POTD: Heavy Metals (LLFTP #8)

Daniel Ye · March 6, 2025 ·

Today's POTD will be based on the continuation of one of the cases I mentioned in my previous email.

Spoilers?

I originally wanted to talk about Latrodectus (Black Widow) envenomation (a patient with Crohn's disease presented with isolated severe abdominal cramping, without any fever or other GI symptoms), but Dr. Ervin already wrote a nice POTD about it back in August.

Instead, we'll follow the conclusion of Dr. Mohan's case with the altered beauty influencer. The heavy metal panel comes back at the beginning of the episode (seriously impressive turnaround time), and the patient has a mercury level > 90 mcg/L. The ordered treatment is "chelation TID, 10 mL/kg of DMSO" (which is actually a small scripting error, as you'll see below). Done and done, and Dr. Robby gracefully takes his lumps and acknowledges that "Slo-Mo" had handled the case appropriately.

Let's learn about mercury toxicity as well as some of the other heavy metals that love to appear in test questions!

Mercury (Hg/Hydrargyrum)

3 common forms — elemental mercury, mercury salts, and organic mercury

Elemental — found in devices such as thermometers; volatile and easily aerosolizes, inhalation --> pulmonary, CNS, and renal symptoms
Salts — found in batteries, skin cream, dental products; absorbed by GI tract and across skin --> GI and renal symptoms
Organic — found in paint, skin cream, fish; absorbed by GI tract and across skin --> neurological symptoms

Hg bonds to various functional groups on proteins, leading to widespread dysfunction
Hg can cause direct oxidative damage to lung/GI membranes and renal tubules
CNS deposition of mercury (more common in elemental and organic mercury exposure) leads to posterior encephalopathy/atrophy --> sensory neuropathies, vision changes/deficits, ataxia
Neurological deficits likely longstanding or permanent, especially if chronic/subacute
Above symptoms are fairly nonspecific, diagnosis relies on thorough history
Supportive care is key, chelation (compounds that bind heavy metal ions, allow excretion) can help lower Hg levels

Elemental/salts — IM dimercaprol 5 mg/kg q4h x 48 hours, then 2.5 mg/kg q6h x 48 hours, then 2.5 mg/kg q12h x 7 days; PLUS PO succimer (DMSA) 10 mg/kg q8h x 5 days, then q12h x 14 days
Organic — only succimer (DMSA), as dimercaprol has been shown to increase neurotoxicity
For acute ingestions, consider GI decontamination
HD can be considered as part of supportive care regimen if there is significant renal impairment, but does not effectively lower Hg levels
Exchange transfusions trialed in past with no proven benefit

Lead (Pb/Plumbum)

Previously had widespread presence in paint, gasoline (and exhaust), pipes; paint and pipes in older homes continue to be a source today, despite being banned in 1978 and 1986, respectively

Leaded gasoline banned in the US in 1996, but fumes could still cause agricultural contamination in imports; worldwide ban achieved in 2021
Childhood exposure through exhaust fumes reduced the intelligence (and worsened the health) of many Americans born between the 60's and 90's; i.e. petrol company lobbying and obfuscation (lead toxicity has never been unexpected, it has an older historiography than some modern religions) robbed multiple generations
Other exposure sources include industrial occupations, contaminated pewter/ceramics, contaminated spices, contaminated cosmetics, alternative pseudomedical practices, lead bullets
Children are at higher risk — they absorb more Pb for their body weight in both ingestion and inhalation, store more Pb in metabolically-active tissue, and excrete less Pb in their urine

Like mercury, lead binds many proteins and inhibits their function, especially calcium and zinc related proteins

High blood Pb levels can lead to acute syndrome of lead-induced encephalopathy from cerebral edema --> AMS, seizures, coma, death
Chronic toxicity harms neurocognitive development, inhibits RBC production and maintenance ("basophilic stippling" on smear), dysregulates proximal renal tubule function, and impairs sex, growth, and thyroid hormones

