Background: In medicine, guidelines are valuable tools that help guide care. However, they are not rigid rules that must be strictly followed. Clinicians often find themselves grappling with the challenge of balancing the demands of meeting Center for Medicaid & Medicare (CMS) requirements while also addressing the unique needs of each individual patient. For those with sepsis, the administration of intravenous fluids (IVF) at the volumes recommended in the Surviving Sepsis Campaign (SSC) requires careful consideration of an individual’s chronic medical conditions and subsequent sensitivity to IVF. The available studies providing insights into clinical practices in these situations are limited in number and quality, leaving clinicians to rely on judgment and anecdotal experiences.

This systematic review and meta-analysis attempts to elucidate whether a more conservative fluid resuscitation approach is warranted in volume sensitive sepsis patients, such as those with congestive heart failure (CHF). Current SSC guidelines recommend fluid resuscitation with at least 30mL/kg IV crystalloid in patients with sepsis induced hypoperfusion or septic shock within the first three hours of resuscitation, regardless of comorbidities.

Article: Vaeli Zadeh A, Wong A, Crawford AC, Collado E, Larned JM. Guideline-based and restricted fluid resuscitation strategy in sepsis patients with heart failure: A systematic review and meta-analysis [published online ahead of print, 2023 Aug 9]. Am J Emerg Med. 2023;73:34-39. PMID: 37597449

Clinical Question: In sepsis patients with CHF, does a restricted volume resuscitation strategy of less than 30mL/kg IV crystalloid initiated within the first three hours of sepsis identification, compared to volume resuscitation with 30 mL/kg IV crystalloid, decrease in-hospital mortality?

What They Did: 

• Researchers performed a systematic review and meta-analysis.
• The study was conducted according to PRISMA guidelines.
• The authors searched Embase, PubMed, and Scopus.
• Utilized the Newcastle-Ottawa Scale to assess risk.
• Utilized Egger’s linear regression and Begg and Mazumdar’s rank correlation test to assess publication bias.

Population:

Inclusion Criteria:

• Studies with sepsis patients with a history of HF and in-hospital mortality data on patients that did or did not meet the 30×3 SSC guidelines.

Exclusion Criteria: 

• Studies that focused on a period longer than 3 h from diagnosis of sepsis.
• Studies without a clear timeframe for fluid administration.
• Studies without a mortality breakdown for patients.
• Studies without IRB approval
• Studies older than 2016

Intervention: 

• Administration of <30 mL/kg IV crystalloid fluids within three hours of sepsis identification.

Comparator: 

• Administration of at least 30 mL/kg IV crystalloid within three hours of identifying sepsis. 

Outcomes: 

• Primary Outcome: In-hospital mortality.
• Secondary Outcomes: Delayed hypotension, increased ICU stay, and other relevant outcomes.

Results:

• 26,069 studies met initial inclusion criteria. 
• 2,549 studies remained after screening for duplicates,
• 9 studies remained after screening for irrelevant titles or abstracts
  • 3 studies were removed due to lack of mortality data
  • 2 studies were removed due to lack of a clear timeframe for fluid administration. 
• 4 studies remained, with a total of 571 patients with sepsis and a history of CHF

Critical Result:

• The weighted OR for death was significantly higher in the <30 × 3 vs. 30 × 3 
• OR = 1.81, 95% CI = 1.13–2.89, p = 0.01.
• Heterogeneity analysis resulted in an I2 of 0%, demonstrating a high degree of homogeneity among the results of the selected studies and pooled data.

Strengths: 

• Investigators addressed a practical and pertinent clinical question. 
• The study investigates a narrow clinical question, enhancing the study’s precision. 
• Authors used the PRISMA guidelines, promoting transparency and reproducibility.
• Investigators conducted a thorough evaluation of the four included trials and provided a detailed assessment. 
• They employed two standardized tools to assess bias —selected studies were rated favorably based, increasing external validity.
• The point estimates are similar and the confidence intervals overlap across all 4 trials indicating low variability in study results.
• Patients across all studies exhibited sufficient similarity to enable a pooled estimation.

Limitations: 

• The investigators excluded studies published before 2016, non-English studies, and non-published studies, potentially missing valuable data.
• Study selection was the responsibility of a single author, introducing the possibility of bias and random errors in the selection process.
• The authors didn’t report the level of agreement regarding article selection, making it unclear how consistent the selection process was.
• It’s not mentioned whether the authors attempted to identify additional studies by checking the references of the selected articles or by contacting the original paper authors for more information. These steps could have potentially uncovered more relevant studies.
• The included studies were case-control studies, which are limited to demonstrating correlation and cannot establish causation.
• The authors did not register the paper through Prospero, missing an opportunity to enhance the study’s transparency, reproducibility, and credibility.
• There was no specified time-frame for the primary outcome, potentially affecting the precision of the findings.
• The sample sizes of the individual papers were relatively small.
• One paper contributed nearly half the weight of the meta-analysis.
• Funnel plots require a large number of studies to provide an accurate assessment of publication bias, but this meta-analysis included just four trials decreasing confidence in the data.

Discussion: 

The critical details from key studies are instrumental in shaping our understanding. Kuttab et al’s findings, constituting 45% of the review’s weight, suggest that administering <30cc/kg IVF is associated with increased odds of mortality, delayed hypotension, and increased ICU utilization. However, the ≥30cc/kg IVF group showed a higher prevalence of septic shock, reduced time to antibiotics by 1hr, and increased recognition of sepsis on presentation, introducing potential bias. Uchel et al’s contribution (21% weight) indicates that ≥30cc/kg IVF is linked to 2.5 times more intubations and 2.15 times more readmissions at 30 days. Interestingly, <30cc/kg IVF had a 2 times higher mortality, with over 50% of patients exhibiting diastolic HF. Taenzer et al (26% weight) suggests that <30cc/kg IVF is associated with higher mortality, albeit in a small cohort. Rai et al (8% weight) found no difference in mortality regardless of the amount of fluids given, but the sample size was very small. All four trials included in the review were retrospective, observational studies introducing significant confounders. Additionally, three of the four trials were abstracts with missing granular details, and strict inclusion/exclusion criteria severely limited the number of papers included in the systematic review and meta-analysis.

Considering these findings, specific recommendations for patients with sepsis and septic shock at risk for volume overload include checking for fluid responsiveness with passive leg raise, administering fluids based on ideal body weight rather than actual body weight, documenting reasons for not adhering to the 30mL/kg IVF guideline, and considering early vasopressor use. It is crucial for physicians to exercise clinical judgment and discretion when administering crystalloid fluids, avoiding indiscriminate fluid administration based on these nuanced considerations.

Author’s Conclusion: “Based on the published research, our meta-analysis revealed that a restricted fluid resuscitation strategy (<30 mL/kg fluid bolus within 3hrs of sepsis identification) in patients with a history of HF was associated with increased risk of in-hospital mortality, although the included primary studies didn’t achieve a statistical significance, except for the Taenzer et al. study.”

Our Conclusion: 

In conclusion, this systematic review and meta-analysis provides valuable insights into the fluid resuscitation strategies for sepsis patients with a history of CHF. Although the findings suggest that a restricted fluid resuscitation approach (<30 mL/kg) may be associated with increased in-hospital mortality, it’s important to note the limitations of the current research, including small sample sizes and the retrospective nature of the studies. These limitations highlight the need for larger, more diverse, and prospective studies to establish clearer guidelines. Future research should also explore distinctions between different types of heart failure, the role of early vasopressor use, and variations in sepsis severity. Until then, this study emphasizes the importance of individualized patient care, urging clinicians to weigh guidelines against the specific circumstances and needs of each patient. As the debate continues, one thing remains clear: flexibility and clinical judgment are key to optimizing patient outcomes.

References:

1. Vaeli Zadeh A, Wong A, Crawford AC, Collado E, Larned JM. Guideline-based and restricted fluid resuscitation strategy in sepsis patients with heart failure: A systematic review and meta-analysis [published online ahead of print, 2023 Aug 9]. Am J Emerg Med. 2023;73:34-39. PMID: 37597449
2. Rai A, Dassum SR, Ahmad YR, Ansari S, Kitch BT, Filbin M, Rhee C. Association of the National Center for Medicare and Medicaid Services Sepsis Fluid Resuscitation Measure with Sepsis Outcomes in Patients with and Without Heart Failure. D25. CRITICAL CARE: HARD TIMES – RESUSCITATING MY PATIENT: FLUID, BLOOD AND OTHER STRATEGIES. May 1, 2019, A5999-A5999. [Abstract Link]
3. Taenzer AH, Patel SJ, Allen TL, et al. Improvement in Mortality With Early Fluid Bolus in Sepsis Patients With a History of Congestive Heart Failure. Mayo Clin Proc Innov Qual Outcomes. 2020;4(5):537-541. Published 2020 Aug 19. PMID: 33083702
4. Uchel, T., Hamdon, M. S., Patel, M., Gonzalez, V., & Masso, L. (2019). FLUID RESUSCITATION IN CHF PATIENTS PRESENTING WITH SEPSIS: A RETROSPECTIVE COHORT STUDY. Chest, 156(4), A1719. [Abstract Link]
5. Kuttab HI, Lykins JD, Hughes MD, et al. Evaluation and Predictors of Fluid Resuscitation in Patients With Severe Sepsis and Septic Shock. Crit Care Med. 2019;47(11):1582-1590. PMID: 31393324

Guest Post By:

Imogen Kane, DO
PGY-1, Emergency Medicine Resident
Vassar Brothers Hospital, Poughkeepsie, New York
E-mail: Imogen.Kane@nuvancehealth.org

Marco Propersi, DO FAAEM
Vice-Chair, Emergency Medicine
Assistant Emergency Medicine Program Director
Vassar Brothers Hospital, Poughkeepsie, New York
Twitter: @marco_propersi

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)

The post Congestive Heart Failure and Sepsis: A Closer Look at Fluid Management appeared first on REBEL EM - Emergency Medicine Blog.

Take Home Points:

• All STEMIs should be loaded with dual antiplatelet therapy. Prasugrel (Effient) is avoided as there is an increase in bleeding complications if the patient requires a CABG.

• NSTEMI cases can be challenging to manage. Consult Cardiology early and use all available data.

• The appropriate medical treatment for ACS patients is as important as PCI.

• POCUS is a very valuable tool for ACS patients in the ED.

• Clinical presentation  trumps all other data. Trust your gut!

The post REBEL Core Cast 113.0 – ACS Therapies and Management appeared first on REBEL EM - Emergency Medicine Blog.

A 35-year-old woman presents with 4 days of headache, nasal congestion, ear pain, and mild sore throat. She has been taking an over-the-counter medication for her symptoms, but it doesn’t do anything for her. According to recent FDA news, which medication has she likely been taking?

1. Diphenhydramine
2. Oxymetazoline
3. Phenylephrine
4. Pseudoephedrine

FOR THE RIGHT ANSWER CLICK ON THE ROSH REVIEW LOGO BELOW

References

1. De Sutter AI, Eriksson L, van Driel ML. Oral antihistamine-decongestant-analgesic combinations for the common cold. Cochrane Database Syst Rev. 2022;1(1):CD004976. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780136/
2. Deckx L, De Sutter AI, Guo L, Mir NA, van Driel ML. Nasal decongestants in monotherapy for the common cold. Cochrane Database Syst Rev. 2016;10(10):CD009612. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461189/
3. DeGeorge KC, Ring DJ, Dalrymple SN. Treatment of the common cold. Am Fam Physician. 2019;100(5):281–289. https://www.aafp.org/pubs/afp/issues/2019/0901/p281.html
4. FDA clarifies results of recent advisory committee meeting on oral phenylephrine. U.S. Food & Drug Administration website. Accessed September 21, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-results-recent-advisory-committee-meeting-oral-phenylephrine
5. Gelotte CK, Zimmerman BA. Pharmacokinetics, safety, and cardiovascular tolerability of phenylephrine HCl 10, 20, and 30 mg after a single oral administration in healthy volunteers. Clin Drug Investig. 2015;35(9):547–558.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559581/
6. Laccourreye O, Werner A, Giroud JP, Couloigner V, Bonfils P, Bondon-Guitton E. Benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants. Eur Ann Otorhinolaryngol Head Neck Dis. 2015;132(1):31–34.  https://www.sciencedirect.com/science/article/pii/S1879729614001665 
7. Meltzer EO, Ratner PH, McGraw T. Oral phenylephrine HCl for nasal congestion in seasonal allergic rhinitis: a randomized, open-label, placebo-controlled study. J Allergy Clin Immunol Pract. 2015;3(5):702–708. https://pubmed.ncbi.nlm.nih.gov/26143019/

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)

The post Rosh Review EM Scholar Monthly Question appeared first on REBEL EM - Emergency Medicine Blog.

Background: Hemmorhage is a major cause of preventable death in trauma patients. Early expeditious definitive hemorrhage control is a major focus in trauma resuscitation. Patients with torso hemorrhage present a clinical conundrum often requiring interventional radiology or surgery, both of which take time to mobilize. Theoretically, the use of REBOA with aortic occlusion should help limit hemorrhage, maintain cerebral/myocardial perfusion, and allow more time for interventional and surgical procedures.

Military practice guidelines recommend REBOA for profound shock (SBP <90mmHg)¹ and ACEP along with the American College of surgeons recommend REBOA for traumatic life-threatening hemorrhage below the diaphragm in patients with hemorrhagic shock who are unresponsive or transiently responsive to resuscitation.² Despite these recommendations there are no randomized clinical trials to help guide practice until now.

Paper: Jansen JO, Hudson J, Cochran C, et al. Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial [published online ahead of print, 2023 Oct 12]. JAMA. 2023;e2320850. PMID: 37824132

Clinical Question: In trauma patients aged 16 years or older with life-threatening torso hemorrhage, does the use of REBOA and standard care (SC) compared to standard care alone (SCA)  improve mortality at 90 days.

