Stereochemistry

I like to be reminded from time to time that I have only just scratched the surface. It helps put things in perspective, and I find the realization of depth to be an exciting thing. It is a major part of what I enjoy about this job, that each day holds the opportunity to learn something new, and that each call holds the potential to reorient my view upon everything else. Lately however, I’ve found these lessons coming from a different source. My lectures and laboratory sessions at school are slowly transforming from dull academia into practical application, and I’ve relished a few opportunities to take new depth with me from the classroom to the job.

Organic Chemistry is a beautiful science. It is famously difficult, the “weed out” class for pre-medical students everywhere, and this semester has taught me exactly why. It is a science that requires a particular kind of continuous knowledge, applied together in the assembly of functional chemical compounds. To understand organic chemistry is to understand a particular set of tools that are used to create highly specific, exotic chemicals out of cheap and common starting materials. The process is often arduous, but the fruits of this labor are the fuels and medicines that shape our lives today. There is good reason people have put such work into developing our understanding of this science.

I have been lucky to associate some of this science with my work on the road. These studies have taught me about the importance of detail. To know a thing is to understand how and why it behaves the way it does, to understand it from every angle. This kind of scientific intimacy brings to light exactly how delicate our tools are, and how specifically they are engineered.

Above is a drawing of the chemical structure of epinephrine. These specific orientations of carbon, oxygen, nitrogen, and hydrogen might seem like unnecessary detail, but this structure holds within itself a real power. My studies have taught me how to pull that flat drawing out into three dimensional space, to give life to that compound and make it real.

That drawing above isn’t just epinephrine. It is more specific than that. The forward orientation of the hydroxyl group (the “OH” near the top) is particular to this form of the compound, and is specifically named (R)-(-)-Epineprhine, or Levo-rotary Epinephrine. This is to differentiate this particular orientation from its isomeric sister: (L)-(+)-Epinephrine (Dextro-rotary Epinephrine) in which the “OH” points in the opposite direction. See, epinephrine has a point of rotation (a point of “chirality”) that enables the molecule to exist with the same chemical formula, but slightly different three-dimensional orientations of the components. The phenomenon is called stereoisomerism, and it is more than just academics. A small change in the three dimensional shape of Epinephrine is what differentiates the biologically active from the not biologically active. Levo-rotary Epinephrine is the vaso-constricting, heart-stimulating, bronchi-dilating drug we are familiar with. Dextro-rotary Epinephrine, however, is essentially inactive. Our bodies, in all their wisdom, produce an enantiomerically-pure product: the levo-rotary epinephrine only.

Stereoisomers such as Epinphrine can be separated into their individual isomers (“enantomers,” in this case), or can be combined together into a mixture. When enantomers are combined together in equal proportions, Organic Chemistry calls the mixture a “racemic” mixture. When we give patients the drug we call “Racemic Epinephrine,” we are actually giving a combination of the active form of Epinephrine mixed with an inactive form of the same chemical compound. This technique has a blunting effect on the potency of the drug, which is the desired effect. I was surprised to learn that the technique we use at my service to perform this treatment is slightly different. We don’t technically administer “racemic” epinephrine because we don’t have dextro-rotary Epinephrine in our drug bags. Instead, we take regular levo-rotary Epinephrine and mix it with saline, achieving the same blunting effect.

The same holds true for our diabetic patients to whom we administer Dextrose. I have been asked in the past why we give dextrose to patients who are hypoglycemic. Organic and stereo chemistry provides the answer. In fact, dextrose IS glucose, just the dextro-rotary isomer of it. (Dextro-rotary + Glucose = Dextrose) The chemical compound is oriented in a specific way, like epinephrine, and it is only this orientation that is synthesized by the body to create energy. It is by convention that we call glucose created outside of the body “dextrose,” and that created inside the body “glucose.” They are both the same thing.

