A Woman Couldn’t Sleep for 9 Days.
The medicine she used to help her sleep was less than optimal.
This Is What Happened To Her Colon.
JD is a 27 year old woman, presenting to the emergency room, unconscious.
Her boyfriend Jeff tells the admitting nurse at admission that she had been awake for the
last 48 hours before complaining of severe nausea.
You see, JD had been experiencing a strange insomnia over the past 7 months.
Some nights she would lay in bed, tossing and turning while hearing the morning traffic
build up in her window.
Some mornings, she would dreadfully watch the sun rise.
Without sleep, her quality of life began to rapidly deteriorate.
She was an attorney, and her job performance began to suffer, as she would have trouble
making court dates.
She began losing interest in her hobbies and her relationship began to suffer as she blamed
Jeff for the insomnia, but even after his absence, her sleep trouble worsened.
10 years ago, JD was diagnosed with a mild depression.
She was started on a low dose of quetiapine, with good results and never missed a dose
nor had any complaints about it.
About 3 months ago, JD began trying supplements to help her sleep.
Some nights, she’d sleep great, and others, she’d be wide awake for 2 consecutive nights,
exhausted by the third day.
Some supplements, became many supplements.
She’d mix and match, and take much more than she needed until finally, nothing worked.
She consulted a neurologist for her problems, who prescribed her cognitive behavioral therapy,
but in it, she found limited success.
She finally moved on to over the counter medication.
She started taking the PM branding of a drug named diphenhydramine, which helps with allergies
but also makes one drowsy.
It helped her sleep every night for a whole week, but she noticed that the medicine would
give her not only stomach pain, but also constipation.
Sometimes, she’d sit for 30 minutes, with limited movement, but finally being able to
sleep gave her new life.
Inevitably, the insomnia came back.
JD began to escalate the dose each night until she would take 4 to 5 times the recommended
dose each night to sleep just a few hours, before waking up unrefreshed and exhausted.
One evening, she was at dinner with Jeff.
She barely ate.
She told him that she hadn’t had a bowel movement nor slept more than just a few hours for 9 days.
He stayed with her over night to make sure she’d be ok.
Her skin became pale as she started complaining of nausea and stomach pain.
Jeff fell asleep but as he woke up, he found her laying on her side, in a pool of cold
sweat, huddled up and unresponsive.
In a panic, he called 911 and she was brought to the emergency room where we are now.
Given this history of present illness, there are several clues as to what’s happening.
At physical examination, JD was immediately identified to be in shock.
Her blood pressure was low and her heart, to compensate for this hypotension, was beating
at 150 beats per minute, 3 times that of average.
And she was completely unresponsive.
An abdominal CT scan finds that JD has Acute Megacolon.
Mega meaning enlargement and referring to the dilatation of the colon, or the large intestines
Acute meaning that there are no underlying pathophysiologic conditions that are leading
to this problem except for the massive doses of diphenhydramine JD consumed for her sleep,
which leads us to the first clue.
Diphenhydramine is an allergy medicine.
In most parts of the body, it blocks the chemical named histamine which is responsible for most
common allergic reactions, like itching from mosquito bites, and sneezing from pollen.
But in the brain, diphenhydramine blocks a different chemical that transmits signals.
This means that small amounts leads to mild sedation, helping with sleep, but by affecting
the brain and its nerves, diphenhydramine also slows down the digestive system, which
receives signals from the brain.
Large amounts of diphenhydramine can lead to an almost complete stoppage of the digestive
system which brings us back to the name of JD's condition Acute Megacolon.
If she had no bowel movements for 9 days, and CT scan did not reveal any mechanical
obstructions in her colon, then it means nothing was specifically blocking the way in her intestines.
But if that’s the case, then why is her colon dilated?
Why is it megacolon?
Well, there’s a few things to be known here.
First, the stomach and intestines form their own set of nerves called the enteric nervous
system, sometimes called the second brain.
This "second brain," controls the muscles of your bowel and cannot be actively controlled
by you, meaning you can’t force your stomach to contract at will like you can your biceps.
But if the first brain in the head and the second brain in the gut both use the same
chemicals to transmit signals along the nerves, and JD’s sleep medicine diphenhydramine
blocks the chemicals from transmitting signals in those nerves, then it means that high doses
of JD’s sleep medicine were slowing down her gut to a high degree.
Inside the colon, because the digestive system is a giant tube from your mouth to the other
end, the pressure stays constant within, meaning that if one part is dilated, the pressure
has more or less, stayed the same and hasn’t dropped.
This means that the tension at the wall of the dilated segment is elevated, and as the
colon keeps slowing down from high doses of diphenhydramine, and as tension keeps building
up, then blood can’t flow through it, meaning those blood vessels will begin to crush up
against the sides of the wall, starving the tissue of oxygen as it slowly begins to necrose,
or quite literally die.