What They Did:

• UK Resuscitative Endovascular Balloon Occlusion of the Aorta (UK-REBOA) Trial
• Study Design: Multicenter, open-label, Bayesian, group-sequential, registry-enabled, randomized clinical trial.
• Researchers randomly assigned 90 eligible patients over ≈ 4.5 years, in a 1:1 ratio, to receive treatment with REBOA and standard care or standard care alone.
• Sites: Conducted at 16 major trauma centers in the UK.
• Funding Source: National Institute of Health Research
• Trial Registration: isrctn.org Identifier: ISRCTN16184981

Population:

• Inclusion Criteria: Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso hemorrhage deemed amenable to adjunctive treatment with REBOA.
• Exclusion Criteria: Patients known or thought to be pregnant or with injuries clearly not survivable.

Intervention:

• The placement of REBOA for resuscitation in zone I (the descending aorta) or zone III (above the aortic bifurcation) based on clinician judgment.

Comparator:

• The control group received standard care provided at a major trauma center, including intubation, blood product transfusion, interventions like tourniquet application, and early operative or endovascular hemorrhage control.

Outcome:

Primary Outcome: All-cause mortality at 90 days.

Secondary Outcomes: 

• Mortality at 6 months, while in the hospital, and within 24 hours, 6 hours, or 3 hours
• The need for definitive hemorrhage control procedures
• Time to commencement of definitive hemorrhage control procedures
• Complications
• Length of stay (hospital-free and intensive care unit-free days)
• Blood product use
• Cause of death

Results:

Patient Recruitment: 

• 120 planned—The trial was stopped short due to prespecified stopping rule for harm was met.
• 90 Randomized
  • 46 randomized to REBOA+SC group
  • 44 randomized to SCA group
  • 1 patient decline participation after enrollment

Baseline characteristics

• 69% of enrolled patients across both cohorts were male.
• 97% of patients sustained blunt trauma.
• The median Injury Severity Score was 41
• The median age was 41
• 23% required prehospital CPR 
• All were tachycardic and hypotensive prehospital
• REBOA+SC group had lower median SBP compared with in the SCA  group 84 mm Hg vs 99 mm Hg
• REBOA group had higher median Abbreviated Injury Scores for the head region.

REBOA Treatment Pathways

• 19 REBOA with balloon inflation
• 9 Arterial access; No REBOA
• 8 Arterial access unsuccessful
• 5 Arterial access; REBOA with no balloon inflation
• 3 No arterial access or REBOA attempted
• Additionally 2 patients in the SCA arm received REBOA with balloon inflation
• Zone I inflation 53%
• Zone III inflation: 47%
• Median time from ED arrival to balloon inflation was 32 minutes
• Median duration of inflation was 29 min
• Partial REBOA (titrated balloon deflation was used in 42%

Primary Outcome: All-cause mortality at 90 days:

• REBOA+SC group: 25/46 (54%)
• SCA group: 18/43 (42%)
• OR 1.58; 95% CI 0.72 – 3.52
• OR > 1 indicates treatment with REBOA and standard care increased odds of death.
• The posterior probability of OR > 1 was 86.9%, again indicating treatment with REBOA+SC increased the odds of death.
• Multivariable regression, adjusting for baseline differences, showed higher odds of 90-day mortality in the REBOA and standard care group. 
  • OR 1.80 (95% CrI 0.59-5.59).
  • 84.9% posterior probability of OR > 1
• Post hoc analyses of individual covariates had minimal impact on results.
• Results of principal stratum analyses and learning curve effects analysis remained consistent and did not change the overall findings.

Secondary Outcomes:

• Treatment with REBOA+SC increased the odds of death across all time points measures in the secondary outcomes, as indicated by the ORs for mortality and posterior probabilities of OR > 1 were elevated in the REBOA+SC group across all time points: 6-month, in-hospital, 24-hour, 6-hour, and 3-hour mortality.
• More deaths due to bleeding were observed in the REBOA+SC group (32% of patients) compared to the SCA group (17% of patients), with most of these deaths occurring within 24 hours.
• Definitive hemorrhage control procedures were performed in 30% of patients in the REBOA and standard care group and 43% in the standard care alone group.
• The median time from randomization to definitive hemorrhage control was 19 minutes longer in the REBOA and standard care group.
• Patients in the standard care alone group had more intensive care unit-free and hospital-free days.
• No significant differences were observed between groups in terms of complications.
• No serious adverse device events were reported.

Strengths:

• The study addressed a highly debated and clinically relevant question.
• The UK-REBOA Trial is the first randomzied clinical trial to evaluate the effectiveness of REBOA in trauma patients with exsanguinating hemorrhage.
• The primary outcome focused on patient-centered outcomes.
• Investigators employed a randomized, controlled, multicenter study design, which minimized the risk of bias and enhanced external validity.
• The trial had a pragmatic design with broad inclusion criteria.
• The study used a concealed centralized web-based randomization process for participant allocation, which can help mitigate selection and allocation bias.
• The statistical analysis plan was completed before data analysis.
• Investigators performed an Intention-To-Treat analysis, which preserves randomization, mitigates attrition bias, and more closely resembles clinical reality where not all patients will adhere to treatment.
• Investigators performed multiple sensitivity analyses to address potential between-group imbalances that may arise in smaller trials.
• Follow-up was nearly complete, with only one patient withdrawing consent after enrollment.
• The outcomes were predominantly binary and objective, reducing the potential for subjective interpretation and bias.
• The baseline characteristics of the patient cohort indicated patients were severely injured trauma patients.

Limitations:

• The trial was conducted within a single county, which may limit generalizability to other geographical regions.
• The relatively small sample size raises the possibility that observed outcome differences between groups could be due to chance.
• Notably, 3 of the 16 participating centers recruited nearly half of the patients, potentially introducing variations in patient characteristics.
• Blinding the trial participants and healthcare providers was impossible due to the nature of the intervention..
• Some important baseline differences in demographics, including blood pressure, were noted between the groups. As a result, it is unclear if patients had the same prognosis at the beginning of the study.
• The study cohort was predominantly male (69%) and predominantly involved blunt trauma cases (97%). Additionally, the median age was 41, with a relatively narrow age range of 30-62. These demographic characteristics may limit the generalizability of the findings to a more diverse patient population.
• There was almost no penetrating trauma making It near impossible to draw conclusions about REBOA use in penetrating trauma patients.
• Case volume for operative hemorrhage control is much lower in UK compared to other countries, reflecting better road safety standards and low levels of interpersonal violence. These unique circumstances may not reflect other countries and healthcare systems.
• Pre Arrival times exceeded 90 minutes for both the intervention and standard care groups. Extended pre arrival duration may not accurately reflect the time frames in all clinical settings, potentially affecting the study’s generalizability.
• The study reported numerous protocol violations, with only 19 out of 46 patients in the REBOA+SC group receiving complete catheter insertion and balloon inflation intervention. Likewise, 2 patients in the SCA cohort received REBOA.
• The authors omitted detailed information regarding the training requirements and experience level of the healthcare providers involved in the procedures. These factors can significantly impact the effectiveness of the intervention.
• The type and size of the device used in the intervention were not controlled or described. Variations in device characteristics, such as size and type, could influence study outcomes.
• The study did not offer information on the duration of occlusion during the intervention. Prolonged occlusion times are known to have adverse effects and may impact the study’s outcomes.
• The early termination of the trial due to potential harm introduces uncertainty and limitations when interpreting the findings.

Discussion:

Protracted Treatment:

In severely injured trauma patients, the timeliness of hemorrhage control is paramount. In the UK-REBOA trial, patients faced extended pre-hospital transit times, with a median time exceeding 90 minutes. No patient experienced a transit time of <70 minutes; some endured periods as lengthy as 125 minutes. Despite both patient cohorts encountering prolonged intervals of hemorrhage control, the REBOA+SC group experienced a median time to hemorrhage control 19 minutes longer than the SCA group (83 minutes vs. 64 minutes)—the overall time from injury to definitive hemorrhage control for both cohorts approached 3 hours. 

The enrolled population was severely injured, with a median ISS of 41, and 23% received CPR. While many would likely die under optimal circumstances, protracted periods of exsanguination likely exacerbated their condition, and more patients died due to bleeding in REBOA+SC (32%) vs SCA (17%). The protracted times observed in various metrics measured within the UK-REBOA trial likely reflect the studied healthcare system’s available resources. These times may not be representative of systems with shorter transit times.

Considering the prolonged pre-hospital transit times observed, could the deployment of REBOA in the pre-hospital setting produce earlier definitive hemorrhage control in this study? This proactive approach could address the challenge of delayed access to critical interventions in healthcare systems with long transit times. Exploring the feasibility and effectiveness of pre-hospital REBOA deployment warrants further investigation to enhance trauma resuscitation strategies and potentially improve patient outcomes.

REBOA Placement:

In contrast to randomized clinical trials evaluating medications, this study revolves around a procedural intervention, introducing a distinct set of challenges. Many past procedure based trials have demonstrated that negative outcomes are more likely when implementing procedures that operators are less familiar with (The Beam Trial and Bougie Trial). This underscores the importance of procedural proficiency and operator expertise, suggesting that the success or failure of interventions like REBOA can be significantly influenced by the skill and experience of the clinicians involved.

The experience level of clinicians in the UK-REBOA Trial remains unclear. The trial reported a median time of 32 minutes from ED arrival to successful balloon inflation. However, arterial cannulation was unsuccessful in 17% of patients randomized to the REBOA+SC arm, emphasizing clinicians’ difficulty in deploying the device effectively. The training protocol mandated a two-day session, later condensed to one day, with unspecified details on simulation attempts and trainer mannequins or animal and cadaver models. The individual sites were responsible for additional education and repeat training. While simulation cannot fully replicate the stress of a real-life attempt, it is crucial, especially for high-acuity and low-occurence procedures.

The trial investigators conducted a learning curve sensitivity analysis, excluding the first REBOA attempt from each site from the dataset. However, this assumes subsequent attempts will involve the same care team. Furthermore, among the 16 centers in the trial, 3 contributed half the patients, while 4 contributed none. Notably, one site enrolled 20% of patients, with only 9 randomized to the REBOA+SC arm over 54 months—or 1 REBOA attempt every six months. This frequency may be significantly lower than in larger trauma centers where providers might be more adept with the device due to more frequent usage.

Small Sample Size:

The findings of this trial hinge on a relatively small number of events. While 46 patients were randomized to the REBOA+SC arm, numerous protocol violations occurred, and only 19 underwent arterial access, catheter insertion, and balloon inflation. The remaining cases varied from incomplete REBOA with arterial access and catheter insertion but no balloon inflation to no attempted access at all. In addition, investigators stopped the trial early at a pre planned interim analysis due to evidence of harm. Trials stopped early are at risk of overestimating the potential effect of the intervention.

Baseline differences in demographics, including variations in heart rate, systolic blood pressure, and head injury, persisted despite randomization, suggesting patients in the REBOA+SC arm had a worse prognosis. While randomization theoretically aims to balance these characteristics it is more common to see differences in trials with small sample sizes. The combination of small trial size, numerous protocol violations, and early termination raises the possibility that the resulting data could be attributed to chance alone.

Author’s Conclusion: “The REBOA and standard care group was observed to have a high probability of higher mortality at 90 days compared with the standard care alone group. The findings were not altered in an adjusted analysis. REBOA may not reduce, and might increase, mortality in trauma patients with exsanguinating hemorrhage.”

Our Conclusion:

The UK-REBOA Trial presents pivotal insights into the use of REBOA in trauma patients with exsanguinating hemorrhage. Contrary to expectations, REBOA in conjunction with standard care did not demonstrate a reduction in mortality rates at 90 days when compared to standard care alone. In fact, the probability of increased mortality was higher in the REBOA group. Suggestsing that REBOA may not be the universally beneficial intervention it was hoped to be.

However, it’s crucial to interpret these findings with caution. The trial faced several methodological challenges, including extended prehospital transport times, limited operator experience, and a smaller-than-anticipated sample size. These factors, alongside early termination of the trial, introduce a degree of uncertainty to the results. The predominantly male and blunt trauma demographic of the study cohort further limits the generalizability of these findings to a broader patient population.

This study underscores the need for more extensive research in diverse clinical settings to fully understand the role of REBOA in trauma care. It highlights that the path to optimizing trauma care is complex and requires continuous evaluation and adaptation of our approaches. While REBOA might not be the one-size-fits-all solution, it could still hold potential for specific patient subsets. Future research should focus on identifying these subsets and exploring the pre-hospital deployment of REBOA, especially in systems with long transit times.

In conclusion, the UK-REBOA Trial is a significant step in our ongoing pursuit to enhance trauma care. It serves as a reminder of the importance of rigorously testing medical interventions in varied settings and populations.

References:

1. Butler FK Jr, Holcomb JB, Shackelford SA, et al. Advanced Resuscitative Care in Tactical Combat Casualty Care: TCCC Guidelines Change 18-01:14 October 2018. J Spec Oper Med. 2018;18(4):37-55. PMID: 30566723
2. Bulger EM, Perina DG, Qasim Z, et al. Clinical use of resuscitative endovascular balloon occlusion of the aorta (REBOA) in civilian trauma systems in the USA, 2019: a joint statement from the American College of Surgeons Committee on Trauma, the American College of Emergency Physicians, the National Association of Emergency Medical Services Physicians and the National Association of Emergency Medical Technicians. Trauma Surg Acute Care Open. 2019;4(1):e000376. Published 2019 Sep 20. PMID: 31673635

Post By:

Marco Propersi, DO FAAEM
Vice-Chair, Emergency Medicine
Assistant Emergency Medicine Program Director
Vassar Brothers Hospital, Poughkeepsie, New York
Twitter/X: @marco_propersi

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)

The post UK-REBOA on Trial: Innovative or Over-Inflated? appeared first on REBEL EM - Emergency Medicine Blog.

Take Home Points:

• Dose your RSI meds correctly. 
• Reach for post-intubation sedation at the same time you are asking for your induction agent and paralytic.  
• Propofol is a great choice for post-intubation sedation, and if your patient becomes hypotensive do not be afraid of adding on a pressor! 

