REBEL Cast

By Salim R. Rezaie, MDMedicine Health & Fitness

REBEL Cast episodes

May 29, 2024 REBEL Core Cast 123.0 – Posterior Epistaxis
Take Home Points: Posterior epistaxis is a rare, life-threatning presentation. The key is in identifying and rapidly gaining control with a posterior pack or foley catheter. These patients often require surgical intervention so get ENT to the bedside and admit to a place with a higher level of monitoring. REBEL Core Cast 123.0 – Posterior ... Read more
The post REBEL Core Cast 123.0 – Posterior Epistaxis appeared first on REBEL EM - Emergency Medicine Blog.
7 min
May 23, 2024ANNEXA-1: Andexanet Alfa Associated with Harm in DOAC Reversal
Background: In May of 2018, Andexanet alfa gained accelerated approval by the FDA for the reversal direct oral anticoagulants (DOACs) despite a lack of robust evidence for use. The 2022 AHA/ASA guidelines give the drug a level 2A recommendation and recommend it over the use of 4F-PCC (Greenberg 2022). FDA approval alongside guideline endorsement has led to the drug seeing a remarkable growth in use without a single high-quality study to support its use. The available data reports good hemostatic control: a subjective measure that is highly biased by unblinding and selection bias. More importantly, there are no studies comparing andexanet alfa to 4F-PCC or even placebo looking at important, patient-centered outcomes.
REBEL Cast WEE – ANNEXA-1 – Andexanet Alfa Associated with Harm in DOAC Reversal
Click here for Direct Download of the Podcast.
Article: Connolly SJ et al. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage (ANNEXA-1). NEJM 2024; 390(19): 1745-55. PMID: 38749032
Clinical Question: Does the use of andexanet alfa in patients on DOACs with intracerebral hemorrhage improved hemostatic efficacy?
Population: Patients > 18 years of age on a factor Xa inhibitor (taken within 15 hours of randomization) with an acute intracerebral hemorrhage.
Outcomes:
Primary: Hemostatic efficacy assessed at 12 hours after randomization. Hemostatic efficacy was defined as:
Excellent hemostatic efficacy: Change in hematoma volume < 20%
Good hemostatic efficacy: Change in hematoma volume < 35%
Increase in NIHSS < 7 points at 12 hours
No receipt of rescue therapies within 3-12 hours from randomization
No surgery to decompress the hematoma within 3-12 hours from randomization.
Secondary: Percent change from baseline in anti-factor Xa activity during the first 2 hours from randomization
Safety Endpoints (assessed at 30 days)
Thrombotic events (ischemic stroke, myocardial infarction, VTE).
Death
Intervention: Andexanet alfa high-dose or low-dose bolus followed by infusion depending on time and dose from last DOAC use.
Control: Usual care
Design: Non-blinded, randomized controlled trial performed at 131 centers across 23 countries over 4 years.
Exclusions
GCS < 7 at the time of consent
NIHSS > 35
Surgery planned within 12 hours of enrollment
Thrombotic event within 2 weeks of enrollment
Time from symptom onset > 6 hours
Pregnancy
Results:
Primary results
581 patients were assessed for eligibility across 131 sites over 4 years
31 excluded prior to randomization
20 excluded after randomization due to consent issues
530 analyzed for the safety outcomes
263 patients assigned to andexanet alfa arm
267 patients assigned to usual care arm
452 patients were analyzed for the primary outcome
85.5% (195/228) patients in the usual care arm received 4F-PCC
78.1% (175/224) patients in the andexanet arm received the low-dose regimen
Critical Results
Andexanet alfa
Usual Care
Difference (95% CI)
P Value
Primary Outcome
Hemostatic Efficacy
67% (150/224)
53.1% (121/228)
13.4 (4.6 – 22.2)
0.003
NIHSS change < 7 points
87.9% (188/214)
83.0% (181/218)
4.6 (-2.0 – 11.2)
Secondary Outcome
Anti-Factor Xa % Change
-94.5% (-96.6 – 88.9)
-26.9% (-54.2 – -9.5)
Safety Outcome
Thrombotic Events
10.3%
5.6%
4.6 (0.1 – 9.2)
0.048
TIA
0
0
Ischemic Stroke
6.5%
1.5%
Myocardial Infarction
4.2%
1.5%
DVT
0.4%
0.7%
PE
0.4%
2.2%
Arterial Embolism
1.1%
0.7%
Death
27.8%
25.5%
0.51
Strengths:
This is the first randomized trial comparing andexanet alfa to standard care in this patient group.
Multicenter, multinational study increasing applicability of findings.
Outcome assessors were blinded to treatment arm.
Hematoma measurements were made with a standard protocol and central site adjudication.
12 hour NIHSS assessments were performed by health care professionals who were unaware of group assignments
Limitations:
Study funded, designed, and supervised by AstraZeneca Pharmaceuticals the maker of Andexanet alpha. Although, this does not refute the findings of this study, it should make readers skeptical.
Clinicians were not blinded to the treatment arm patients were randomized to. This may introduce bias particularly in terms of subsequent treatments (treatments outside of reversal are not detailed in the study).
Primary endpoint is not patient centered.
Convenience sample of patients which introduces bias.
There are some baseline differences between groups and it’s hard to say how this may have influenced the results.
Exclusion criteria are likely to be difficult for clinicians to assess real time leading to protocol violation (particularly items like planned surgery and recent thrombotic event).
Dose adjustment for time from ingestion likely to lead to protocol violation as this info difficult to assess.
Exclusion criteria: Removed the sickest patients.
Discussion:
The positive primary and secondary outcomes
Both the primary (hematoma expansion) and secondary (anti-factor Xa reduction) outcomes were better in the andexanet group.
Unfortunately, these are disease-oriented outcomes instead of patient centered outcomes: the patient doesn’t care if their hematoma expands by 20% or 25% or 30%. They care about clinically important outcomes like disability or death.
The authors note that in other studies, hematoma expansion has been associated with worse outcomes, but this was clearly not demonstrated in this study as 90d mRS and death were the same between groups.
Bottom line is that there wasn’t even a hint of improved clinical outcomes in the andexanet group.
Safety outcomes favored the usual care group
In general, larger studies or registries of patients are required to determine safety of a treatment.
In this study, however, there is a clear signal for harm even with a small group of patients under ideal circumstances (ie enrolled within a study).
Though death was not statistically different, the raw numbers favor usual care.
Thrombotic events were clearly increased in the andexanet group.
Across a larger group of patients outside of the pristine setting of a study, it is likely that we would see an increase in thrombotic events and death.
Only 85.5% of patients in the usual care group received 4F-PCC
Though there isn’t abundant evidence for the use of 4F-PCC in this setting, it does represent standard practice.
The authors do not report about the subgroup of patients who did not receive 4F-PCC and their outcomes.
If this data shows worse outcomes with no reversal treatment, it would suggest that usual care with 4F-PCC may be superior to andexanet alfa for clinical outcomes.
If this data shows improved outcomes with no reversal treatment, it would suggest that specific reversal agents aren’t necessary.
There were multiple protocol changes during the study. Typically, protocols should not be changed while the study is enrolling patients. This is often done to try to steer the data towards benefit.
