Early administration of antibiotics (within 60 min) in patients with fever and neutropenia is life saving.
Fever in sickle cell is an emergency and always requires cultures and antibiotics even if the child appears well.
Avoid sedation and lying supine and steroids in patients with mediastinal masses.
Red flags in patients with headaches that may suggest a brain tumor include signs of increased intracranial pressure, focal neurological signs, seizures or ataxia.
Note: Unlikely to have effect in patients taking beta-adrenoreceptor blocker medications
Sodium Bicarbonate (NaHCO3)
Evidence for the efficacy of NaHCO3 to lower serum potassium is scant and contradictory (Elliott 2010, Weisberg 2008)
Eliminate potassium from the body (see above)
Asymptomatic Patients with Minor EKG Changes
Minimal recommendations on managing this clinical entity
Eliminate potassium from the body (see above)
Consider calcium salt administration: patients can rapidly progress through EKG changes and calcium administration may prevent this from occurring. However, the effects of calcium are temporary and offer no long-term protection
Consider medications to shift potassium intracellularly while waiting for elimination
Take Home Points
Always obtain an EKG in patients with ESRD upon presentation
Always obtain an EKG in patients with hyperkalemia as pseudohyperkalemia is the number one cause
If the patient with hyperkalemia is unstable or has significant EKG changes (wide QRS, sine wave) rapidly administer calcium salts
In patients who are anuric, early mobilization of dialysis resources is critical
References
Elliott MJ et al. Management of patients with acute hyperkalemia. CMAJ 2010; 182(15): 1631-5. PMID: 20855477
Wrenn K et al. The ability of physicians to predict hyperkalemia from the ECG. Ann Emerg Med 1991; 20(11): 1229-32. PMID: 1952310
Aslam S et al. Electrocardiography is unreliable in detecting potentially lethal hyperkalaemia in hemodialysis patients. Nephrol Dial Transplant 2002; 17: 1639-42. PMID: 12198216
Montague BT et al. Retrospective review of the frequency of ECG changes in hyperkalemia. Clin J Am Soc Nephrol 2008; 3:324–330. PMID: 18235147
Mattu A et al. Electrocardiographic manifestations of hyperkalemia. Am J Emerg Med 2000; 18: 721-9. PMID: 11043630
Allon M, Copkney C. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kidney Int 1990; 38:869–872. PMID: 2266671
Weisberg LS. Management of hyperkalemia. Crit Care Med 2008; 36: 3246-51. PMID: 18936701
Moussavi K et al. Reduced alternative insulin dosing in hyperkalemia: a meta-analysis of effects on hypoglycemia and potassium reduction. Pharmacotherapy 2021; 41(7): 598-607. PMID: 33993515
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
Management of severe beta-blocker and calcium-channel blocker toxicity should occur in a stepwise fashion: potential gastric decontamination, multiple lines of access, judicious fluids, calcium, glucagon, and vasopressors as needed.
Initiation of high dose insulin therapy requires a tremendous amount of logistical and cognitive resources as it requires cross-disciplinary collaboration and is prone to mismanagement.
If the patient doesn’t respond to maximum pharmacologic therapy, venous-arterial ECMO should be considered.
Shock secondary to beta-blocker (BB) or calcium-channel blocker (CCB) toxicity bears a tremendous degree of morbidity and mortality.
According to the 2022 Annual Report of the National Poison Data System from America’s Poison Center, CCBs and BBs account for the sixth and seventh largest number of fatalities from overdose.1
Recall that cardiac output is a function of both stroke volume and heart rate. The natural response to diminishing stroke volume is a compensatory rise in heart rate (tachycardia). Keep a low threshold to search a patient’s medication list for BB/CCBs, when a hypotension is seen with a “normal heart rate.”
Clinical Manifestations
Both BBs and CCBs ultimately cause reduced levels of intracellular calcium within myocytes. Depending on the degree of toxicity, subsequent effects include: decreased systemic vascular resistance, vasodilation, bradycardia, various conduction delays, and ultimately hypotension and cardiogenic shock.
In addition to abnormal vital signs, look for surrogates of poor clinical perfusion: acidemia, lactate, decreasing urinary output
Traditional Management
Consider GI decontamination to reduce systemic absorption: 1g/kg up to 50g of activated charcoal. Patient must be alert or the airway must be secured as to avoid aspiration.
REBEL Core Cast 123.0 – Posterior Epistaxis
mercredi 29 mai 2024 • Durée 06:30
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.
