. With the surgical resident and a medical student assisting me, I made a long up-and-down incision in the mid-line of Grace’s very distended abdomen. As I opened the innermost layer, the peritoneum, a gush of malodorous yellowish fluid poured out onto the drapes. When we had finished sucking it into several large trap bottles, the nurse told us it amounted to some six pints. With Grace positioned on her back, the gas-filled gut had been floating on top of the fluid, explaining the drumlike resonance produced by percussion.
We inspected the small bowel. Although most of it was alive, there was a length of about 15 inches near its origin that was either dead or barely viable. It was suffused with a dusky bluish hue and was completely without peristalsis, even when I tried to stimulate it into some kind of action. The discoloration gradually faded out at the upper and lower margins of the involved segment, so that there was no definite line of demarcation between healthy and sick tissue. The vessels entering the darkened piece looked normal, and the arteries pulsated vibrantly. When the electronic listening device called the Doppler was applied, we heard the healthy whooshing sound of good circulation. And yet the bowel looked asphyxiated.
I explored every portion of the abdominal cavity, seeking an instigating factor for the imminent intestinal gangrene, but when I had concluded my probing and peering, I knew no more than I had at the outset. No obvious cause revealed itself that might explain the rapid death of an otherwise normal-appearing length of intestine in a youthful, pristine-looking abdominal cavity. The gut’s blood supply appeared perfect, there were no adhesions or similar fibrous bands that might have pinched off the involved segment, and the bowel wall seemed free of inherent pathology–nevertheless, it was near death. My puzzlement is summarized in a sentence of the operative note I dictated shortly after the conclusion of the surgery: “It is very difficult to know the cause of this ischemic [lack of blood] pattern, which is a form that no member of the operating team has seen before.”
There is only so much time to cogitate when the belly of a failing patient is wide open and begging that some action be taken. No encouraging words were heard from the head of the table, where three anesthesiologists were huddled, periodically issuing glum summaries of Grace’s dwindling condition. I fired a surgical stapler across the intestine an inch above and then an inch below the dying segment, divided its blood supply, removed the specimen, and handed it off to the pathology resident, whom I had summoned to the OR on the slim chance that he could add something of value. He looked at the piece of gut, made a few cuts into it, and pronounced himself as stymied as we were.
nothing was left but to reestablish the continuity of Grace’s digestive tract. In a brief series of steps, the surgical resident and I reconstructed the gut, again with staples. The entire sequence of removing and restoring took less than 15 minutes. Before stapling came into common use about a dozen years ago, this part of the procedure had to be done by hand, and it would have taken at least three times as long. I still prefer old-fashioned manual cutting and stitching, not only because I relied on it for two decades before the current mechanical era but for the simple reason that I love the way delicate steel instruments feel between my fingers. I find the technical sequences of cutting, suturing, and tying to be such aesthetically pleasing exercises that I’ve been loath to abandon them. Nonetheless, stapling provides the same result and is much faster. Grace’s precarious condition required speed as much as it did technical precision, and in such a situation aesthetics must yield to expeditiousness.
As soon as I was satisfied that we had made a good reconstruction of the gut and its blood supply, we poured at least ten quarts of warmed antibiotic-laced saline into our patient’s gaping abdomen, in order to rinse out as much bacterial and other debris as possible. We sucked it clean and ascertained that we had stopped any oozing of blood. Then we removed all sponges and instruments and began to close. I passed a heavy polypropylene stitch through all layers under the skin of the topmost part of the incision, and then whipped it quickly all the way down the length of the wound until I reached the bottom. I stepped back from the table, and the resident placed a row of some 30 staples into the skin. Not until one of the nurses began untying my gown did I realize that I was exhausted.
I went out to the waiting room to tell Anne that the operation had gone well, at least from the technical point of view. Grace was still septic and not much further from death than she had been when we wheeled her into the OR suite, but at least the source of her infection was removed, and she now stood some chance of recovery. When I was through speaking, Anne asked me the obvious question, and I had no answer for it. “No,” I said, “we have no idea why this happened to her intestine. Maybe the pathologist will be able to tell us, after he puts it under the microscope.”
