TOX: Chasing the Dragon Away

“Acknowledged.” You calmly reply, and pointing to your intern, you state in a loud clear voice, “Head tilt. Chin lift. Bag.”

You walk to the foot of the bed. Inside your skull your mind races through diagnostic and therapeutic possibilities, but to the outside world, you start your resuscitation the same way you always do. You indicate to the nurses to start an IV, draw blood specimens, and place the patient on a monitor.

You ask the ambulance team as you note a normal blood pressure, heart rate, and oxygen saturation on the monitor.

“This is a twenty-something year old woman, found unconscious on a sofa with drug paraphernalia. Her respiratory rate was 8 breaths per minute. We picked her up five minutes ago and came straight here!”

“Understood.” You reply, then glide over to the bedside to check the patient’s pupils, noting their size to be 1mm. “What do you want to do?” you ask of your intern.

“There’s no head or neck trauma — we have a comatose patient with respiratory depression and pinpoint pupils. We should intubate.”

“I was thinking about naloxone, but can’t that cause pulmonary edema?” your intern replies.

“It can, but I doubt it will here.”

“Can you please . . . elaborate?”

“Of course. Keep bagging. Imagine you are in a coma breathing 8 times per minute. What is your blood pH and pCO2?”

“My pH is low and my carbon dioxide is high.”

“Good. Now imagine some jerk injects you with a fast-acting coma reversal agent. Within seconds you are fully awake with a pCO2 of 80 mmHg and in fulminant opiate withdrawal.”

Says your intern.

“It is horrible. That first huge gasp of air can cause negative pressure pulmonary edema – fluid is literally sucked into the alveoli by the forceful inhalation against a closed glottis. On top of this, there is a tremendous surge in sympathetic tone leading to major systemic venoconstriction as well as pulmonary vasoconstriction. As a result right ventricular preload goes way up. The catecholemine surge also increases alveolar capillary permeability. That extra preload is transmitted right through the capillary bed, and fluid extravasates into the alveoli.”

“So . . . why are we giving naloxone?”

“You’ve been effectively ventilating the patient for several minutes now. Her pCO2 should be nearly normal.”

You give the nurse a thumbs up, and he hands your intern a syringe loaded with 4mg of naloxone.

“This seems like a lot of naloxone” says your intern.

“It might be. It might not be. The patient will be the judge of that. Start with 0.1 milligrams. Double the dose every minute until she wakes up.”

After 6.4 mg of naloxone, there is no change in status.

“This is weird for a heroin overdose,” muses your intern.

“I agree it would be a lot of naloxone if this were heroin. Sadly, it’s no longer the early 1990s and I bet there is more going on here than simply heroin. A significant amount of what is marketed as ‘heroin’ is actually mixed with fentanyl, carfentanil and sufentanil. It can take inordinate amounts of naloxone to reverse the effects of the same dose of the more potent drugs.”

After almost 13 milligrams of naloxone the patient starts blinking at you, slowly sits up, and in a slurred voice says, “Crap. I didn’t want to end up here. I was trying to treat myself!”

You think to yourself, but it’s far from the oddest thing you’ve heard in the Emergency Department. “Complete the history and physical examination . . . and please try to find out what she meant,” you whisper to your intern, sidestepping the unopened crash cart and moving on to see another patient.

A few minutes later your intern approaches you and begins to present the patient. “The patient is a 26 year-old woman with a history of intravenous drug abuse . . . lives in Coney Island . . . recently broke up with her . . . been feeling weak and tired . . . a little short of breath so she took extra heroin to ‘feel better’ . . . 3/5 strength in all muscle groups . . . erythematous track marks . . . and I don’t like the way she’s breathing. Could this be the naloxone wearing off? Should we start a naloxone infusion?”

. . . than a simple opioid intoxication, you think to yourself. You peek a quick glance at her normal chest radiograph, then walk over to reassess the patient. You want to stall from answering your intern’s question and ask, “how would you set up a naloxone infusion?”

“I would start 2/3 the initial dose of naloxone per hour and then titrate to effect.”

“Very good,” you respond, and with a frown examine your patient who is breathing 30 times per minute. “You’re correct that this is abnormal breathing, but this is not central respiratory depression. It’s the opposite actually . . . and you said she had 3/5 strength globally? What could be going on here?”

“Yes, she was weak everywhere. Should I get an ABG?”

“No, don’t get an ABG. Call respiratory and measure a Negative Inspiratory Force (NIF) and Forced Vital Capacity (FVC). Where was this erythematous track mark?”

Your intern indicates a necrotic skin lesion on the inner thigh.

“This is an abscess. Perform a quick incision and drainage while we wait for respiratory. Send cultures on this one.”

Moments later the respiratory therapist reports a NIF of 15 cm H2O and and FVC of 800 mL.

