How Not to Kill Your Patients with Medication: Part Deux



You may have noticed this is the second article in a series called, “How Not to Kill Your Patient with Medications.” The first article addressed three different patient presentations and medications that have the potential to harm each of those patients. The question was asked, “How many times do we cause harm with the tools we have and don’t even know it?” I hope the information in this series makes you just nervous enough to keep your eyes open and invest in the “thinking game.” Even the most benign treatment – Normal Saline, can cause harm if we don’t use it the right way. No patient and no treatment should be “routine.” But it’s so overwhelming! How can one person, or even a pair of vested, smart clinicians possibly remember everything about every condition and every drug? You can’t! The goal is that you will hopefully be able to retrieve some of this information from the back of your brain when you need it.

Fluid bolus/insulin/Diabetic Ketoacidosis (DKA)

You are picking up a 23-year-old female from an outlying facility. She is a known Type 1 Diabetic. Her blood sugars have been high all week, and she suspected her insulin pump has been malfunctioning. She reported giving herself extra Humalog injection at school. This evening, she finally admitted she was in trouble, so her roommate drove her to the ED. The lab draw BG was 562 and her serum beta-hydroxybutyrate was positive (fancy lab name for ketonemia). Your HEMS team is paged out, but you aren’t flying anywhere due to fog and icing conditions. (This is my story… welcome to Idaho!) So you load your gear into an ambulance with a third crew member and drive 45 minutes to the facility. 

You arrive to find this patient flushed and tachypneic. Her arterial blood gas shows a PH of 6.8, HCO3 of 1, a PaCO2 of 22, and a serum anion gap of 23. She has received 3000mls of Normal Saline and the sending RN tells you that her BG is down to 285. No insulin has been given yet, but it looks like her blood sugar is coming down nicely… and its just a 45-minute drive, right?

You anticipated a rapid transfer but ended up waiting in the ED for paperwork. After 20 minutes, you load her into your ambulance and take off. After 50 minutes of drive time, you reach the receiving facility. Her heart rate is 135, her BP has dropped from 146/90 to 115/70. Her respiratory rate has gone from 26 to 32. She seems really tired, but she is sick and has had a long day. You give your report to the ICU nurse and you don’t think much of it.

Here is what you may not see: The receiving MD is slammed and doesn’t make it to her bedside for 2 hours. Her RN sees her blood sugar coming down – now it’s 215. She is also busy dealing with her intubated patient next door and isn’t really concerned about the lack of insulin. The patient, however, looks like crap. Her pH drops to 6.75, her BP drops to 90/62, her heart rate climbs to 150 and her respiratory rate is now 45. She is altered, her respiratory muscles are tired and she is hemodynamically unstable. She finally gets placed on an insulin infusion, which her body desperately needs, but her blood sugars are too low to tolerate it and it keeps getting turned off. She ends up on an insulin infusion, a D10 infusion, and sodium bicarbonate for her acidosis with hemodynamic compromise. She recovered but earned several extra days in the ICU.

What in the world happened?

It was just a DKA patient! Amy, are you making stuff up? Nope, this is based on a real patient. Why did this scenario go south? Let’s look at the real problem in DKA.

We like to think of DKA as a “sugar problem,” but it’s not. It’s an insulin problem. The blood sugar is just a symptom of the lack of insulin. Sure, we all know that patients in DKA can lose an incredible amount of fluid – on average, 6-9 liters, and we need to replace it. This is a contributing factor to morbidity, but not the main problem.

DKA is a problem of insulin deficiency – the lack of insulin stimulates an increase in the insulin counter-regulatory hormones: cortisol, glucagon, catecholamines and growth hormone. These hormones increase the patient’s blood sugar – the body is unable to use glucose without insulin, so it is fooled into thinking it needs more sugar. Unfortunately, the hyperglycemia is getting worse, but the body still needs an energy source. Fat gets broken down into ketones (causing a metabolic acidosis), while glycogen and protein are catabolized to form more glucose – and the problem gets worse. Hyperglycemia leads to the osmotic diuresis mentioned above, causing dehydration, increasing metabolic acidosis and worsening the hyperosmolar state. We aren’t even going to talk about the shifts in potassium. You can give the patient multiple liters of fluid to try and combat the dehydration, and this will make her blood sugar drop – but at this point, it doesn’t matter if her blood sugar reads 92 or 592, the problem is that her body still can’t use it without insulin and the vicious cycle continues as her PH drops further and she gets sicker and sicker (Gosmanov,Gosm anova, & Dillard-Cannon, 2014).

So how in the world can we tell if she is getting better? DKA patients require multiple lab studies, but the big one that tells us about their state of ketoacidosis is the “anion gap.”