Initial power calculation was for 900 patients to achieve a 90% power to detect and absolute difference of 10% points in terms of hemostatic efficacy but then made an addendum to the protocol to stop after 450 patients.
After this stop point, the safety and monitoring board recommended the trial be stopped.
Though the authors state they had no knowledge of the effect prior, there is no clear explanation given for this change and it raises the possibility that the trial was stopped prior to additional data showing harm was collected.
Drug cost
Andexanet alfa costs between $30 – 50,000/treatment. This only takes into account drug costs (ie not monitoring, nursing costs etc).
4F-PCC costs around $5-6,000/treatment.
Author Conclusion: “Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke.”
Clinical Take Home Point: The authors conclusions are correct. However, they don’t properly stress the findings.
Treatment of patients with intracerebral hemorrhage on a DOAC with Anexanet alfa did not improve clinical outcomes when compared to usual care. Based on safety data, andexanet alfa resulted in increased harm to patients. Andexanet alfa should not be part of the standard treatment in this scenario based on the available evidence.
References:
Greenberg SM et al. 2022 Guidelines for the Management of Patients with Spontaneous Intracerebral Hemorrhage: A Guideline from the American Heart Association/American Stroke Association. Stroke 2022; 53(7). PMID: 35579034
Connolly SJ et al. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage (ANNEXA-1). NEJM 2024; 390(19): 1745-55. PMID: 38749032
For More Thoughts on This Topic Checkout:
REBEL EM: ANNEXA-4 – Andexanet Alfa and Factor Xa Inhibitors
First10EM: Andexanet Alfa – More Garbage Science in the New England Journal of Medicine
EM Lit of Note: Disutility, thy Name is ANEXXA-4
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
The post ANNEXA-1: Andexanet Alfa Associated with Harm in DOAC Reversal appeared first on REBEL EM - Emergency Medicine Blog.
19 min
May 15, 2024REBEL Core Cast 122.0 – Neutropenic Fever
Take Home Points:
There are many causes of neutropenia, chemotherapy being by far the most dangerous.
Febrile neutropenia is a condition conveying high mortality. Early administration of antibiotics is the only factor known to reduce this mortality.
For a patient with neutropenic fever, remember that the body’s own flora is the greatest danger. Isolate, but do not wait to initiate treatment.
Check old blood cultures and obtain new cultures prior to starting treatment.
Identify low risk patients and send them home with PO antibiotics and close oncology follow-up in conjunction with your oncologist.
REBEL Core Cast 122.0 – Neutropenic Fever
Click here for Direct Download of the Podcast.
Neutropenia and Neutropenic Fever
Neutropenia: An absolute neutrophil count less than 500 cells/mm3 or less than 1000 cells/mm3 with a predicted decline to less than 500 cells/mm3
ANC = WBC x (neutrophil% + band%)
Mild: 1000 – 1500
Mod: 500 – 1000
Severe: 100 – 500
Profound: <100
Background
Neutrophils directly combat infection and are important to coordinating the body’s overall immune response.
The loss of these cells leads to immunosuppression as well as decreased responsiveness of the immune system as a whole
Patients with neutropenia will not only get very sick very quickly, but also will have blunted immune response and may not localize signs of infection well
Fever or malaise may be their only presenting symptoms.
Patients with hematologic malignancies are at highest risk for suffering profound and prolonged neutropenia. Particularly high risk are those undergoing induction chemotherapy or stem cell transplant. Allogeneic stem cell grafting is higher risk than autologous.
Neutropenic Fever: Fever (one reading of 38.3C or sustained 38.0C) + ANC < 500 cells/mm3 or expected to fall to < 500 cells/mm3 within the next 48 hours
Common problem during chemotherapy:
10-50% of patients with solid malignancy and >80% of patients with hematologic malignancy will experience at least one episode of neutropenia (IDSA 2010, Klastersky 2004)
Associated with high morality:
~90% without antibiotics (Perron 2014, Klastersky 2009)
~2-21% when treated with early antibiotics (Clarke 2011, Kruderer 2006)
Higher mortality rates with co-morbidities and hematologic malignancies
Time to antibiotic administration has been shown to directly impact mortality (Perron 2014, Rosa 2014, Marín 2015)
Causes of neutropenia (Gibson 2014):
Overconsumption
Sepsis
Autoimmune disease (SLE, rheumatoid arthritis, etc)
Underproduction by bone marrow
Malnutrition – alcoholism, anorexia, etc
Myelodysplastic syndrome
Post-viral: varicella, measles, rubella, influenza, hepatitis, Epstein-Barr virus, HIV
Drug induced: clozapine, methimazole, sulfasalazine, bactrim, b-lactam antibiotics, NSAIDs, ticlopidine, cephalosporins, chemotherapy
Chemotherapy:
Includes many drugs and drug regimens, all with the goal of killing rapidly dividing cells. Of note, this particularly affects:
Cancer cells – this is the reason chemotherapy works as treatment
Neutrophils – with a life cycle of only 1-6 days, their numbers are impacted dramatically by chemotherapy
Mucosa – destruction of dividing cells thins mucosal barriers, putting these patients at high risk for mucositis and bacterial invasion
This creates a dangerous situation where the body’s barriers against bacterial invasion are broken down and, thus, the ability to combat infection is severely blunted. Antibiotics are effectively the only thing standing between these patients and overwhelming sepsis.
Pathogens (Gudiol 2013):
The pathogens responsible for neutropenic fever have changed over time.
Initially, Gram (-) organisms translocated from the gut caused majority of cases of neutropenic fever
This changed in the 1990s. Gram(+) infections became more common due to more fluoroquinolone prophylaxis against Gram (-) organisms and due to more prevalent use of indwelling catheters for outpatient treatment
Over the past decade, there has been a resurgence of Gram (-) organisms due to increasing antibiotic resistance, particularly multidrug resistant E coli and klebsiella
Given the increasing rates of antibiotic resistance, antibiotic stewardship is becoming increasingly important
In the ED, we can contribute to antibiotic stewardship by checking old cultures and obtaining new ones prior to initiation of antibiotics
ED Evaluation and Management:
Resuscitate if necessary
Patients with neutropenic fever may rapidly progress to septic shock.
Give appropriate fluids, vasopressors, and antibiotics.
Antibiotics need to be given as quickly as possible if unstable
Perform a complete review of systems and physical exam looking for signs of focal infection
Basic Blood Work
CBC, BMP, LFTs, bilirubin levels
Blood cultures
If indwelling catheter present: 1 set from each line of indwelling catheter + 1 peripheral set
If no indwelling catheter present: 2x peripheral sets
Additional testing based on signs and symptoms:
Respiratory symptoms
CXR
Sputum cultures
Dysuria
Urinalysis
Urine culture
Abdominal pain
CT abdomen and pelvis
If diarrhea present, consider C difficile PCR (if available)
Isolation
Good hand hygiene is the most effective way to prevent these patients obtaining nosocomial infections
Use standard barrier precautions
Keep anyone with potentially communicable illness out of the patient’s room – visitors, other patients, or healthcare workers
No plants in the treatment room or nurse’s station
Any stem cell transplant patient should be in a private room. If they have an allogenic transplant, use a HEPA filter with >12 air exchanges per hour
Isolation is important for neutropenic patients, but do not let waiting on an isolation room delay obtaining cultures and initiating antibiotics
Specific Pathologies
Mucositis
Mucositis is a high risk feature indicative of bacterial invasion through thinned mucus membrane barriers.