Nonspecific multisystemic symptoms, usually at Pb > 10mcg/dL

"Asymptomatic" children at risk for IQ loss (highest rate of IQ decrease is at 1 to 10mcg/dL)
Children may display irritability, constipation, and/or anorexia
Adults may also have cardiovascular disease, peripheral neuropathy, gout, infertility
Levels >70mcg/dL have high risk for lead encephalopathy

Careful history is once again key to the path to diagnosis
Care is centered around screening and decontamination

All children with Medicaid are screened at 12 and 24 months (5mcg/dL is threshold for further testing)
All children recommended to be screened by age 3-5
Supportive care (including supplementation with iron, zinc, and calcium)
Chelation indicated for levels of >45mcg/dL in children, >70mcg/dL in adults, or any patient with encephalopathy

BAL (dimercaprol) + calcium disodium EDTA is most common regimen, +/- succimer
Chelation may increase release of Pb from bones, leading to temporary exacerbation of symptoms

Developmental deficits from chronic toxicity likely to remain permanent
Permanent neurological sequelae from lead encephalopathy also likely

Iron (Fe/Ferrum)

Easily available as an OTC dietary supplement, ingestion of such is the primary exposure

325mg ferrous sulfate contains 65mg elemental iron
300mg ferrous gluconate contains 36mg elemental iron
100mg ferrous fumarate contains 33mg elemental iron
For prenatal vitamins and children's vitamins, check label/manufacturer's site
Ingestion of >20 mg/kg associated with moderate toxicity
Ingestion of >60 mg/kg associated with severe toxicity

Less commonly, iron toxicity can result from multiple transfusions for leukemia, thalassemia, etc.
Toxicity divided into two mechanisms

Caustic/corrosive effect results in direct injury to GI mucosa, can lead to perforation, peritonitis --> hemorrhage, death

Typically occurs during the first 6 hours
Iron tablets are visible on XR

Cellular toxicity is due to disruption of oxidative phosphorylation in the mitochondria, free radical formation and oxidative damage

GI symptoms may resolve prior to appearance of systemic symptoms
Nephropathy, cardiomyopathy, hepatopathy, and coagulopathy follow
Serum Fe levels >350μg/dL associated with moderate symptoms, >500μg/dL associated with severe symptoms

Treatment indicated for those a) with symptoms, or b) who have ingested potentially toxic quantities

Patients with resolved GI symptoms should continue observation/care for emergence of systemic symptoms
Decontamination with WBI indicated if large amount of pills are visible on XR
Patients with severe symptoms (acidosis, hemodynamic compromise) or high serum Fe level should receive deferoxamine chelation at 15 mg/kg/hr (max 35 mg/kg/hr) for up to 24 hours (or up to 6g)
Can give VitK and FFP to treat coagulopathy
Otherwise, supportive care as appropriate

Copper (Cu/Cuprum)

Exposure is most commonly from copper-containing cookware, contaminated water, or copper-containing pesticides or creams
Wilson's disease is also associated with high bioaccumulation of copper
Ingestions, like with iron, cause a direct gastropathy resulting in abdominal pain, vomiting, GI bleeding, et al. w/ potential for blue-green emesis (think how copper-containing surfaces like the Statue of Liberty develop verdigris)
High serum levels of copper can lead to:

Neuro — cognitive changes, encephalopathy
Cardiac — cardiomyopathy
Hepatic — necrosis
Heme — coagulopathy, hemolysis, methemoglobinemia
Renal — rhabdomyolysis, AKI

Treatment, again, is mostly supportive + decon/chelation

High-dose zinc can help lower GI absorption
Classically, D-penicillamine is the chelating agent of choice, given at a starting dose of 750mg QID
Can also use "single pass albumin dialysis" vs other extracorporeal cupriuresis
Symptoms generally reversible with successful elimination of copper

Other little lessons from episode #8:

If you have a backyard pool, invest in locked rigid covers and alarms, because otherwise the kids will find a way to get in
You're not dead until you're warm and dead — unless you're in rigor mortis, have obvious traumatic injuries incompatible with life, have snow in your airway after being buried by snow, or have a K > 12
If you lose any part of your body, to maximize the chances of replantation, you or someone else (if you're unstable) should retrieve it, wrap it in a moist towel/napkin/cloth, place it in a plastic bag, then put that plastic bag on ice
Peter Safar, the University of Pittsburgh, and the Freedom House Ambulance Service are the progenitors of the modern EMS model — a public service staffed by trained personnel tthat can provide care en route to the hospital, as opposed to a taxi service
Have a high index of suspicion for human trafficking (and/or other forms of abuse) when the patient is accompanied by someone who answers questions for them and refuses to allow a private history/exam; do your best to finagle a private conversation and assess safety, and consult social work to help provide resources if needed

References:
https://www.ncbi.nlm.nih.gov/books/NBK560920/
https://www.ncbi.nlm.nih.gov/books/NBK499935/
https://www.ncbi.nlm.nih.gov/books/NBK541097/
https://www.ncbi.nlm.nih.gov/books/NBK459224/
https://www.ncbi.nlm.nih.gov/books/NBK557456/

POTD: Mandated Reporters (LLFTP #7)

Daniel Ye · March 4, 2025 ·

We're back to our regular installments of "Lesson Learned From The Pitt", now covering episode 7 as we slowly catch up to the releases.

Spoilers, oh boy are there spoilers. Here's a link to a quick reference guide for the TL;DR crowd.

And a trigger warning for allegations of CSA.

To me, episode 7 is where the Grey's Anatomy-esque drama really starts to kick off. We've been seeing signs of various teakettles slowly reaching their boiling points across the first third of the season, and the first to boil over is — unsurprisingly — the man who's been crushed by a multiple days' worth of critical patients in a single morning, while juggling patient satisfaction concerns, while dealing with increasingly-frequent PTSD flashbacks. When Whitaker eats lunch at a desk, he tells him off for not eating in the lounge (and for spilling a boatload of crumbs on the workstation, get that boy a SLP evaluation!) while also implying that it's too busy for the student to be eating. When Dr. Mohan orders additional labs on a patient he'd medically cleared for psych evaluation (premature closure after not taking an actual history, nice!) he berates her rather than appreciate her ability to tease out highly relevant and plan-changing information in the history, with Dr. Collins being caught in the crossfire for supporting her junior. But Dr. Robby's real explosion is yet to come, so let's turn to someone else who crosses the Rubicon this episode.

Dr. Mohan isn't the only one who's a bloodhound on tiny details — we've been seeing Dr. Santos investigate the mystery of the hard-to-open benzo vial in the background, and in this episode her vigilantism will continue. Previously, a trauma patient (s/p mechanical fall from ladder) had needed intubation and a chest tube; Dr. Santos had noticed gynecomastia (enlarged breast tissue) which could be a sign of an underlying condition like alcoholism, and decides this needs to be investigated further in the ED before she sees any new patients. On questioning the wife, we find out that she's been doping her husband's coffee with progesterone. Why? Because she suspects her husband of molesting their daughter, and wanted to "kill his libido".

Dr. Santos appropriately brings this to the attention of Dr. Robby (hey, she does know how to escalate to the right person!), knowing that they are mandated reporters in this state. However, Dr. Robby and social worker Kiara (both heavily overworked by this point) proceed to make one of the biggest fumbles of the show so far — telling her that they cannot make a report without "proof" and that this is all speculation. That they "can't do anything" unless the daughter comes forward. They are right in that they need to report the wife for poisoning her husband, which would at least be a first step (if suboptimal) in getting an authority involved in the situation.

Detective Santos goes around her attending and tries speaking to the daughter after a clumsy (and failed) attempt at building rapport. The daughter denies everything and is obviously uncomfortable with this conversation. And so our brilliant intern decides to take matters into her own hands, by entering the room of an intubated and vulnerable patient, confronting him, and threatening him ("blink once if you want me to let you die"). Whether Mr. Dunn is an abuser or not (at this point we only have allegations, and in America we believe in "innocent before proven guilty"), for a physician to behave in this manner is beyond the pale. Our ethical duty is to provide unbiased and professional care to everyone regardless of their standing, and certainly not to threaten a patient with prison rape or even murder (imagine being an innocent man or woman and having your doctor come into the room accusing you of heinous crimes, while you're powerless to do anything if they decide to disconnect your ventilator). Taken in context with Dr. Santos's pattern of reckless behavior and disregard for others, I can only hope that the trauma bay is recorded (like ours) and this leads to disciplinary action.