The post REBEL Core Cast 112.0 – Awareness During Paralysis appeared first on REBEL EM - Emergency Medicine Blog.

Background Information:

Vasoplegic shock is defined as hypotension with normal or increased cardiac output and can commonly occur in post-cardiac surgery patients having received cardiopulmonary bypass. This dysregulation of vasodilation is associated with a mortality of close to 25%. After catecholamine vasopressors, treatment options include angiotensin II, corticosteroids, methylene blue and hydroxocobalamin. The latter two have been investigated in limited comparative studies leading to no significant differences in vasopressor requirements. The authors of this retrospective cohort study sought to evaluate the impact of hydroxocobalamin compared with methylene blue on vasopressor requirements and other hemodynamic parameters in vasoplegic shock.

Paper: Hiruy A, et al. Hydroxocobalamin Versus Methylene Blue for the Treatment of Vasoplegic Shock Associated With Cardiopulmonary Bypass. J Cardiothorac Vasc Anesth. 2023 Jul 19. Epub ahead of print. PMID: 37586951

Clinical Question:

• In patients requiring cardiopulmonary bypass and developing vasopressor-resistant vasoplegic shock, what is the impact of hydroxocobalamin compared to methylene blue in improving vasopressor requirements over the first 24 hours?

What They Did:

• Retrospective cohort analysis of post-cardiothoracic surgery patients at a single large academic center
• Methylene blue (IV bolus with or without continuous infusion) was utilized between January 2016 and August 2019, then hydroxocobalamin was the primary agent used from July 2019 to July 2021
• The dosing for the study medications were as follows:
  • Hydroxocobalamin Dose = 5g IV over 15min
  • Methylene Blue Doses:
    • Bolus: 1.2mg/kg (1 to 2mg/kg)
    • Infusion: 0.25mg/kg/hr for a median duration of 10hrs (0.25 to 1mg/kg/hr)
• Information regarding the vasopressors used in the study is as follows:
  • Norepinephrine equivalents = norepinephrine mcg/kg/min + (phenylephrine mcg/kg/min/10) + epinephrine mcg/kg/min + (vasopressin units/min x2.5)
  • Angiotensin II was not available at the institution and dopamine was not used in any patients included in the analysis during the study period
    

Inclusion Criteria:

• Adult patients > 18 years of age
• Vasopressor requirements were higher than 0.2 ug/kg/min of norepinephrine equivalent at time of hydroxocobalamin or methylene blue administration
  

Exclusion Criteria:

• Administration of hydroxocobalamin or methylene blue for non-VS indications
• Hydroxocobalamin or methylene blue given > 48 hours after CPB
• Pre-intervention cardiac index < 2.0 L/min/m2 (measured either with thermodilution or calculated using the Fick Method)
• Administration of both hydroxocobalamin and methylene blue
• Return to the OR for postoperative hemorrhage within 48 hours of initial surgery
  

Outcomes:

Primary

• Change in vasopressor requirement over time after methylene blue or hydroxocobalamin initiation assessed at 1, 3, 6, 12 and 24 hours post study drug administration
  • Expressed as Norepinephrine Equivalent (NEE)
  • NEE = Norepinephrine (ug/kg/min) + (Phenylephrine (ug/kg/min)/10) + epinephrine (ug/kg/min) + (vasopressin (units/min) x 2.5)

Secondary

• Hemodynamic outcomes such as MAP, SVR and lactate evaluated at baseline and 1, 3, 6, 12 and 24 hours post study drug administration
• ICU length of stay
• Hospital length of stay
• Hospital mortality
  

Results:

Critical Results:

Strengths:

• Largest comparative cohort of cardiothoracic surgery patients treated with hydroxocobalamin or methylene blue for refractory vasoplegic shock
• Builds upon current evidence regarding the use of these two therapies for vasoplegic shock
• Excluded patient with cardiogenic and hemorrhagic shock to only focus on those with vasoplegic shock
• Included a wide range of cardiothoracic surgery procedures (ie. CABG, Valve repair/replacement, LVAD and Heart/Lung Transplants)
• Helps answer a clinically relevant question related to a serious post-surgery complication
• Included in-depth pertinent surgical characteristics in addition to typical demographic information

Limitations:

• Limited external validity given this was done at a single large academic medical center
• Retrospective study with no placebo group
• Dosing of inotropes and other supportive factors impacting hemodynamics were not captured
• Missing secondary data such as SVR and lactate was estimated based on a model
• This study did not address potential adverse effects of either medication investigated
• Lack of patient oriented primary and secondary outcomes
• Unbalanced groups in terms of baseline characteristics and especially with regard to the amount of intraoperative vasopressors received between the two groups. More patients in the methylene blue group received vasopressin (98% vs 81%), phenylepinephrine (61% vs 1%) and dobutamine (14% vs 4%) compared to the hydroxocobalamin group 
• Patients in the methylene blue group had lower mean preoperative LVEF (35%) compared to the hydroxocobalamin group (46%)
• Methylene blue group patients received preoperative RAS inhibitors (21%) more frequently than the patients in the hydroxocobalamin group (6.5%)
• Higher baseline MAPs in hydroxocobalamin group may have led to an underestimation of treatment effect 
• Higher percentage of surgical cases were redo procedures in the methylene blue group compared to the hydroxocobalamin group (63% vs 43%)
• There are many confounding variables that may have impacted an accurate comparison between these two medications which are elaborated further in the discussion section below

Discussion:

• It’s worth noting that the baseline MAPs were higher in the hydroxocobalamin group and that it’s possible the patients who received methylene blue were in more severe shock states that may not have been amenable to pharmacologic agents alone. 
• The above point may suggest that because the patients receiving hydroxocobalamin were less sick, the results are skewed to favor that intervention over methylene blue
• There are many internal and external confounding variables that the authors suggest gives hydroxocobalamin it’s added benefit:
  • Dosing differences between the two medications (Bolus +/- continuous infusion for methylene blue vs standardized dose for hydroxocobalamin)
  • Differences in medical practice between 2016 – 2019 and 2019 – 2021
  • Differences in practice settings were the medications were administered (Methylene blue was more commonly given in the OR, which may signal a more profound state of vasoplegic shock compared in this group)
• What the authors fail to recognize, is that the above confounding variables actually serve to significantly limit the accurate comparison of these two medications for a post-surgical complication such as vasoplegic shock
• The lack of a placebo group makes it difficult to compare these medications to standard therapy/something else 
• Patients in the methylene blue group were much sicker than the hydroxocobalamin group as demonstrated by a significantly lower EF, higher percentage of redo procedures and higher use of perioperative inhibitors of RAS thus it makes sense the patients in these group got more intraoperative phenylepinephrine, vasopressin, dobutamine and milrinone. 
• So with yet another confounding variable added (sicker patients at baseline in methylene blue group), the comparison of these two medications is yet again even more difficult
• There was no difference in ICU and hospital length of stays or hospital mortality between the two groups. Which should prompt the question, how much of a difference does hydroxocobalamin actually make in decreasing the vasopressor requirement and increasing the MAP if this had no impact on ICU/hospital LOS or hospital mortality?
• Until further evidence presents itself, what this study offers is building upon what we do know. Both these medications continue to serve as options for treating post-cardiac surgery patients in vasoplegic shock. Whether one is truly better than the other remains to be seen.

Author’s Conclusions:

• Hydroxocobalamin was associated with a greater reduction in vasopressor requirements than methylene blue in treating VS associated with cardiopulmonary bypass

Our Conclusion:

• This single-center retrospective trial with no placebo group had too many confounding variables to accurately compare hydroxocobalamin to methylene blue for vasoplegic shock. From a sicker baseline patient population in the methylene blue group to variations in dosing and practice setting administration, the efficacy of hydroxocobalamin should not come as a surprise given it was set up for success. 

Clinical Bottom Line:

• This retrospective single-center study failed to accurately compare the use of hydroxocobalamin to methylene blue in reducing vasopressor requirements when treating vasoplegic shock associated with cardiopulmonary bypass. While it builds upon the current evidence suggesting either of these medications can be used, we can not definitively say one is more effective than the other without more methodological sound studies.

REFERENCES:

1. Hiruy A, et al. Hydroxocobalamin Versus Methylene Blue for the Treatment of Vasoplegic Shock Associated With Cardiopulmonary Bypass. J Cardiothorac Vasc Anesth. 2023 Jul 19. Epub ahead of print. PMID: 37586951 
2. Mehaffey JH, et al. Methylene Blue for Vasoplegic Syndrome After Cardiac Operation: Early Administration Improves Survival. Ann Thorac Surg. Epub 2017 May 24. PMID: 28551045
3. Bak MA, et al. High-Dose Hydroxocobalamin for Refractory Vasoplegia Post Cardiac Surgery. Cureus. 2022 Aug 22. PMID: 36039127
   

Post Peer Reviewed By: Salim Rezaie, MD (Twitter: @Srrezaie)

The post Hydroxycobalamin vs Methylene Blue for Vasoplegic Shock from Cardiopulmonary Bypass appeared first on REBEL EM - Emergency Medicine Blog.

What is Flow? 

Simply put, flow is the peak of human performance, maximum focus with maximum responsiveness, an optimal state of consciousness. This state of mind is accessible to anyone under the right circumstances and has huge implications to how we live, work and train. 

REBEL Cast Book Club Episode 4 — The Rise of Superman: Decoding the Science of Ultimate Human Performance

In “The Rise of Superman,” Steven Kotler details the flow state through the journey of extreme sports athletes, and how these incredible human beings are utilizing flow to push the limits of their respective sports at an ever accelerating pace. Performing on the brink of life or death acts as a shortcut to achieving flow, allowing for these huge leaps in extreme sports that are rarely seen in safer, more mainstream sports.

But what about the rest of us? How can we achieve flow in a less extreme environment, much less utilize flow to become better in our everyday lives.  Getting into flow is often linked with being engaged in life or death activities, something that we as ED physicians are intimately failure with on a regular basis.

In this podcast episode, three Emergency Medicine Physicians, Marco Propersi, Dan Wolf and Will Smith, discuss flow in relation to working in the ED, how it intersects with medical training, on shift performance and even in daily life outside the hospital. 

• • Does the high stakes life or death environment in the ED allow us to access a flow state, even though our own lives are not at risk? 
  • How can you set yourself up to achieve flow?
  • While on shift how does being ‘in flow’ facilitate mastery of our profession?

We will discuss these topics and many more on this episode of REBEL Reflections!

After you are done listening, leave a comment with some of your thoughts about flow or share an experience or two.  Also, don’t forget to like and subscribe!

The Rise of Superman on Amazon.com

Post Authors

Will Smith, MD
EMRACast Podcast Fellow
The Socials: @WTSmithMD
Email: WTSmithMD@gmail.com

Daniel Wolf, DO
EMS Fellow – Maimonides Medical Center
Email: DWolf@maimonidesmed.org

Marco Propersi, DO FAAEM
Vice-Chair, Emergency Medicine
Assistant Emergency Medicine Program Director
Vassar Brothers Hospital, Poughkeepsie, New York
Twitter: @marco_propersi

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)

The post REBEL Cast Book Club Episode 4 — The Rise of Superman: Decoding the Science of Ultimate Human Performance appeared first on REBEL EM - Emergency Medicine Blog.

Background: Hemorrhage is the leading cause of trauma related mortality. The initial injury is often complicated by multifactorial coagulopathy that can exacerbate bleeding.  Fibrinogen is the precursor to fibrin and a major component of stable clot formation. Fibrinogen and fibrin are often depleted during major trauma as a result of consumption, breakdown, and dilution. Most major hemorrhage protocols give a balanced transfusion of PRBCs, FFP, and platelets in ratios approaching concentrations found in whole blood. Fibrinogen products may also be needed to stabilize clots and stem bleeding. The optimal approach to fibrinogen administration in massive hemorrhage protocols is unknown.

Paper: Davenport R et al. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial. JAMA 2023. PMID: 37824155

 Clinical Question: Does transfusion of early and empiric high-dose cryoprecipitate in addition to standard care improve survival in bleeding patients with trauma who require activation of a major hemorrhage protocol?