Signs and Symptoms
oral pain, erythema, edema, or lesions
sinus pain or pressure
rectal pain or lesions, any swelling suggestive of perirectal abscess
abdominal pain
Inspect the rectum for swelling possibly indicative of perirectal abscess.
Digital rectal exam is generally discouraged due to concern of inducing bacteremia if mucus membranes are damaged in the process
Neutropenic Enterocolitis (Typhlitis):
A feared complication of neutropenic fever is direct bacterial invasion of the intestinal mucosa causing necrotizing infection
Most commonly at the ileocecal junction
It presents with classic triad of neutropenia, fever, and RLQ pain. Mortality approaches 50% when present (Gorschlüter 2005)
Surgery is avoided unless the bowel perforates, as these patients have poor wound healing and high surgical complication rates
Determine whether the patient is high or low risk:
High Risk Factors:
HD instability
Hematologic malignancy
Uncontrolled or widespread malignancy
Induction chemotherapy / hematopoietic stem cell transplant
ANC <100
>7 days of ANC <500
Medical comorbidities (particularly COPD, cardiac disease, or diabetes)
Low Risk Factors:
HD stable
Solid tumor malignancy
ANC >500
Neutropenia expected to last <7 days
No comorbidities
MASCC and CISNE risk calculators:
MASCC Score
Low risk = 21-26
High risk = <21
The MASCC Score will identify more patients as low risk, but will have more treatment failures / bounce-backs than the CISNE score (Ahn 2017, Coyne 2016)
CISNE Score
Low risk = 0
Intermediate risk = 1-2
High risk = 3-8
The CISNE score will identify fewer patients as low risk, but will result in fewer treatment failures/bounce-backs than the MASCC score (Ahn 2017, Coyne 2016).
Default to using whichever score your oncologist is more comfortable with.
Antibiotic Selection
Check old cultures for prior infections and sensitivities (if available).
Follow your hospital’s protocol (if available). This will have been formulated based on local resistance patterns and likely with input from your institution’s oncologists.
High Risk Patients will need hospitalization and IV antibiotics.
General approach for IV antibiotic therapy:
Begin with single broad spectrum agent which includes pseudomonas coverage such as cefepime, piperocillin-tazobactam, or a carbepenem
Penicillin allergies other than anaphylaxis are not considered a contraindication to the use of cephalosporins such as cefepime
If patient has anaphylactic reaction to penicillins, consider broad coverage with ciprofloxacin plus clindamycin or aztreonam plus vancomycin (IDSA 2010)
Do not routinely start vancomycin. Add vancomycin if there is clinical suspicion for Gram (+) infection
Signs of mucositis or cellulitis
Indwelling catheter present on arrival
Prior MRSA infection
Patient already on Gram (-) prophylaxis such as fluoroquinolone
Consider adding additional agents for unstable patients, or patients in which antibiotic resistant organisms are suspected (patient has known colonization or patient population has high endemic rates).
MRSA: vancomycin, linezolid, or daptomycin
VRE: linezolid or daptomycin
Extended spectrum beta lactamase (ESBL) producing organisms: carbapenem
Carbapenemase producing organisms (such as klebsiella): polymixin-colistin or tigecycline
If there is clinical suspicion for influenza (or positive PCR testing), treatment with oseltamivir is recommended
Other antiviral and antifungal agents should NOT be started routinely.
Only start antiviral or antifungal therapies if the patient has a known viral or fungal infection (ex: patient spikes a fever while already on antifungal treatment) or if they have a clinical picture strongly suggestive of viral or fungal etiology
Antifungals are generally not initiated until a patient has had >4 days of fever unresponsive to antibiotic treatment with no clear source identified
Low risk
If the patient has no high risk features, is found to be low risk on MASCC or CISNE scoring, and has good oncology follow-up, it may be preferable to discharge them home with 24hr oncology follow-up
Send patients home ONLY after discussion with the patient’s oncologist and only if there are no high risk features present
Outpatient antibiotic choice:
Ciprofloxacin plus amoxicillin-clavulanate is recommended by IDSA guidelines for oral empiric therapy (IDSA 2010)
Levofloxacin or ciprofloxacin monotherapy, or ciprofloxacin plus clindamycin are less well studied but are commonly used
Avoid fluoroquinolones if the patient is already on fluoroquinolone prophylaxis
Take Home Points:
There are many causes of neutropenia, chemotherapy being by far the most dangerous.
Febrile neutropenia is a condition conveying high mortality. Early administration of antibiotics is the only factor known to reduce this mortality.
For a patient with neutropenic fever, remember that the body’s own flora is the greatest danger. Isolate, but do not wait to initiate treatment.
Check old blood cultures and obtain new cultures prior to starting treatment.
Identify low risk patients and send them home with PO antibiotics and close oncology follow-up in conjunction with your oncologist.
Read More:
Infectious Disease Society of America 2010 Clinical Practice Guidelines
Life in the Fast Lane: Febrile Neutropaenia
Uptodate: overview of neutropenic fever syndromes
EMRAP: Risk stratification of neutropenic fever
MDCalc: MASCC Score
MDCalc: CISNE Score
References:
Ahn S, Rice TW, Yeung SJ, Cooksley T. Comparison of the MASCC and CISNE scores for identifying low-risk neutropenic fever patients: analysis of data from three emergency departments of cancer centers in three continents. Support Care Cancer. 2018 May;26(5):1465-1470. doi: 10.1007/s00520-017-3985-0. Epub 2017 Nov 22.
Clarke, R. T., Warnick, J., Stretton, K., Littlewood, T. J., Improving the immediate management of neutropenic sepsis in the UK: Lessons from a national audit. British Journal of Haematology. 2011 Jun;153(6):773-9. doi: 10.1111/j.1365-2141.2011.08693.x. Epub 2011 Apr 22
Coyne CJ, Le V, Brennan JJ, Castillo EM, Shatsky RA, Ferran K, Brodine S, Vilke GM. Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department. Ann Emerg Med. 2017 Jun;69(6):755-764. doi: 10.1016/j.annemergmed.2016.11.007. Epub 2016 Dec 29.
Ellis M. Febrile Neutropenia. Annals of New York Academy of Sciences. 2008 Sep;1138:329-50. doi: 10.1196/annals.1414.035.
Freifeld, A. G., Bow, E. J., Sepkowitz, K. A., Boeckh, M. J., Ito, J. I., Mullen, C. A., Raad, II, et al., Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america, Clinical Infectious Diseases, 2011, 52(4):e56-93.
Gibson C, Berliner N. How we evaluate and treat neutropenia in adults. Blood. 2014 Aug 21;124(8):1251-8; quiz 1378. doi: 10.1182/blood-2014-02-482612. Epub 2014 May 28.
Gorschlüter M, Mey U, Strehl J, et al. Neutropenic enterocolitis in adults: systematic analysis of evidence quality. Eur J Haematol 2005; 75:1.