The specimen I had handed to the pathology resident had the appearance of a segment of organ that had lost its blood supply, and yet I knew that the flow into it was normal right up to the very wall of the gut. I expected the explanation to be found in the microscopic vessels that traverse the bowel wall. For reasons yet obscure (but in some way related to Grace’s diabetes), the tiny arteries, I supposed, must have become acutely occluded by an inflammation called arteritis, or vasculitis. That diagnosis provided a neat, all-inclusive package, because it would also explain the livedo reticularis and neurological symptoms. If our patient could be proved to have some form of vasculitis, the surgical resident might still save some face, even though he had completely missed the diagnosis of dying bowel. Over the next 24 hours, vasculitis or one of its close nosological relatives became the fashionable diagnosis agreed upon by nearly every one of the doctors hovering around Grace’s bedside in the MICU.
A consultation was obtained with the chairman of the dermatology department the next morning, because the livedo reticularis had not lessened as much as we might have liked. His list of possible diagnoses reads like a tabulation of esoterica, a group of diseases I’ve almost never encountered in any patient during my entire clinical career: livedo vasculitis; polyarteritis nodosa, Wegener’s, cryoglobulinemia. He added a much more familiar entity at the end–collagen vascular disease–but obscured it beyond my recognition by parenthetically adding, “including Sneddon’s syndrome,” as though he expected anyone other than his own staff to know what he meant. Like the rest of us, the professor was looking for a rare disease to explain Grace’s rare symptoms.
When it was finally revealed, the true diagnosis proved far more esoteric than even the dermatologist anticipated. While on rounds that afternoon, I received a phone call from Brian West, the pathologist in our hospital whose specialty is diseases of the gastrointestinal tract. West had been at our institution for less than four years, yet in that relatively brief period he had quite transformed his department’s capabilities in the area of his expertise. With his arrival from the medical school of Dublin’s Trinity College, Yale GI pathology had become what West’s colleagues call world-class.
I find the lilting ups and downs of West’s soft County Cork brogue to be one of the few reassuring sounds I ever perceive in the jumbled cacophony that is the background noise of a modern university medical center. If hearing could somehow be transformed to vision, it might be said that West speaks with a gentle smile. The first time I saw his voice, it was over the telephone, and I distinctly remember visualizing not only the smile, but his blue eyes and the reddish beard that makes his still-young face appear craggy and wise. Soft though it may be, West’s smiling voice speaks with persuasiveness and the authority that comes from an impressive ability to interpret the arcane microscopic clues left in the gut by obscure diseases.
“Do you have a minute to come over to the lab?” he asked, and there was a hint of expectant promise in his rising rhythm that told me it would be well worth my while to get there right away–the words weren’t said with any sense of urgency but more in the tone he might have used to invite me in for a pint of some long-awaited brew just arrived. “I want to show you what I’ve found in the specimen you sent me yesterday.” Anticipating his discovery, I burst in before he could continue: “What do the microscopic vessels look like?” His answer surprised me. “The vessels are fine. What I think she has is enteritis necroticans–the thing they call pigbel.”
It was an embarrassing moment, and I was grateful to be on the end of a phone in a far-distant part of our sprawling medical campus. I’m sure there must have been a confused look on my face while I paused for just a second, uncertain of how to reply. But speaking to West, I knew I’d stumble over my tongue if I feigned familiarity with these abstruse terms, so I confessed my ignorance. “Okay, Brian, what’s that?” He gave me a brief explanation, but it wasn’t until I got down to the lab a few minutes later that I really began to understand what he was talking about.