What should Dr. Santos have done?

She's absolutely right about being a mandated reporter. In both PA and NY law, most professions that come into contact with vulnerable populations (such as children) fall into that category. The threshold to make a report is not "we need proof", it's "reasonable cause to suspect". PA law clearly states that a specific disclosure by a third party to a mandated reporter that an identifiable child is the victim of child abuse meets that standard; that the accuser is the alleged victim's other parent heightens the need to make a report. NY law, which is what matters for us, specifies that a report should be made "when they have reasonable cause to suspect that a child coming before them in their professional or official capacity is an abused or maltreated child, or when they have reasonable cause to suspect that a child is an abused or maltreated child where the parent, guardian, custodian or other person legally responsible for such child comes before them in their professional or official capacity and states from personal knowledge facts, conditions or circumstances which, if correct, would render the child an abused or maltreated child". #Believe when it comes to the threshold for making a report. Let the police do the investigation.

Both PA and NY have hotlines for mandated reporters to make reports. In New York, we can call the State Central Register Mandated Reporter hotline directly at (800) 635-1522. Reports can also be made anonymously at (800) 342-3720. For mandatory reports, a written report must be made and sent within 48 hours of the call. Reports are confidential. One does not need the approval of a supervisor to make reports. One cannot be held liable for good faith reports. One is theoretically shielded from backlash/retributions from making reports. Not reporting when you have reasonable suspicion is a thoughtcrime for which one can be hit with a Class A misdemeanor. PA offers similar protections as NY, and even harsher penalties for failure to report (up to a 2nd degree felony).

It's hard for someone, especially a transitional year intern, to gainsay the attending. But would you be willing to commit a crime for the attending? We already know Dr. Santos is willing to commit crimes for herself :D

Other little lessons from episode 7:

To quote Dr. Collins, "leave your baggage at the door like everyone else". An impaired physician, nurse, paramedic, etc. is a terrible thing for a patient.
Dr. King demonstrated an excellent conversational approach to patients with autism spectrum disorder. She minimized distractions by closing the doors, shutting off alarms, and turning down the lights. She invited the patient to speak about their concerns and verbalized empathic statements. She was patient with her clarifications. She took time to explain the diagnosis at the patient's level of understanding. Note that these are things that can be done with all patients to improve their experience.
During a cardiac arrest code, the team attempts double sequential defibrillation for refractory v-fib. The 1st shock theoretically potentiates the effect of the 2nd. Unfortunately, meta-analyses have found no overall benefit to v-fib termination (or survival), and it is not recommended by the AHA for routine use.
For that same code, the team activates their ECMO team. Extra-Corporeal Membrane Oxygenation is a technology that oxygenates a patient's blood outside the body and then returns it, analogous to hemodialysis. Broadly-speaking, it is indicated for acute cardiac or pulmonary failure that is potentially reversible, has failed conventional treatment, and carries a high risk of death. In-hospital cardiac arrest is an example of a condition that has a decent chance (~30%) of survival with ECMO.

References:
https://www.pa.gov/content/dam/copapwp-pagov/en/dhs/documents/keepkidssafe/clearances/documents/FAQ_Mandated%20Reporter.pdf
https://www.nyc.gov/site/acs/child-welfare/mandated-reporters.page
https://www.nysmandatedreporter.org/SocialServiceLaw.aspx|
https://www.ncbi.nlm.nih.gov/books/NBK544231/
https://www.ahajournals.org/doi/10.1161/res.135.suppl_1.Mo035
https://pmc.ncbi.nlm.nih.gov/articles/PMC7867121/

POTD: Platelet Transfusions

Daniel Ye · March 3, 2025 ·

We're going to kick this week off with a PSA requested by the admins and blood bank — a clarification on the kind of platelets we have and how (and when) to order them, especially as part of a massive transfusion protocol.