Gudiol C, Bodro M, Simonetti A, et al. Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients. Clin Microbiol Infect 2013; 19:474
Klastersky J. The changing face of febrile neutropenia-from monotherapy to moulds to mucositis. Why empirical therapy? J Antimicrob Chemother. 2009;14(Suppl 1):i14–i15
Klastersky J. Management of fever in neutropenic patients with different risks of complications. Clin Infect Dis. 2004;39(Suppl. 1):S32–S37
Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006 May 15;106(10):2258-66.
Marín M, Gudiol C, Ardanuy C, Garcia-Vidal C. Jimenez L, Domingo-Domenech E, Pérez FJ, Carratalà J. Factors influencing mortality in neutropenic patients with haematologic malignancies or solid tumours with bloodstream infection. Clinical Microbiology and Infection. Volume 21, Issue 6, June 2015, Pages 583-590
Perron T, Emara M, Ahmed S. Time to antibiotics and outcomes in cancer patients with febrile neutropenia. BMC Health Services Research. 2014;14:162. doi:10.1186/1472-6963-14-162.Radiologypics, P. B. (2014, November 10). Neutropenic Colitis (Typhlitis). Retrieved from https://radiologypics.com/2014/11/10/neutropenic-colitis-typhlitis/Rosa RG, and
Goldani LZ. Cohort Study of the Impact of Time to Antibiotic Administration on Mortality in Patients with Febrile Neutropenia. Antimicrob Agents Chemother. 2014 Jul; 58(7): 3799–3803. doi: 10.1128/AAC.02561-1

Stiff, PJ. Coding for Mucositis. From presentation at ICD-9-CM Coordination and Maintenance Committee Meeting. Loyola University Medical Center. Centers for Disease Control. September 30, 2005. Retreived from https://www.cdc.gov/nchs/ppt/icd9/att_mucositis_sep05.ppt
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
The post REBEL Core Cast 122.0 – Neutropenic Fever appeared first on REBEL EM - Emergency Medicine Blog.
9 min
May 13, 2024REBEL Cast Ep126: Should We Not Be Recommending Small Adult BVMs in OHCA?
Background: The holy grail of outcomes in OHCA is survival with good neurologic outcome. The only interventions proven to increase this outcome are high quality CPR and defibrillation in shockable rhythms. Ventilation is also an important component of resuscitation in OHCA. Excess minute ventilation can adversely affect hemodynamics due to increased intrathoracic pressure (i.e. decreased venous return). Additionally, low CO2 levels from hyperventilation can lead to cerebral vasoconstriction which could lead to worsened secondary brain injury.
Most organizations recommend adults to be ventilated with tidal volumes of 500 to 600mL/breath during ongoing CPR. Large adult BVMs can have maximum tidal volumes of ≈1500mL and deliver about 750mL per one handed ventilation. Simulation studies have shown that health care professionals often provide minute ventilation well above these recommended ranges.
One of the recommendations from many experts to mitigate the perceived risk of large adult BVMs is using smaller adult BVMs. This change would result in decreasing the maximum volume from 1500 to 1000mL and an expected delivered tidal volume from 750 to 450mL/breath (much more inline with recommended ranges). However, evidence that this approach makes is difference is lacking.
REBEL Cast 126: Should We Not Be Recommending Small Adult BVMs in OHCA?
Click here for Direct Download of the Podcast
Paper: Snyder BD et al. Association of Small Adult Ventilation Bags with Return of Spontaneous Circulation in Out of Hospital Cardiac Arrest. Resuscitation 2023. PMID: 37805062
Clinical Question: Is large adult BVM or small adult BVM associated with more ROSC in adult patients treated with advanced airway placement for nontraumatic OHCA?
What They Did:
Retrospective, observational cohort analysis of prospectively obtained data from a single urban EMS system
Evaluating adults treated with advanced airway placement for nontraumatic OHCA
Jan 2015 to Dec 2021
Changed from large adult BVMs to small adult BVMs in summer of 2017 (3 month crossover period was allowed and excluded from analysis)
Used a Mercury medical CPR-2 small ventilation bag
Compared rates of ROSC, ventilation rate, and mean end tidal carbon dioxide (ETCO2) by minute before and after small adult BVM implementation
Outcomes:
Primary: ROSC at the end of EMS care (i.e. Arrival to ED or terminated efforts in the field)
Secondary:
Ventilation rate
Mean end-tidal CO2 (ETCO2) during CPR
Inclusion:
Adult patients with nontraumatic OHCA
Treated with an advanced airway (i.e. Endotracheal intubation or iGel)
Exclusion:
Age <18 years
Received basic life support only
Termination of resuscitation due to advanced directives
ALS interventions prior to EMS arrival
Insufficient capnography data
Cricothyrotomy
Advanced airway placed while patient had spontaneous circulation
Airway was managed with BVM only
Did not receive CPR while under EMS ALS care
Results:
1994 Patients included in analysis
1331 (67%) treated with small adult BVM
663 (33%) treated with large adult BVM
21% had an initial shockable rhythm
ROSC
Small Adult BVM: 33%
Large Adult BVM: 40%
uOR 0.74; 95% CI 0.61 to 0.90; P = 0.003
After adjustment for age, sex, witnessed arrest, bystander CPR, and initial rhythm this finding remained statistically significant (aOR 0.74; 95% CI 0.61 to 0.91)
Ventilation rates did not differ between cohorts (≈12BPM)
ETCO2
Small Adult BVM: 36.9 +/- 19.2mmHg
Large Adult BVM: 33.2 +/- 17.2mmHg
P <0.01
Strengths:
Written records are compared to cardiac monitor files and audio recordings to adjudicate differences before integrating information into the registry
Intubations confirmed with ETCO2
Took into account the COVID-19 pandemic time period
Also took into account the potential for trends over time by visualizing the incidence of ROSC by month over a seven year period and found no significant change in the slope before and after the implementation of the small adult BVM
Limitations:
Only included patients that were intubated with an endotracheal tube or iGel (these results may not apply in patients without these devices)
There were some confounding baseline differences (explained more in discussion)
Unclear what other interventions were performed in terms of ACLS medications or what the specific causes of the cardiac arrest were from
This was a before and after study not allowing for a control group. Before and after studies can introduce numerous biases particularly if other pieces of care changed between the two time periods. (Can also go in the discussion)
The actual tidal volume delivered was not measured in this trial and therefore the delivered minute ventilation is unknown
As this is a retrospective study, we can only show association, BUT NOT causation of the size of the adult BVM affecting ROSC outcomes
Discussion:
There are some key BASELINE DIFFERENCES that could account for the results of this trial (i.e. confounders):
More patients in the small adult BVM cohort received bystander CPR (64% vs 59%). This would favor more ROSC in the small adult BVM cohort
Unwitnessed arrest was slightly greater in the large adult BVM cohort (58% vs 53%)…This would favor more ROSC in the small adult BVM cohort
Fewer patients in the small adult BVM cohort arrested in public (22% vs 27%…Unclear how this would impact ROSC
