The Parkinson’s Patient

In 1817, Dr. James Parkinson, an English surgeon, scientist, and political activist, wrote in An Essay on the Shaking Palsy about a new medical pathology. In this work, he
describes the characteristics of what would later be called Parkinson’s Disease (PD). The essay is worth
examining because it offers a perspective on a disease that we see quite often — PD is one of the most common debilitating neurologic disorders
today, affecting about 1 percent of people over sixty.

Parkinson set out to characterize the illness by doing what a scientist ought to do, observing and taking notes:

The disease is of long duration: to connect, therefore, the symptoms which occur in its later stages with those which mark its commencement, requires a
continuance of observation of the same case, or at least a correct history of its symptoms, even for several years.

The onset of PD is extremely subtle; its initial symptoms are “slight and nearly imperceptible.” Nevertheless, patients generally experience a sense of
weakness and a minor unilateral hand tremor at rest (the typical tremor is exhibited in this video). Soon, “the morbid influence is felt in some other part,” perhaps the leg on the side
of the affected hand. Other symptoms arise over months to years, too, making precise manipulation, for instance when writing, more challenging:

As the disease proceeds, similar employments are accomplished with considerable difficulty, the hand failing to answer with exactness to the dictates of
the will. Walking becomes a task which cannot be performed without considerable attention. The legs are not raised to that height, or with that promptitude
which the will directs, so that the utmost care is necessary to prevent frequent falls.

In addition to falling frequently, patients’ handwriting shrinks in size (this is known as micrographia); they experience difficulty sleeping and increased severity of
tremors (eventually affecting both hands and both legs); the disease even alters speech, causing patients to speak softly (hypophonia); and uncontrolled drooling occurs along with increased muscle rigidity. Patients often feel
frozen in space, trapped by the inability of their muscles to obey their commands.

Parkinson describes the last stages of the disease as follows:

The chin is now almost immoveably bent down upon the sternum. The slops with which he is attempted to be fed, with the saliva, are continually trickling
from the mouth. The power of articulation is lost. The urine and fæces are passed involuntarily; and at the last, constant sleepiness, with slight
delirium, and other marks of extreme exhaustion, announce the wished-for release.

And yet, despite Parkinson’s detailed knowledge of the disease course, there was no real indication as to the etiology or pathology of it. One can sense Parkinson’s frustration with the ignorance of the scientific community:

We are in fact as little informed respecting the nature of the affection, inducing the carious state of the vertebræ, as we are respecting the peculiar
change of structure which takes place in this disease. Equally uninformed are we also as to the peculiar kind of morbid action, which takes place in the
ligaments of the joints; as well as that which takes place in different instances of deep seated pains and affections of the parts contained in the head,
thorax, and abdomen….

As for “the means of cure,” Parkinson writes, “nothing direct and satisfactory has been obtained.” Indeed, he proposed a treatment that seems absolutely
bizarre to us today: drain blood from the upper part of the neck. One theory held that the disease came from irritation of the theca, a covering of the spinal cord, leading to inflammation and pressure. According to Parkinson,
draining the blood could release that pressure and mitigate symptoms.

Though this treatment amounted to very little, Parkinson does conclude his work with some hope:

There appears to be sufficient reason for hoping that some remedial process may ere long be discovered, by which, at least, the progress of the disease may
be stopped. It seldom happens that the agitation extends beyond the arms within the first two years; which period, therefore, if we were disposed to divide
the disease into stages, might be said to comprise the first stage. In this period, it is very probable, that remedial means might be employed with
success: and even, if unfortunately deferred to a later period, they might then arrest the farther progress of the disease, although the removing of the
effects already produced, might be hardly to be expected.

*     *     *

Looking back at Parkinson’s essay with today’s knowledge about the disease, we can say that his descriptions are unusually accurate for a medical text that is two centuries old. In fact, many of the
patients I’ve seen in clinic today with Parkinson’s disease have stories identical to those described by Parkinson. However, there are a few corrections
that we need to make. First, Parkinson neglects to mention the dramatic changes in facial expressions among these patients — a practiced observer can pick out a PD patient
merely by making eye contact.