This necrotic tissue begins to lose it’s muscular integrity, and as time continued
through JD’s abdominal pain and distention starting from several days ago, the walls
of her colon began to weaken so much, that they finally perforated, spilling her intestinal
contents into her peritoneal cavity, causing bacteria from the gut to spill into her blood
stream, as they begin to flow freely, all throughout her body.
Just like how when you get an infection on your skin it becomes swollen, red and warm,
an infection that spreads into your blood causes your entire body to become "swollen,"
which translates to the body sending white blood cells systemically, promoting inflammation.
Because JD’s situation isn’t self-limiting, meaning it isn’t containing itself, her
blood vessels have begun to vasodilate, causing her blood pressure to drop.
Her heart detects this and begins to beat faster in order to compensate for the loss
in pressure so that her organs can still receive blood, but as her brain starts to lose oxygen,
JD loses consciousness.
This dramatic escalation in signs and symptoms due to colonic perforation is known as septic shock
and means almost imminent death in JD’s case, if treatment isn’t initiated within
the next few minutes.
The notion of motor dysfunction in the gastrointestinal system is a persistent underlying theme that
has far reaching implications when it comes to seemingly unrelated causes of disease in
humans.
Opioids for pain control in the hospital can often cause gastric hypomotility.
This is a time when constipation becomes a common occurrence leading to fecal impaction.
If the patient is elderly and doesn’t receive a stool softener, then it means they will
have to strain to pass a movement.
If they strain hard enough, their heart will temporarily stop and they can rupture blood
vessels in the brain causing a stroke, which leads to cerebral vasospasm days later, which can starve
the brain of oxygen leading to brain damage.
In the case of gastroesophageal reflux disease, stomach acid commonly splashes into the esophagus,
which isn’t equipped to handle the low pH.
While laying down, this acid can enter the bronchioles of the lungs and trigger asthma
as well as damage the larynx and erode the enamel of the teeth.
The integrity of the esophageal mucus membrane is disrupted and the cells are damaged, leading
to Barrett’s Esophagus which predisposes the patient to esophageal cancer, which can then undergo
a malignant transformation and then spread all throughout the body.
A common inflammatory bowel disease known as Crohn’s Disease affects any part of the
digestive tract, at all layers of the bowel walls.
This is a state of mucosal inflammation that can seep into the smooth muscle of the colon,
paralyzing it, causing it to dilate.
The deep ulcerated parts of the intestines begin to degenerate and necrose as white blood
cells begin to swell into the tissue, causing it to rupture, giving way to toxic megacolon,
a more chronic condition with an underlying pathophysiology compared to JD’s acute megacolon.
Her history of present illness all point to this.
The prior stomach pain.
The nausea.
The high doses of diphenhydramine in a desperate attempt to finally fall asleep.
Since the onset of shock appears to be relatively recent, it may not yet be too late for her,
she could still be resuscitated.
The first line of treatment is to remove the source of bacteria spreading into her blood.
She is admitted immediately to surgery and at laparotomy, or incision into the abdominal
cavity, massive colonic distention was found with evidence of perforation.
Her small intestines, and distal parts of her rectum were found to be viable and her
entire colon was removed.
Admission into the intensive care unit led to immediate initiation of antibiotics and
early goal-directed resuscitation as her condition began to stabilize over the following days.
The final thing to note here, is that JD’s condition sould have been easily caught by
any health care provider, at any point.
Diphenhydramine as a medicine is a well known anti-cholinergic.
If a cholinergic does things like promote smooth muscle movement in the digestive system
and promote a “rest and digest” state of the body, then an anti-cholinergic prevents
digestive system movement.
Do you remember that quetiapine that JD was taking for her depression?
Well, quetiapine is also a well known anti-cholinergic, meaning the dangerous dual blockade of diphenhydramine
in large, prohibited doses in combination with quetiapine, which also exhibits anti-dopaminergic
and anti-serotonergic activity, both important neurotransmitters in "both" brains, virtually
stopped her digestive system from moving completely, and caused her colon to swell, crushing the
blood vessels, starving it of oxygen and causing the walls to perforate, leaking enteric contents
including gut bacteria into her blood.
JD’s anticholinergic excess, produced from a drug interaction that should have been caught
by physicians, nurses and the pharmacist at the store where she bought the medicine, caused
this set of symptoms.
Luckily for her, it wasn’t too late to begin early goal directed resuscitation in the intensive
care unit, and over a few weeks, her septic shock was resolved as she regained consciousness,
and her gut was surgically anastomosed, or rejoined together, without her colon.
And upon arriving home, a good nights sleep in her own bed, was waiting for her.
Thank you so much for watching.
Take care of yourself.
And Be well.