“It’s time to intubate our patient,” you instruct your intern. “As soon as she’s stable you need to call the New York State Department of Health to get the antidote!”

Botulism. That was botulism.

Although rare, wound botulism is a potential complication of intravenous drug use. Either due to “skin popping” or missing the vein, drugs contaminated with clostridium botulinum spores may be injected into the subcutaneous space where they flourish in the anaerobic environment. The bacteria release botulinum toxin into the patient’s blood stream, and the patient develops clinical botulism.

Botulinum cleaves the SNARE docking proteins which permit exocytosis of synaptic vesicles and release of acetylcholine from the terminal axon into the synaptic cleft. Without acetylcholine, there is no signal transmission from neuron to myocyte. The clinical result is flaccid paralysis.

The most lethal manifestation of this is hypercarbic respiratory failure caused by weakness of the respiratory muscles. This is distinct from the hypercarbic respiratory failure of opiate intoxication in which there is decreased respiratory rate and tidal volume due to decreased respiratory drive without muscle weakness.

Our patient started with a respiratory rate of 8/min which was caused by the central respiratory depression of opiate intoxication. Once the CNS effects were reversed, she was unable to maintain adequate tidal volumes because of botulinum-induced respiratory muscle weakness. Her pCO2 level rose to the point where it caused central respiratory stimulation and resulting tachypnea.

The Negative Inspiratory Force (NIF) and Forced Vital Capacity (FVC) can be thought of as tests of respiratory muscle strength. NIF and FVC should be considered when there is concern for diseases such as Guillain-Barre Syndrome, Myasthenia Gravis, Amyotrophic Lateral Sclerosis, or any disease impacting respiratory muscle strength.

The normal range for vital capacity is 60 – 70 mL/kg (4 – 5 liters in a standard sized adult).

Consider intubation and intensive care unit admission when:

FVC is less than 20 mL/kg (1.5 liters) or NIF is less than 30 cm H2O.

A patient with neurogenic respiratory failure can be maintained indefinitely with airway maneuvers and a bag-valve-mask. Don’t panic. Bag. Think.

Botulism is a rare disease, but the mortality is very high. There are several antitoxin preparations available in the US. There are seven forms of botulinum toxin, botulinum A, B, C, D, E, F, and G.

A trivalent (types A, B, and C) equine antitoxin is available through the Centers for Disease Control and Prevention (the CDC).

A bivalent (types A and B) human antitoxin is available through the California Department of Health Services for the treatment of Infant Botulism. The trade name is BabyBIG.

A heptavalent (types A – G) “despeciated” equine antitoxin composed of F(ab)2 fragments is available from the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).

Test a small quantity of any equine medication with an intradermal injection as life threatening anaphylaxis or serum sickness may occur. If necessary, you may desensitize the patient. Epinephrine should be immediately available whenever administering equine antibodies.

You may contact your state health department for access to antitoxin.

In New York call (212) POISONS for assistance acquiring the antitoxin. Nationwide you may call 1 – (800) 222 – 1222 for the nearest poison center. You may also call the CDC Emergency Operations Center at (770) 488 – 7100 or 1 – (800) 232 – 4636.

In addition to antitoxin, provide antibiotics for wound botulism. Penicillin G is the antibiotic of choice for wound botulism with clindamycin and chloramphenicol as alternative agents.

Utilize basic resuscitative efforts (airway maneuvers, bag-valve-mask, peripheral IV placement, collection of vital signs) to give yourself time to think about the patient — as well as to save their life!

Consider neurological etiologies of respiratory failure. Consider botulism in high risk patients including infants.

Utilize your state Health Department or Poison Center when in need of rare antidotes.

Naloxone should never be given directly intracardiac except by John Travolta

1. After the 2002 Moscow Theater Hostage Crisis, large number of casualties were brought to medical attention with respiratory depression or respiratory arrest. How would you manage a similar Mass Casualty Incident?
2. What factors do you consider when determining the disposition for an opiate overdose patient?
3. How do you recognize and manage infant botulism?

This is Mycroft Alex de Large Blumenberg. He is prepared for a scombroid epidemic at the 2017 Tuna convention.

In the television show Breaking Bad, what was the mechanism of Lydia’s flu-like symptoms?

www.usamriid.army.mil

www.wiser.nlm.nih.gov

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Heroin Epidemic’s New Terror: Carfentanil. Rolling Stone. September 8, 2016. Melissa Locker.
http://www.rollingstone.com/culture/news/heroin-epidemics-new-terror-carfentanil-w438712

Heroin laced with elephant tranquilizer hits the streets. CNN. August 25, 2016. Nadia Kounang and Tony Marco.
http://www.cnn.com/2016/08/24/health/elephant-tranquilizer-carfentanil-heroin/