I saw a seventy-year-old female in clinic with a new diagnosis of the disease. She had the classic hand tremor and muscle rigidity, but I
remember her face the most. It was haunting. She rarely blinked and stared with the utmost intensity, not quite sure when to look away. That small social
grace of breaking eye contact had been lost. The eyes peered, not vapidly, but creepily. They challenged you to speak or break the stare. The whole face
seemed devoid of a crucial aspect of its human expressiveness. I noticed no smile or frown even when I joked around with her. Her expressions contained a strange mixture of repressed
anger and stoicism. Facial signals, emotions, and features are dampened and even nonexistent in PD to a frightening extent. And imagine the emotional pain
that comes with the knowledge that your face publicly separates you from everyone else.

Parkinson also did not know anything about the pathology of the disease. We now understand that the disease can be linked to the death of neurons. Specifically, neurons that release dopamine in the brain in the substantia nigra die off, leading to an overall reduction in dopamine in the brain. The disease
causes symptoms after 80 percent of these dopamine-producing neurons are lost. Why this happens is still unclear — approximately 85 to 90 percent of the cases are idiopathic
(meaning the cause is unknown) and 10 to 15 percent of affected patients have a first-degree relative with the disease (and we’ve identified at least some of the genes that are associated with PD). But there
are interesting non-genetic factors that contribute to the risk for developing the disease. Pesticide exposure and the drinking of well water have been linked to PD (see for instance chapter 77 of the textbook Neurology of Movement Disorders by Haq, Foote, and Okun). And the use of tobacco, bizarrely, has been
inversely associated with risk for the disease.

Thankfully, though, the treatments for PD have improved tremendously over the last few decades. Dopamine agonists and medications like carbidopa-levodopa stimulate
dopaminergic receptors in the brain, freeing patients from their feelings of bradykinesia (slow movement) and rigidity. One patient I spoke with called his
medications “a miracle.”

Deep Brain Stimulation
(DBS) also dramatically improves patient’s symptoms. Neurosurgeons implant a thin electrical wire either in the globus pallidus internus or the subthalamic nucleus — two different parts of the brain — which then connects to a pulse
generator. This generator sends electric pulses into the brain, and symptoms can change almost immediately. I clearly recall my first encounter with a patient who received DBS. In the
exam room, the attending physician increased the voltage going through the generator and the patient’s tremor gradually
decreased until it disappeared. It was absolutely incredible to witness.

There are, of course, side effects to these medications and procedures. Impulsivity is one that I have had a particular interest in: patients on dopamine
agonists and with DBS can take up gambling, excessive shopping or risky sexual activity. Additionally, the medications can cause nausea, vomiting,
dizziness, hallucinations, and constipation. The most serious side effects of a drug like carbidopa-levodopa are dyskinesias, which occur after long-term use. Dyskinesias are involuntary movements: patients writhe sometimes fluidly and sometimes suddenly. An arm shoots up in the air and is forcefully pushed down into
one’s lap; the tongue hangs out of the patient’s mouth and licks the upper and lower lips; the lips smack together uncontrollably; legs kick. The patient
seems to be possessed. Since these are uncontrollable, patients are not only forced to do things they don’t desire but are also faced with
the stigma of their unusual behavior when they leave the home.

Dr. Oliver Sacks, the late neurologist, writer, and professor at NYU, describes one unusual method of dealing with parkinsonian symptoms in his book, Musicophilia. He observes the fascinating, rare, and still mysterious response a particular patient had to
playing music:

If one walked her down the hallway, she would walk in a passive, wooden way, with her finger still stuck to her spectacles…. As soon as she sat down on the
piano bench, her stuck hand came down to the keyboard, and she would play with ease and fluency, her face (usually frozen in an inexpressive parkinsonian “mask”) full of expression and feeling. Music liberated her from her parkinsonism for a time — and not only playing music, but imagining it.
Rosalie knew all of Chopin by heart, and we had only to say “Opus 49” to see her whole body, posture, and expression change, her parkinsonism vanishing as
the F-minor Fantasie played itself in her mind.