The interval from 911 call to start of CPR (10 vs 9min) and advanced airway placement (20 vs 18min) were longer in the small adult BVM cohort…Not sure 1 to 2min of difference would result in more ROSC in the large adult BVM cohort
Adherence to guideline recommended ventilation rates of 10 BPM was more common in the small adult BVM cohort (28.4% vs 31.2%)…This would favor more ROSC in the small adult BVM cohort
It would appear most things at baseline favored the small adult BVM cohort (Although the authors did account for most of these in adjusted analyses)
The end of this trial took place during the COVID-19 PANDEMIC:
Anyone who took care of cardiac arrest patients during the COVID-19 pandemic knows that there were significant delays in care
According to the authors any cases of OHCA that occurred after the start of the pandemic (Feb 2020) were censored from the analysis and the results were evaluated again
When looking at cases of OHCA that occurred prior to Feb 2020 the small adult BVM cohort had a similarly lower odds of ROSC (OR 0.75; 95% CI 0.60 to 0.93; p = 0.008) as the entire time period this intervention was implemented
This remained the case even after adjusting for initial rhythm, age, sex, witnessed arrest and bystander CPR (aOR 0.76; 95% CI 0.61 to 0.95; p = 0.018)
While I would imagine during a code most people are bagging faster than 10BPM, in this study 6 to 18 BPM were delivered in 82.5% of the measured ventilations. Is this a result of Hawthorne effect or the implementation of a metronome to guide chest compression and ventilation rates (implemented June of 2015) or simply a well trained EMS system? This addition would seem to favor the small adult BVM group
This EMS organization appears to be very high functioning with lots of training and education which may not be the standard at other agencies. The fact that the medics are providing a good RR and good TV throughout a 7-year period would suggest this and in doing so a simple change from a large adult BVM to a small adult BVM may have resulted in the association of lower ROSC whereas an agency that does not get as much training or high functioning may actually still be causing harm with the large adult BVM
Finally, there was a higher ETCO2 in the small adult BVM cohort compared to the large adult BVM cohort. As ventilatory rate was essentially similar between groups, this most likely means a smaller tidal volume was delivered with each breath. This smaller tidal volume could have lead to physiologic changes that are potentially harmful:
Hypoventilation
Increased dead space fraction
Alveolar decruitment
Atelectasis causing shunt physiology
Author Conclusion: “Use of small adult bag during OHCA was associated with lower odds of ROSC at the end of EMS care. The effects on acid base status, hemodynamics, and delivered minute ventilation remain unclear and warrant additional study.”
Clinical Take Home Point: This is a really messy trial, with lots of methodological and confounding issues that make it difficult to interpret. It does show that when experts recommend an intervention it is important to study it. Until better evidence shows us differently it is probably best to stick with a large adult BVM but use one hand for bagging and maintain a rate of 10BPM.
References:
Snyder BD et al. Association of Small Adult Ventilation Bags with Return of Spontaneous Circulation in Out of Hospital Cardiac Arrest. Resuscitation 2023. PMID: 37805062
Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)
The post REBEL Cast Ep126: Should We Not Be Recommending Small Adult BVMs in OHCA? appeared first on REBEL EM - Emergency Medicine Blog.
13 min
May 01, 2024REBEL Core Cast 121.0 – Acute Sinusitis
Take Home Points
Acute rhinosinusitis is a clinical diagnosis
The vast majority of acute rhinosinusitis cases are viral in nature and do not require antibiotics
Consider the use of antibiotics in select groups with severe disease or worsening symptoms after initial improvement.
REBEL Core Cast 121.0 – Acute Sinusitis
Click here for Direct Download of the Podcast.
Definition:
Acute rhinosinusitis (ARS) – Symptoms for less than four weeks
Subacute rhinosinusitis – Symptoms for 4 to 12 weeks
Chronic rhinosinusitis – Symptoms persisting greater than 12 weeks
Recurrent acute rhinosinusitis – Four or more episodes of ARS per year, with interim symptom resolution
Epidemiology: (Anon 2004)
20 million cases of sinusitis annually in the US, costing $3.5 billion/year
Source of 1 in 5 antibiotic prescriptions for adults
Presentation:
Sinusitis is most commonly diagnosed by clinical symptoms
Common symptoms
Purulent nasal discharge
Nasal congestion
Facial pain or pressure, especially over a sinus or unilaterally
Anosmia
Hyposmia
Fever
Cough
Fatigue
Maxillary pain
Ear pressure or fullness.
Classification of Sinusitis:
●Acute viral rhinosinusitis (AVRS)
ARS with viral etiology (i.e. rhinovirus, influenza, and parainfluenza)
Most common form of ARS
●Uncomplicated acute bacterial rhinosinusitis (ABRS)
ARS with a bacterial etiology without clinical evidence of extension outside the paranasal sinuses and nasal cavity
Bacterial superinfection: 0.5-2% of all ARS
●Complicated acute bacterial rhinosinusitis
ARS with bacterial etiology with clinical evidence of extension outside the paranasal sinuses and nasal cavity
Sinusitis: Viral vs. Bacterial:
Color change in sputum does not determine whether infection is viral or bacterial
Viral infections
Tend to begin resolution by 7-10 days
Rarely have associated fevers
If fever present, usually only in the first 48 hours.
Guidelines for diagnosing ABRS are
Presence of URI/cold symptoms that
Don’t improve after 10 days
Worsen after 5-7 days of improvement
Severe symptoms including high fever, purulent discharge or facial pain for 3-4 days
The Data Behind Antibiotic Use
Clinically diagnosed acute sinusitis
Multiple studies show the same cure rate at 7 days, but improved cure rate at 7-14 days for those who use antibiotics (Lemiengre 2012, Berg 1986, Gwaltney 1996)
Overall Treatment Effect NNT = 18
Overall Harm NNH = 8 (mostly GI side effects)
Radiographically-diagnosed acute sinusitis (Ahovuo-Saloranta 2008)
Endpoint: clinical cure at 7-15 days
NNT = 15
NNH = 8
IDSA Recommendations for Antibiotic Treatment (Chow 2012)
Patients that should be treated
Persistent symptoms w/o improvement (> 10 days)
Severe symptoms (> 3-4 days)
Worsening (“double-sickening”) (> 3-4 days)
Antimicrobials
1st Line
Amoxicillin 875 mg PO BID X 5-7 days
Doxycycline 100 mg PO BID X 5-7 days
2nd Line
Amoxicillin/Calvulanate 875/125 mg PO BID X 5-7 days
Levofloxacin 500 mg PO Q24 X 5 days
Bottom Line: Given the risk for adverse events associated with antibiotic use, the growing specter of resistance and the lack of significant differences in outcomes with antibiotic use, it is better to avoid antibiotics in most patients with ARS. Antibiotics should be considered in those with severe disease and in immunocompromised patients
Take Home Points
Acute rhinosinusitis is a clinical diagnosis
The vast majority of acute rhinosinusitis cases are viral in nature and do not require antibiotics
Consider the use of antibiotics in select groups with severe disease or worsening symptoms after initial improvement.