It is all scientific detail. Esoteric, to be sure, but the depth is there for anyone who is willing to look. For a paramedic and pre-medical student such as myself, I find the incredible complexity of these subjects fascinating. To learn about epinephrine and dextrose in this way makes me wonder about everything else we do. There are layers and layers of understanding underneath each of our drugs, underneath our procedures, policies, and practice. We do what we do out of little but faith that there exists science and understanding to provide a foundation for these treatments. We accept our protocols wholesale because we have to, as they are the assimilation of greater minds with greater perspective. To scratch the surface of this knowledge, as I have done in class, does little more than add a sense of humility and wonder for that which I do not yet understand, and to provide a motivation to move forward and learn more.

In the future, I have bigger plans for this surface than a mere scratch.

Expectations

This neighborhood is particularly bad. Stout, two-story brick buildings are tightly clustered around an intersection of narrow, pot-holed streets. Through their iron barred vantages, these unfortunate residents overlook a scene of densely overgrown brambles, adorned with rubbish and punctuated with rusty iron poles pointing out at bent angles. Slackened laundry lines hang from a few of the poles, dipping close to the ground as if the life had been sucked right out of them. One of the ropes leads to our patient’s building, and she sits there with the door half-cocked, waving us over from down the street.

She is in a pair of neon pink pajama pants and a long white t-shirt. Against the sullen gray background of her neighborhood, the woman looks suddenly three-dimensional. Her image pops out towards us as if she had been drawn in, rack focused by an artist looking specifically for contrast. There is a smile, too, and it seems equally out of place.

“Oh thank you so much for coming,” she says. There is genuine appreciation in her voice, and warmth in character that we did not expect to hear.
“Please, follow me right up this way.”

She turns around and leads us up a darkened staircase, around to the right and into a small room. There is a single air mattress on the floor and an older TV sitting on a milk crate. On the screen is the title menu from a 101 Dalmations DVD, which plays a hushed Disney lullaby on continuous loop. A small boy of perhaps two or three years is sleeping prone on the mattress.

She’s whispering now.
“I feel so silly calling you guys, but he just fell asleep. His asthma was really bad all night. I gave him three or four puffs of his medicine but it kept coming back. It’s so scary hearing him wheeze like that, I just didn’t know what to do.”

The woman looks younger now as she tells the story. For the first time I notice that she can’t be more than eighteen or twenty years old. Despite her bright clothing and young face she looks haggard and worn out. Exhausted. At the end of her story she throws her hands up and lets them fall limply to her sides. She is wide-eyed and eager for help, looking at us searchingly for our reply.

I wonder if she honestly believes we might just pack our things and go. Perhaps we would decide she lacked merit and leave them both there in that apartment to rot.

The way she looked at us then, it seemed she was ready for anything.

Blind Faith

Working alongside so many medical professionals of varying qualification and experience has given me a profound respect for that which I do not know. It is not a rare occurrence that I am confronted with a patient who suffers from a condition that I have never heard of, or with which I am only lightly familiar. These circumstances are particularly frustrating for me, because instead of drawing from my own experience and knowledge, I am forced to rely entirely on what I am told by the nurse or doctor on scene. Many times I feel I am not getting enough information, and other times I feel like the information may be incorrect. Still, my personal lack of education on the subject limits my ability to question, and hampers my greater understanding of this patient who will soon be under my care.

We were called last week to a small clinic for a patient who we were told had shortness of breath. The patient had undergone a procedure during which he was sedated with Propofol and placed on his left side while maintaining his own airway. When the procedure was over and the sedative discontinued, the patient complained of “a little sore throat” and some nasal congestion. At that point in time the measured oxygen saturation (SPO2) dropped from a baseline of 97% to 92% for a few minutes (then returning back to baseline). Concerned, the clinic performed a chest x-ray and thought they saw some infiltrates in the lower lobe of the left lung. They wanted this patient brought to the emergency room for evaluation and, as they put it, twenty-four hour monitoring of the oxygen saturation. They were apparently worried that the patient had aspirated during the procedure and was on the verge of some sort of pulmonary emergency. The patient, now completely without complaint having never noticed any shortness of breath with an oxygen saturation of 99% on room air, looked confused and frightened.

