Happy Thursday, and welcome to #2 in "Lessons Learned from the Pitt"!
Obligatory spoiler warning.
Episode 2 of The Pitt is packed with new cases, and befitting the show's messaging most of them highlight classic presentations or common challenges that we see in the ED. Two of the cases — Nick Bradley (unintentional opioid overdose with likely severe anoxic brain injury) and Mr. Spencer (acute respiratory failure + pneumonia + septic shock with family controversy over his advanced directives) — become Dr. Robby's focus over several episodes, and I'll try to cover them in subsequent POTDs. Today I'm going to highlight the case of Joyce, who presents in sickle cell pain crisis, which is something that we don't see quite as often at Maimonides compared to some other institutions due to our location / patient demographics (I myself have seen more sickle cell pain crisis patients at a Houston public hospital as a medical student than throughout residency).
The case begins at around 8:30 AM when EMS wheels in a screaming woman, stating "drug-seeking woman kicked off a city bus for disrupting and disturbing passengers, screaming for narcotics nonstop, we found an empty Percocet bottle from 5 days ago. She's been uncooperative and combative since we picked her up". One of the ED staff tells her to "calm the f*** down or I'll call the cops". The patient at last is able to say that she was the one who called 911 for help, and that she has sickle cell. PGY3 Dr. Mohan steps in at that point, deescalates the situation, and orders 10mg IV morphine (repeated x1 more dose in 5 minutes prn) and a dilaudid drip. On reassessment several minutes later, MS4 Whitaker expresses some surprise/uncertainty regarding the safety of the analgesic dosing (20mg IV morphine total), and gets himself pulled aside and learned about sickle cell pain. Apparently the patient's initial workup is already done in this < 10 minute span (my main complaint with the show is how fast the results come, which I understand is for the sake of pacing but I worry will increase unrealistic expectations by the public) as the hemoglobin has dropped and Dr. Mohan plans to admit the patient for exchange transfusion.
Let's first review the pathophysiology of sickle cell disease. The textbook cause is a single nucleotide mutation of the β-globin gene, a Glu → Val substitution which subsequently causes abnormal protein folding (and as the old biochemistry mantra states, "structure denotes function"). When oxygen concentration is low (such as in capillary beds), this abnormal hemoglobin S (HbS) aggregates and leads to deformation of the red blood cells into a rigid "sickle" shape; in young erythrocytes this reverses upon returning to an oxygen-rich environment, but after multiple cycles they become more rigid and permanently "sickled". These "sickle cells" have a tendency to adhere to vessel walls and occlude small vessel lumens, which can lead to vaso-occlusive (ischemic) pain crises. Sickle cells are also destroyed in the spleen, which leads to sequestration, scarring, and eventual autosplenectomy. Release of heme and other intracellular products from these destroyed cells also signals the body to produce pro-inflammatory factors, leading to a vicious cycle of worsening disease.
The gene for HbS can be found across most ethnic groups, but is most prevalent by far in populations originating from tropical/sub-tropical regions with longstanding endemic malaria (sickle cell is protective against malaria). The majority of patients by far are African, with South Asian and Middle Eastern populations also at risk. Patients with sickle cell face numerous challenges in both chronic and acute management of their condition: limited access to primary care, limited access to specialists (especially for adults), limited access to effective pain medications, limited ability to obtain disease-modifying medications (my most recent SCD patient had recently been denied continued coverage of her hydroxyurea by UnitedHealthcare, even with her history of 2 prior strokes and trimonthly admissions for vaso-occlusive pain crises), limited access to curative hematopoeitic stem cell transplantation and adjuncts (in 2023, the FDA approved exagamglogene autotemcel [Casgevy] and lovotibeglogene autotemcel [Lyfgenia] for patients with recurrent vaso-occlusive crises; both carry a price tag upwards of $1-2M); overall resulting in poorer disease outcomes, with median age of death at 45, and a notable increase in mortality rate during the transition from pediatric to adult care.