Peering down the twin barrels of West’s microscope, I could see that almost the entire mucosa–the inner lining–of the specimen was dead, although most of the main layer of encircling muscle, called the muscularis propria, was still within the definition of being viable. The most striking structures on the slide were the thousands upon thousands of rod-shaped bacteria forming a lengthy rank along the surface of the mucosa, palisaded like an irregular picket line of soldiers standing at attention. Their appearance and later lab tests showed that they were a genus of bacillus called Clostridium, closely related to the organisms that cause tetanus and gas gangrene. In fact, microscopic gas-filled spaces were visible within the layers of the bowel wall. The toxins produced by these particular microbes are capable of causing inflammation and necrosis (death and decay) of intestinal wall–hence the process is called enteritis necroticans. Grace’s sepsis was caused by the clostridia, and all the bowel, neurological, and skin symptoms were the result of the bacterium and its toxins.
By this time I knew that Grace had begun to exhibit various signs indicating destruction of the cells of some of her voluntary muscle tissue, a process called rhabdomyolysis. This too was attributable to the toxins. The combination of massive clostridial growth in her intestine, sepsis, rhabdomyolysis, and the resultant diabetic chaos were the explanation for the entire spectrum of destructive events that our patient had been experiencing. We could only hope that the removal of the nonviable bowel and the consequent diminution in the volume of bacterial load would enable our antibiotic and other treatments to reverse the process.
Clostridia in moderate numbers are normal inhabitants of the gut. Ordinarily they live in harmony with other bowel organisms and with the various physiological substances with which they come into contact. Unless some event occurs to disrupt the balance among the gut’s organisms and chemicals, the clostridia do not become sufficiently numerous to be a source of danger. For those of us involved in Grace’s care, the clinical challenge was to pull her through; but the intellectual challenge was now to figure out what had so upset the intestinal homeostasis that a massive overgrowth of clostridia occurred. For this, Brian West didn’t have a definitive answer, but he had identified a disease model that so closely resembled Grace’s that I was persuaded they were one and the same. Within a few days, and especially after West’s diagnosis was confirmed by an expert in Southampton, England, the evidence had become inescapable.
DURING OUR DISCUSSION THAT AFTERnoon, West answered an important question without my having to ask it: How did he know that this huge increase in the population of clostridia had not occurred between the time I excised the gut during the previous afternoon and the time it was put into the germ-killing preservative, which was perhaps not until the next morning?
“The pathology resident was in a hurry. He had promised to take his fiancee to dinner and the theater that evening, and he had to finish the day’s work quickly in order to pick her up on time. As soon as he got back from the OR, he dropped the gut into formalin. If he hadn’t done that, it might have putrefied overnight, and our finding all these clostridia would be meaningless. But this way, we can be sure that what we see here was the specimen’s exact condition when you cut it out of the patient. This gut really does have all the earmarks of enteritis necroticans.”
It’s not easy to tell the mother of an attractive young American Girl that her daughter has a disease whose name is pidgin English for “pig belly,” but no more likely diagnosis has appeared in the four years since Grace’s narrow escape. Except for the complications added by diabetes, the clinical course of Grace’s disease and the microscopic appearance of the excised tissue are exactly the same as they are in the thousands of New Guinea tribespeople who have died of the same process. Acute pigbel is a major cause of premature death in the highlands of Papua New Guinea, with a mortality rate among those contracting the disease of almost 85 percent. Second only to respiratory disease, it is a leading killer of children in the area. Its prevalence is highest at times of the year when ceremonial pig feasting takes place, and the disease has been so carefully studied that it is possible to describe its evolution with considerable certainty.
The pig feast is an integral part of many of the ceremonials attached to various kinds of highland celebrations and sacrifices. The meal is always prepared in a traditional manner. After the animals are clubbed to death, their intestines are removed, washed, and wrapped in leaves. Alternating layers of filleted carcass, guts, fern fronds, banana leaves, and breadfruit are placed into earth pits along with sweet potatoes or bananas, chopped greens, and stones that have been preheated. Tier by tier, a mound of the ingredients is fashioned, with insulation provided by a final packing of pigs’ quarters and flanks. After a large quantity of water is poured into the vapory, structured mass, more leaves and an outer layer of earth are added as a covering. In this way, a large steam oven is created whose internal mean temperature, when visiting health officers have tested it, has been 172 degrees Fahrenheit.
