Krishna Acharya, Joanne Lagatta, Steven Leuthner
A baby is born with severe muscle weakness, and is unable to breathe on his own. He is dependent on a ventilator. He does not respond to stimuli. He likely has a severe neuromuscular condition which cannot be cured. Doctors order diagnostic tests, but parents struggle with the thought of their child suffering while they wait for test results. Doctors revise their diagnostic strategy to provide a timely and meaningful prognosis in accordance with parental goals. This narrative discusses issues of diagnostic uncertainty and the value of relying on clinical gestalt when trying to prioritize medical tests for a sick patient.
To become comfortable with uncertainty is one of the primary goals in the training of a physician.
—Sherwin Nuland, Surgeon and Bioethicist
The nurse called me to the bedside for the new admission. “The parents of the new baby are here, and they are really upset.”
Great, I thought: angry parents.
I quickly reviewed the notes I had taken from the overnight fellow: This was a full-term male infant who had been transferred to our NICU for severe hypotonia at one day of life for further evaluation. Mom had felt little fetal movement since 32 weeks and had polyhydramnios, suggesting that the baby was not swallowing the amniotic fluid in utero. Parents were both healthy, and had two other healthy children. Baby was delivered vaginally, and was apneic and hypotonic at birth. He was intubated at birth and transferred to the NICU. On exam, he was noted to be limp with limb contractures and a flat face. He had no reflexes.
He was placed on a ventilator. A brain and spine MRI were normal. Overnight, the on-call team had taken his breathing tube out as he was on the lowest ventilator support, but the tube had to be replaced within a few hours. As I walked up to the family, I was already tired, dreading the conversation to be had with them. I introduced myself as the neonatology fellow who was assuming care of their baby, and explained the events of the night.
“J was taking a lot of breaths over the ventilator, and his carbon dioxide level was very low. A low carbon dioxide level when someone is on a ventilator often means that they may be ready to come off and breathe on their own. The overnight team wanted to give him a trial off the ventilator to see if he would be able to sustain his breathing. He had been breathing on his own, but after a few hours, he was tiring out and struggling to breathe, so they had to put the breathing tube back in.”
Mom and dad looked tired, not unlike other parents in the NICU. They also seemed frustrated, and were trying to hold back tears. “Why did they put they put the breathing tube back in?” Mom asked, without making eye contact. “If we knew he was going to get it back, we would have said no.”
This was not what I had expected to hear. I had often been asked by the parents of a sick baby in the NICU if more could be done for their child. Often, I had sensed myself getting impatient when parents held on to the hope that their child would recover from an irreversible illness, against all medical judgment. I could understand why, in this case, parents would be upset that the intubation had been done, and they had only been informed about it after the fact. However, I had yet to hear a family ask me why we had intubated their child when it was medically necessary, only why we hadn’t informed them about it sooner.
“I am sorry this happened without your knowledge, and that we did not communicate this with you,” I said.
“He is not moving much. If he doesn’t have something that can be treated or get better, we want to stop. We don’t want him to suffer,” dad added. “We wish the doctor hadn’t put the breathing tube in back in the delivery room. If he was destined to die, we wish it had happened then. That would have been shorter, and less painful, for him than all this stuff that he is going through now.”
This was all new information to me. I had assumed that since the baby had been transferred for further diagnostic evaluation, his parents would want to pursue all possible medical interventions until the diagnosis was reached. Isn’t that what most parents ask?
“I am so sorry. Our team was not aware about your feelings regarding continuation of intensive care. You are an integral part of all decision-making for J. We want to know what your goals for him are, so we can provide the best possible care for him. Could you tell me a little more about what you have been told and what your expectations are from us?”
“We were told during the pregnancy that since J isnot moving a lot or swallowing amniotic fluid that hemay not survive. We want to know if he has anything that can be treated or that will get better. If he is not going to get better from this, we want to take him off the ventilator and let him pass peacefully.”
I reassured them that our team would do their best to give them more information about his condition, and we would work with them to figure out the best possible treatment course.
I scratched my head, thought of the differential diagnoses, trying (and failing) to remember theelements of the reflex arc, the neural pathway thatruns from the nerves in the various parts of our body, to the muscles and all the way up through the spineto the brain. A baby could be floppy due to a problemin any one of the many junctions along this pathway. Whatever he has, it can’t be good, I thought to myself.