While our individual ability to effect systemic change is limited, it is within our power to improve the management of the acute pain of patients with sickle cell disease. Although the NHLBI officially recommends opioid medications for vaso-occlusive pain crises, past studies have shown that sickle-cell-related pain is routinely undertreated, with "pain medication seeking" concerns often being cited as a prevailing attitude. Whether this comes from a place of implicit/explicit bias or from a place of opioid stewardship, the end result is that patients experience unnecessary prolongation of suffering in the short term, and in the long term are discouraged from seeking care (avoiding particular hospitals, or delaying presentation) and bear the burden of additional psychosocial distress.
Many patients with sickle cell associated pain will have a home pain regimen that usually includes escalating dosage/frequency/types of opioids, and at time of presentation to the ED their home regimen has been insufficient in controlling their pain. Information might be available as to what hospital-administered medications have been efficacious in the past, either from the EMR or endorsed by the patient. UpToDate provides the following workflow for treatment of the patient who presents with sickle cell pain crisis, with the mainstays being 1) frequent reassessment of pain and dose escalation, and 2) medical workup.
One of the most dangerous complications of sickle cell disease is acute chest syndrome, where vaso-occlusion occurs in the pulmonary vasculature and leads to ischemic injury of the lung parenchyma. This is often precipitated by a disease process that lowers the oxygen saturation, such as lung infection. Acute symptoms, physical exam findings, lab results, and imaging findings are often similar between acute chest syndrome and pneumonia; patients will usually be able to proffer a history of sickle cell disease, which should raise concern for the former, and if past results are available a drop in Hgb may be present as well. The differential diagnosis also includes pulmonary embolism, acute coronary syndrome, etc. Patients are also at risk for complications in other systems including acute liver injury, acute kidney injury, and stroke.
Treatment of acute chest syndrome (beyond pain control) can be divided into two major buckets: 1) treat the underlying cause, and 2) reduce sickling. For the former, we start with giving broad-spectrum antibiotics for pneumonia (e.g. ceftriaxone/doxycycline), with consideration for presence of risk factors for MRSA and pseudomonas. For the latter, we can give supplemental O2, bronchodilators if asthma/bronchospasm are suspected, and most importantly transfusions.
Simple RBC transfusion increases the oxygen carrying capacity and reduces the overall proportion of sickled cells. The American Society of Hematology recommends simple RBC transfusion for cases of "moderate" acute chest syndrome with Hgb < 9 gm/dL (thresholds of < 5 gm/dL have also been proposed, as there is a risk of hyperviscosity syndrome (which would lead to end-organ injury) with elevated Hgb in this disease process); "moderate" here refers to cases without large drop in Hgb (<20% decrease from baseline if known), without hemodynamic instability, without need for invasive respiratory support.
Exchange transfusion comprises large-volume removal of the patient's blood and replacement with donor blood. This allows rapid removal of a large proportion of sickled cells and HbS without significant risk of hyperviscosity. The ASH recommends exchange transfusion for severe disease, rapidly-progressing disease, multilobar pulmonary involvement, multi organ failure, failure to respond to simple transfusion, Hgb > 9 and cannot receive simple transfusion. Automated red cell exchange is preferred over manual, and transfer should be considered early in patients with manifestations of severe sickle cell crisis.
Other little lessons from Episode 2:
Always wear a helmet when riding a bike or scooter!
Fentanyl testing strips are available to the public; however, newer (and more potent) synthetic opioids might not be detected.
Watch out for compartment syndrome after electric shock injury (or other thermal injuries).
The only person you can count on 100% to honor your advanced directives is yourself. Do what you need to do protect yourself and your right to self-determination.
A "kill list" is probably the worst kind of list a teenaged boy can write, and as Dr. McKay points out (and will continue to repeat) it should raise high concern for imminent harm especially if said boy then goes radio silent.
References:
https://journals.sagepub.com/doi/full/10.1177/0033354919881438
https://www.ncbi.nlm.nih.gov/books/NBK441872/
https://www.uptodate.com/contents/acute-vaso-occlusive-pain-management-in-sickle-cell-disease
https://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-sickle-cell-disease
https://www.uptodate.com/contents/acute-chest-syndrome-acs-in-sickle-cell-disease-adults-and-children
https://www.hematology.org/-/media/hematology/files/education/clinicians/guidelines-quality/documents/watermarked-pocket-guides/watermarked-ash-scd-transfusion-pocket-guide.pdf (this is a PDF download)