What They Did:

• Interventional, randomized, open-label, parallel-group, controlled, international, phase 3, multicenter study
• Patients enrolled at 26 UK and US major trauma centers
• Injured adults requiring activation of major hemorrhage protocol with evidence of active hemorrhage, SBP < 90mmHg at any time, and receiving at least 1U of any blood component
• Patients within 90 minutes of randomization and 3 hours of injury were randomized to:
  • Standard Care: Local major hemorrhage protocol
    • 1:1:1 ratio of PRBCs, FFP, and Platelets
  • Cryoprecipitate: Local major hemorrhage protocol + 3 pools of cryoprecipitate (6g fibrinogen equivalent)

Outcomes:

• Primary: All-cause mortality at 28d (intention to treat population)
• Secondary: 25 Prespecified outcomes
• Safety: Thrombotic events at 28d 

Inclusion:

• Adult trauma patient (≥16 years of age)
• Severe injury with evidence of active hemorrhage requiring activation of local massive hemorrhage protocol
• Started or received at least 1U of any blood component
• SBP<90mmHg at any point

 Exclusion:

• Patient being transferred from another hospital
• Injuries incompatible with life as assessed by the trauma team leader
• >3hrs elapsing from the time of injury 

Results:

• 1604 eligible patients (1531 (95%) of patients were included in the primary analysis population)
  • Most patients recruited from UK (1555 patients); US recruited 49 patients
  • Median Age: 39 years (26 to 55years)
  • Median ISS: 29 (18 to 43)
  • Penetrating Injury: 36%
  • Blunt Injury: 64%
  • SBP <90mmHg at Hospital Arrival: 33%
• Timing/Interventions
  • Prior to hospital arrival 43% of patients received a blood component and 79% received TXA (96% of patients received TXA either before or in the hospital)
  • Median time from injury to ED arrival: 76 minutes
  • Median time from admission to randomization: 15 minutes
  • 85% of patients in cryoprecipitate group received cryoprecipitate vs 32% in the standard care group
  • Median time from admission to first administration of cryoprecipitate: 68 minutes (cryoprecipitate group) vs 120min (standard care group)
• All-Cause 28d Mortality:
  • Standard Care Group: 26.1%
  • Cryoprecipitate Group: 25.3%
  • OR 0.96; 95% CI 0.75 to 1.23; p = 0.74
• Mortality at 6 hours ad 24 hours was similar between groups
  • The proportion of deaths from bleeding in the 1^st 6 and 24 hours was not different between groups
  • Median time to death from hemorrhage: 191min in cryoprecipitate group vs 86min in the standard care group
• Penetrating trauma 28-day mortality: significantly higher in the cryoprecipitate group than the standard care group (16.2% vs 10%; OR 1.74; 95% CI 1.20 to 2.51)
• No difference in safety outcomes, incidence of thrombotic events, or transfusion requirements between groups

Strengths:

• Asks a clinically important question with limited prior data
• Randomized, international trial
• Independent data monitoring committee reviewed interim data analysis and monitored patient safety
• Used an intention-to-treat plan which does a better job of estimating real world practice (as opposed to per protocol)
• Both groups were well-matched in baseline clinical characteristics
• Included patients who were severely injured, hypotensive, and received substantial blood component transfusions (i.e. very sick cohort)
• Minimal loss to follow up for primary analysis

Limitations:

• Convenience sample of patients which could cause selection bias (888 patients not randomized due to unavailability of research team)
• Due to a lack of a placebo group it is difficult to examine the effect of timing of cryoprecipitate administration on outcomes
• Some cross-over between groups: 15% of patients in the cryoprecipitate group did not receive cryoprecipitate and 9% of patients in the standard care group got cryoprecipitate within 90 minutes (32% within 24 hours). This could dilute any beneficial effects seen
• Lack of blinding may bias results (Although mortality is a solid objective primary outcome, bias may still creep in terms of management)

Discussion:

• Authors were looking for an absolute mortality difference of 7% from baseline mortality of 26% with a 90% power. The 26% mortality rate was based on the 28% mortality rate in the feasibility study (CRYOSTAT-1)
• Giving early, empiric cryoprecipitate most likely results in a substantial proportion of patients receiving fibrinogen who do not develop hypofibrinogenemia (i.e. a negative trial). This trial would advocate for a precision-guided coagulation therapy
  • A blood sample to determine fibrinogen level prior to cryoprecipitate administration was not required (some patients may have received cryoprecipitate without having low fibrinogen levels)
• Cryoprecipitate was given to 85% of the intervention group and 32% of the standard card group. This would normally make me worry about dilution of results and biasing the results to the null hypothesis, but in the per protocol analysis (170 patients excluded from the full cohort, due to no longer requiring blood transfusion, dying within 90 minutes of arrival or being randomized in error) didn’t seem to affect this result either.
• Interestingly the use of early, empiric cryoprecipitate did impact 28 mortality in the prespecified subgroup of patients with penetrating trauma (16.2% vs 10%; OR 1.74; 95% CI 1.20 to 2.51). As this is a secondary outcome this is hypothesis generating but does require further research to see if blunt vs penetrating trauma are phenotypically different

Author Conclusion: “Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality.”

Clinical Take Home Point: Among adult patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empiric cryoprecipitate to standard care did not improve all cause 28-day mortality. Until better evidence is presented this trial would advocate for a precision-guided coagulation therapy (i.e. based on fibrinogen levels).

References:

1. Davenport R et al. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial. JAMA 2023. PMID: 37824155

For More Thoughts on This Topic Checkout:

• First10EM: CRYOSTAT-2 – Empiric Cryoprecipitate in Traumatic Massive Hemorrhage
• Emlyn’s: CRYOSTAT-2
• The Bottom Line: Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)

The post CRYOSTAT-2: Early Empiric Cryoprecipitate in Major Trauma appeared first on REBEL EM - Emergency Medicine Blog.

Background: There is a shifting paradigm towards shorter durations of antibiotics in pediatric infections. Conflicting international guidelines recommend treatment of urinary tract infection (UTI) with antibiotic courses ranging from just 3 days to 7–14 days.^1–4 Antimicrobial resistance is a global health crisis, underscoring the importance of antibiotic stewardship. Investigators in the SCOUT Trial examine the impact of short-course (5 day) antibiotic therapy in UTI, with potentially far reaching implications.

Paper: Zaoutis T, Shaikh N, Fisher BT, et al. Short-Course Therapy for Urinary Tract Infections in Children: The SCOUT Randomized Clinical Trial. JAMA Pediatr. 2023;177(8):782-789. PMID: 37358858

Clinical Question: In children aged 2 months to 10 years who exhibit clinical improvement after 5 days of antimicrobial therapy for UTIs, is short-course (5 days) oral antimicrobial therapy as effective as standard-course (10 days) therapy in preventing treatment failure and related outcomes?

What They Did:

• Study Design: Multicenter, randomized, double-blind, placebo-controlled, non inferiority clinical trial.
• Enrollment: Recruited patients from primary care offices, emergency departments, and inpatient wards at Children’s Hospital of Philadelphia and UPMC Children’s Hospital of Pittsburgh.
• Summary: Potentially eligible children being treated for UTI who were afebrile and had no clinical signs or symptoms of UTI were assessed in person on days 2–5. After consent, children were randomized 1:1 to receive 5 additional days of antibiotics or 5 days of a matching placebo. Investigators assessed clinical outcomes via 2 in-person visits on days 11–14 and days 24–30.

• Definitions: 
  • UTI: Presences of all 3 of the following criteria:
    1. One or more of the following: fever, pain in the suprapubic, abdominal, or flank area; urinary frequency, urgency, or hesitancy; dysuria in children ≥2 years old; in children < 2 years old, poor feeding and vomiting.
    2. Pyuria: ≥10 WBC/mm3 or ≥5 WBC/HPF (centrifuged specimen) or leukocyte esterase ≥ trace on dipstick urinalysis.
    3. Positive urine culture—growth of a single uropathogen at counts ≥5 x 104 or higher per CFU/ml (suprapubic aspiration or catheterized s specimen) or 105 or higher CFU/ml (clean voided specimen)

• • Asymptomatic Bacteriuria: positive urine culture with the same colony counts as above and without regard to pyuria, but in the absence of symptoms.
• Funding: The National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases funded the study.
• Trial Registration: ClinicalTrials.gov: NCT01595529

Population:

Inclusion Criteria:

• Children aged 2 months to 10 years.
• Diagnosed with UTI.
• Prescribed one of five frequently used antimicrobials:
  • Amoxicillin-clavulanate
  • Cefdinir
  • Cefixime
  • Cephalexin
  • Trimethoprim-sulfamethoxazole
• Recruited from primary care offices, emergency departments, and inpatient wards.

Exclusion Criteria:

• Recovery of a second uropathogen (>104 colony forming units [CFU] per mL for samples collected by suprapubic aspiration or catheterization, or >5 × 104 CFU per mL for samples collected by clean catch) at the time of diagnosis.
• Hospitalization for bacteremia.
• Admission to the intensive care unit.
• Urine culture yielding a pathogen resistant to the initially prescribed antimicrobial.
• Catheter-associated UTI.
• History of UTI within 30 days.
• Phenylketonuria.
• Congenital or anatomic abnormalities of the genitourinary tract 
• Previous genitourinary tract surgery (except circumcision).
• Inability to tolerate oral medications.
• Presence of an immunocompromising condition.
• Type I hypersensitivity or anaphylactic reaction to study products.
• Previous enrollment in the study.
• Enrollment in another therapeutic drug study (excluding vaccine studies).
• Gestational age of <36 weeks (only for children younger than 2 years of age at enrollment).
• Not available for follow-up visits.

Intervention

• Short-course therapy: Patients received 5 days of antibiotics and 5 additional days of a matching placebo.

Comparator

• Standard-course therapy: Patients received 10 days of antibiotics.

Outcome

Primary Outcome:

• Treatment Failure: Defined as the occurrence of UTI between day 6 and the day 11–14 visit.

Secondary Outcomes:

• UTI at any time after the day 11–14 visit.
• Asymptomatic bacteriuria at the day 11–14 visit.
• Gastrointestinal colonization with antimicrobial-resistant Escherichia coli or Klebsiella pneumoniae.
• Clinical symptoms of UTI between day 6 and the day 11–14 visit.
• Positive urine culture between day 6 and the day 11–14 visit.
• Proportion of children with reported adverse events between days 6 and 38–44.

Results:

Study Population: 

• 32,271 children were screened.
  • 20,391 children were excluded due to negative cultures.
  • 4,391 children were excluded for “other” reasons.
  • 1175 parents could not be reached.
  • 933 children did not receive 1 of the accepted antibiotics.
  • 103 children were excluded because their symptoms had not resolved at day 5.
  • 986 parents declined participation.
• 693 children were randomized.
  • 348 allocated to Standard-course therapy.
    • 20 excluded after randomization.
  • 345 allocated to Short-course therapy.
    • 9 excluded after randomization.
• Median age of children enrolled was 4 years (Range 2mo to 10 years)

Primary Outcome: 

• Standard-course (10 day) therapy had a lower rate of treatment failure (0.6%) compared to short-course therapy (4.2%).
• The upper limit of the CI for the absolute difference was 5.5%, which exceeded the prespecified 5% margin.
• Treatment failure was not related to age, fever, prescribed antimicrobial therapy, or study site.
• Short-course therapy DID NOT prove to be statistically noninferior to Standard-course (10 day) therapy.

Secondary Outcomes: 

• Short-course therapy was associated with higher rates of asymptomatic bacteriuria and positive urine cultures at the day 11–14 visit. 
• No significant differences were observed in other secondary outcomes or adverse events.

Strengths:

• Investigators asked a patient-oriented research question.
• The double-blind, randomized, placebo-controlled trial study design is the gold standard for medical literature and helps to limit bias.
• Investigators appropriately employed a noninferiority trial design to assess whether a new shorter course of an existing therapy, with the potential for fewer side effects, cost savings, and lessening the global burden of antimicrobial resistance, is not worse than the standard length treatment. 
• Researchers chose a narrow noninferiority threshold of 5%, making it more difficult to prove noninferiority.
• They used strict criteria to diagnose UTI, ensuring that the population being studied was likely to have the disease in question.
• Researchers enrolled patients in multiple clinical environments, including the ED, hospital wards, and primary care offices, which increases generalizability.
• Investigators enrolled a large sample size, increasing external validity.
• There were no major differences in baseline demographics, indicating that randomization was sound and patients had a similar prognosis at the start of the trial.
• The placebo had the same volume, appearance, flavor, consistency, and bottle as the study drug, decreasing the possibility of unblinding.
• Trial participants, their parents, investigators, and trial personnel were blinded to the treatment assignment.
• Investigators analyzed patients with an intention-to-treat and per-protocol analysis, allowing for a comprehensive assessment of the results.
• Loss to follow-up was very low and similar in each cohort.

Limitations:

• A single-country study limits generalizability to patients outside the United States.
• The definition of UTI used by investigators included some clinical signs typically attributed to pyelonephritis, which most clinicians would treat with a longer duration of antibiotics.
• Enrollment required treatment with 1 of 5 predefined antibiotics, limiting generalizability to patients prescribed other antibiotics.
  • >900 patients were excluded due to treatment with other antibiotics.
• Follow up required an in-person visit (at child’s home or at an affiliated clinic) on days 2–5, and two additional in-person visits on days 11–14 and days 24–30, potentially limiting the generalizability to an ED population outside of a clinical trial.
• There were some important demographic considerations which may further limit generalizability: 
  • 96% of patients were female
  • 64% were white
  • 91% were non-Hispanic
  • 58% were aged 2–6 years old
  • Very few children in the 2 mo – 23 mo age range
  • 87% of patients were treated with cephalosporins
  • E. coli was the isolated pathogen in 90%
• 32,000 patients were initially assessed, but only 693 were enrolled. More than 20,000 patients were excluded due to negative urine cultures, while an additional 4,300 were excluded for unspecified “other” reasons, raising suspicion of potential selection bias.
• The trial protocol called for assessment of the primary outcome between day 6 and the 11–14 day visit while some patients in the standard therapy group were still receiving antibiotic treatment, which introduces detection bias.
• Investigators achieved much better failure rates than they initially assumed. In a noninferiority trial, inaccurate assumption rates may make it easier for the new treatment to meet the noninferiority limit.
• Researchers excluded patients with missing data from the primary outcome. Patients lost to follow-up are known to have worse outcomes than those who completed the study. While seemingly a relatively small number, the 9 patients lost to follow-up in the standard-course therapy arm would be 4.5x larger than those who failed treatment.
• Researchers had limited information on adherence to originally prescribed antibiotics on days 1–5.

Discussion:

Inside The Numbers:

In the intention-to-treat (ITT) analysis, the upper bound of the 95% CI for treatment failure (5.5%) exceeded the 5% noninferiority threshold. ITT analysis includes all patients based on their original randomization, regardless of adherence to the trial protocol, generally providing a more cautious estimate of treatment benefit. However, hypothetical inclusion of many non-adherent patients in a control group could potentially lead to a false interpretation of statistical noninferiority. In the SCOUT Trial, overall adherence was good after randomization during days 6–10, but we know little about adherence during the initial 5 day treatment period.

In a noninferiority trial the per-protocol analysis holds equal importance. Eliminating non adherent patients introduces some bias, but can provide reassurance that patients received the appropriate treatment. In the per-protocol analysis of patients who adhered to at least 80% of their assigned study therapy, the upper bound of the 95% CI for treatment failure was 3.9%—below the preset 5% noninferiority margin.

The Relative Risk of 6.8 indicates that patients who received 5 days of antibiotics were nearly 7 times more likely to have a treatment failure compared to 10 days of therapy. However, cautious interpretation is warranted as relative risk can exaggerate the magnitude and impact of the results. Moreover, the Absolute Risk Difference of 3.6 indicates that approximately 4 more patients out of 100 would experience a treatment failure with short-course (5 day) therapy compared to standard-course (10 day) therapy.