Even with all these treatment options, nothing halts the progression of the disease. Many patients I have met in the neurology clinic have had PD for
almost twenty years, and their symptoms severely affect their lives. They have dyskinesias; their medications last for a much shorter period of time than
they did years ago; they use a wheelchair; some of their voices barely rise above a whisper; and some have drool constantly leaking from the corners of
their lips. Modern therapeutics hold the symptoms at bay for only so long.

But perhaps we, like Dr. James Parkinson, can hold out some semblance of hope. In an

article in the New York Times in February 2015, Jon Palfreman, a professor of broadcast journalism at the University of Oregon and author of the book Brain Storms, described his own experience with PD. He explains that one biotech company is now
experimenting with genetically engineered compounds from viruses to neutralize specific proteins that build up in the brain and may be implicated in PD. This is a
very interesting development and one that we ought to keep our eyes on. Clearly, we have come a long way from draining blood in
order to treat PD. But we are also far from being able even to slow it down, much less stop it.

Denying and Romanticizing Mental Illness

Reactions to mental illnesses or disorders vary. (I wrote about some of them
in a 2012 essay in
the pages of The New Atlantis
.) I’ve noticed, however, that some of
the responses among physicians differ from their reactions to other medical
pathologies. There are several reasons why this might be the case, having to do
with the fact that psychiatric pathology is far more difficult to comprehend
and thus more easily misunderstood than the pathology of other diseases we
usually associate only with the body, such as cancer or pneumonia.

Image via Shutterstock

Unlike bodily illnesses, mental disorders primarily affect patients’
emotions and actions. As a consequence, our implicitly held beliefs about human
behavior, especially our views of free will, can color how we react to people
suffering from mental illness. A strong belief in free will helps validate a
sense of justice and morality: generally speaking, people choose their actions
and are thus responsible for them. So if a person with a psychiatric diagnosis
commits suicide, kills another person, or runs onto a highway screaming at
imaginary beings, it is easiest to hold the person morally responsible if we
believe he acted freely. Or, in the case of suicide, we might say that the
person “should have done” this or that to make life better: he should have seen
a psychiatrist, or he should have realized how wonderful his life was. We want
to hold the person responsible for his actions rather than deal with an illness
that so often makes people completely irrational and incapable of choosing
their actions.

Additionally, the fact that most medical pathology is visible to us makes it
simpler to understand. In the emergency room we easily see the
effects of a chopped-off leg
. We can feel
a large spleen
, hear an irregular heartbeat, or view an abnormal lab
finding. Psychiatric pathology, however, is not palpable in the same way. With
schizophrenic patients, for example, we cannot see the beings they see. We do
not inhabit the world they inhabit. Nor can we easily visualize their brain
chemistry. It is as if we are looking for the culprit in a pitch-black world.

With these difficulties in understanding psychiatric disease, some
physicians, patients and observers dismiss mental illness as a product of the
weak-willed or obstreperous. Or they romanticize it, focusing on the
interesting and provocative aspects of mental illness. These are minority
views, but they are not without influence — which is unfortunate, because if
they are followed, they can lead us to deny treatment to those who need it.

Dr. Robert Youngson, a British doctor-turned-author,
is an instructive example of someone espousing dangerous views of this sort. In
his 1999 book, The
Madness of Prince Hamlet and Other Extraordinary States of Mind
, he
writes:

Doctors and lay people talk, quite casually, of ‘mental
illness,’ the implication being that conditions like schizophrenia are much the
same as conditions like tuberculosis or meningitis. In fact, they are not.
Mental disorders have hardly anything in common with organic physical
disease…. The observable changes occurring in the body — including the brain —
in the course of organic disease are called pathology. So far as current
research can demonstrate, there are no corresponding organic changes causing
schizophrenia.