References
Anon JB et al. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg 2004; 130(Suppl 1): 1-45. PMID: 14726904
Lemiengre MB et al. Antibiotics for Clinically Diagnosed Acute Rhinosinusitis in Adults. Cochrane Database Syst Rev 2012. PMID: 23076918
Berg O et al. Occurence of asymptomatic sinusitis in common cold and other acute ENT-infections. Rhinology 1986; 24(3): 223-5. PMID: 3775189
Gwaltney JM. Acute community-aquired sinusitis. Clin Infect Dis 1996; 23(6): 1209-23. PMID: 8953061
Ahovuo-Saloranta A et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Syst Rev 2008. PMID: 18425861
Chow AW et al. IDSA Clinical practice guideline for acute bacterial rhino sinusitis in children and adults. Clin Infect Dis 2012; 54(8): e72-e112. PMID: 22438350
Read More
The NNT.com: Antibiotics for Clinically Diagnosed Acute Sinusitis in Adults
The NNT.com: Antibiotics for Radiologically-Diagnosed Acute Maxillary Sinusitis
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
The post REBEL Core Cast 121.0 – Acute Sinusitis appeared first on REBEL EM - Emergency Medicine Blog.
6 min
April 09, 2024 REBEL EM Book Club – MicroSkills
Podcast Direct Download: Link
Release Date: April 16th, 2024
Show Notes
The Visible Voices Podcast
Dr. Glaucomflecken: Power of Ultrasound with Emergency Medicine Dr. Resa Lewiss
Adaira I Landry MD
Resa E Lewiss MD is a Professor of Emergency Medicine at the University of Alabama at Birmingham. A TEDMED speaker and TimesUp Healthcare founder, she’s an internationally renowned point-of-care ultrasound educator and champion for diverse, equitable, and inclusive workplaces. She attended college at Brown, medical school at Penn, Emergency Medicine residency at Harvard, and fellowship at Mount Sinai St. Luke’s Roosevelt. She led point-of-care ultrasound sections at St. Luke’s Roosevelt, the University of Colorado, and Thomas Jefferson. A physician healthcare design consultant for Perkins&Will, her design focus has been ultrasound hardware and workflows. She’s helped to redesign the built environment of a Harvard ICU and an infectious diseases unit in Malawi. As host and founder of the Visible Voices Podcast, she’s interviewed dozens of subject matter experts in healthcare, equity, and current trends. Her writings are published in the popular press and scientific journals, such as Harvard Business Review, Slate, Nature, and Fast Company. Her new book, MicroSkills : Small Actions, Big Impact is forthcoming from HarperCollins in 2024.
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
The post REBEL EM Book Club – MicroSkills appeared first on REBEL EM - Emergency Medicine Blog.
39 min
April 03, 2024 REBEL Cast – EMTALA + Reproductive Health Rights
REBEL Cast – EMTALA + Reproductive Health
Click here for Direct Download of the Podcast.
Dr. Dara Kass is a practicing emergency medicine physician who was most recently as the Regional Director of Region 2 for the US Department of Health and Human Services.
She currently works with organizations and institutions to advance and implement policies that affect the care of individuals in this new healthcare landscape, most specially related to all forms of reproductive health care from contraception and pregnancy termination to addressing the maternal mortality crisis in the United States.. Doctor Kass’s impact is broad as a tireless advocate, spearheading initiatives, and campaigns formatting improvements on issues such as gender equity, reproductive healthcare, and organ donation. Doctor Kass lives in Scarsdale NY with her husband and three children.
Dr. Monica Saxena is a practicing emergency physician and assistant professor at Stanford University School of Medicine.
Her research focuses on reproductive justice and women’s health in the emergency department setting. Dr. Saxena is the 2022 recipient of the Rising Star Faculty Award from the American College of Emergency Physicians. She holds a law degree from the University of Michigan and a medical degree from Wayne State University School of Medicine.
MedPage Today: The Ethos of Emergency Medicine Hangs in the Balance
Resources:
Reproductiverights.gov
Submit your complaint to the State Survey Agency in the state where the hospital is located.
The post REBEL Cast – EMTALA + Reproductive Health Rights appeared first on REBEL EM - Emergency Medicine Blog.
35 min
April 01, 2024REBEL Cast Ep125: 1st 48 Hours of PE Management – How Good Is Unfractionated Heparin?
Background: The mainstay of treatment for symptomatic pulmonary embolism (PE) is anticoagulation (AC). Patients with higher-risk PE may require advanced interventions such as thrombolytic therapy, surgical thrombectomy, or even extracorporeal membrane oxygenation (ECMO). Because of its short half-life and availability of a reversal agent, unfractionated heparin (UFH) is commonly used when percutaneous or surgical interventions are being considered.
The standard weight based dosing of UFH is 80U/kg bolus followed by an infusion started at 18U/kg/hr, titrated to a target activated partial thromboplastin time (aPTT) of 1.5 to 2.5x the control range or an anti-Xa level of 0.3 to 0.7u/mL. The efficacy of UFH in reaching and maintaining appropriate anticoagulation is poorly understood.
REBEL Cast 125: 1st 48 Hours of PE Management – How Good is Unfractionated Heparin?
Click here for Direct Download of the Podcast
Paper: Prucnal CK et al. Analysis of Partial Thromboplastin Times in Patients With Pulmonary Embolism During the First 48 Hours of Anticoagulation With Unfractionated Heparin. Acad Emerg Med 2020. PMID: 31625654
Clinical Question: How effective is UFH in obtaining appropriate anticoagulation during the first 48 hours of administration to patients with acute PE?