Hidden In Plain Site:

The SCOUT trial included only patients who demonstrated clinical improvement by day 5 of antibiotic treatment. While this cautious approach prioritizes safety, information regarding response to therapy would be unavailable to most ED clinicians outside of a clinical trial. Consequently, implementing this strategy in a real-world clinical setting could be challenging, as clinicians making decisions about antibiotic treatment may lack a reliable means of assessing whether a patient would improve by day 5.

Utilizing strict exclusion criteria, investigators eliminated patients with negative urine cultures. More than 20,000 patients prescribed antibiotics DID NOT have a UTI,  highlighting the sheer magnitude of the problem and difficulty associated with diagnosing UTI in a pediatric population. Patients with nonspecific findings such as fever and trace leukocyte esterase on a urine dipstick would meet 2 of 3 inclusion criteria. The third criterion, a positive urine culture, would not be available immediately to inform real-time clinical decisions. In a clinical trial, ensuring the cohort under investigation has the disease in question is pivotal to obtain accurate data and guide clinical recommendations. Yet, in practice, clinicians ubiquitously treat patients based on probability and risk assessment when diagnostics are unavailable. A pragmatic trial, with less stringent inclusion criteria, investigating all patients treated for UTI would presumably yield more favorable results, albeit with the inclusion of many patients without infection. Nonetheless, such a trial would be more reflective of actual clinical practice and the uncertainty embedded in point-of-care clinical-decision making.

Shared Decision Making:

Short-course (5 day) therapy DID NOT prove to be statistically non inferior to standard-course (10 day) therapy. However, exceeding the noninferiority margin by 0.5% would result in one additional treatment failure in 200 patients. Clinicians willing to accept 5 treatment failures per 100 patients might also accept 5.5. 

A 5.5% failure rate in patients diagnosed with UTI may be unpalatable for some clinicians and parents. However, in the SCOUT Trial, thousands of patients prescribed antibiotics had negative urine cultures, underscoring the fact that many patients treated with antibiotics will not have a UTI. Furthermore, very few clinical institutions have the resources to call patients with a negative urine culture and discontinue unnecessary antibiotic therapy.

When making decisions with incomplete information, short-course antibiotics seem appropriate, and shared-decision making is required. If prescribing short-course therapy, it is prudent that parents understand the increased likelihood of failure and the need for close follow-up to determine if their child needs a longer course of antibiotic therapy.

Author’s Conclusion: “In this noninferiority trial, short-course therapy was not statistically noninferior to standard-course therapy. However, given the infrequent occurrence of treatment failure in the short-course group and the results of a post hoc analysis, short-course therapy may be considered a reasonable option for children with clinical improvement after 5 days of antimicrobial treatment.”

Our Conclusion:

The SCOUT trial did not demonstrate statistical noninferiority for short-course therapy compared to the standard-course in pediatric patients with UTI. However, considering the low failure rate and the diagnostic uncertainty embedded in clinical decision making, short-course therapy may be a reasonable option. It is crucial for clinicians and parents to engage in shared decision-making, recognizing the slightly higher risk of treatment failure with short-course therapy and the need for close monitoring to assess the necessity of a longer antibiotic course.

Clinical Bottom Line:

Consider short-course antibiotic therapy for treatment of pediatric patients with UTI. Engage in shared decision-making with parents, and prioritize close follow-up to assess for treatment failure.

References:

1. National Institute for Health and Care Excellence.Urinarytract infection in under 16s: diagnosis and management (NICE guideline 224). 2022. Accessed 24 October, 2023. Available from: https://www.nice.org. uk/guidance/ng224/ resources/urinary-tract-infection-in-under-16s-diagnosis-and-management-pdf- 66143835667141
2. Buettcher M, Trueck J, Niederer-Loher A, et al. Swiss Consensus Recommendations on Urinary Tract Infections in Children. Eur J Pediatr. 2021;180:663-74. PMID: 32621135
3. SubcommitteeonUrinaryTractInfection,SteeringCommittee on Quality Improvement and Management; Roberts KB. Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months. Pediatrics. 2011;128:595-610. PMID: 21873693
4. Robinson JL, Finlay JC, Lang ME, Bortolussi R; Canadian Paediatric Society, Infectious Diseases and Immunization Committee, Community Paediatrics Committee. Urinary Tract Infections in Infants and Children: Diagnosis and Management. Paediatr Child Health. 2014;19:315-25. PMID: 25332662
5. Zaoutis T, Shaikh N, Fisher BT, et al. Short-Course Therapy for Urinary Tract Infections in Children: The SCOUT Randomized Clinical Trial. JAMA Pediatr. 2023;177(8):782-789. PMID: 37358858

Post By:

Marco Propersi, DO FAAEM
Vice-Chair, Emergency Medicine
Assistant Emergency Medicine Program Director
Vassar Brothers Hospital, Poughkeepsie, New York
Twitter/X: @marco_propersi

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)

The post Pediatric UTIs: Short-Course vs. Standard-Course Antibiotics — Is It Time for a Change? appeared first on REBEL EM - Emergency Medicine Blog.

Take Home Points:

• A CCTA is an anatomic test to determine if a patient has normal coronary arteries, non-obstructive disease, or obstructive disease. The warranty period for a CCTA is anywhere from 3-10 years depending on the characteristics of the plaque. 
• A nuclear stress test is a functional study that allows for ischemia-driven management. The warranty period of a nuclear stress test is 2 years. 
• A test is only as good as the data and its interpretation! Trust yourself!

The post REBEL Core Cast 111.0 – Cardiac Testing appeared first on REBEL EM - Emergency Medicine Blog.

A 5-year-old boy is brought in by his parent for a dental injury. The patient was walking his dog when it ran after a squirrel. The patient was pulled forward, causing him to hit his tooth on the asphalt. His parent noticed a dental problem and immediately brought the patient to the ED. The physical exam is shown below. Which of the following is the best next recommendation?

1. Follow up with the dentist in the morning
2. Reinsert the tooth and avoid solid food
3. Reinsert the tooth and stabilize it with a bridge
4. Remove the tooth and repair the gingival laceration
5. Remove the tooth and wrap it in saline-soaked gauze

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References

1. Day PF, Flores MT, O’Connell AC, et al. International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 3. Injuries in the primary dentition. Dent Traumatol. 2020;36(4):343–359. https://www.aapd.org/media/policies_guidelines/e_injuries.pdf
2. Goswami M, Aggarwal T. Prevalence of traumatic dental injuries among 1- to 14-year-old children: a retrospective study. Int J Clin Pediatr Dent. 2021;14(4):467–470. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585904

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)

The post Rosh Review EM Scholar Monthly Question appeared first on REBEL EM - Emergency Medicine Blog.

Take Home Points:

• Patients with recent onset atrial fibrillation can safely be cardioverted if they are 1) on anticoagulation 2) Low risk based on CHADS-VASC with onset < 48 hours or 3) High risk based on CHADS-VASC with onset < 12 hours.
• In anaphylaxis, think, “If A, B or C, give E.” If the patient has compromise to airway, breathing or circulation, they should get immediate epinephrine.
• D-dimer can effectively rule out a larger portion of low risk patients if age adjustment or the YEARS criteria are employed.
• When reviewing a syncope ECG, scour it for WPW, Brugada, Hypertrophic Cardiomyopathy, Prolonged/Short QTc and ARVC.

The post REBEL Core Cast 110.0 – On Shift Learning Pearls appeared first on REBEL EM - Emergency Medicine Blog.

Background: Community-acquired pneumonia (CAP) can lead to pulmonary and systemic inflammation, resulting in impaired gas exchange, sepsis, organ failure, and an increased risk of death. Corticosteroids have excellent anti-inflammatory and immunomodulatory effects that could mitigate some of the inflammation caused by pneumonia. There have been several randomized trials that have shown glucocorticoids have positive effects in patients with CAP. However, except for one trial, none showed a between-group difference regarding mortality.^1-6 We now have the Community-Acquired Pneumonia: Evaluation of Corticosteroids (CAPE COD) Trial.

Paper: Dequin P, Meziani F, Quenot J, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941. PMID: 36942789. ClinicalTrials.gov: NCT025174897

Clinical Question: In adult patients with severe community-acquired pneumonia admitted to the ICU, does early hydrocortisone treatment, compared to standard therapy, reduce mortality at 28 days?

What they did:

• Investigators conducted a phase 3, multicenter, double-blind, randomized, controlled, superiority trial.
• Patients enrolled from 31 Intensive Care Units in France.
• Patients admitted to the ICU with severe community-acquired pneumonia were randomized in a 1:1 ratio to receive hydrocortisone or a placebo. 
• The study was funded by the French Ministry of Health. 

Population

Inclusion Criteria:

• Adult patients (≥18 years old).
• Admitted to participating ICUs with severe community-acquired pneumonia.
• Pneumonia diagnosis supported by clinical and radiologic criteria.
• Severity of pneumonia was defined by at least one of the following criteria:
  • Invasive or noninvasive mechanical ventilation with a PEEP of 5 cm of water
  • High-flow nasal cannula oxygen therapy with a Pao2:Fio2 ratio of less than 300; With FiO2 ≥50%
  • Non-rebreather with PaO2:FiO2 ratio <300
  • Pao2:Fio2 ratio less than 300
  • Pulmonary Severity Index score > 130 (Category V, which is associated with the highest mortality)

Exclusion Criteria:

• DNR
• Pneumonia caused by influenza
• Pneumonia caused by septic shock
• Patient treated by vasopressors for septic shock at the time of inclusion
• Clinical history suggesting aspiration of gastric content
• Patient treated by invasive mechanical ventilation within 14 days before current hospital admission
• Patients treated by antibiotics for a respiratory infection for more than seven days at the admission to the hospital (except if a pathogen resistant to these antibiotics is isolated)
• History of cystic fibrosis
• Post-obstructive pneumonia
• Patients in which rapid PCR test is positive for flu
• Active tuberculosis or fungal infection
• Active viral hepatitis or active infection with herpes viruses
• Myelosuppression
• The decision to withhold mechanical ventilation or endotracheal intubation
• Hypersensitivity to corticosteroids
• Patients needing anti-inflammatory corticosteroids or substitutive hydrocortisone for any reason
• Patients under treatment with more than 15 mg/d of prednisone (or equivalent) for more than 30 days
• Patients already enrolled in another drug trial with mortality as an end-point. If the patient already participates in another therapeutic trial with a different endpoint, the investigator must verify that inclusion in CAPE COD can not prejudice it.
• Pregnant or breastfeeding woman
• Patient on judicial protection

Interventions:

• Hydrocortisone 200mg daily (continuous infusion) for 4 days. On the 4th day, the medical team used predefined criteria to decide whether to administer hydrocortisone for a total of 8 or 14 days, depending on whether the patient’s condition had improved.

Control:

• Normal Saline via continuous infusion according to the same regimen used in the hydrocortisone group. 

Outcome:

Primary

• Death from any cause by day 28

Secondary

• Death from any cause by day 90
• The length of ICU stay
• Noninvasive ventilation or endotracheal intubation among patients who were not receiving any type of ventilation at baseline
• Endotracheal intubation among patients who were receiving noninvasive ventilation at baseline
• The initiation of vasopressor therapy by day 28
• Number of ventilator-free days and vasopressor-free days by day 28
• Change in the PaO2:FIO2 ratio by day 7
• Change in SOFA score by day 7

Safety Outcomes:

• Secondary infections or GI bleeding by day 28
• The daily amount of insulin administered by day 7
• Weight gain by day 7

Results:

• 5948 patients were assessed for eligibility.
  • 5148 excluded
• 800 enrolled and randomized in the trial.
  • 401 in the hydrocortisone group
  • 399 in the control group.
• 795 patients were included in the primary analysis
  • 1 patient from the hydrocortisone group died before receiving treatment
  • 2 patients in the control group withdrew their consent
  • 2 did not have the legal capacity to give consent
• Type of respiratory support
  • IMV ≈22%
  • NIV ≈22%
  • HFNC ≈42%
  • NRB ≈14%
• Median Interval from Hospital Admission to ICU Admission ≈5hrs
• Median Interval from ICU Admission to Initiation of Trial Agent ≈15hrs

Primary outcome

• 28-day mortality was 6.2% in the hydrocortisone group vs. 11.9% in the placebo group (p = 0.006).

Secondary Outcome

• By day 90, mortality was 9.3% in the hydrocortisone group and 14.7% in the placebo group (absolute difference, −5.4 percentage points; 95% CI, −9.9 to −0.8).
• Among 442 patients who had not received any mechanical ventilation at baseline:
  • Endotracheal intubation was performed in 18.0% of the hydrocortisone group.
  • Endotracheal intubation was performed in 29.5% in the placebo group.
  • Hazard ratio: 0.59 (95% CI, 0.40 to 0.86).
• Among 618 patients who had received no invasive ventilation at baseline:
  • Cumulative incidence of invasive mechanical ventilation before day 28:
    • 19.5% in the hydrocortisone group.
    • 27.7% in the placebo group.
  • Hazard ratio: 0.69 (95% CI, 0.50 to 0.94).
• Among the 703 patients who had not received vasopressors at baseline:
  • Cumulative incidence of vasopressor initiation:
    • 15.3% in the hydrocortisone group.
    • 25.0% in the placebo group.
  • Hazard ratio: 0.59 (95% CI, 0.43 to 0.82).

Adverse Events

• During the first 28 days after randomization, 169 serious adverse events occurred in 151 of 795 patients (19.0%).
  • 70 events in the hydrocortisone group.
  • 99 events in the placebo group.
• ICU-acquired infections were observed in:
  • 9.8% of patients in the hydrocortisone group.
  • 11.1% of patients in the placebo group.
  • Hazard ratio: 0.87 (95% CI, 0.57 to 1.34).
• Gastrointestinal bleeding was rare in both groups.
• By day 7, patients receiving insulin therapy during the first week of the trial received a median of:
  • In the hydrocortisone group, 35.5 IU per day (interquartile range, 15.0 to 57.5).
  • In the placebo group, 20.5 IU per day (interquartile range, 9.4 to 48.5).