Not only does such a heating system result in inadequate cooking of the meat, it also provides plenty of opportunity for bacterial contamination. After all the festive cooking is completed, the banquet takes place under conditions that would throw a sanitation inspector into fits of apoplectic convulsion. Those conditions are ideal for the proliferation of dangerous organisms, particularly clostridia.
Ordinarily much of the clostridial toxin would be destroyed in the body by an enzyme called trypsin, to which it is very sensitive. Unfortunately, sweet potatoes contain a chemical that inhibits the action of trypsin, and sweet potatoes are not only a major constituent of the pig feast but also a staple of the highland diet. The ingestion of large amounts of clostridiarich meat accompanied by plentiful doses of trypsin inhibitor provides the perfect concoction to induce fulminating outbreaks of pigbel. The situation is made even more egregious by the common presence in local children of the intestinal roundworm Ascaris lumbricoides, a parasite that secretes its own brand of trypsin inhibitor, adding to what is already in the poisoned food.
As for the clinical aspects of the disease, they are precisely those that were exhibited some 10,000 miles away in New Haven, Connecticut, by Grace Lopat, absent of course the components attributable to diabetes.
If massive overgrowth of clostridia is the cause of enteritis necroticans, the disease might be expected to occur in places other than Papua New Guinea, and without the necessity for ingesting a witches’ brew quite so potent as the one cooked up during pig feasting. This is in fact the case. An epidemic disease of identical nature made its appearance in northern Germany shortly after World War II. It was called Darmbrand, or fire bowels, and the doctors who studied it concluded that it was caused by unaccustomed intake of excessive amounts of protein-rich food by a malnourished population. Outbreaks of the same thing have been reported sporadically in several African countries, China, Bangladesh, the Solomon Islands, and at an evacuation site for Khmer children in Thailand.
A contributing factor in such areas is that chronically undernourished people do not ingest enough protein to make sufficient quantities of trypsin. When access to meat is suddenly provided, the meal may for one reason or another be contaminated, and then the levels of clostridial toxin become very high in the bodies of people with not enough trypsin to counteract it. This is consistent with an observation made by several of the first investigators of Darmbrand, which was that it seemed to have made its appearance when the diet was suddenly changed. The German patients were indeed chronically malnourished during the terminal phases of the war and for an extended period afterward. Those who became sick had very likely overeaten on occasions when meat, perhaps contaminated, was made available to them.
Although there have been scattered reports of individual patients dying of enteritis necroticans in prosperous Western countries, no real epidemics have occurred among populations living in areas where sanitation levels are high. But a few of the single cases are instructive because they illustrate some of the most dramatic aspects of the disease. In 1983, for example, a surgeon and a pathologist at England’s Royal Liverpool Hospital described in the journal Gut (the British tend to be quite direct in their medical terminology, and this is the name of their most highly regarded gastroenterology journal) the case of a 23-year-old photographer’s model who walked into their hospital’s emergency room at eight o’clock one Sunday morning complaining of abdominal pain and bloating. She told the staff doctor that she ordinarily tried to remain very thin but periodically went on an eating binge. Between midnight and four that morning she had eaten the following: 2 pounds of kidney, 1 1/2 pounds of poorly cooked liver, 1/2 pound of steak, 2 eggs, 1/2 pound of cheese, 2 large slices of bread, 1 whole cauliflower, 1 pound of mushrooms, 2 pounds of carrots, 10 peaches, 4 pears, 2 apples, 4 bananas, 2 pounds of plums, and 2 pounds of grapes. She had then gone to sleep for a few hours and been awakened by the abdominal pain.
AS THE MEDICAL STAFF TRIED UNSUC-cessfully to empty the young woman’s stomach with a wide-bore tube, her condition rapidly deteriorated, and she had to be rushed to the operating room. On opening her abdomen, it was seen that a section of the upper small bowel appeared to have lost its blood supply. As the surgical team watched, doubtless horrified, the area of ischemia gradually extended until it involved most of the length of the gut. Soon small gas bubbles became visible in the intestinal wall. Their patient died shortly afterward. Autopsy revealed massive clostridial overgrowth in the esophagus, stomach, and upper portion of the small intestine.