What They Did:
Retrospective analysis of a PE response team (PERT) data base
Single, large, urban academic teaching hospital (Massachusetts General Hospital)
October 2012 to April 2017
2 Standard Dosing Regimens Evaluated
Bolus + Drip (Low Risk of Bleeding): 80U/kg + Continuous titrated infusion starting at 18U/kg/hr
Drip Only (Higher Risk of Bleeding): Continuous titrated infusion starting at 18U/hr
Subsequent aPTT (seconds) and Rate Changes
<40: +3U/kg/hr
40 – 49.9: +2U/kg/hr
50 – 49.9 +1U/kg/hr
60 to 80: No change
1 to 100: -2U/kg/hr
>100: Hold for 60minutes then -3U/kg/hr
Outcomes:
Proportion of patients with a therapeutic aPTT value during each 6 hour time period
A therapeutic aPTT was defined as a value of 60 to 80seconds
A therapeutic Anti-Xa level was defined as a value of 0.3 to 0.7u/mL
Inclusion:
Adult patients
Acute PE
PERT team consulted
Received anticoagulation with UFH according to guideline standard dosing
Exclusion:
Patients treated with nonstandard dosing regimens
Results:
505 patients met inclusion criteria
PE Severity
Saddle: 17.4%
Rt Heart Strain on CT: 46.9%
Hemodynamic Collapse: 7.9%
Massive PE: 28.3%
Right Heart Strain on Echo: 21.4%
Elevated Troponin Level: 55.3%
Interventions Received:
Systemic thrombolysis: 4.0%
Catheter-Based Intervention: 5.9%
Surgical Thrombectomy: 2.0%
ECMO: 1.4%
IVC Filter: 5.0%
30d Outcome:
Mortality: 5.7%
Re-Thrombosis: 3.9%
Bleeding: 3.0%
Therapeutic aPTT in patients receiving bolus and infusion of UFH
At 6hrs: 13.9% (10.2 to 18.5%)
At 12hrs: 19% (14.2 to 25.0%)
At 24hrs: 26.3% (25.3 to 33.1%)
At 36hrs: 28.3% (22.0 to 35.4%)
At 48hrs: 28.4% (20.8 to 37.5%)
Therapeutic aPTT in patients receiving infusion only of UFH
At 6hrs: 14.5% (9.5 to 21.5%)
At 12hrs: 23.3% (15.2 to 32.3%)
At 24hrs: 41.4% (31.6 to 51.9%)
At 36hrs: 37.0% (26.8 to 48.5%)
At 48hrs: 42.1% (30.2 to 55.0%)
No patients had all therapeutic aPTT values
Strengths:
Asks a clinically important question
Study was stratified for patients being treated with bolus plus titrated infusion or titrated infusion only
Used UFH standard dosing strategies used by most physicians
Performed a sensitivity analysis that excluded all patients treated with systemic or catheter-directed thrombolysis, surgical embolectomy, or ECMO
Limitations:
Initiation of AC was defined as the order start time for UFH in the electronic medical record. There could have been delays in actually starting the UFH
No real details on chart extraction methodology (i.e. how they handled incomplete or conflicting data)
Only one abstractor where there is no assessment of the abstractors performance or comparison to another abstractor
Unclear why one strategy was chosen over another
Selection bias: Only patients consulted by PERT
For patients with more than one aPTT value in a given 6 hour time period, the first therapeutic value was selected for analysis. If there was no therapeutic value, the first aPTT value reported was used
Single center study meaning local factors may limit generalizability to other institutions
Time outside therapeutic aPTT is not all equal. An aPTT that is slightly above or below the reference range would be considered outside the range (i.e. values close to the therapeutic cutoff were considered equivalent to those far from the cut-off range)
This study does not determine whether time spent in the therapeutic range affects morbidity and mortality (Very low mortality rate = 6%)
Discussion:
Only a minority of patients in whom the PERT team was consulted treated with UFH using standard dosing had a therapeutic aPTT during the first 48 hours of anticoagulation with the majority of patients being subtherapeutic
The proportion of patients in therapeutic range was lowest at 6 hours (14%) and highest at 42 hours (35%)
Approximately 40% of patients failed to reach the therapeutic range in the first 48 hours of AC
It wasn’t until 36 hours after the initiation of UFH that >50% of patients had at least one therapeutic aPTT
There were no patients who had all aPTT values within the therapeutic range during the first 48hours of UFH therapy
Something to Think About: Thrombus burden can be substantial and heparin resistance may be present, so standard dosing may be inadequate in these patients
My Opinion: LMWHs offer several advantages over unfractionated heparin including a longer half-life, increased bioavailability, and a more predictable dose response. In addition, LMWHs are dosed by weight, administered subcutaneously, and usually do not require dose adjustments or laboratory monitoring. Whereas unfractionated heparin is largely hepatically cleared, LMWHs are renally cleared
In 2017 [2], there was a Cochrane review that compared LMWH to UFH for the initial treatment of VTE. This included 29 RCTs with over 10,000 patients. The authors concluded that with moderate quality of evidence fixed dose LMWH reduced the incidence of recurrent thrombotic complications and occurrence of major hemorrhage during initial treatment with no difference in overall mortality compared to UFH
The 2019 European Society of Cardiology [3] also states: “LMWH and fondaparinux are preferred over UFH for initial anticoagulation in PE, as they carry a lower risk of inducing major bleeding and heparin-induced thrombocytopenia. Neither LMWH nor fondaparinux need routine monitoring of anti-Xa levels. Use of UFH is nowadays largely restricted to patients with overt hemodynamic instability or imminent hemodynamic decompensation in whom primary reperfusion treatment will be necessary. UFH is also recommended for patients with serious renal impairment [creatinine clearance ≤30mL/min] or severe obesity. If LMWH is prescribed in patients with CrCl 15 – 30mL/min, an adapted dosing scheme should be used.”
Author Conclusion: “The majority of patients with acute PE spend most of their first 48 hours outside of the therapeutic range of AC when treated with guideline standard dosing of UFH. Over half of the patients fail to achieve any therapeutic PTT level within 24 hours of UFH initiation, and no patient had all therapeutic aPTTs. Future research should focus on identifying factors associated with achieving therapeutic AC with UFH.”
Clinical Take Home Point: In this single center study of PERT team consulted PE patients standard dosing of UFH left most patients with a subtherapeutic aPTT level in the first 48 hours of treatment. Either we need to question the dosing regimen we use for UFH or we should consider switching to LMWH in the initial treatment of PE patients.
References:
Prucnal CK et al. Analysis of Partial Thromboplastin Times in Patients With Pulmonary Embolism During the First 48 Hours of Anticoagulation With Unfractionated Heparin. Acad Emerg Med 2020. PMID: 31625654
Robertson L et al. Fixed Dose Subcutaneous Low Molecular Weight Heparins Versus Adjusted Dose Unfractionated Heparin for the Initial Treatment of Venous Thromboembolism. Cochrane Database Syst Rev 2017. PMID: 28182249
Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)
The post REBEL Cast Ep125: 1st 48 Hours of PE Management – How Good Is Unfractionated Heparin? appeared first on REBEL EM - Emergency Medicine Blog.
17 min
March 18, 2024REBEL Cast Ep124: Nitrates in Right Sided MIs?
Background: Nitrates can help improve symptoms and ischemia in the setting of acute myocardial infarction. Current teaching holds that nitrates should be avoided in patients with potential right ventricular myocardial infarction (RVMI), due to the risk of decreasing preload and precipitating hypotension. This belief is based on a single 1989 study of 40 patients with RVMI and endorsed by both the AHA and ESC guidelines [2].
In that 1989 study, of the 40 patients with RV infarction 20 had a decrease in blood pressure of ≥30mmHg and associated symptoms after the administration of nitrates (SL, Oral, Transdermal, or IV) and 20 did not. The conclusion of this paper was that inferior AMI with RV involvement has a strong association with hypotensive response to nitrates. The major issue is the study is limited by the fact that we are given no information on dosage and multiple routes of administration making clinical application difficult. Better data is needed to guide management.
REBEL Cast 124: Nitrates in Right Sided MIs?
Click here for Direct Download of the Podcast
Paper: Wilkinson-Stokes M et al. Adverse Events From Nitrate Administration During Right Ventricular Myocardial Infarction: A Systematic Review and Meta-Analysis. Emerg Med J 2023. PMID: 36180168
Clinical Question: Is giving nitrates to patients with right ventricular myocardial infarction (RVMI) associated with increased adverse events compared with nitrate administration to patients with myocardial infarctions in other regions of the heart?
