EM Quick Hits 58 – HIV PEP and PrEP, PREOXI Trial, Blast Crisis, Nitrous Oxide Poisoning, Vasopressors in Trauma

Topics in this EM Quick Hits podcast

Megan Landes on providing HIV PEP and PrEP in the ED (1:05)

Justin Morgenstern and George Kovacs on evidence for pre-oxygenation with NIPPV before intubation in RSI (19:05)

Brit Long on recognition and management of blast crisis in the ED (41:31)

Leah Flanagan and Liam Loughrey on the rise of nitrous oxide toxicity (50:40)

Andrew Petrosoniak on the role of vasopressors in the hemorrhaging trauma patient (59:55)

Podcast: Play in new window | Download (Duration: 1:11:42 — 65.7MB)

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Podcast production, editing and sound design by Anton Helman

Podcast content, written summary & blog post by Brandon Ng and Brit Long, edited by Anton Helman, July, 2024

Cite this podcast as: Helman, A. Morgenstern J. Landes, M. Kovacs, G. Long, B. Flanagan L. Loughrey, L. Petrosoniak, A. EM Quick Hits 58 – HIV PEP and PrEP, PREOXY Trial, Blast Crisis, Nitrous Oxide Poisoning, Vasopressors in Trauma. Emergency Medicine Cases. July, 2024. https://emergencymedicinecases.com/em-quick-hits-month-year/. Accessed October 9, 2024.

HIV Post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP)

This is part 2 of our 2-part EM Quick Hits series on HIV. We suggest reviewing part 1 if you haven’t already – Part 1 of this 2-part EM Quick Hits series on HIV

• PEP is an effective method for reducing the risk of transmission for persons who have been exposed to HIV. It needs to be given less than 72 hours from initial exposure to be maximally effective and is prescribed as a 28-day course of Anti-retroviral therapy (ART).
• PEP reduces the relative risk of a single exposure event to HIV by 80% (reduces risk of percutaneous exposure and mucocutaneous exposure to HIV positive blood to 0.3% and 0.09%, respectively).
• Note that every risk of exposure to HIV is relatively low, and PEP reduces that to an even more minuscule risk.

HIV post-exposure risk stratification and indications for post-exposure prophylaxis (PEP)?

1.Determine the source risk for transmissible HIV, which can be categorized into substantial, low but nonzero, and negligible/none:

Source: Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis by Tan et al. EMAJ 2017

• Concomitant STIs increase the risk of transmitting HIV through methods such as breaking down mucosal barriers and increasing inflammatory states.

2.Determine the type of transmission:

Source: Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis by Tan et al. EMAJ 2017

• There is no good data on the risk of HIV transmission via mucocutaneous splash. Refer to your local occupational health policies.

Who should we advise to start PEP?

• Consider PEP if the source risk is in the substantial category and the type of exposure is high/moderate risk.
• PEP is not recommended if the source’s risk is negligible/none and the exposure type is low risk.

Indications for pre-exposure prophylaxis for HIV (PrEP)?

• PrEP is ARTs (e.g. Truvada®) on an ongoing basis due to expecting repeated high-risk exposures to HIV.
• There is a relative risk reduction of 44% and a NNT of <15.
• People who should consider taking PrEP include: sexually active adults who have ongoing exposure (e.g. ongoing condomless sex with known HIV exposure), patients with recent STI, and those presenting to ED for recurrent PEP.
• There are also current studies and ongoing evidence for adding doxycycline to PrEP regimen to reduce the risk of bacterial STI and syphilis.

Bottom line => Early diagnosis and initiation of treatment is important in the management of HIV; Consider having easy access to the tables from the Canadian guideline for referencing in the ED to help guide counselling patients on PEP and PrEP; know resources that are available to you and your patients.

Part 1 of this 2-part EM Quick Hits series on HIV

Additional resources on HIV risk and PrEP/PEP:

• Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis by Tan et al. EMAJ 2017
• PrEP for health provide or patients: ontarioprep.ca
• Online access to PrEP for patients:
  • https://www.gofreddie.com
  • https://www.prepclinic.ca

Pre-oxygenation with positive pressure ventilation – PREOXI Trial

Background: There are potential benefits of using non-invasive positive pressure ventilation (NIPPV) for pre-oxygenation in preparation for intubation in RSI. In abnormal airways with VQ mismatch and shunt physiology (e.g. CHF or pneumonia), desaturations may still occur despite receiving oxygen via a non-rebreather through a patent airway. This abnormal physiology may be improved with devices that provide PEEP (e.g. BIPAP, CPAP).