I reviewed the case history with my attending, and explained my sense that this family was really struggling with the baby’s condition, and wanted quick answers. In all honesty, we hadn’t gotten off to a good start with these parents, and they were probably feeling like they wouldn’t be included in the clinical decision- making. We agreed that we should promptly consult the neurology and genetics team, and then sit down with the family to discuss diagnostic options. In the meantime, J’s parents agreed that he should remain on the ventilator until we had a tentative plan of action. However, they made clear that they did not want him to be on long-term ventilation. Their goals were for him to be able to interact with others, to be able to do things other kids do, and to not be completely dependent on others for his care.
We consulted the neurologists. In their opinion, J likely had a congenital myopathy, but other diagnoses such as congenital muscular dystrophy, spinal muscular atrophy, congenital or transient myasthenia gravisa and Prader-Willi syndromeb were also possible. They agreed that J’s presentation was severe, but they wanted to reserve prognostication until further testing was done. They recommended an electromyogram (EMG) and a muscle biopsy, as well as genetic testing for spinal muscular atrophy (SMA)c and Prader-Willi syndrome, and acetylcholine receptor antibody testing for myasthenia gravis. We consulted the genetics service, who added X-linked myotubular myopathyd to the differential diagnoses, a condition for which a new gene therapy in dogs has shown remarkable promise, but is still in experimental stages and not FDA approved for human use. A muscle biopsy would diagnose this condition.
Our team considered the following questions in ordering diagnostic tests: Which, among the conditions considered in the differential diagnoses, is treatable or reversible with time, or has a favorable prognosis? What is the likelihood that this baby, with his severe presentation, has this condition? Which tests are invasive and potentially avoidable?
Following discussion with the specialists and the family, we agreed that the only potentially treatable condition with a favorable prognosis was congenital myasthenia gravis. The test for this condition was ordered but results could take up to a week. An EMG was also done but results were inconclusive. Gene testing for Prader Willi and SMA was sent but would take weeks to return. We offered a muscle biopsy to the parents. In the meantime, J’s clinical condition was unchanged, and he remained on the ventilator. Nasogastric feeds were started, and parents were encouraged to hold and bond with him. Comfort measures were optimized, and the family was moved to a more private room.
As the days went by, we sensed the parents’ frustration and sadness with their child’s condition, and their struggle to make the best decision for their child. Although they were certain they did not want prolonged aggressive interventions for J if he had an incurable disease, they were conflicted about withdrawing life-sustaining interventions if there was a chance he could recover. Every day they would ask, “Do you think he is getting better?”
No, he was not getting better. His clinical exam was unchanged, and no one on the medical team thought he could survive without a long-term ventilator.
We reconsidered our diagnostic strategy: if their baby had myasthenia gravis, then the treatment for this condition would be pyridostigmine (an acetylcholine esterase inhibitor), which can be given through a feeding tube, and should show us some improvement in symptoms within a few hours of administration. Even though pyridostigmine challenge is not normallyused in babies because of the difficulty in measuring neurologic exam changes, could we attempt it anyway to see if it would help this infant with independent respiratory effort and movement? This wouldprovide an answer in a more time efficient mannerfor the only disorder with a favorable prognosis. The family agreed. A physical exam was performed by the neonatology and neurology team 3 hours after medication administration but showed no change. The parents also agreed that J was the same.
The next day, following this test, dad said to us, “We can’t do this any longer. We want to take him off the ventilator. He still isn’t moving or breathing on his own. He has had enough done to him already.”
J was extubated in mom’s arms soon after and died within minutes of this event. He was 7 days old.
As physicians, we often feel obligated to discover a diagnosis before we can determine prognosis with any level of certainty. This is for good reason. Discovering a diagnosis allows us to offer appropriate therapies, and indicates a prognosis [1,2]. Indeed, medical training is steeped in the art and science of discovering a diagnosis, and doctors are trained tofirst, recognize a disease, and then, to prescribe (orproscribe) treatment . This obligation is particularly acute when withdrawing life-sustaining intervention, as in this case. If a patient has a diagnosis which can be treated with the expectation of a ‘good’ outcome, then failure to find the diagnosis and provide its treatment could prove catastrophic.
