Emergency Medicine
Management of Adult Sepsis in Resource-Limited Settings: A Global Delphi-Based Consensus
24 Dec, 2024 | 13:35h | UTCIntroduction: This summary presents key points from a recent expert consensus on managing adult sepsis under limited-resource conditions, where patients may lack access to an ICU bed, advanced monitoring technologies, or sufficient staffing. The statements were developed through a Delphi process involving an international panel of clinicians, aiming to complement existing sepsis guidelines by focusing on pragmatic approaches and context-specific adaptations. These consensus statements address unique challenges such as limited diagnostic tests, alternative strategies for hemodynamic monitoring, and management of sepsis in areas with tropical infections.
Key Recommendations:
- Location of Care and Transfer
- When an ICU bed is unavailable, care can be provided in a non-ICU setting if minimum monitoring (neurological status, blood pressure, peripheral perfusion) is ensured.
- Before transferring a patient, ensure airway patency, initiate intravenous fluids and antimicrobials, and maintain safe transport conditions.
- Incorporate telemedicine or phone consultation with critical care specialists whenever feasible.
- Diagnostic Considerations
- Employ screening tools (e.g., qSOFA) in areas with limited resources, acknowledging its diagnostic constraints.
- Use clinical parameters like altered mental state, capillary refill time (CRT), and urine output to gauge tissue perfusion when lactate measurement is unavailable.
- Insert an indwelling urinary catheter in septic shock to monitor urine output accurately, balancing infection risks against close monitoring needs.
- Hemodynamic Management
- Rely on clinical indicators (CRT, urine output) to guide fluid resuscitation when serum lactate is not accessible.
- Use fluid responsiveness tests (e.g., passive leg raising, pulse pressure variation) if advanced hemodynamic monitoring is impractical.
- Consider balanced solutions such as Ringer’s lactate or Hartmann’s solution for fluid resuscitation.
- Recognize that patients with tropical infections (e.g., malaria, dengue) may require cautious fluid volumes to avoid overload.
- Initiate epinephrine if norepinephrine or vasopressin is unavailable, and use vasopressors through peripheral lines if central access cannot be established.
- Antimicrobial Therapy
- Administer antibiotics without delay (ideally within one hour) in suspected sepsis or septic shock.
- In severe infections of parasitic origin (e.g., malaria), start antiparasitic agents promptly.
- In settings where laboratory investigations are limited, begin broad-spectrum antimicrobial coverage when infection cannot be ruled out.
- De-escalate or discontinue therapy based on clinical improvement, declining white blood cell counts, and adequate source control.
- Respiratory Support
- For acute hypoxemic respiratory failure in septic patients, noninvasive ventilation (NIV) can be used if high-flow nasal oxygen is not available, provided close monitoring for potential failure is ensured.
Conclusion: These consensus-based statements offer practical guidance for clinicians treating sepsis in resource-limited environments. By adapting globally accepted recommendations and incorporating alternative strategies—such as clinical markers of perfusion, use of peripheral vasopressors, and prioritizing immediate antimicrobial therapy—these principles aim to improve patient outcomes where healthcare resources are scarce. Further research and context-specific adaptations will be essential to address remaining uncertainties and refine these expert recommendations.
Reference:
Thwaites, L., Nasa, P., Abbenbroek, B. et al. Management of adult sepsis in resource-limited settings: global expert consensus statements using a Delphi method. Intensive Care Medicine (2024). https://doi.org/10.1007/s00134-024-07735-7
RCT: Adjunctive Middle Meningeal Artery Embolization Reduces Reoperation in Subdural Hematoma
24 Nov, 2024 | 13:53h | UTCBackground: Subacute and chronic subdural hematomas are common neurosurgical conditions with a high recurrence rate after surgical evacuation, affecting 8% to 20% of patients. Middle meningeal artery embolization (MMAE) is a minimally invasive procedure targeting the blood supply to these membranes. Preliminary studies suggest that adjunctive MMAE may reduce hematoma recurrence, but its impact on reoperation risk remains unclear.
Objective: To determine whether adjunctive MMAE reduces the risk of hematoma recurrence or progression leading to repeat surgery within 90 days compared to surgery alone in patients with symptomatic subacute or chronic subdural hematoma.
Methods: In this prospective, multicenter, randomized controlled trial, 400 patients aged 18 to 90 years with symptomatic subacute or chronic subdural hematoma requiring surgical evacuation were randomly assigned to receive either MMAE plus surgery (n=197) or surgery alone (n=203). The primary endpoint was hematoma recurrence or progression leading to repeat surgery within 90 days after the index treatment. The secondary endpoint was deterioration of neurologic function at 90 days, assessed using the modified Rankin Scale.