Dr. Youngson goes on to assert that we classify schizophrenia as an illness
in order to maintain a society of “normal” people. He claims that British
psychiatrists “carry out a tidying-up function much more closely equated with
that of the police and the judiciary than with that of the medical profession.”
Then he asks, disturbingly, whether there is “really any difference between
what happened in Russia, when political dissidents were deemed to be mad and
were incarcerated in mental hospitals, and what happens in Britain and America
when people who do not conform to current social mores are legally certified
and locked up.”

For support of his position, Dr. Youngson refers the reader to the work of the
late Thomas Szasz, who,
as a professor of psychiatry at the State University of New York Upstate
Medical University at Syracuse, New York, published a number of controversial
books arguing that mental illness is a myth. The status quo of medical practice
that considers mental conditions like schizophrenia as illnesses, Dr. Youngson
writes, is a “convenient fiction about a state of the mind.” (A critical essay
about Dr. Szasz appeared
in The New Atlantis
in 2006.)

But Dr. Youngson’s premise, that schizophrenic patients lack cerebral
pathology, is wrong. We know, for example, that patients with schizophrenia
have a disruption in certain neurotransmitters in their brains. Dopamine is
increased in patients with schizophrenia, and this possibly relates to the
effects of genetic alterations. There are specific (and multiple) gene
variants associated
with this disease. Furthermore, medications do sometimes
work, as I explained in another
recent post
. They inhibit dopamine’s actions on certain receptors in the
brain and, despite their side effects, can rid patients of awful and
belligerent visions and voices. If there were truly no pathology, why would
blocking receptors work? If there were truly no pathology, why would there be
significant elevations of certain neurotransmitters? There is indeed pathology
here — Youngson apparently just chooses to ignore it because it contradicts his
preferred explanations.

Dr. Paul McHugh, a
professor of psychiatry at Johns Hopkins University School of Medicine, wrote
about this particular topic in a 1995
issue of The American Scholar
. He argues that “the context of a life
should not be confused with the cause of all mental disorders or made the sole
focus of therapeutic attention as though guidance were always synonymous with
cure.” Unfortunately, “the assumption that something must have happened
if a mental disorder is present has provided an entry for zealots and
charlatans into psychiatry.” If we believe that mental disorders like
schizophrenia or depression are always rooted in life experiences and never in physical
pathology, we can easily misunderstand patients, their families, and the
possibilities for therapies. Not only is Dr. Youngson’s view wrong; it is injurious
to those whom it is meant to help.

Dr. McHugh also addresses the romanticization of depression in a 2005 Commentary
essay
(which I quoted in another
recent post
). McHugh reviews Andrew Solomon’s book The
Noonday Demon: An Atlas of Depression
(2001), in which Solomon writes
about his own experiences with depression. Solomon, McHugh argues, romanticizes
depression by making it seem mysterious like sex and curable most effectively
by a sheer act of will. Similar to Dr. Youngson, Solomon mischaracterizes a
terrible sickness. As McHugh writes,

the particular disorder at issue here is a disease,
an affliction that disrupts a natural function of emotional control. This
disease, like other diseases both physical and mental, renders the afflicted
person impaired in ways that are essentially the same from case to case….
[Depression] is not a you but an it, a thing unto itself and not
just the dark side of human emotion.

Again, depression, like schizophrenia, clearly involves pathologies in the
brain. It is a real disease that tears apart human lives.

What’s so striking about these cases is that those who are denying or
romanticizing mental illnesses are familiar with the diseases. Surely, Dr.
Youngson saw schizophrenics in his family practice. Solomon experienced
depression himself. And Dr. Szasz also saw patients with these disorders.
Seeing or experiencing the illness, then, is not enough to understand it. An
understanding of disorders of the mind requires that we not only learn about
symptoms, social context, and pharmacology, but also that we understand the
underlying pathology.