The microscopic appearance of the young model’s digestive tract fit exactly the description of enteritis necroticans. As the authors of the report state in their discussion, “The features of this case are strikingly similar to pigbel.” They considered their patient to have been bulimic, and her chronic undernutrition to be the cause of a presumed inadequate level of the trypsin that might have counteracted her sudden huge intake of protein, at least some of which was undercooked and possibly contaminated.
The unanswered question about Grace Lopat is not whether she was the victim of enteritis necroticans–it seems almost certain that she was. What is not known is the underlying reason for the unchecked growth of clostridia in her intestine. The amount of pork she had eaten before her ealiest symptoms was not excessive; she was not malnourished; she did not inhibitor. The only possible clue is her diabetes. The disease is well known to be capable of causing a degree of immunodeficiency, which is one of the reasons diabetics are more infection prone than the rest of us. But any indictment of a diabetic immunodeficiency is weakened by the absence of previous of subsequent evidence that she is particularly susceptible to abscesses, inflammations, or other manifestations of decreased resistance to bacteria. In searching for some underlying cause, we were left with the succinct summarizing comment entered in Grace’s chart by Ann Camp, one of the interns who took such good care of her in the MICU. She called her patient’s disease “interesting and mysterious.”
Another of the few individual case reports of pigbel in the medical literature describes a young diabetic nurse in the Netherlands who died 24 hours after being admitted with characteristic symptoms, in 1984. He had eaten an unspecified quantity of pork at a party the day before becoming sick, but no other guests were affected. As the paper’s authors write, “It is well known that diabetic patients have a lowered resistance to infections. It is therefore tempting to speculate that this may have been a contributing factor.” Neither the Dutch doctors nor those of us who treated Grace can go any further than that.
GRACE IMPROVED ONLY TRANSIENTLY IN the hours following her operation. At first her acidosis responded to treatment, and her blood pressure stabilized. She developed a sepsis-related condition of inadequate blood clotting, called disseminated intravascular coagulation, but it wasn’t severe enough to cause serious trouble. Her subnormal temperature rose to 103, indicating a more appropriate response to infection. On the morning after surgery, we were cautiously hopeful, even though the mottling had decreased only slightly, and blood tests continued to show evidence of rhabdomyolysis. But it became increasingly difficult to maintain the balance of minerals and fluids in her body, and the generalized swelling of her tissues progressed as her kidneys began to fail. Dialysis was begun late that day, shortly after Brian West called me with the diagnosis.
The number of consultants was multiplying. By evening Grace had been seen by specialists in infections disease, dermatology, neurology, kidney disease, gastroenterology, surgery, and anesthesia, and every one of us continued to monitor her condition closely. Besides the minerals added to her intravenous solutions, she was receiving five medications, three of which were antibiotics. The intern’s summary note takes up seven pages of closely written script in which 14 distinct problem areas are identified: sepsis, recent necrotic bowel, blood pressure, kidney failure, ventilation of lungs, rhabdomyolysis, low calcium, low magnesium, the effect of shock on the liver, disseminated intravascular coagulation, diabetes, pain control, skin mottling, and nutrition. The white blood count, which had dropped to 16,000 in the immediate postoperative period, was beginning to rise again and had reached 21,000. By the next morning, the evidence of worsening sepsis was mounting. Almost certainly, the process in Grace’s bowel was extending to the area that had appeared univolved two days earlier. When I made the decision to reexplore her, there was universal agreement. Her belly had begun to distend again.
By then the kidney failure was rapidly worsening. Grace’s tissues had retained so much fluid that her presickness weight of 125 had risen to 185–her entire body was bloated and swollen. It was decided to give her another dialysis treatment and then go directly to the operating room.