The Paper: Noninvasive Ventilation for Preoxygenation during Emergency Intubation by Gibbs et al. NEJM 2024.

• P: Critically ill adult patients to receive pre-oxygenation prior undergoing tracheal intubation.
• I: Use of NIPPV during pre-oxygenation.
• C: Oxygen by bag mask ventilation or non-rebreather during pre-oxygenation.
• O: Peri-intubation hypoxemia (defined as oxygen saturation <85% between induction of anesthesia and 2 minutes after intubation): 9% in the noninvasive group, 19% in the oxygen mask group, NNT = 10. Hypoxemia with saturations <70%: 2% in noninvasive group, 6% in oxygen mask group. Peri-intubation arrest: n=1 (0.2%) in the noninvasive group, n=7 (11%) in the oxygen mask group. There was no difference in rate of aspiration or other safety outcomes.

Limitations of the PREOXI trial:

• being unblinded, errors related to measuring oxygen saturation
• primary outcome being a surrogate monitor based outcome rather than a patient oriented outcome
• having a broad trial population

Bottom line => Use of NIPPV for pre-oxygenation prior intubation in RSI may be beneficial. Consider using PEEP in preoxygenation phase if unable to improve oxygen saturation despite using non-rebreather mask at flush rate.

Additional insights into the PREOXI trial and tips on pre-oxygentation from Dr. Kovacs

• Patients should be divided to those with “normal lungs” and those with “abnormal lungs”, which the PREOXI trial did not do.
• Patients with normal lungs can be pre-oxygenated via nitrogen wash out with 100% O2 up to flush rate to exceed inspiratory flow rates. They have more time for safe apnea, and generally do not require PEEP. Those with abnormal lungs likely require PEEP to recruit alveoli that are filled due to pathology (akin to newborn lungs filled with fluid or “baby lungs”), which can be accomplished either by NIPPV or by utilizing the PEEP valve on a BVM and providing gentle ventilation (‘gentilation’) during pre-oxygenation after induction of anesthesia.
• The PREOXI trial’s primary outcome does not account for clinical outcomes such as hypotension and hypoxemic events which have been shown to cause significant delayed morbidity.
• Consider simple nasal prongs at maximal flow during the entire pre-oxygenation, anesthesia induction and apneic phase during laryngoscopy
• Emerging evidence suggests that high-flow nasal cannulae (such as Optiflow or Vapotherm) are also effective for pre-oxygenation in patients with abnormal lungs. They are well tolerated and can be used in all but patients who are in the most critical condition.

Deep dive video presentation on pre-oxygenation with Dr. George Kovacs:

Blast crisis – recognition and management

• Definition: > 20% of blasts in the peripheral blood or bone marrow, or an accumulation of blast cells outside of the bone marrow (lymph nodes, skin, spleen, or central nervous system).
• In most cases, blast crisis occurs in CML. Up to 30% of patients with ALL or AML can present with leukocytosis and high blast numbers.
• The median survival is 7-11 months after diagnosis.
• 4 issues in blast crisis
  1. Anemia and thrombocytopenia due to crowding in bone marrow by blasts
  2. Immunocompromised state as blasts are poorly functioning WBCs
  3. Leukostasis which leads to end-organ injury
  4. Tumor lysis syndrome due to rapid cell death
• Presentation: Fever, night sweats, weight loss, and bone pain are common in patients with blast crisis. Fever occurs in up to 80%.
• Pulmonary and neurologic systems most commonly affected in leukostasis.
• Evaluation/workup focuses on evaluating for anemia/thrombocytopenia, infection, leukostasis (WBC > 100,000), pulmonary/neurologic issues, and tumor lysis syndrome. Consider CBC with differential and peripheral smear, renal & liver function, electrolytes, uric acid, phosphorous, coagulation panel, type and screen, fibrin split products, fibrinogen.
• Management of blast crisis
  • Oncology consultation early to facilitate induction chemotherapy and/or leukapheresis
  • Anemia: Avoid transfusing RBCs if possible (may worsen leukostasis)
  • Thrombocytopenia: Transfuse platelets if < 20,000 (increased risk of intracranial hemorrhage), severely symptomatic, unstable, or have severe bleeding
  • Immunocompromised state: Administer broad-spectrum antibiotics
  • Leukostasis: Induction chemotherapy and/or leukapheresis (needs oncology involvement). Avoid diuresis
  • Tumor lysis syndrome: IV fluids, avoid giving calcium unless the patient has arrhythmias due to hyperkalemia, and rasburicase. Possible hemodialysis