Diagnosis, however, is a means to optimizing prognosis, not an end in itself. Ethical decision making should be based on prognosis, not diagnosis. Determining a child’s best interests means helping a family determine the meaning of a prognosis given their values and perspectives. [4,5] In addition, many diagnostic tests are invasive and painful, results take a long time to return, and maynot be completely definitive. Thus, the burdens and limitations of testing may outweigh the benefits ofdiagnostic clarity.
In most instances, the problem with centering our ethical decision making on a diagnosis is that each diagnosis contains a range of prognoses, which complicates decision-making about withdrawing intensive care intervention. In this case, the opposite was true. We had a range of diagnoses, but nearly all of them had a similar prognosis. The infant presented with a disease that was severe, began early on in life, and had an unrelenting clinical course. In such cases, a ‘diagnostic category’ (such as myopathy) and its prognosis were implied based on the severe clinical presentation. Indeed, pursuing invasive diagnostic tests for a condition with a predicted poor outcome arguably violates the ethical principle of nonmaleficence, because the potential harm involved in diagnostic testing (for example, general anesthesia for a muscle biopsy) may outweigh the benefits of such testing (i.e. obtaining a diagnosis).  A baby who has severe hypotonia with minimal movement, has never independently breathed on his own, and has failed attempts at extubation multiple times, is certain to not survive without long-term ventilation. These predictions are true regardless of the exact neurologic condition. Is it then necessary to wait for diagnosis if the prognosis is clear? Shouldn’t the family’s need for certainty regarding prognosis weigh at least as heavily as the physician’s desire for diagnostic clarity?
In this case, the parents indicated they considered a need for long-term ventilation for their child to be an overly burdensome quality of life. This provided the meaning of the prognosis. They struggled with concerns of their infant suffering, yet also not wanting to stop if there was a reversible process. Indeed, some families may not want to wait for the final diagnosis if all possibilities considered in the differential diagnoses have similarly poor prognostic outcomes, especially if the tests involved are invasive. Rather, they may be interested in ruling out any possible favorable diagnosis, so they can make decisions about continuation versus withdrawal of care. In this case, the medical team and parents recognized that all that was needed to help make a decision was to rule out the one disorder, myasthenia gravis, because that condition alone would not require long-term ventilation. This was the only certainty the family needed. Once the baby did not respond to that one test, the prognosis and meaning of that prognosis for the parents became certain enough to make a clinical decision.
That doesn’t eliminate our obligation to continue searching for a final diagnosis for reasons other than describing the already certain prognosis. Confirming the diagnosis for the family allows the medical team a chance to continue supporting a family even after a patient’s demise, connecting them to family supports and ongoing research efforts, and helping to guide reproductive decisions in the future. The burdens of continued therapy, however, are not always worth invasive measures while alive or waiting for final results before withdrawing intervention.
Physicians are trained to recognize patterns of diseases, consider possible diagnoses, achieve a diagnosis, and provide a prognosis. But, often we get too caught up in ordering one diagnostic test after another, checking off the boxes for the tests which we ‘must’ do, forgetting to ask ourselves what prognostic information the results would yield beyond what we already know from the patient. [7,8] Some clinicians are also reluctant to discuss prognosis with parents in cases of critical illness, where communication is essential.  Coupling a prognosis with an understanding of parental goals helps inform it’s meaning, thus guiding decisions. Often, our clinical gestalt about the big picture prognosis can provide information that is more meaningful to families than any test results, such as fora specific neuromuscular disease. There are degreesof uncertainty in almost everything we do in medicine, but some outcomes are less uncertain than others. When we explain the purpose of diagnostic tests in the context of our clinical impression in an open and honest way, we better support families in their decision-making for their loved ones.
The findings of J’s autopsy were consistent with nemaline rod myopathy. Gene sequencing revealed a mutation in the ACTA1 gene, which is associated with nemaline myopathy. The disease’s severe form presents in the neonatal period with severe hypotonia, arthrogryposis, and respiratory insufficiency. No treatment is currently available. Results for SMA and Prader-Willi were negative.
Krishna Acharya MBBS, MPH
Assistant Professor, Division of Neonatology
Department of Pediatrics
Medical College of Wisconsin
Joanne Lagatta MD, MS
Associate Professor, Division of Neonatology
Department of Pediatrics
Medical College of Wisconsin
Steven Leuthner MD, MA
Professor, Division of Neonatology
Department of Pediatrics
Professor of Bioethics
Medical College of Wisconsin
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