Strengths:

• The investigators framed a research question centered on patient outcomes, ensuring the study’s relevance and practicality.
• The researchers employed a double-blind, placebo-controlled, randomized controlled trial design to minimize potential biases, enhancing the reliability of the results.
• Multiple centers were involved, increasing the study’s external validity and making the findings more applicable and generalizable to diverse patient populations.
• The trial’s registration with clinicaltrials.gov enhanced transparency and allowed other researchers to replicate the study, promoting scientific rigor.
• The study included a substantial number of participants, increasing the statistical power and precision of the results.
• Researchers used concealed, centralized electronic web-based randomization to ensure the equitable allocation of participants to treatment arms, reducing selection bias.
• The research team assessed patients for eligibility consecutively, minimizing selection bias and ensuring a more representative study population.
• The treating physicians and research personnel were all unaware of the treatment arm, reducing the potential for bias in treatment administration and outcome assessment.
• The researchers labeled placebo and hydrocortisone bottles identically, decreasing the likelihood of unblinding bias and ensuring that neither patients nor healthcare providers could differentiate between the two.
• Researchers conservatively assumed that patients with missing data for the primary outcome had met the primary outcome (death), addressing potential attrition bias in the analysis.
• Enrolled patients represented a critically ill cohort; nearly 45% were on mechanical ventilation.

Limitations:

• The study was conducted exclusively in one country, limiting its external validity.
• The researchers applied strict exclusion criteria, likely introducing some selection bias.
• The researchers initially estimated a mortality rate of 27% for the placebo group and 20% for the hydrocortisone group but observed a lower mortality rate of 11.9% for placebo and 6.2% for hydrocortisone, which may impact the study’s validity. 
• Although the investigators calculated a necessary sample size of 1200, they enrolled only 800 participants, potentially affecting the study’s statistical power.
• 45% of the enrolled patients came from just 4 ICUs, limiting the generalizability of the results.
• Approximately 70% of the enrolled cohort consisted of men, limiting the generalizability of the findings to women.
• The median age of the participants was 67, potentially limiting the study’s generalizability to younger age groups.
• There were important differences in baseline demographics.
  • Participants in the placebo arm had a median PSI score of 130 compared to 127 in the hydrocortisone arm. 
  • No pathogen was identified in 47% of patients in the hydrocortisone group and 42% in the placebo group.
• The trial was stopped early due to observed benefits, which could potentially overestimate the study’s results.
• While patients received respiratory support, supportive care, and antibiotics at the discretion of the medical team, the specific interventions provided outside the study were not documented, potentially leading to co-intervention bias.
• The search for pathogens was left to the discretion of the medical team, introducing variability in the diagnostic process.
• More than 75% of patients did not complete the treatment course.

Discussion:

• The potential benefits of corticosteroids in severe community-acquired pneumonia patients likely depend on several key factors. Firstly, corticosteroids may benefit pneumonia but are most likely effective in the sickest patients requiring ICU admission without contraindications. This represents a niche population where the benefits outweigh the risks.
• Secondly, while corticosteroids can be beneficial in severe pneumonia, the magnitude of this benefit may not be substantial. Demonstrating a significant reduction in mortality with a single medication in the critical care setting is challenging.
• Thirdly, the potential benefit of corticosteroids in severe pneumonia is most likely associated with early treatment, ideally administered within 24 hours from patient presentation.
• Lastly, although C-reactive protein (CRP) is not typically used in the emergency department to diagnose bacterial pneumonia, patients with CRP levels exceeding 15mg/dL (or > 150 mg/L) may derive benefits from corticosteroid therapy. CRP is a marker of inflammation, and corticosteroids are known to attenuate this inflammatory response.
• More research is needed to identify specific subgroups that may benefit from early corticosteroid therapy.

Inside The Numbers

• Early hydrocortisone treatment significantly reduced 28-day mortality in severe community-acquired pneumonia ICU patients (6.2% vs. 11.9% in the placebo group, p = 0.006), with consistent benefits across secondary outcomes. 
• The Relative Risk reduction, which represents the decrease in risk relative to the placebo group, was 47%. This corresponds to an absolute risk difference of 5.7%, meaning there was a 5.7% lower chance of mortality at 28 days in the hydrocortisone group compared to the placebo group. This translates to a Number Needed to Treat (NNT) of 17.5, indicating that for nearly every 18 severe CAP ICU patients treated with hydrocortisone, one additional patient’s life was saved in 28 days compared to the placebo group.
• However, the fragility index of 6 warns that these benefits hinge on relatively few events, emphasizing the need for cautious interpretation. Furthermore, truncated RCTs can overestimate treatment effects due to random error. This effect is neutralized as the number of enrolled patients increases toward the planned sample sizes.

Bias

• Investigators excluded 86% of initially screened patients based on the stringent selection criteria to eliminate those who might be harmed or benefited from hydrocortisone treatment. However, some criteria were rather subjective. For instance, more than 10% of excluded patients were suspected of having aspiration pneumonia, a diagnosis often relying on a suggestive medical history and classic X-ray pattern that may not apply to all. 
• About 25% of the excluded patients had septic shock, but the classification of hypotension as septic shock was at the discretion of the treating team. Notably, 45% of the enrolled patients required positive pressure mechanical ventilation, which often includes sedation, both of which could lead to hypotension, necessitating vasopressor therapy. 
• Influenza patients were also excluded due to potential harm from corticosteroids, and although no significant differences in post-enrollment positive influenza tests were observed between groups (3.8% in the hydrocortisone group vs. 4% in the placebo group), the treatment teams made testing decisions, and specific testing patterns for each cohort were not disclosed.
• The placebo group had a higher percentage of patients in category V PSI compared to the hydrocortisone group. (49.2% vs 45.7), category V PSI carries a 30% mortality rate, whereas the mortality rate is 10% for category IV PSI. Additionally, 47% of the patients in the hydrocortisone group and 42% in the placebo group had no identified pathogens. Subgroup analysis of patients with PSI > 130 and those with isolated pathogens showed confidence intervals that crossed 0, indicating no clear benefit.
• Considering that the placebo group had 12 more patients with more severe baseline illness who were more likely to die and 16 more patients with an identified bacterial infection, given the trial’s fragility index of only 6, these disparities could have greatly impacted the observed outcome differences.

Current Events

• In a recent study by Meduri et al. (2022) involving 586 ICU-admitted patients with severe community-acquired pneumonia (CAP), no benefit was observed from methylprednisolone administration.⁸ But, it’s crucial to distinguish between this study and the CAPE COD trial. Notably, the Meduri trial had 96% male participants, while CAPE COD had 67%. Subgroup analysis in CAPE COD revealed a more pronounced benefit of hydrocortisone in women. Additionally, hydrocortisone was administered within 24 hours in CAPE COD, differing from the Meduri trial’s 96-hour window.
• However, a recent meta-analysis (Pitre 2023) of 18 RCTs involving 4,661 patients similarly concluded that corticosteroids reduce mortality in severe CAP, lessen the need for invasive mechanical ventilation, and lower ICU admission rates.⁹

Author’s Conclusion: “Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo.”

Our Conclusion:

The CAPE COD trial findings suggest that administering corticosteroids within the first 24 hours can significantly reduce mortality in severe community-acquired pneumonia patients admitted to the ICU. However, it’s worth noting that more than three-quarters of enrolled patients didn’t complete the treatment protocol, and statistical variations among different subgroups require further investigation. Nevertheless, the best available evidence supports the conclusion that early corticosteroid administration can reduce mortality in severe community-acquired pneumonia patients in the ICU.

Clinical Bottom Line:

Early administration of corticosteroids can reduce mortality in severe community-acquired pneumonia patients in the ICU.

References:

1. Confalonieri M, Urbino R, Potena A, et al. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med 2005;171:242-8. PMID: 15557131
2. Snijders D, Daniels JMA, de Graaff CS, van der Werf TS, Boersma WG. Effi- cacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial. Am J Respir Crit Care Med 2010;181:975-82. PMID: 20133929
3. Meijvis SCA, Hardeman H, Remmelts HHF, et al. Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. Lancet 2011;377:2023-30. PMID: 21636122
4. Fernández-Serrano S, Dorca J, Garcia- Vidal C, et al. Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial. Crit Care 2011;15(2):R96. PMID: 21406101
5. Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015;385:1511-8. 12. PMID: 25608756
6. Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA 2015;313:677-86. PMID: 25688779
7. Dequin P, Meziani F, Quenot J, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941. PMID: 36942789
8. Meduri GU, Shih M-C, Bridges L, et al. Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia. Intensive Care Med 2022;48:1009-1023. PMID: 35723686
9. Pitre T, Abdali D, Chaudhuri D, Pastores SM, Nei AM, Annane D, Rochwerg B, Zeraatkar D. Corticosteroids in Community-Acquired Bacterial Pneumonia: a Systematic Review, Pairwise and Dose-Response Meta-Analysis. J Gen Intern Med. 2023 Aug;38(11):2593-2606. Epub 2023 Apr 19. PMID: 37076606

Guest Post By:

Marco Propersi, DO FAAEM
Vice-Chair, Emergency Medicine
Assistant Emergency Medicine Program Director
Vassar Brothers Hospital, Poughkeepsie, New York
Twitter: @marco_propersi

Chanel Thomas, MD
PGY-1, Emergency Medicine Resident
Vassar Brothers Hospital, Poughkeepsie, New York
E-mail: Chanel.thomas@nuvancehealth.org

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)

The post Corticosteroids in Severe Community Acquired Pneumonia: Could CAPE COD catalyze a change in critical care management? appeared first on REBEL EM - Emergency Medicine Blog.

Background: DKA is traditionally treated with fluid resuscitation, electrolyte replacement, and intravenous infusions of insulin. However, it is unclear if all degrees (mild, moderate, severe) of DKA require the same intensive treatment. Mild to moderate DKA represents a subgroup of patients that often require admission to the ICU due to hospital policies not allowing insulin infusions outside of this clinical setting. One solution to decrease ICU admission is to treat these patients in the ED until their anion gap is closed and the patient can be transitioned from IV insulin infusion to SQ insulin.  This is not an optimal solution as these patients still require long stays in the ED, EDs are overcrowded as it is, the staffing is not the same in an ED compared to an ICU (don’t have the same nursing to patient ratios), all while more patients continue to come into the ED with other emergent conditions. A more optimal, and promising, solution may be the use of SQ insulin in mild to moderate DKA.

Paper: Griffey RT et al. The SQuID Protocol (Subcutaneous Insulin in /diabetic Ketoacidosis): Impacts on ED Operational Metrics. Acad Emerg Med 2023. PMID: 36775281

Clinical Question: In adult patients with mild to moderate DKA, does a subcutaneous insulin protocol reduce ED length of stay compared to a traditional IV infusion DKA protocol?

What They Did:

• Implemented the SQuID (Subcutaneous Insulin in Diabetic Ketoacidosis) protocol for adults with mild to moderate DKA in an urban academic ED
• Prospectively derived, quasi experimental (pre-post) study
• Authors used retrospectively obtained electronic data in evaluating their outcome measures
• DKA severity was stratified as mild, moderate, or severe
• Not explicitly stated in the manuscript but it seems reading between the lines that initiating SQuID protocol or traditional insulin infusion was left to judgement of clinician once mild to moderate DKA was diagnosed

SQuID Protocol

“Traditional” IV Infusion DKA Protocol

Outcomes:

• Fidelity: Frequency of required q2hr glucose checks
• Safety: Proportion of patients administered rescue dextrose for hypoglycemia
• Operational: ED LOS and ICU Admission Rate
  • ED LOS was the primary outcome of this trial

Inclusion:

• Adult ED patients meeting criteria for Mild to Moderate DKA
  • Hyperglycemia (Glucose >300)
  • Positive ketone test (≥1.1mmol/L)
  • Presence of an anion gap
  • Discharge diagnosis of DKA and having received insulin

Exclusion:

• Severe DKA
  • HCO3 <10mmol/L
  • Arterial pH < 7.0
• Patients <18 years of age
• Pregnancy
• Concomitant serious infections
• Concerns for MI
• AMS
• Active comorbidities (ESRD, CHF, Active use of inmmunosuppressants)
• Need for surgical procedure
• Determination by the ED or inpatient team that a patient was too ill for the designated floor

Results:

• 177 mild to moderate DKA adult patients
  • SQuID: 78pts
  • Traditional cohort: 99pts
  • Historical controls:
    • Preintervention: 163pts (Nov 1^st, 2020 to May 31^st, 2021)
    • Pre-COVID: 161pts (Aug 1^st, 2019 to Feb 28^th 2020)
  • Fidelity (Frequency of q2hr Glucose Checks)
    • SQuID: 1.0 tests/hr (0.8 to 1.1)
    • Traditional: 1.0 tests/hr (0.8 to 1.1)
    • Pre-Intervention: 1.0 tests/hr (0.9 to 1.2); No Reduction/Increase 0.0%
    • Pre-COVID: 1.0 tests/hr (0.8 to 1.1); No Reduction/Increase 0.0%
    • High fidelity for patients on the SQuID pathway
    • Performance of blood glucose checks exceeded the q2hr testing requirement: Median 1.0 tests/hr
  • Safety (Proportion of patients administered rescue dextrose for hypoglycemia)
    • SQuID: 2.7%
    • Traditional: 3.6%
    • Pre-Intervention: 2.3%; Decrease by 0.4%
    • Pre-COVID: 0%; Increase by 2.7%
    • No statistical differences in safety between groups
  • Operational Impact
    • Median ED LOS (PRIMARY OUTCOME):
      • SQuID: 8.9hrs (6.5 to 11.5hrs)
      • Traditional: 11.9hrs (9.6 to 18.6hrs)
      • Pre-Intervention: 10.3hrs (7.7 to 12.9hrs); Reduction by 1.4hrs
      • Pre-COVID: 12.5hrs (8.7 to 19.3hrs); Reduction by 3.6hrs
      • ED LOS was shorter for the SQuID cohort
    • ICU Admissions:
      • SQuID & Traditional (Post Intervention): 42.9%
      • Pre-Intervention: 46.0%; Reduction by 3.1%
      • Pre-COVID: 49.1%; Reduction by 6.2%
      • Not Statistically Significant