Again I went out to speak to my patient’s mother, and again I described the situation to her exactly as I saw it. Anne had not left the hospital since Grace’s admission, sleeping in the MICU waiting room and eating in the cafeteria. When it was permitted, she would stand at her daughter’s bedside, holding her hand and stroking her face–speaking quiet words of encouragement, even though Grace didn’t know she was there. In her thoughtful, analytic way, she listened to every consultant and always came to the right conclusion. Anne had added everything up, and before I said a word she knew what I had come to tell her. Our conversation was a reprise of the one we had had two days earlier, but the outlook was even worse. I had thought it impossible for Grace to have been any sicker than she was before the first operation, and yet the impossible had happened. Anne signed the consent form and took my hands in hers, just for a moment. This time nothing needed to be said.
When the abdomen had been sterilized and draped, we reassembled on each side of Grace exactly as we had 48 hours earlier, but now there was a larger group around the head of the table. When a patient is very sick, anesthesiologists cluster about, trying to help each other as much as possible. During 30 years of a surgical career, it has been my not quite tongue-in-cheek observation that a patient’s chance of survival is inversely proportional to the number of anesthesiologists required to get the operation under way; a figure of six or higher is a virtual guarantee of death. As I looked up at the assembled group, I counted six. I made a wry comment that they seemed not to appreciate, and then went right to work.
Grace’s abdomen was bulging so tightly that it strained against the stitches holding it together. As soon as they were removed, the contained fluid and gut exploded out onto the drapes. Quickly, the surgical resident and I put everything in some approximation of order and assessed the findings. Starting just at the point where we had placed the staples to restore continuity, a bit beyond an anatomic point called the duodenal-jejunal junction, the next 18 inches of intestine looked exactly like the segment removed two days before. The preoperative impression was correct–the process of necrosis and clostridial overgrowth had extended and would require further excision. This time Brian West had come to the OR himself. When I completed the removal of the specimen, I handed it directly to him. He scrutinized it silently for a few minutes, and then we spoke briefly about its appearance before he took it off to his lab for further testing.
I carried out the operation much as I had done before, except that this time I closed the wound with a series of individual large stitches of heavy nylon, placed in such a way that they exerted a pulley effect–abdominal distension would bring the wound edges closer together. It’s a time-consuming and not very pretty closure, but the strongest I know of, and I wasn’t taking any chances with the possibility of a burst incision.
Afterward, Grace’s improvement was more sustained. Within 24 hours the rhabdomyolysis had decreased, and her kidneys began to function better–she went from nearly zero urinary production to the beginnings of what would soon be a reasonable amount of output. Moreover, her clotting mechanism was satisfactory, the white count had dropped to 15,000, and the pH of her blood was normal. The evidence of sepsis was much less. The livedo reticularis had begun to recede, and within another day it would be gone. Twenty-four hours after the surgery, Mike Bennick wrote in his note, “Improvement on all fronts.” For the first time, the campaign was beginning to look winnable.
There was to be one more scare, a few days later. Grace’s fever began to rise in a sequence of ascending spikes, and her white blood count went up to 33,000 by the fourth postoperative day. I thought the problem was an infection in one of her many intravenous lines, but I couldn’t find any proof of it. I then began to worry that leaking intestinal contents might be contaminating my surgical wound, but I couldn’t find any evidence of that either. The most frightening concern was the possibility of yet another extension of the clostridial infestation, into the remaining length of bowel. To evaluate this, a radioisotope scan was done, of a type designed to light up areas of infection or necrosis. I looked forward to having my fears laid to rest by the absence of any troubling findings, but when I reviewed the study with the superspecialist who had done it, I felt my knees weaken. The entire length of remaining small bowel showed an irregular pattern of involvement with the process I had seen in two successive specimens of excised bowel. My mind’s eye could visualize the now-familiar carpet of clostridia lining Grace’s gut.