I admit I don’t know much about the risks involved with laterally positioned patients under Propofol sedation. I don’t know how to read a chest x-ray and I only understand a little about what a lung infiltrate is. I have a good familiarity with pulse oximetry and clinical assessment though, and this case raised a few flags with me. I was skeptical, but the doctor told me this story with such earnest interest and concern that I couldn’t help but be impressed. He had the paperwork all ready and asked us if we were capable of monitoring the pulse oximetry while transporting this patient with the lights and sirens on. He said that he had spoken with the physician in the receiving ER and they would be anxiously awaiting our arrival. Barring what I was told and what I saw with the patient, everything about this call seemed to suggest something serious was going on. Still, there the patient sat with a weak story, no complaint, and no sign of any trouble.

I wanted to raise my eyebrows and ask a few tough questions. Are you sure the pulse ox was reading correctly? Didn’t you listen to lung sounds? Didn’t you listen to your patient? How likely is it that the shadow you saw on the chest x-ray is a physiologic change and no emergency at all? Are you sure this patient really needs to go to the EMERGENCY room? Is there something I’m missing here?

…But I couldn’t. The truth is, I don’t really know enough about any of this to be questioning a physician’s impression so directly. I am anecdotally familiar with pulse oximetry and the tendency for the sensor to slip and read low. I know that even healthy patients sometimes read low on the pulse-ox for benign reasons, but I am not sure of the exact mechanisms and science behind pathologic reductions in those same readings. Surely this physician was much more familiar, and I feel I must have some (if even blind) respect for the decisions that come from such experience and training. He must know something that I don’t. The same goes for the x-ray. Surely the radiologist understands the difference between pathologic and physiologic changes on a plain film. Who am I to question him, even if the story just doesn’t seem right?

And so we transported the patient as we were told. I sat in the back and plugged in the pulse-ox, talked with the patient and did my regular assessment. I didn’t find anything wrong with him, and the pulse ox sat at 99% for the duration of the trip. When we got to the emergency room the triage nurse rolled her eyes. She sent the lady to the waiting room.


I know a lot of medics who would have argued with the doctor. Some of them have no problem asking those pointed questions and wearing their distain for a questionable call on their sleeves. Relaying this story to an experienced medic I know, I was chastised and told to rely on my own assessment. “Did the patient look sick to you,” I was asked. When I replied that he didn’t, the answer was “Then he probably wasn’t.”

He’s right, the patient probably wasn’t sick. It was probably a bunch of trumped up nonsense arising from a cautious physician worried about iatrogenic disease and the resulting repercussions. I saw that within my first minute with these people on scene. …But I had no way of being sure. I trust my assessment and I trust my experience. I am proud of my abilities and I think I am a capable provider. Still, I know that there are sharp lines that divide what I know for sure and what I do not, and there is much more of the latter than there is of the former. If a doctor tells me his patient is sick and I don’t think he really is, would it really be prudent to follow my instincts over his? I’m not so sure.



**



Research after the Fact:


A pulmonary infiltrate is the filling of airspaces within the lungs with fluid, inflammatory exudates, or cells that increase the visual impression of soft tissue density on a chest x-ray. Sometimes this can be a pathologic finding, but there a is also a potential that the condition may be physiologic, where normal airspace folding and collapse creates the same visual impressions (“Atelectasis”). The left lower lobe is the most frequent location of benign atelectaisis in ICU patients. (source)

In a recent study on critical care monitoring, pulse oximetry accounted for almost half of 2525 false alarms (1). In another study looking at patients recovering from anesthesia (2), 77% of low pulse-ox alarms were false in nature. A recent survey (3) found that highly trained medical professionals may have little understanding of pulse oximetry and it's clinical application. In that survey, 30% of physicians and 93% of nurses thought that the pulse-ox measured PaO2. (It actually uses a measure of hemoglobin oxygen saturation to esimate arterial saturation, SpO2).