Results: Hematoma recurrence or progression requiring repeat surgery occurred in 8 patients (4.1%) in the MMAE plus surgery group versus 23 patients (11.3%) in the surgery-alone group (relative risk, 0.36; 95% CI, 0.11 to 0.80; P=0.008). Functional deterioration at 90 days was similar between groups (11.9% vs. 9.8%; risk difference, 2.1 percentage points; 95% CI, −4.8 to 8.9). Mortality at 90 days was 5.1% in the MMAE group and 3.0% in the control group. Serious adverse events related to the embolization occurred in 4 patients (2.0%), including disabling stroke in 2 patients.
Conclusions: Adjunctive MMAE combined with surgery significantly reduced the risk of hematoma recurrence or progression requiring reoperation within 90 days compared to surgery alone. However, there was no significant difference in neurologic functional deterioration, and the procedure was associated with procedural risks.
Implications for Practice: MMAE may be considered as an adjunct to surgical evacuation in patients with subacute or chronic subdural hematoma to reduce reoperation risk. Clinicians should carefully weigh the potential benefits against the risks of procedural complications, including stroke.
Study Strengths and Limitations: Strengths include the randomized controlled design and multicenter approach, enhancing generalizability. Limitations involve the open-label design, introducing potential bias since the primary endpoint was based on surgeon judgment. A substantial loss to follow-up (13.2%) could affect results, and the study was not powered to detect differences in mortality or serious adverse events.
Future Research: Further studies with larger sample sizes are needed to fully evaluate the safety and efficacy of MMAE, including long-term outcomes. Research should focus on optimizing patient selection and assessing the procedure’s impact on mortality and serious adverse events.
Review: Acute Respiratory Distress Syndrome
28 Nov, 2024 | 13:06h | UTCIntroduction: Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung condition characterized by diffuse alveolar damage, leading to hypoxemia and respiratory failure. Since its initial description in 1967, the understanding and definition of ARDS have significantly evolved, integrating advances in basic science and clinical practice. A newly recommended global definition expands diagnostic criteria to enhance early recognition and management, especially in resource-limited settings. This review summarizes current insights into the epidemiology, pathophysiology, and evidence-based management of ARDS, highlighting key updates and future research priorities.
Key Recommendations:
- New Global Definition of ARDS: Adoption of an expanded definition that includes patients receiving high-flow nasal oxygen (HFNO) support and allows diagnosis using pulse oximetry and thoracic ultrasonography. This makes ARDS identification feasible in diverse clinical environments, including those with limited resources.
- Established Critical Care Interventions: Emphasis on early implementation of proven strategies such as low tidal volume ventilation (6 mL/kg predicted body weight) with plateau pressures ≤30 cm H₂O, prone positioning for patients with PaO₂/FiO₂ <150 mm Hg, and conservative fluid management after initial resuscitation. These interventions have consistently reduced mortality and are recommended as standard care.
- Personalized Approaches and Phenotyping: Recognition of the heterogeneity in ARDS pathophysiology underscores the need for personalized treatment strategies. Identification of hyper-inflammatory and hypo-inflammatory phenotypes may guide targeted therapies and improve outcomes, although prospective validation is required.
- Impact of COVID-19 on ARDS: Acknowledgment of the significant increase in ARDS incidence due to the COVID-19 pandemic. While COVID-19 ARDS shares similarities with traditional ARDS, notable differences in endothelial dysfunction and immune response highlight the necessity for tailored management approaches in these patients.
- Pharmacologic Interventions: Updated guidelines provide conditional recommendations for the use of corticosteroids in ARDS, particularly in early moderate to severe cases. Ongoing research into pharmacologic agents such as statins, mesenchymal stromal cells, and other cell-based therapies shows potential but requires further clinical trials to establish efficacy.
- Future Research Priorities: Identification of key areas for investigation, including the long-term sequelae of ARDS, optimization of non-invasive and invasive ventilation strategies, exploration of genetic and environmental risk factors, and development of rapid biomarker assays for real-time phenotyping and targeted therapy.
Conclusion: The evolving definition and understanding of ARDS aim to improve early detection and standardization of care across various clinical settings. Reinforcing established critical care interventions while advancing personalized and novel therapeutic approaches holds promise for reducing mortality and enhancing long-term patient outcomes. Continuous research into the pathophysiology and management of ARDS, enriched by insights from the COVID-19 pandemic, is essential to address ongoing challenges and improve patient care.
RCT: 7-Day Antibiotic Therapy Noninferior to 14-Day for Bloodstream Infections
20 Nov, 2024 | 18:19h | UTCBackground: Bloodstream infections are a significant cause of morbidity and mortality worldwide. Early and appropriate antibiotic therapy is essential, but the optimal duration remains uncertain. Prolonged antibiotic use can lead to adverse events, Clostridioides difficile infection, antimicrobial resistance, and increased healthcare costs.
Objective: To determine whether a 7-day course of antibiotic treatment is noninferior to a 14-day course in hospitalized patients with bloodstream infections regarding 90-day all-cause mortality.