A World of Nightmares

O Rose thou art sick.
The invisible worm,
That flies in the night
In the howling storm:

Has found out thy bed
Of crimson joy:
And his dark secret love
Does thy life destroy.
—William Blake, “The Sick Rose

As I rotate through psychiatry, I have noticed that certain facial features and dispositions uniquely characterize diseases. I wrote this in a previous post about a depressed patient:

Corridor of psychiatric hospital Saint Anne, Paris.
By Jules Gaildrau, 1868.
Image via Shutterstock

I need not speak to him to know he is not well. A simple glance tells me all. The patient’s unshaven face wears no smile and, at once, no frown. His vapid
gaze lingers longer than it should on various objects or people or nothing at all…. His visage is neither pale nor tan nor some variation on one of these —
it is like a bare tree on a late and chilly fall day. His brow barely responds even when he speaks and his susurrant replies to our questions are scarcely
audible over the ambient sounds in the room.

Much of this description also applies to a schizophrenic patient whom I saw, a young adult in his twenties whose life had been thrown into disarray by psychiatric disease.
But there are some differences. The schizophrenic patient was far more active than the depressed patient, rocking back and forth the way some Orthodox Jews shuckle when they pray. And while his façade was inexpressive, we could tell when speaking with him
that his mind was as active as ever. He stared, not lazily or vapidly, but intensely, as if analyzing each of our movements and expressions.

The hospital staff had taken the shoelaces out of his sneakers so he could not use them to strangle himself. He was not allowed to shave with a razor
because of the risk of suicide. Not being able to grow a full beard, a five o’clock shadow grew only over his upper lip. His fingernails were cut and
neatly blunted (again, a safety measure) and he had been wearing the same clothes for weeks. When he did get up, he simply paced around the psychiatric
unit, occasionally muttering to himself as he stared at the ground. He ignored everyone else around him even though many of the other patients were manic,
depressed, or bombastic. He believed that aliens were coming down from outer space and putting thoughts into his head; other ghost-like creatures told him
to do “violent things” to himself. As he rocked back and forth he seemed to be entreating the voices to go away.

It is tempting when hearing descriptions like this to laugh. The claims are so absurd and so beyond the realm of normalcy that they drag us into the land
of poorly made sci-fi movies. However, patients with schizophrenia sincerely believe in these sorts of delusions and hallucinations.

Schizophrenia
usually occurs in younger adults and involves paranoid delusions, hallucinations (mostly auditory), social withdrawal, disorganized speech and other
symptoms. Here is a video of a schizophrenic patient which gives a sense of the illness. The
voices which patients hear demand, in many cases, that the patient hurt himself, leading eventually to suicide (the voices more rarely implore the patient
to hurt others). Patients have no control over these and don’t comprehend that they are fictitious. These victims are secluded from reality and trapped by
their minds.

The pathophysiology of this disease, as is true of depression, is not completely clear. But we do know that patients have an unusually increased amount of dopamine within the brain. Additionally, the brains of persistent schizophrenics shrink and the ventricles of the brain, which contain cerebrospinal fluid, enlarge. The etiology of schizophrenia is also complex, with
genetic and environmental factors both presumably playing a role

Abandoned building from the Manteno State Mental Hospital,
Manteno, Illinois.
Image via Shutterstock

The prognosis can be devastating. In this case, a young adult in the middle of a budding career in academia could no longer work, attend university, or interact
with fellow human beings. Fearful of violent outbursts his family had no choice but to place him in a psychiatry ward. According to the numbers, this is not a singular outcome. Only 15 percent of patients with the diagnosis eventually function again at their pre-illness level, while one third are
severely and permanently debilitated. About 80 percent of patients with schizophrenia at some point in life also experience major depression, and substance abuse plays an important role in about 50 percent of patients.

The prognosis is not necessarily better for those who take antipsychotic medications, which block dopamine receptors in the brain. The treatments
themselves can affect the patient negatively. Side effects from antipsychotic medications like OlanzapineChlorpromazineClozapine, and Risperidone include diabetes, decreased white blood cell counts, myocarditis (inflammation of the heart), tic-like
movements, sedation, and neuroleptic malignant syndrome (a syndrome consisting of
fever, altered mental status, and muscle rigidity). No wonder, then, that patients frequently dislike taking their medications.