In your blood, you have anions and cations (negatively and positively charged ions). We see these on our patient’s metabolic panels. Potassium (K+), sodium (Na+) and calcium (Ca2+) are positive, while chloride (Cl-) and bicarbonate (HCO3-, but disguised at CO2 on the chem panel) are negative. These are all “measured” on the chem panel, so they are accounted for. There are other anions in your blood that are not specifically measured on your serum chemistry panel, and these are accounted for with the “anion gap” value. Everyone has a degree of anion gap with varying ranges, generally less than 15. Things like lactate and ketones are negatively charged, so when the amount of lactate and ketones in your blood increase, the anion gap increases (because these anions aren’t normally measured on your chem panel). So basically, we are following the degree of ketosis and general metabolic acidosis in DKA, by monitoring the anion gap. When your patient finally gets insulin, her body will cease to burn fat to produce ketones and her metabolic/lactic acidosis will resolve, resolving the high anion gap (Kraut & Madias, 2007).

This patient may have had a decreasing blood sugar from the fluid, which looks nice; but her main problem (lack of insulin), was not being addressed. So, her body continued this vicious cycle and her PH continued to drop and she became sicker and sicker. She was put on a D10 drip later because her body desperately needed insulin to close the anion gap, but her blood sugar had been diluted – so she got more “sugar,” so she could get insulin to fix her real problem.

If this was really your patient, what could you have done? The theory of “the patient can wait for insulin for 45 minutes” resulted in the patient waiting well over 3 hours (and that is just from the time our clock started with the patient) – we just don’t see all of this when we hand them off. Had this patient received an insulin infusion 3 hours earlier, she may very well have avoided a lot of the complications that she went through – she was essentially heading down the pathway of total hemodynamic collapse. We can provide care that is “good enough” to get them to where they are going “alive”, or we can provide excellent care.  I realize that many crews may not carry insulin and may not have the ability to just start an infusion in their protocols – Don’t go rogue in the name of all that is “just.” This is a great opportunity to either: 1.) have a quick discussion with the sending provider about the need for an infusion (and finding a way to make it “their” idea goes a long way), or 2.) if you do carry insulin, call your medical control (if needed) about starting an infusion on the way. And if your patient is on an infusion and their blood sugar drops – turn it down, way down if you have to, but try to avoid shutting the insulin completely off.

Serotonin Syndrome & all kinds of drugs

You have just settled into bed for the evening when you are paged to pick up a 32-year-old woman for a medical rendezvous with a rural BLS crew. Your HES crew has a 40 minute ETA.  You arrive on scene and find a lady that seems restless, jittery and confused, but is able to answer most of your questions. She just doesn’t “feel right.” She has had a nasty cold lately and has been taking cold medicine with pseudoephedrine and dextromethorphan (because “you know its the only one that works…”) every 6-8 hours for a few days. Her sister tells your partner that the patient had a bad headache this morning, so she gave her some of her Sumatriptan (Imitrex) and now she is just acting strangely. She has not been eating or drinking much, and you note that her lips look chapped and her skin is dry, but flushed. Her medical history includes depression and headaches, and she takes Sertraline (Zoloft).

Her vital signs show a blood pressure of 85/52, HR of 120, SPO2 of 99%, RR of 22 and an oral temp of 38 C. Sepis is briefly mentioned, but there is no clear source of infection and she probably just has “some virus.” You load her up into your helicopter and meet your partners’ eyes; you are both questioning utilization in this specific instance. As you begin to fly, you start the patient on a modest fluid bolus, thinking that this may resolve some of your tachycardia and blood pressure issues (after all, she hasn’t been drinking much and she looks dehydrated). Her pressure comes up to 109 systolic, but her heart rate isn’t really coming down. She is still complaining of a 7/10 headache and you note that she isn’t allergic to anything, so 50 mcg of Fentanyl it is. She is also complaining of nausea, so you give an 8mg Ondansetron (Zofran) chaser – no one is throwing up today on your freshly shined boots!

Unfortunately, your boots lose and she throws up on them anyway. Your partner smirks, as you agree to give her 6.25mg of Promethazine (Phenergan) – she is a little confused, so you give a small dose. Now her BP is 155/96 as you are 5 minutes out from the receiving facility. You don’t want to take her in hypertensive, throwing up and in pain (total loss of style points), so you give her an extra 50 mcg of Fentanyl to top her off – she’s probably just hypertensive and throwing up from the headache. At this point, you are both a little a concerned about why she seems to be getting worse on your watch. You drop her off in the receiving Emergency Department and vow to follow up later.

You call and check on her in the morning. Her BP had increased to 195/115, her heart rate increased to 130 and her temperature had risen to 104.8 overnight. She also had a high CK and lactate, as well as a high creatinine. She was admitted to the ICU and the Intensivist had just diagnosed her with Serotonin Syndrome.

For starters, the patient was on Sertraline… an SSRI. It doesn’t appear that she took more than prescribed, though she was on a moderately high dose. Okay, but she was on one SSRI! What?!?! How in the world did they come up with that? Did we miss something? You call your medical director to discuss this one and as the conversation evolves, a pit develops in your stomach.

I give up… what happened? (Nope… not making this one up either.)