Strengths:

• Asks a clinically important question
• Clearly defined protocol that can be reproduced at other institutions
• Evaluated historical pre-intervention and pre-COVID patients to ensure the findings were consistent
• Performed a sensitivity analysis and quantile regression model to confirm findings of the primary outcome

Limitations:

• SQuID protocol required more frequent glucose monitoring (median q1hr) which may be too much for medical floors and EDs
• ED LOS and ICU admission is determined by subjective clinical decisions and hospital policy. This will likely vary from institution to institution
• Single center study at a busy level 1 academic urban trauma center which may limit generalizability to smaller community hospitals
• As this is a prospectively-derived quasi-experimental (pre-post) study there are most likely confounders not accounted for that only a RCT would be able to discern (Before and after design doesn’t take into account changes that may have occurred over time that weren’t studied but could affect outcomes)
• Hypoglycemia events were a secondary outcome and therefore this trial was not powered appropriately for this outcome. Additionally compared to historical controls hypoglycemia events seem to be increased
• Unclear why we don’t have ICU admission just in the SQuID group instead of a combination of the two (SQuID and Traditional IV Insulin)

Discussion:

• The SQuID protocol did reduce ED LOS (by a few hours), reduced ICU admissions (although not statistically significant), and had equivalent safety compared to a traditional insulin infusion pathway in patients with mild to moderate DKA
• SQ insulin for DKA was considered an existing standard of care rather than an experimental protocol based on the published literature
• Overall patients in the SQuID protocol were younger, more likely to be female, had lower acuity on emergency severity index, and more likely to be discharged from the ED compared to patients in the traditional protocol
• SQuID protocol will require significant education including education sessions not just for the ED, but hospitalists, ICU, and nurses throughout the hospital before safe implementation
  • There were several patients misclassified who actually had severe DKA or met exclusion criteria for which SQuID was started
  • A few cases of under-dosing or delayed administration of long-acting insulin which resulted in recurrence of hyperglycemia
  • Failure to initiate dextrose-containing fluids in a timely fashion

Author Conclusion: “In this single-center study at an academic ED, treatment of patients with MTM-severity DKA with a SQ insulin protocol was effective, demonstrated equivalent safety, and reduced ED length of stay.”

Clinical Take Home Point: For patients with mild to moderate DKA, the SQuID protocol (SQ insulin) has the potential to be an alternative treatment pathway to decrease ED LOS.  However, the ED LOS was only decreased by 3 hours, the ICU admission rate was only decreased by several percentage points, the need for hospital wide education to implement this protocol, the frequency of glucose monitoring (q1hrs), and unclear safety (secondary outcome that seems to be increased compared to historical controls) this protocol is not ready for primetime.

References:

1. Griffey RT et al. The SQuID Protocol (Subcutaneous Insulin in /diabetic Ketoacidosis): Impacts on ED Operational Metrics. Acad Emerg Med 2023. PMID: 36775281

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

The post The SQuID Protocol: SQ Insulin in DKA? appeared first on REBEL EM - Emergency Medicine Blog.

Background: Primary PCI is the recommended reperfusion strategy in patients with STEMI and should be initiated within 2 hours after first medical contact.  In non-PCI-capable hospitals this goal is not always achievable due to delays in transfer.  In these cases, thrombolysis is recommended to improve morbidity and mortality.

The STREAM-1 trial found that for [2] patients with STEMI presenting within 3 hours of symptom onset and unable to attain PCI within 1 hour of first medical contact, a pharmaco-invasive strategy resulted in similar rates of death, shock, heart failure, or reinfarction compared to primary PCI. The initial data demonstrated an excess of ICH in patients ≥75 years of age and prompted halving the dose of weight-adjusted tenecteplase with no subsequent ICH in the remaining 97 patients.  Based on this, the authors did a literature review and found that there is an increasing rate of ICH and major non-intracranial bleeding starting at ≈60 years of age.

Paper: Van de Werf, F et al. STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial. Circ 2023. PMID: 37439219

Clinical Question: Is half-dose tenecteplase an effective and safe pharmaco-invasive treatment in older patients with STEMI, presenting within 3 hours of symptom onset, and unable to undergo primary PCI within 1 hour compared to standard primary PCI?

What They Did:

• Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction (STREAM-2)
• Investigator-initiated, open-label, prospective, randomized, multicenter trial
• Conducted in 49 centers in 10 countries
• Patients ≥60 years of age with ≥2mm STEMI in 2 contiguous leads, unable to undergo primary PCI within 1 hour sere randomly assigned (2:1) to:
  • Pharmaco-Invasive Treatment: Half-Dose Tenecteplase followed by coronary angiography and PCI if indicated) 6 to 24 hours after randomization
    • Tenecteplase Dosing:
      • ≥55 to <60kg = 15mg
      • ≥60 to <70kg = 17.5mg
      • ≥70 to <80kg = 20mg
      • ≥80 to <90kg = 22.5mg
      • ≥90kg = 25mg
    • Primary PCI

Outcomes:

• Primary:
  • Reperfusion Efficacy: ST Segment Resolution ≥50% in the lead with worst ST-Segment Elevation
  • Resolution of ST Deviations (in percentages and in millimeters) afger last angiography
  • 30d Composite of Death, Shock, Heart Failure, or Reinfarction
• Safety:
  • Stroke
  • Non-Intracranial Bleeding

Inclusion:

• Original protocol included patients ≥70 years of age, but due to slow recruitment and amendment was made to include patients ≥60 years of age
• Patients weighed ≥55kg
• Presented within 3 hours after symptom onset
• EKG evidence of STEMI (ST-Segment Elevation of at least 2mm in 2 contiguous leads)
• Unable to undergo primary PCI within 1 hour but before 3 hours after first medical contact

Exclusion:

• Expected performance of PCI <60min from diagnosis (qualifying ECG) or inability to arrive at the catheterization lab within 3 hours
• Previous CABG
• LBBB or Ventricular Pacing
• Cardiogenic Shock (Killip Class IV)
• Body weight <55kg
• Uncontrolled HTN (sustained BP ≥180/110mmHg)
• Known prior stroke or TIA
• Recent administration of any IV or SC anticoagulation within 12 hours or current use of oral anticoagulation
• Active bleeding or known bleeding disorder/diathesis
• Known history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) or recent trauma to head or cranium (i.e. <3 months)
• Major surgery, biopsy of a parenchymal organ or significant trauma within the past 2 months
• Clinical diagnosis associated with increased risk of bleeding including known active PUD and/or neoplasm with increased bleeding risk
• Known severe renal insufficiency
• Prolonged CPR (>2min) with past 2 weeks
• Known acute pericarditis and/0r subacute bacterial endocarditis
• Known acute pancreatitis or known severe hepatic dysfunction
• Dementia
• Previous enrollment in the study or treatment with an investigational drug./device under another study protocol within the past 7d
• Known allergic reactions to tenecteplase, clopidogrel, enoxaparin, and aspirin
• Inability to follow protocol and comply with follow-up requirements

Results:

• 604 patients recruited
  • Pharmaco-invasive treatment: 401pts
  • Primary PCI: 203pts
  • Symptom onset to randomization: ≈95min
  • Median time from randomization to tenecteplase or sheath insertion: 10 and 81min respectively
  • Mean Age: ≈70 years
  • PCI:
    • Pharmaco-Invasive Treatment: 86.0%
    • Primary PCI: 95.7%
  • Stents Placed:
    • Pharmaco-Invasive Treatment: 97.4%
    • Primary PCI: 95.7%
  • ECG Results:
    • Repeat ECG 90min after tenecteplase indicated 70.3% of patients in the pharmaco-invasive treatment achieved ≥50% resolution in the lead with the greatest ST-segment elevation
      • Median decline from 3.0 to 1.0mm
      • Median amount of ST deviations declined from 15.0 to 6.5mm
    • ≥50% Resolution of ST-Segment Elevation
      • Pharmaco-Invasive Treatment: 85.2%
      • Primary PCI: 78.4%
      • Thrombolysis in Myocardial Infarction Flow Grade 3 at Last Angiography was ≈87% in both groups
    • Composite of Death, Shock, Heart Failure, or Reinfarction:
      • Pharmaco-Invasive Treatment: 12.8%
      • Primary PCI: 13.3%
      • RR 0.96; 95% CI 0.62 to 1.48
    • All-Cause and Cardiac Deaths:
      • Pharmaco-Invasive Treatment: 9.3 and 7.3%
      • Primary PCI: 8.9 and 8.4%
    • Intracranial Hemorrhage:
      • Pharmaco-Invasive Treatment: 6 (1.5%); 3 were fatal
      • Primary PCI: 0 (0%)
    • Incidence of major non-intracranial bleeding was low in both groups (<1.5%)

Strengths:

• Multicenter, randomized clinical trial
• Groups well balanced at baseline
• Baseline ECGs in both groups had similar time of symptom onset to qualifying ECG, Worst-lead ST-segment elevation and Sum ST deviations
• There was a balanced distribution of ambulance and community hospitals included in the trial between arms

Limitations:

• Study was funded by Boehringer-Ingelheim (Had no role in the study design, data collection, analysis, and interpretation) which was given the opportunity to review the manuscript for medical and scientific accuracy
• Large exclusion list making this a very niche population of patients
• ECG elevation and deviation resolution is not a patient-oriented outcome
• Trial had very wide 95% CI making it difficult to really say one strategy is similar to another
• Unblinded study can create confounders not measured and bias not only reporting but treatments
• Convenience sample of patients, not consecutive enrollment

Discussion:

• In the STREAM-2 trial patients with STEMI, ≥60 years of age who presented within 3 hours after symptom onset, unable to undergo primary PCI within 1 hour receiving pharmaco-invasive treatment of half-dose tenecteplase, showed rates of resolution of ST-segment elevation and deviation similar to those patients in the primary PCI arm
• 2% of patients in the pharmaco-invasive arm received urgent angiography at a median time of 142 minutes after randomization. It is unclear whether these patients had insufficient ST resolution after tenecteplase or other indications for rescue PCI
• In this trial the median time from qualifying ECG to commencing PCI was a median of 99 minutes. The upper range of this time was 120 minutes from diagnostic ECG in the majority of patients. Interestingly there was an additional 45 minute delay to PCI in patients presenting with ambulances compared to community hospitals (110 min vs 65min)
• 4 of the non-cardiac deaths in the pharmaco-invasive groups and one in the primary PCI group were related to respiratory failure (study took place at the height of the COVID-19 pandemic)
• There was no comparison of full dose tenecteplase to half dose tenecteplase. Without comparison we can’t say if half dose is as good as and as safe as full dose tenecteplase for patients who can’t get to the cath lab in a timely fashion
• There was a higher rate of ICH in the pharmaco-invasive strategy, BUT 3 of the 6 ICH were protocol violations:
  • Excess anticoagulation in 2; Received both lovenox and heparin
  • Uncontrolled HTN in 1; ≥180/110mmHg

Author Conclusion: “Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic endpoints occurred in both treatment groups.  The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI.  If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided.”

Clinical Take Home Point: In older patients presenting with STEMI, within 3 hours of symptom onset, and unable to undergo primary PCI within 1 hour, with no contraindications to fibrinolysis a half-dose tenecteplase strategy prior to PCI seems to be an option in these select patients. However, there was no comparison to full dose tenecteplase.  The more important question: Is half dose as good as and as safe as full dose tenecteplase for patients who can’t get to the cath lab in a timely fashion? It is good to know how ½ dose tenecteplase performs compared to PCI, but that’s not the question we should be asking.

References:

1. Van de Werf, F et al. STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial. Circ 2023. PMID: 37439219
2. Armstrong P et al. Fibrinolysis or Primary PCI in ST-Segment elevation Myocardial Infarction. NEJM 2013. PMID: 23473396

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

The post STREAM-2: Half-Dose Tenecteplase vs Primary PCI in Older Patients with STEMI? appeared first on REBEL EM - Emergency Medicine Blog.

Take Home Points:

• In the context of poisoning, a “wide QRS” is anything greater than 100 milliseconds.
• A newly “wide QRS”, especially with hemodynamic instability, should prompt consideration of sodium channel blockade and not ventricular tachycardia. Treatment is guided by administration of sodium-bicarbonate.
• Recall that the resultant alkalemia driven by sodium-bicarbonate will shift potassium intracellularly. As a result, if a bicarbonate infusion is started, potassium should
  simultaneously be given as to avoid life-threatening hypokalemia.

The post REBEL Core Cast 109.0 – Na Channel Blocker Poisoning appeared first on REBEL EM - Emergency Medicine Blog.

Bottom Line Up Top: Troponins should not be routinely sent in patients presenting with SVT. Rarely, they may be necessary if the patient has concerning ischemic symptoms that persist after conversion to sinus rhythm.

Clinical Scenario: A 44-year-old man presents with palpitations that started 45 minutes ago. He has no medical problems and denies any prior similar symptoms. ECG shows a regular, narrow-complex, tachycardia at 190 bpm consistent with SVT. The patient is hemodynamically stable and you request diltiazem 0.3 mg/kg for cardioversion. After the push, the patient reverts to normal sinus rhythm and is symptom free. The nurse asks if you want to send labs and a troponin.

What Your Gut Says: The patient has a tachydysrhythmia which may be the presentation of acute coronary syndrome (ACS) even though the patient has no ischemic symptoms. Send the troponin just to make sure.