Yet the study, scientifically precise as it was, seemed strangely inconsistent with what I kept finding each time I returned to examine Grace’s abdomen, something I did over and over again. Despite the radiographic appearance of necrosis, her belly was flat and she didn’t grimace or in any other way display evidence of pain when I pressed deeply inward. Through my stethoscope, I could hear the unmistakable and very comforting sounds of peristalsis. Most important, although she was still quite sick, Grace’s general appearance was improving each day. My patient looked hardly at all like the deathly ill girl I had twice rushed to an operating room.
THERE WAS A GREAT DEAL OF PRESSURE ON me to open Grace’s abdomen again. High-tech gadgetry is very impressive to young doctors, and has long since, in the hearts of many, usurped the revered place once reserved for the clinical skills of history taking and physical examination. Except for the senior infectiousdisease consultant, I was by some two decades older than any of Grace’s panoply of caregivers, and I decided it was time to pull rank. I went upstairs to the MICU and wrote a long note in Grace’s chart, the gist of which was expressed in two sentences: “Her abdomen is simply not the abdomen of a person with necrotic bowel. I do not think she should be operated on.” Then I got up to tell Anne. She was standing at the entrance to Grace’s cubicle, deep in conversation with Mike Bennick.
Anne recalls that morning’s events very well. She had followed every step of the previous days’ evaluations and knew that all the doctors were talking about another operation. She also knew that the operator (she now tells me this is what she and her family called me during the first hectic day in the hospital) seemed reluctant. The operator was now leading her and Bennick into the only empty cubicle in the MICU.
I have no recollection of what I said, but Anne remembers the exact words. Thinking back on them now, they sound unnecessarily magisterial, but perhaps that was what was needed at the time. Anne tells me I looked directly at her and said, “I’m going to make a command decision,” and then to Bennick, “Mike, come with me.” What I do remember is that Bennick and I went to Grace’s bedside and carefully reviewed the physical exam of her abdomen. Anne tells me we took a good long time to do it, but when we emerged from the cubicle, we were of one mind. Bennick had agreed that we should sit tight.
During my training years, I worked with a surgical resident who had been a star athlete at a large southern university, and he seemed to have a down-home Carolina bon mot for every clinical occasion. He would have said that this kind of decision making was “playing guts football”–we absolutely had to be right. Actually, Bennick and I were taking less of a chance with Grace’s life than some might have thought. She almost certainly would not have survived a third operation, in which I might have been forced to remove all of her remaining small bowel. I was betting that only the mucosa of her intestine was involved in the process of necrosis, and her present benign physical exam meant that she had already marshaled the forces necessary to overcome the infection and heal that layer.
Fortunately for all of us, that thesis proved to be right. By the next day Grace had improved sufficiently so that her breathing tube could be disconnected from the respirator. Twentyfour hours later, in her first fully alert moment since admission, she opened her eyes. Within minutes she saw her mother looking down at her, holding a large card printed with the alphabet, which Anne had made ready for just such use. Grace gestured for the card, and pointing very slowly to each letter, she spelled out, “I have a history exam on Friday.” Eleven days had passed since her first operation, and she had lost every moment of them.
“My mother said, ‘No, honey, that was two weeks ago.’ I felt like ‘Oh, my gosh’–you know, total amazement. Then she asked, ‘How did you make it? You weren’t supposed to.’ And I spelled out, ‘I got my strength from my daddy.'”
The improvement continued, although very slowly. It took almost three more weeks in the MICU before Grace was ready to be transferred to an acute-care floor. She stayed there an additional two months and then moved to the hospital’s rehabilitation unit. She had lost a great deal of weight and considerable muscle mass in her legs, but she knew that everything was recoverable with hard work. She was finally ready for discharge from the hospital 18 weeks after she had entered it.
It would be another four months before Grace regained enough strength to return to college. Her mother considers her graduation two years later to have been the final step in a triumph not only of perseverance and luck but of Bill’s protecting spirit, too. A few hours after Grace’s return to wakefulness on that joyful morning four years ago, a rainbow appeared in the sky, even though there had been no rain. Anne remembers looking at it and being sure it was a good omen.
(*)This woman’s name and the names of her relatives have been changed.
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