Typically will have heavy bleeding both anteriorly and posterior into the oropharynx. These patients have a tough time because they’re continually trying to spit out or swallow blood
Tachycardia is common and hypotension while not common isn’t unexpected. Very different from anterior epistaxis where VS usually unremarkable or maybe a bit of hypertension
Failure of anterior pressure or packing to stop bleeding: apply pressure but still see brisk posterior bleeding or even place b/l pack and see continued posterior bleeding
Start with the basics
IV, Supp O2, Monitor
Consider blood products if the patient appears to be losing a lot of blood or they report heavy blood loss. VS abnormalities can drive this as well
Strongly consider reversal of AC (this will typically come after control)
Stopping the Bleeding
PPE: these things bleed like stink. Anecdote. Gown, gloves and most importantly eye and face protection
Ideal: commercial posterior pack
Two balloons – one for anterior, one for posterior
Place the device (straight back parallel to the floor)
Inflate anterior balloon (10-15 cc) of air
If still bleeding, inflate posterior balloon (5-10 cc of air)
Foley: if no commercial device
Place foley catheter just as you would place a nasal tampon
When you see the tip of the foley in the posterior pharynx, inflate balloon (5-10 cc)
ANNEXA-1: Andexanet Alfa Associated with Harm in DOAC Reversal
jeudi 23 mai 2024 • Durée
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
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.
REBEL Cast Ep126: Should We Not Be Recommending Small Adult BVMs in OHCA?
lundi 13 mai 2024 • Durée 12:48
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?
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:
REBEL Core Cast 121.0 – Acute Sinusitis
mercredi 1 mai 2024 • Durée 05:07
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.
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)
Toxic alcohols generally refer to methanol and ethylene glycol as these substances pose significant metabolic derangement and end-organ damage.
Patient who present shortly after ingestion will simply look inebriated – no different than ethanol intoxication. At this point, patients will have an elevated osmolar gap and little to no anion gap.
Patient who presents in a delayed fashion after ingestion may have a normal osmolar gap however will manifest the signs of end-organ damage: anion gap metabolic acidosis, visual impairment, or renal dysfunction.
The osmolar gap is poorly sensitive, specific surrogate measure that is used to detect the presence of toxic alcohols. A normal osm gap does not rule out a toxic alcohol ingestion.
Management includes fomepizole, hemodialysis, and vitamin supplementation.
Reference: Wiener SW. Chapter 106. Toxic Alcohols. In: Nelson LS, Howland MA, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS, , Flomenbaum NE. eds. Goldfrank’s Toxicologic Emergencies, 11e New York, NY: McGraw-Hill; 2019. Accessed October 2, 2024.
Obtain multiple lines of intravenous access (3 PIVs or triple lumen CVC) and provide a judicious amount of fluids. (more on this below)
Pharmacotherapy
Calcium Gluconate: 1-3g intravenous
Glucagon: 3mg-5mg slow intravenous push. Rapid administration may induce nausea and emesis.
Vasopressors as a bridge to…
HIET
Mechanism of action is still not fully elucidated however several factors are implicated:
Insulin augments cardiac contractility by activating “reverse-mode” Na-Ca exchange and subsequently increasing calcium concentration in the sarcoplasmic reticulum. 2
At a resting physiologic state, the heart utilize free fatty acids as its primary energy course. Under stressed conditions, glucose is used instead. Insulin helps to facilitate glucose metabolism.
HIET Dosing: 1 unit/kg IV bolus. Then infusion starting at 1 unit/kg/hr infusion and titrate q30-60 minutes, keeping in mind that effects are not instant. Relative maximum is ~10 unit/kg/hr.
If glucose <250 mg/dL, administer a bolus of dextrose 25-50 g (or 0.5-1 g/kg) IV.
Ask pharmacy to concentrate insulin from 1 unit/mL to 10 units/ml.
Patients often succumb to volume overload given pre-existing cardiac disease and the volume of medical resuscitation through their hospital stay.