What The Evidence Says:

Gabrielli and colleagues demonstrated that troponin testing in patients with SVT is common. Up to 80% of patients will have at least one troponin sent (Gabrielli 2022). Additionally, they found that up to 30% of the troponins sent are positive. This would seem to argue that troponin testing should be standard practice in those presenting with SVT regardless of symptoms. However, this conclusion confuses the significance of the positive troponin.

A troponin is a protein (not an enzyme) that is detected when there is breakdown of muscle in the body. Troponins are highly specific to cardiac myocytes but do exist in other muscle types as well. In clinical practice, a troponin is used to determine whether a patient has had myocardial damage resulting due to coronary atherosclerosis or an acute coronary occlusion (ACO). This is a Type I myocardial infarction. Essentially, we are using the troponin assay to find patients with ACO who may be benefited by coronary interventions or risk factor modification.

There are other reasons aside from ACO for troponin elevations:

• Type 1: MI due to a spontaneous coronary atherosclerotic event.
• Type 2: MI secondary to ischaemia, but not related to coronary atherosclerosis.
• Type 3: Sudden death with symptoms or signs of ischaemia (not requiring elevated biomarker confirmation).
• Type 4: MI associated with percutaneous coronary intervention (Subtype 4a), or stent thrombosis (Subtype 4b).
• Type 5: MI associated with coronary bypass surgery.

Type 2 MI is common in the ED and can result from vigorous exercise (common in athletes after marathons), sepsis, trauma and tachydysrhythmias including SVT. The available literature shows that SVT is not associated with ACO, Type I MI or serious outcomes either in the short term or after prolonged follow up (Gabrielli 2022). Thus, while we find a large number of positive troponins in patients with SVT, these troponins are false positives for type I MI and can result in prolonged length of stay, higher risk of hospitalization, increased downstream testing and, ultimately, harm (Allen 2021).

Who should have troponins sent? After conversion to sinus rhythm, do a good history, physical and analysis of the ECG. If the patient continues to have symptoms concerning for ACS, troponin testing should be pursued.

Bottom Line: The vast majority of patients presenting with SVT do not need, and should not have, a troponin sent. SVT is not a presenting dysrhythmia consistent w/ ACS. Obtaining a troponin is wasteful and may result in a false positive with additional downstream testing and resultant harms. After cardioversion, if the patient has concerning ischemic symptoms, a troponin can be contemplated but this is an extremely uncommon situation.

Bonus Pearls:

• SVT ECGs will often demonstrate diffuse ST depressions. These depressions (while the patient is in SVT) should not drive troponin testing. Being in SVT is not the equivalent of a stress test (ST depressions here are an electrical phenomena not a reflection of ischemia). Continued ST deviation after conversion should prompt consideration of ACS.
• While adenosine is the most commonly used medication for cardioversion of SVT, calcium channel blockers (ie diltiazem, verapamil) are as effective as adenosine, have a lower rate of SVT recurrence and avoid the sense of dread experienced by patients. Calcium channels blockers should be considered in patients with no history, signs or symptoms of heart failure.

Read More

• EMRAP: Cardiology Corner: Troponins in SVT
• CoreP: Tachydysrhythmias

References

1. Gabrielli M et al. Troponin testing in adult patients presenting to the ED for paroxysmal supraventricular tachycardia: a review. Cardiol Rev. 2022. PMID: 35148534
2. Allen R, deSouza IS. Troponin testing in patients with supra ventricular tachycardia—are we overcasting? A teachable moment JAMA Int Med. 2021;181(6):842-843. PMID: 33779679
3. Foy A, Mandrola J. Updating our thinking on troponin use and interpretation. JAMA Int Med. 2021;181(6):843-844. PMID: 33779692

Post Peer-Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)

The post Clinical Conundrum: Should a Troponin Routinely be Ordered in Patients with SVT? appeared first on REBEL EM - Emergency Medicine Blog.

An 85-year-old man presents for evaluation of left wrist pain. Last night, he missed the last step while descending the stairs at his house. He fell and landed on his hands and did not have other injuries. Acetaminophen and ibuprofen have not alleviated his pain. X-ray imaging is shown below. His physical exam reveals limited left wrist flexion and extension. There is no obvious deformity, weakness of his intrinsic hand muscles, or wrist drop. His pain is out of proportion to his exam. Which of the following nerves is most likely injured?

1. Axillary
2. Median
3. Radial
4. Ulnar

FOR THE RIGHT ANSWER CLICK ON THE ROSH REVIEW LOGO BELOW

References

1. Guo RC, Cardenas JM, Wu CH. Triquetral fractures overview. Curr Rev Musculoskelet Med. 2021;14(2):101–106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991068/
2. Skalski M. Triquetral fracture – pooping duck sign. Radiopaedia website. Accessed June 22, 2023. https://radiopaedia.org/cases/triquetral-fracture-pooping-duck-sign?lang=us

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)

The post Rosh Review EM Scholar Monthly Question appeared first on REBEL EM - Emergency Medicine Blog.

Background: Cardiogenic shock develops in up to 10% of patients with acute myocardial infarction (AMI) and carries a 30 day mortality rate around 50%. Revascularization of the culprit lesion remains one of the few established treatments though there are numerous other unproven modalities including extracorporeal life support (ECLS). Many centers have attempted ECLS to achieve hemodynamic stabilization in this group of patients. The benefits of this strategy may be outweighed by the risk of the device-related complications (i.e. bleeding, stroke, limb ischemia, and hemolysis). The evidence for this practice has been sparse until now.

Paper: U. Zeymer HT et al. Extracorporeal Life Support in Infarct-Related Cardiogenic Shock. NEJM 2023. PMID: 37634145

Clinical Question: Does early routine ECLS use (along with usual medical therapy) compared with usual medical therapy alone result in improved survival in patients with AMI complicated by cardiogenic shock for whom early revascularization is planned?

What They Did:

• Investigator-initiated, randomized, multicenter, open-label trial in two European countries (Germany and Slovenia)
• Immediately after the performance of coronary angiography examining coronary anatomy, patients with AMI complicated by cardiogenic shock (SCAI stage C, D, or E) for whom early revascularization was planned were randomly assigned 1:1 to receive:
  • ECLS: Early ECLS + Usual Medical Treatment
    • Initiated during index catheterization, preferably before PCI
  • Control: Usual Medical Treatment Alone
    • Crossover to ECLS was to be avoided according to the trial protocol but could be performed under specific predefined criteria for HD deterioration under medical therapy, escalation therapy using other devices such as IABP or a microaxial transvalvular flow pump was allowed. Criteria included:
      • Severe HD instability with impending HD collapse
      • Increase in arterial lactate level >3mmol/L during a 6hr period
      • Increase in vasopressor use by 50% from baseline to maintain a MAP >65mmHg

SCAI (Society for Cardiovascular Angiography and Interventions) Criteria

Outcomes:

• Primary: Death from any cause at 30d
• Secondary:
  • Time until HD stabilization
  • ICU LOS
  • Acute renal failure warranting RRT
  • Recurrent MI
  • Rehospitalization for CHF
  • Initiation and duration of catecholamine therapy
  • Use and duration of mechanical ventilation
  • Poor neurologic outcome (CPC 3 or 4) at 30d
• Safety:
  • Moderate or severe bleeding (Type 3 to 5 according to Bleeding Academic Research Consortium [BARC] Criteria)
  • Stroke or systemic embolization
  • Peripheral vascular complications warranting interventional or surgical therapy

Inclusion:

• Adult patients (18 to 80 years of age)
• AMI complicated by cardiogenic shock
  • Cardiogenic shock defined as:
    • SBP <90mmHg for >30min OR the initiation of catecholamines to maintain a SBP >90mmHg
    • Arterial lactate >3mmol/L
    • Signs of impaired organ perfusion with at least one of the following criteria
      • AMS
      • Cold or clammy skin and limbs
      • UOP <30mL/hr
    • Planned early revascularization by either percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG)

Exclusion:

• Patients who had undergone cardiopulmonary resuscitation for more than 45 minutes before randomization
• Mechanical cause of cardiogenic shock
• Severe peripheral-artery disease precluding insertion of ECLS cannulas

Results:

• 420 patients underwent randomization:
  • 417 patients were included in final analyses
  • Median Age ≈63yrs
  • Median SBP ≈96mmHg
  • Oliguria ≈72%
  • AMS ≈95%
  • Cold, Clammy Skin/Limbs ≈97%
  • STEMI ≈67%
  • Most Common Coronary Culprit = LAD (47.6%)
  • Multivessel Disease ≈67%
  • Cardiac Arrest Prior to Randomization ≈77%
  • Median Time Until ROSC = 20min
  • Median LVEF = 30%
  • Median Lactate 6.9mmol/L
  • SCAI Shock Stage:
    • C
      • ECLS: 49.8%
      • Control: 53.4%
    • D
      • ECLS: 18.2%
      • Control 8.7%
    • E
      • ECLS 32.1%
      • Control 38.0%
    • Majority of patients had PCI performed (96.6%)
    • Impella CP was most common mechanical circulatory support in patients without ECLS (85.7%)
  • Death From Any Cause at 30d
    • ECLS: 47.8%
    • Control: 49.0%
    • RR 0.98; 95% CI 0.80 to 1.19; p = 0.81
    • Results of the sensitivity analyses in the per-protocol and as-treated populations were similar to the findings of the primary analysis
    • Pre-specified and post hoc analyses showed results across all subgroups that were consistent with those of the primary analysis
  • Median Duration of Mechanical Ventilation
    • ECLS: 7d (Range 4 to 12d)
    • Control: 5d (Range 3 to 9d)
    • Median Difference: 1d; 95% CI 0 to 2
  • No difference between treatment groups regarding
    • Duration of catecholamine therapy
    • Time until HD stabilization
  • Other Secondary Outcomes of Note (ECLS vs Control)
  • Renal-Replacement Therapy: 8.1% vs 13.9% (RR 0.58; 95% CI 0.33 to 1.03)
  • Poor Neurologic Outcome (CPC 3 or 4): 24.8% vs 22.6% (RR 1.03; 95% CI 0.88 to 1.19)
  • Moderate or Severe Bleeding:
    • ECLS: 23.4%
    • Control: 9.6%
    • RR 2.44; 95% CI 1.50 to 3.95
  • Peripheral Vascular complications Warranting Intervention
    • ECLS: 11.0%
    • Control 3.8%
    • RR 2.86; 95% CI 1.31 to 6.25

Strengths:

• Asks a clinically important question with sparse evidence
• Multicenter randomized controlled trial
• Groups were well balanced at baseline
• Included only patients with more advanced cardiogenic shock (Required a lactate level >3mmol/L)
• Randomization appropriately performed
• Primary outcome was objective reducing chance for bias

Limitations:

• Open-label trial and therefore blinding of the ECLS intervention not possible. This can have impacts on therapeutic decisions of the treating physicians
• 39 patients crossed over from the control group to ECLS which could dilute any effect that would have been seen between groups
• Convenience sample of patients (non-consecutive enrollment) which causes selection bias
• Groups had some baseline differences
  • Prior PCI (ECLS 13% vs Control 20.9%)
  • Triple vessel disease (ECLS 30% vs Control 42.0%)
• Unclear time to ECLS (i.e. Door to randomization). Was ECLS instituted to late in this cohort?

Discussion:

• Possible Reasons for absence of benefit of ECLS in cardiogenic shock?
  • Device-related complications counterbalance any potential benefit (More bleeding and peripheral ischemic complications warranting intervention occurred more frequently in ECLS group)
  • Duration of mechanical ventilation (Longer in the ECLS group which could alter outcomes)
  • VA ECMO is associated with increased LV afterload (More dobutamine used in ECLS group suggests increased LV afterload which can be associated with increased oxygen consumption)
  • Cause of poor outcomes (Poor outcomes not primarily related to circulatory failure (77% of patients had cardiac arrest prior to randomization and this resulted in 25% of patients having neurologic causes of death)
  • It is unclear what the timing of ECLS was. It could be that ECLS was initiated too late in the patient’s clinical course and therefore would not show any benefit.
• Interestingly a subgroup analysis according to shock-severity stage was not included in this trial
  • There will most likely be some patients where ECLS is necessary and lifesaving
  • The results of the ECLS-SHOCK trial do not tell us which ones
• Patient selection and timing are everything when it comes to ECLS
  • How long were the patients down for? What was their initial rhythm? Did they get bystander CPR? We don’t know any of this information unfortunately and all are key in patient selection
  • The median lactate level before revascularization was 6.9mmol/L (Range 4.6 to 9.9). This makes me think these patients were down for some time.
  • At our institution patients do not go for diagnostic heart catheterization and then get put on ECMO, they are initiated on ECMO during the time of their initial resuscitation and then go for heart catheterization once they are stabilized.
  • I have a feeling that the lack of benefit in this trial is due to poor patient selection and the delayed timing of ECMO.

Author Conclusion: “In patients with acute myocardial infarction complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone.”

Clinical Take Home Point: In patients with acute myocardial infarction complicated by cardiogenic shock and needing revascularization, the incidence of death from any cause at 30 days was not decreased among patients receiving ECLS compared to those receiving medical therapy alone. However I have a feeling that the lack of benefit in this trial is due to poor patient selection (We don’t have details of the arrest) and the initiation of ECLS may have simply been too late in the patient’s clinical course (after diagnostic cath instead of during the resuscitation).

References:

1. Zeymer HT et al. Extracorporeal Life Support in Infarct-Related Cardiogenic Shock. NEJM 2023. PMID: 37634145

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)

The post The ECLS-SHOCK Trial: ECPR in Infarct-Related Cardiogenic Shock appeared first on REBEL EM - Emergency Medicine Blog.

Take Home Points:

• Airway management is paramount; expect a challenging intubation and consider controlling the airway early if there is apparent airway compromise.
• Understanding the cause of angioedema (mast cell vs. bradykinin mediated) helps dictate directed management.
• Urticaria and pruritus = MAST CELL mediated, which is treated like a standard allergic reaction.

The post REBEL Core Cast 108.0 – Angioedema appeared first on REBEL EM - Emergency Medicine Blog.