Serotonin Syndrome occurs when too much serotonin accumulates in the central nervous system. It is often underdiagnosed because mild cases aren’t always recognized. There is a triad of symptom “clusters” that increase in severity, depending upon the seriousness of the syndrome. These patients have a degree of Altered Mental Status (AMS), which may present as excitability, disorientation, agitation or anxiety. You will find neuromuscular abnormalities, such as tremors, hyperreflexia, akasthesia (quivering/inability to sit still), muscle rigidity or clonus. The third symptom cluster is autonomic hyperactivity, which may present as hypertension, tachycardia, tachypnea, diaphoresis, flushed skin, vomiting, diarrhea, arrhythmias, etc. (Volpie-Abadie, Kaye & Kaye, 2013).

Why do we care? I mean, we care…, but why is this so dangerous? Serotonin regulates attention, behavior, and temperature management in the Central Nervous System (CNS) and in the Peripheral Nervous System (PNS). Serotonin helps regulate gastrointestinal motility, vasoconstriction, and bronchoconstriction, as well as being involved in platelet aggregation. As a result, these patients can experience large, rapid hemodynamic swings, high fevers and can even go into Disseminated Intravascular Coagulation (DIC), as well as experiencing muscle damage and rhabdomyolysis (Boyer, 2018).

We know that Selective Serotonin Reuptake Inhibitors inhibit serotonin uptake… easy enough. What we didn’t take into account is that lots of other drugs mess with serotonin in ways we don’t think about. Many other classes of antidepressants inhibit serotonin reuptake, including: SSNRI’s, MAOI’s, Tricyclic Anti-depressants, Dopamine-Norepinephrine Reuptake Inhibitors (Wellbutrin), as well as Buspirone, Trazadone and Mirtazapine and more (Beakley, Kaye & Kaye, 2015).

She had taken several doses of cold medicine containing Dextromethorphan over the last couple of days. Dextromethorphan also inhibits the reuptake of serotonin and promotes serotonin release. The cold medicine also contained Pseudoephedrine. Pseudoephedrine, in and of itself, is not directly implicated in Serotonin Syndrome, but amphetamines are.

Her sister gave her Sumatriptan (Imitrex), which is used to treat migraine headaches. Sumatriptan is a serotonin receptor agonist.

You gave her 100mcg of Fentanyl and 8mg of Ondansetron. Both Fentanyl and Ondansetron are “serotonin-enhancing” drugs and in ICU patients diagnosed with Serotonin Syndrome, they were the most often administered “serotonin-enhancing” drugs (Pedavally, Fugate & Rabinstein, 2014).

Serotonin Syndrome can occur from the initiation or the increase in dosage of one serotonin-modulating drug. There is no “thresh-hold” that Serotonin Syndrome typically occurs at, and is thought to happen easier in more “serotonin sensitive” individuals. The more drugs combined that have an effect on serotonin, the higher risk an individual has of developing it. If you want to get really unnerved, go study how Cytochrome P450 affects all of this!



We aren’t physicians… I get it. But there are definitely things that we can do to help or harm our patients. No crew wants to find out later that the treatment they initiated caused harm, especially when a little knowledge may have prevented it. We have to remember to not let our guards down with things we see a lot, like DKA… or give a lot, like Fentanyl and Zofran. Encourage your staff to get a follow-up on all transported patients. Don’t feel bad if you don’t catch all of the zebras – just be smart and engaged providers.



Beakley, B.D., Kaye, A.M & Kaye, A.D. (2015). Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician, 18(4), 395-400.

Boyer, E.W. (2018). Serotonin syndrome (serotonin toxicity). Up to Date. Retrieved on April 13, 2018, from

Fowler, M.. (2009). Hyperglycemic crisis in adults: Pathophysiology, presentation, pitfalls and prevention. Clinical Diabetes, 27(1), p. 19-23.

Gosmanov, A.R., Gosmanova, E.O. & Dillard-Cannon, E. (2014). Management of adult diabetic ketoacidosis. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 7:255-264.

Kraut, J.A. & Madias, N.E. (2007). Serum anion gap: Its uses and limitations in clinical medicine. Clinical Journal of the American Society of Nephrology, 2: 162-174.

Pedavally, S., Fugate, J.E. & Rabinstein, A.A. (2014). Serotonin Syndrome in the Intensive Care Unit: Clinical presentations and precipitating medications. Neurocritical Care, 21:108-113.

Volpie-Abadie, J., Kaye, A.M. & Kaye, A.D. (2013). Serotonin Syndrome. The Ochsner Journal: Winter 2013, Vol. 13, No. 4, pp. 533-540.

Westerberg, D.P. (2013). Diabetic ketoacidosis: Evaluation and treatment. American Family Physician, 87(5), p. 337-346.

Weiderkehr, M.R. & Moe, O.W. (2012). Core concepts in the disorders of fluid, electrolytes and acid-base balance. Chapter 8: Assessment and treatment of metabolic acidosis. Springer

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