The patient we saw on the psychiatry ward did not respond to any of these pharmaceutical options. In fact, no matter what medication he took, the voices
continued to haunt him, telling him to do terrible things to himself. In an act of desperation we turned to electroconvulsive therapy (ECT, which I
wrote about here). After the first couple of treatments,
the patient improved slightly. But the illness quickly came roaring back. The attending physician proposed other combinations of medical therapies and more
ECT. But at this point, we persevered in searching for treatments only to delay lifelong institutionalization and a helpless retreat to a dark world of nightmares.

On Evidence-Based Medicine

Physicians throw around the term “evidence-based medicine” a lot. Whether it’s an antibiotic, IV fluid, or blood-pressure pill, the decision about how to
use a drug often comes down to the question: is the treatment evidence-based? But what does that mean? Evidence-based medicine is “the conscientious, explicit, and judicious use of current best evidence in making decisions” about patient care. This definition suggests that clinicians or researchers fastidiously tested and confirmed the effectiveness of an intervention with a robust, replicable, and
accurate scientific study.

Designing a valid study, however, is difficult because there are many potential biases that can render its conclusions inaccurate. Here are some examples:

  • Selection bias occurs when subjects are assigned in a nonrandom manner to different study groups.
    If a physician runs a trial to test the efficacy of a drug he may put those who have a better prognosis in the treatment group, as opposed to the
    non-treatment group. Consequently, scientists can claim this new treatment is successful even though it was tested on those who were most likely to improve
    anyway.
     
  • Sampling bias, where subjects chosen for the study do not represent the general
    population, can mean that a study’s findings do not apply to the general population.
     
  • The Hawthorne effect arises when subjects change their behavior because they know they’re being
    watched by a researcher or physician.
     
  • Confounding bias describes a situation in which one factor can
    distort the effect of another. If a researcher studies the effects of alcohol on health but ignores the fact that many people who drink alcohol also smoke, alcohol
    will appear to have a worse effect on one’s health due to the consequences of smoking.
     

Another kind of bias has been in the news a lot recently with regard to prostate-cancer screening.
Here’s how Dr. Michael S. Cookson, a urologist at Vanderbilt University, describes this kind of bias:

Lead-time bias suggests that the natural history of the disease is not truly affected by screening. For example, a patient may be diagnosed with prostate
cancer at 50 years of age through … screening. He then undergoes treatment but ultimately progresses and dies at 60 years of age. Accordingly, the same
patient without screening develops symptomatic bony metastases [late stage cancer] at age 58, undergoes treatment with androgen deprivation therapy, and
dies at age 60. Thus, in this theoretical scenario, even though he was diagnosed 8 years prior through screening, his death was not affected by screening
or early detection.

In other words, early detection of cancer makes it seem as if your lifespan is increased simply because you know that you have cancer for a longer period
of time. But you don’t necessarily live longer because of that.

Image via Shutterstock

There are many other kinds of bias but the descriptions above give a sense of how difficult it is to design experiments without it. The most powerful
studies account for bias with a double-blindedrandomized, and controlled trial. Participants and researchers are both blind in that they do not
know who is getting the placebo treatment and who is getting the trial treatment. Participants must also be randomized to the treatment group or the
placebo group — that way, there is no selection bias and there is less confounding bias. Controlled just means that there must be a control group, which is
a group that does not receive the disease therapy or that receives the current best therapy for the disease. Researchers can then compare the effectiveness of
the newest therapy to the current best available therapy. Another way to avoid confusing results is to use crossover studies, where a patient serves as his or her own control. The patient receives the
real therapy for a given period of time and then receives the placebo for a given period of time thereby eliminating confounding bias.