Once HIET is initiated, dextrose and potassium infusions should simultaneously be started to obviate hypoglycemia and hypokalemia
Dextrose: 0.5-1 g/kg/hr via D50/D20
Replete potassium to a minimum of 3.5mEq/L
A central venous catheter (often a triple lumen) is often needed to emergently replete potassium and provide D50/D20 safely (given its high osmolarity)
Serial monitoring of dextrose (q15-30 minutes) and potassium (q1 hour) is critical
HIET has been demonstrated to improve perfusion without necessarily increasing SVR/MAP – while MAPs may not markedly increase dramatically in the short term, obtain serial blood gases, lactate, and track urinary output to track perfusion. 3
Hyperinsulinemia Euglycemia Therapy (HIET) for BB/CCB Toxicity
Management of severe beta-blocker and calcium-channel blocker toxicity should occur in a stepwise fashion: potential gastric decontamination, multiple lines of access, judicious fluids, calcium, glucagon, and vasopressors as needed.
Initiation of high dose insulin therapy requires a tremendous amount of logistical and cognitive resources as it requires cross-disciplinary collaboration and is prone to mismanagement.
HIET Dosing: 1 unit/kg IV bolus. Then infusion starting at 1 unit/kg/hr infusion and titrate q30-60 minutes, keeping in mind that effects are not instant. Relative maximum is ~10 unit/kg/hr.
HIET therapy requires simultaneous dextrose and potassium infusions as insulin will induce hypoglycemia and shift potassium intracellularly.
If the patient doesn’t respond to maximum pharmacologic therapy, venous-arterial ECMO should be considered.
References
Gummin DD, Mowry JB, Beuhler MC, et al. 2022 Annual Report of the National Poison Data System® (NPDS) from America’s Poison Centers®: 40th Annual Report. Clin Toxicol (Phila). 2023;61(10):717-939. doi:10.1080/15563650.2023.226898
von Lewinski D, Bruns S, Walther S, Kögler H, Pieske B. Insulin causes [Ca2+]i-dependent and [Ca2+]i-independent positive inotropic effects in failing human myocardium. Circulation. 2005;111(20):2588-2595. doi:10.1161/CIRCULATIONAHA.104.497461
Holger JS, Engebretsen KM, Fritzlar SJ, Patten LC, Harris CR, Flottemesch TJ. Insulin versus vasopressin and epinephrine to treat beta-blocker toxicity. Clin Toxicol (Phila). 2007;45(4):396-401. doi:10.1080/15563650701285412
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
Need to pull back a bit and secure (can do this with tape on the nose)
Post Placement Care
Antibiotics: standard practice to give cephalexin or amox/clav. Literature doesn’t defend this approach but, the lit is pretty sparse. The idea behind abx is to prevent things like AOM and TSS but neither should be much of an issue with short term placement
ICU Admission?
Traditional teaching is that these patients are at risk for life-threatening bradydysrhythmias and should go to the ICU
Literature here is non-existent. Two oft-cited articles
Cassisi Laryngoscope 1971 – no mention of cardiac events in the article but widely cited
Zeyyan Laryngoscope 2010 – slightly lower HR in the packing group but no bradydysrhythmias
Before throwing ICU out
Hypoxia can occur – Cassisi found about a 20 mm Hg drop in PaO2 but all the patients in this publication were sedated so the packing may not have been the issue
look at Viducich 1995 Acad Emerg Med – showed that 18% of the 88 patients with posterior epistaxis required a surgical intervention. With that in mind, you want to consider placing patients into a setting where they can be frequently reassessed – perhaps SDU. This will be pretty location specific. If you treat a posterior bleed at a hospital without ENT, I would transfer as surgical intervention is pretty common
Cassisi NJ et al. Changes in arterial oxygen tension and pulmonary mechanics with the use of posterior packing in epistaxis: a preliminary report. Laryngoscope 1971; 81(8): 1261-6. PMID: 5569677
Zeyyan E et al. The effects on cardiac function and arterial blood gas of totally occluding nasal packs and nasal packs with airway. Laryngoscope 2010; 120: 2325-2330. PMID: 20938948
Loftus BC et al. Epistaxis, medical history and the nasopulmonary reflex: what is clinically relevant. Otolaryngol Head Neck Surg 1994; 110: 363-9. PMID: 8170679
Viducich RA et al. Posterior epistaxis: clinical features and acute complications. Acad Emerg Med 1995; 25(5): 592-6. PMID: 7741333
Corrales CE, Goode RL. Should patients with posterior nasal packing require ICU admission. Laryngoscope 2013; 123: 2928-9. PMID: 24114977
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
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
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)
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.
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:
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)
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).
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.
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)
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)
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)
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
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
Découvrez des podcasts liées à REBEL Cast. Explorez des podcasts avec des thèmes, sujets, et formats similaires. Ces similarités sont calculées grâce à des données tangibles, pas d'extrapolations !