Subacute combined degeneration of the spinal cord secondary to nitrous oxide toxicity

Nitrous oxide is increasingly being used as a recreational drug. Nitrous oxide use is associated with subacute combined degeneration of the spinal cord.

Subacute combined degeneration of the spinal cord clinical clues:

• Clumsiness, stiff or awkward movements
• Mental changes, which can range from mild memory problems, irritability, apathy, and confusion, to severe dementia and psychosis
• Blurry vision, decreased visual acuity
• Unsteady gait and loss of balance with positive Romberg
• Paresthesias lower extremities, loss of vibration sense
• Hoffman sign may be present (flexion and adduction of the thumb and flexion of the index finger)

Investigations:

• CBC (looking for macrocytic anemia), renal and liver function, electrolytes, thyroid function. HIV & syphilis if indicated.
• B12 (which may be normal) and folate.
• Methylmalonic acid (MMA) and homocysteine levels before initiating treatment.
• Semi-urgent MRI should be arranged within a few days of presentation

Management:

• B12 and folate supplementation (evidence in unclear)
• Counselling on ceasing nitrous oxide use

Without cessation of nitrous oxide use, there is a risk of long-term irreversible neurological impairment.

Bottom line => Have nitrous oxide toxicity on your differential in patients with vague/progressive neurological symptoms or a history of other recreational use, or suggestive physical exam findings in the absence of patient disclosure. Order B12, folate, methylmalonic acid (MMA), and homocysteine on the day of presentation. Consider starting them on B12 and folate.

The role of vasopressors in the bleeding trauma patient

There is a long-held belief that vasopressors have no role in the management of bleeding trauma patients. Typically, priorities in managing bleeding trauma patients include hemostasis and restoration of adequate blood volume for organ perfusion. Administering vasoconstricting agents is unlikely to help when there is not enough blood volume to perfuse the vital organs. Additionally, restoring perfusion before hemostasis can be counterproductive, and patients can bleed more with increased pressure and flow. However, vasoplegia can occur in hemorrhaging trauma patients and there is a theoretical upside to vasopressors to reduce blood loss, improve hemodynamic instability, and buy time for the patient to go to the OR to achieve hemostasis.

The evidence for or against vasopressors in trauma patients is scant at best, with most being from cohort studies where critically ill patients who worsened with vasopressors:

• In the AVERT shock trial published by Sims et al. JAMA Surgery 2018: there is a significant decrease in the need for blood product in bleeding patients who received low dose vasopressin (not surprising as clinicians are likely to hold additional blood products with increased BP). There were no differences in patient-centered outcomes such as length of ICU stay, mortality, which were secondary outcomes in the trial. The author’s concluded based on their primary outcomes that early administration of AVP during the resuscitation of trauma patients with hemorrhagic shock leads to decreased use of blood products at 48hours without increased complications (except .
• There is a strong recommendation (but low-quality evidence) by the European guideline published by Spahn et al.,Crit Care 2019 which states: “In the presence of life-threatening hypotension, we recommend administration of vasopressors in addition to fluids to maintain target arterial pressure. (Grade 1C)”

Bottom line => There is insufficient evidence to guide the use of vasopressors in early trauma resuscitation despite guideline recommendations for its use. There is no substantial evidence for their benefits, however they may decrease the need for blood products. There is theoretical harm that has not been shown in studies to date. They may be useful in a minority of cases where there is a significant delay to obtaining blood products in the shocky patient and in patients refractory to blood products with a delay to source control who are in shock. Vasopressors should rarely be your first option. Efforts should be directed towards blood volume restoration and hemostasis.

None of the authors have any conflicts of interest to declare