First, let's start with a quick review. The most common definition of "massive transfusion" is replacement of one blood volume (approximately 10 units, or 5 liters) within a 24-hour period; but more useful to us in the emergency setting are the alternative definitions of transfusion of >4 units of pRBC within 1 hour, or 50% of blood volume within 3 hours, with foreseeable ongoing need. In this setting, the patient is at risk from the lethal triad of hemorrhagic shock — hypothermia, acidosis, and coagulopathy. Healthcare institutions have developed their own "massive transfusion protocols" as streamlined workflows to expedite delivery/administration of blood products and mitigate the lethal triad.

As we've learned in prior POTDs, in MTPs we transfuse blood products in specific ratios in order to mitigate dilutional coagulopathies — fresh frozen plasma (FFP) provides the fibrinogen, protein C and S, and coagulation factors that are missing in packed RBCs, and platelets are platelets. Sometimes a protocol also calls for cryoprecipitate, which is derived from FFP and contains fibrinogen, factor VIII, factor XIII, and vWF. The "textbook" ratio that you'll hear is a 1:1:1 ratio of pRBCs:FFP:platelets, though some protocols call for a 2:1:1 ratio which has not been found to be inferior.

Here at Maimonides we use the 1:1:1 approach. However, that doesn't mean that we order 4 units of pRBCs, 4 units of FFP, and 4 units of platelets in SCM. Each "unit" of platelets in the 1:1:1 approach refers to a unit of platelets derived from whole blood donation, which yields >55 billion platelets in ~50 mL. However, as technology has advanced, most platelets are now gathered through apheresis — a procedure that removes platelets from blood and returns the remainder to the donors, yielding >300 billion platelets in ~250-300 mL. Thus, our single unit of platelets here is roughly equivalent to 5-6 old-school units of platelets.

As you can see on the ED blood bank request form, we order 1 unit of platelets in each round of MTP to go along with 4 units of pRBCs and 4 units of FFP. A similar ratio can be seen in the pediatric weight-based protocol as well. The indications for MTP here are also stated. For adults: massive bleeding, 10 units in short period with uncontrollable blood loss, ruptured aortic aneurysm, abruption placenta, post-partum bleeding. For peds: massive bleeding, anticipated blood loss of 100% TBV within 24 hours, ongoing hemorrhage of >10% TBV/minute, replacement of >50% TBV within 3 hours.

When you place the order for platelets through the "ED Blood Products Order Set", you can also see that 1 unit (at 200 mL/hr) is the default selection. Leave this at 1 unit for the vast majority of cases including MTP. If you order 4 units here, it'll look like you want to give the patient 20+ standard units of platelets. The blood bank won't actually give you extra units of platelets without question, but it creates confusion in the system.

Outside of massive hemorrhage, there are several indications for administering a platelet transfusion. The list of approved indications is found in the drop-down menu when ordering platelets through the order set, and include:

active bleed on antiplatelet medication with documented platelet dysfunction
platelet count < 20K prior to central line placement
platelet count < 20K prior to bone marrow biopsy/aspiration
platelet count < 20K prior to diagnostic lumbar puncture
platelet count < 10K with or without active bleeding
platelet count < 50K with active bleeding or prior to major surgery
platelet count < 100K prior to neurosurgery or ophthalmic surgery

A single unit of apheresis platelets is expected to increase the platelet count by 30K-60K (per µl) in a 70 kg patient. For most of the above indications, transfusing 1 unit is generally sufficient; if the deficit is wide, a 2nd unit can be ordered after rechecking a platelet count.

There are times when the platelet count is low and platelet transfusion is not indicated. In immune thrombocytopenic purpura, treatment is IVIG + steroids with platelets only recommended prior to procedures/surgery or if there is life-threatening bleeding. Meanwhile, platelet transfusion is contraindicated in thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia due to increased risk of arterial thrombosis and death, with the exception of cases of life-threatening bleeding.

Further reading on recent guidelines from the Association for the Advancement of Blood & Biotherapies and Pathology and Laboratory Medicine at Henry Ford Health are linked.