A statue of Avicenna in Tajikistan
Nikita Maykov / Shutterstock.com

Interestingly, this approach to scientific studies, albeit a much less sophisticated version, dates back to the eleventh-century Islamic philosopher and
physician, Avicenna. In his Canon of Medicine, a
multivolume medical encyclopedia, Avicenna expanded upon the work of Galen, the ancient Greek physician. In her 2008 article “Islamic Pharmacology in the Middle Ages: Theories and Substances,” Danielle Jacquart explains that Avicenna endorsed
the concept of using drugs based on past results of experiments:

As for the powers only known through experiment, these were not deduced from the qualities or the appearance of pharmaceutical ingredients, but they rather acted through their whole form or substance. Their action could only be revealed
by an experimental test. Yet this did not mean that ordinary physicians themselves had to undertake such experiments. Rather, they relied upon experiments
carried out by their predecessors.

Similarly, when today’s physicians choose, say, an antibiotic for a bacterial infection, they rely upon experiments carried out
by their predecessors.

When I started medical school, I assumed that everything in medicine was evidence-based; that scientists rigorously studied and validated every treatment.
After all, we should not treat a patient with a drug unless we know it works. But it turns out that there is not always evidence to support every decision physicians make.
Perhaps a study has simply not been done or the evidence collected was equivocal or inconclusive. Or perhaps some real-life situation has arisen that is complicated in ways that could not possibly have been tested in an experiment. In these cases, physicians must base their decisions on
experience.

Let’s take the example of IV fluids, which are a basic staple of medical care, as I’ve mentioned in multiple posts. One would think that the data would be fairly
clear on which types of IV fluids are best. Unfortunately, it’s not at all evident. Some background: there are two major types of IV fluids, colloids and crystalloids. Crystalloids contain water and electrolytes that are similar to those circulating in the blood. Some examples of these are Lactated Ringer’s and Normal Saline. Colloid fluids contain water and electrolytes, too, but they also contain osmotic
substances like albumin, which draw fluid into the vascular space. Fluid in the body can be inside the blood vessels or outside the blood vessels, and
colloids keep fluids in the vessels.

Ostensibly, colloid fluids ought to work better in certain situations. For instance, when a patient has very low blood pressure, the way to increase blood
pressure is to increase fluid within the vasculature. However two studies, one in the New England Journal of Medicine in 2004, and one in the Annals of Internal Medicine in 2001, concluded that there were no
significant differences in mortality in various medical situations when using one type of fluid versus the other. So, barring significant differences in
cost, which fluids does one use in the hospital when patients need hydration or increased blood pressure?

Image via Shutterstock

Given that the evidence is unclear, we use what our mentors use. During surgery rounds, for example, I asked “why are we using Lactated Ringer’s (LR)?” A resident replied that the evidence was inconclusive and the attending used LR so he used LR. Until we have better evidence, this seems completely
legitimate even if it makes us uneasy because there’s no clear consensus. Furthermore, this demonstrates that though certain ideas may make sense in theory, they
fail when standing against the test of scientific rigor. Thus, evidence-based medicine also requires open-mindedness.

Let’s also look at an example of how evidence-based medicine changes medical practice rapidly on a day-to-day basis. This past summer, the treatment for Parkinson’s disease (PD), a disease of certain neurons in the brain, underwent a change. Previously, movement disorder neurologists
recommended dopamine agonists as a first-line treatment for the disease. The alternative is carbidopa-levodopa, a medication that is more effective at controlling PD symptoms. However,
carbidopa-levodopa causes more side effects, such as dyskinesias, or compulsive and uncontrollable
movements (some of these can be irreversible), the longer one takes the medication. And, given that patients with PD can live a long time, neurologists
wanted to put off using it so that patients would not experience these effects so soon after starting medication.