What They Did:
A systematic review and meta-analysis
Exposure of interest: administration of nitrates, via any route and dose
Outcomes:
Primary: All forms of adverse events reported in the included studies (Hypotension, Bradycardia, AMS, Syncope, Cardiac Arrest)
Inclusion:
Patients diagnosed with AMI with a subset of the sample with RV myocardial infarction
Experimental and analytical observational study designs
Studies only published in English
Exclusion:
Patients with coronary vasospasm
Results:
5 studies included in the analysis
Only 2 observational studies using SL NTG 400mcg were used for the meta-analysis
Adverse Events (Hypotension, Bradycardia, AMS, Syncope, Cardiac Arrest)
RVMI: 18/105 (17.1%)
Other MIs: 83/945 (8.8%)
RR 1.31 (95% CI 0.81 to 2.12)
No patients had cardiac arrest or death
Strengths:
Asks a clinically important question
Searched 6 different databases for relevant papers
All included studies underwent quality assessment using standard appraisal tools
If data was missing corresponding authors were contacted for the missing information
Limitations:
None of the included studies were RCTs
All studies samples were of combined inferior and RVMI making it difficult to determine the safety of nitrates during isolated RVMI
One of the included studies was only an abstract
Studies defined hypotension in different ways which could alter frequency of adverse events
Discussion:
Overall this review provides low certainty evidence that there is no statistically significant difference in the rate of adverse events when nitrates are administered to RVMI compared with other cardiac region MIs.
Hypotension is the primary adverse event reported. Nitrates have a serum half-life of 1 to 4 minutes and therefore hypotension is likely to be transient in nature
Transient hypotension is not really clinically meaningful, especially since it can be treated with cessation of nitrates and fluid challenges
Author Conclusion: “This review suggests that the AHA and ESC contraindications are not supported by evidence. Key limitations include all studies having concomitant inferior and RVMI, not evaluating beneficial effects and very low certainty of evidence. As adverse events are transient and easily managed, nitrates are a reasonable treatment modality to consider during RVMI on current evidence.”
Clinical Take Home Point: From a clinical perspective, the potential benefit of analgesia and reduced sympathetic stimulation in the setting of RVMI seems to outweigh the potential of transient hypotension with the use of nitrates. Although better studies are needed, this systematic review and meta-analysis argues against a contraindication against nitrates in the setting of RVMI and maybe one of precaution.
References:
Wilkinson-Stokes M et al. Adverse Events From Nitrate Administration During Right Ventricular Myocardial Infarction: A Systematic Review and Meta-Analysis. Emerg Med J 2023. PMID: 36180168
Ferguson JJ et al. Significance of Nitroglycerin-Induced Hypotension with Inferior Wall Acute Myocardial Infarction. Am J Cardiol 1989. PMID: 2502902
Neumar RW et al. Part 1. Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015. PMID: 26472989
Ibanez B et al. 2017 ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting with ST-Segment Elevation. Eur Heart J 2018. PMID: 28886621
For More Thoughts on This Topic Checkout:
REBEL EM: The Death of MONA in ACS – Part III – Nitroglycerin
Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)
The post REBEL Cast Ep124: Nitrates in Right Sided MIs? appeared first on REBEL EM - Emergency Medicine Blog.
13 min
March 06, 2024REBEL Core Cast 119.0 – Sleep Hygiene
REBEL Core Cast 119.0 – Sleep Hygiene
Click here for Direct Download of the Podcast
Employ sleep strategies:
Anchor sleep: a period of sleep that overlaps each day regardless of your night shift schedule to provide a guidepost for your body clock. Ideally would overlap with when you would normally be asleep if you were not on night shift.
Split sleep: sleep 3-4 hours immediately after shift then another 3-4 hours immediately before shift
Melatonin timing/dosing:
Most sleep specialists recommend 1-3 mg 30 minutes before desired onset of sleep
Align timing to bolster your circadian rhythm, not fight it
Caffeine:
Limit intake 4-8 hours before bed and no more than 400 mg a day
Diet:
Choose healthy foods and snacks and consume them in patterns that align with your normal day-night cycle (i.e. eat dinner before your night shift and eat breakfast afterwards)
Residency/hospital leadership should consider having healthy low-cost/free food options available for residency and staff, particularly on night shifts
Don’t drive sleepy:
Practice recognizing signs of sleep deprivation (yawning, drifting lanes, falling asleep at signout or at red lights) and do not drive home if present
Residency/hospital leadership should provide a comfortable place for residents/faculty to sleep and/or provide rideshare options to safely get home when signs of sleep deprivation are recognized
References
Sleep strategies:
Minors DS, Waterhouse JM. Does ‘anchor sleep’ entrain circadian rhythms? Evidence from constant routine studies. J Physiol. 1983 Dec;345:451-67. doi: 10.1113/jphysiol.1983.sp014988. PMID: 6663508; PMCID: PMC1193807.
Crowley SJ, Lee C, Tseng CY, Fogg LF, Eastman CI. Complete or partial circadian re-entrainment improves performance, alertness, and mood during night-shift work. Sleep. 2004 Sep 15;27(6):1077-87. doi: 10.1093/sleep/27.6.1077. PMID: 15532201.
Melatonin
Farahmand S, et al. Comparison of exogenous melatonin versus placebo on sleep efficiency in emergency medicine residents working night shifts: A randomized trial. World J Emerg Med. 2018;9(4):282-287. doi: 10.5847/wjem.j.1920-8642.2018.04.008. PMID: 30181797; PMCID: PMC6117540.
Morgenthaler TI et al; Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep. 2007 Nov;30(11):1445-59. doi: 10.1093/sleep/30.11.1445. Erratum in: Sleep. 2008 Jul 1;31(7):table of contents. PMID: 18041479; PMCID: PMC2082098.
Caffeine
Walsh JK, Muehlbach MJ, Schweitzer PK. Hypnotics and caffeine as countermeasures for shift work related sleepiness and sleep disturbance. J Sleep Res. 2009;4;80-83.
Nehlig A. Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption. Pharmacol Rev. 2018;70(2):384-411. doi:10.1124/pr.117.014407
U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020. Available at DietaryGuidelines.gov.
Stephanie Centofanti, Siobhan Banks, Scott Coussens, Darren Gray, Emily Munro, Johnathon Nielsen & Jillian Dorrian (2020) A pilot study investigating the impact of a caffeine-nap on alertness during a simulated night shift, Chronobiology International, 37:9-10, 1469-1473, DOI: 10.1080/07420528.2020.1804922.
Diet
Lowden A, Holmbäck U, Åkerstedt T, Forslund J, Lennernäs M, Forslund A [2004]. Performance and sleepiness during a 24 h wake in constant conditions are affected by diet. Biol Psychol 65(3):251–263.
Anderson C, Horne JA [2006]. A high sugar content, low caffeine drink does not alleviate sleepiness but may worsen it. Hum Psychopharmacol 21(5):299–303.
Driving Sleepy
Barger LK, Cade BE, Ayas NT, et al. Extended work shifts and the risk of motor vehicle crashes among interns. N Engl J Med. 2005;352(2):125-34.
Green W, Gao X, Li K, et al. The Association of Sleep Hygiene and Drowsiness with Adverse Driving Events in Emergency Medicine Residents. West J Emerg Med. 2020;21(6):219-224. Published 2020 Oct 27. doi:10.5811/westjem.2020.8.47357
Steele MT, Ma OJ, Watson WA, Thomas HA Jr, Muelleman RL. The occupational risk of motor vehicle collisions for emergency medicine residents. Acad Emerg Med. 1999 Oct;6(10):1050-3. doi: 10.1111/j.1553-2712.1999.tb01191.x. PMID: 10530665.
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
The post REBEL Core Cast 119.0 – Sleep Hygiene appeared first on REBEL EM - Emergency Medicine Blog.
5 min