But this past June, a study in The Lancet compared starting a dopamine agonist with starting carbidopa-levodopa in patients with newly diagnosed, early PD. And the researchers found that there is not a significant difference in patient-rated mobility scores (a fancy way of saying movement difficulties as well as quality of life) when
starting with levodopa rather than dopamine agonists. I observed the direct practice changes as a result of this study. In the neurology clinic, the
attending, after reading this article, changed the way he spoke to patients with newly diagnosed PD. Instead of saying that it is better to avoid
carbidopa-levodopa first, he told patients that it was their choice what drug they wanted to start taking. This is a wonderful example of why
evidence-based medicine and research is so important and how it can affect the practice of medicine — very concretely, very directly, and very soon after the research is published.

PCP Overdose in the Emergency Department

There was a crowd of security guards, physicians, and nurses in an ED room. The patient inside squirmed and writhed on the stretcher while sweating
profusely, soaking his clothing and the hospital bed. Though slender
and slightly cachectic, the patient had fought off the security
entourage multiple times, like a snake slipping from their grasp,
violently twisting and
turning his body.
As he struggled, a nurse tore off the sleeve of the patient’s dark blue jumpsuit in order to get IV
access and administer medications. The 26-year-old man kept his eyes wide open and stared at the ceiling, which made it easy for me to see his
tremendously large and dilated pupils, empty and frightening at once. Seven security guards held him down when the nurse started the IV.

All this went on for about an hour, and as the time passed the monitor above the patient’s bed, which projected his temperature, blood pressure,
and heart rate, changed. The temperature rose: 99…100…101…102…. The heart rate went up to 120 (a heart rate above 100 is considered fast and is called tachycardia). The blood pressure, too, rose
to 160/100 (normal is approximately 120/80). And the patient continued to sweat and writhe. As he exerted himself, his cells produced molecules necessary
for energy, a process which generates heat and increases heart rate and blood pressure.

The patient was experiencing a PCP, or Phencyclidine, overdose. PCP is a drug that was developed in the early twentieth century as an anesthetic. However, the drug also caused
delusions, anxiety, and agitation and was eventually discontinued because of these side effects. In the 1960s, many drug addicts used it illegally in pill
and smoke form. Because PCP acts partially among dopamine receptors in the brain it can cause both
euphoric and, sometimes, psychotic and violent behavior. On medical licensing exams we are expected to recognize the typical PCP symptoms: violent behavior, dilated pupils, profuse sweating and
tachycardia. Additionally, the drug can cause seizures, hyperthermia (very high body temperatures), severe hypertension or high blood pressure – which can
damage the eyes, kidney, and brain as well as other organs – and rhabdomyolysis,
the breakdown of muscle, which can cause further kidney damage. Unfortunately, no medication exists to reverse the drug once it’s been ingested and
treament primarily targets only a patient’s symptoms.

The resident started treating this particular patient with a type of benzodiazepine, a sedative drug
that acts on receptors in the brain to inhibit anxiety and agitation. This class of medications is frequently used for patients who have prolonged
seizures, severe anxiety, or difficulty sleeping. After multiple doses of benzodiazepines over the course of the hour, as well as IV fluids to counteract
possible rhabdomyolysis, the patient continued to fight and his temperature continued to rise. It was almost as if he had not been given any medication at
all.

At this point, the only option was to use drugs to knock the patient out completely, or paralyze him, so that he would stop struggling and his vital signs would
normalize. To ensure the paralytic drugs do not prevent the patient from breathing, a tube is placed down his throat, keeping the airway
open. The resident injected the paralytic into the IV, and once it took effect he
used a glidescope to pry open the patient’s throat in order to visualize
the airway. Then, he stuck a short plastic tube down into the trachea. The hollow tube allows oxygen to pass into the trachea thus acting as the patient’s
mouth and throat. The tube is then connected to a ventilator that pumps air into the lungs and thus keeps the patient oxygenated. A great video
of this procedure with narration is available here.

This last ditch effort worked. Over the next few hours, the patient’s temperature and blood pressure dropped and he avoided the dangerous sequelae of his
toxic ingestion. Although curious to see what would happen to him next, my rotation ended before the patient was admitted to the hospital and I went home
to sleep off the overnight shift.