Methods: In this multicenter, noninferiority randomized controlled trial, 3,608 hospitalized patients from 74 hospitals in seven countries were enrolled. Eligible patients had bloodstream infections but were excluded if they had severe immunosuppression, infections requiring prolonged therapy, possible contaminants, or Staphylococcus aureus bacteremia. Participants were randomized to receive either 7 days (n=1,814) or 14 days (n=1,794) of adequate antibiotic therapy, with antibiotic selection at the clinicians’ discretion. The primary outcome was death from any cause by 90 days post-diagnosis, with a noninferiority margin of 4 percentage points.
Results: At 90 days, mortality was 14.5% in the 7-day group and 16.1% in the 14-day group (difference: –1.6 percentage points; 95.7% CI, –4.0 to 0.8), demonstrating noninferiority of the shorter duration. Noninferiority was confirmed in per-protocol and modified intention-to-treat analyses. Secondary outcomes, including relapse rates, adverse events, and hospital length of stay, were similar between groups. Findings were consistent across subgroups based on infection source, pathogen type, and patient characteristics.
Conclusions: A 7-day antibiotic regimen is noninferior to a 14-day regimen for treating hospitalized patients with bloodstream infections, without increasing mortality or relapse rates.
Implications for Practice: Implementing a 7-day antibiotic course could reduce antibiotic exposure, minimize adverse events, and potentially limit antimicrobial resistance development. Clinicians should consider individual patient factors, such as infection severity and comorbidities, before universally adopting shorter treatment durations.
Study Strengths and Limitations: Strengths include a large, diverse patient population and inclusion of critically ill patients, enhancing generalizability. Limitations involve the open-label design and nonadherence to assigned durations in some cases (23.1% in the 7-day group continued antibiotics longer). Exclusion of S. aureus bacteremia limits applicability to that subgroup. The study may not have been powered to detect differences in rare adverse outcomes like C. difficile infection or antimicrobial resistance emergence.
Future Research: Further studies should explore the efficacy of even shorter antibiotic durations, individualized treatment strategies based on patient response, and the long-term impact on antimicrobial resistance and healthcare costs.
RCT: Colchicine Does Not Reduce Cardiovascular Events After Myocardial Infarction
20 Nov, 2024 | 18:12h | UTCBackground: Inflammation is a key contributor to atherosclerosis and adverse cardiovascular events. Previous trials have suggested that anti-inflammatory agents like colchicine may reduce cardiovascular risks in patients with coronary artery disease.
Objective: To evaluate whether colchicine reduces the incidence of major cardiovascular events when initiated soon after a myocardial infarction.
Methods: In this multicenter, randomized, placebo-controlled trial with a 2-by-2 factorial design, 7,062 patients who experienced a myocardial infarction were assigned to receive colchicine (0.5 mg daily) or placebo, and spironolactone or placebo. The colchicine results are reported here. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization. Median follow-up was 3 years.
Results: A primary outcome event occurred in 9.1% of patients in the colchicine group and 9.3% in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.16; P=0.93). Individual components of the primary outcome were similar between groups. Colchicine significantly reduced C-reactive protein levels at 3 months (adjusted mean difference of –1.28 mg/L; 95% CI, –1.81 to –0.75). Diarrhea was more frequent with colchicine (10.2% vs. 6.6%; P<0.001), but serious infections did not differ significantly.
Conclusions: Among patients post-myocardial infarction, colchicine did not reduce the incidence of major cardiovascular events over a median of 3 years compared to placebo.
Implications for Practice: These findings suggest that initiating colchicine after myocardial infarction may not provide additional cardiovascular benefits. Clinicians should weigh the lack of efficacy and potential gastrointestinal side effects when considering colchicine for secondary prevention in this population.
Study Strengths and Limitations: Strengths include a large sample size and extended follow-up. Limitations involve a higher-than-expected discontinuation rate and underrepresentation of women and diverse populations. The predominance of STEMI patients may limit applicability to NSTEMI cases.
Future Research: Further studies are needed to identify if specific subgroups might benefit from colchicine or if different dosing strategies could be more effective in reducing cardiovascular events post-myocardial infarction.
RCT: Routine Spironolactone Post-MI Does Not Reduce Cardiovascular Events
20 Nov, 2024 | 18:03h | UTCBackground: Mineralocorticoid receptor antagonists (MRAs), such as spironolactone, have demonstrated mortality benefits in patients with heart failure following myocardial infarction (MI). However, the efficacy of routine spironolactone use in all patients post-MI, regardless of heart failure status, remains uncertain.
Objective: To evaluate whether routine administration of spironolactone reduces cardiovascular events in patients after MI who have undergone percutaneous coronary intervention (PCI).
Methods: In a multicenter, double-blind, placebo-controlled trial with a 2-by-2 factorial design, 7,062 patients with MI undergoing PCI were randomized to receive spironolactone (25 mg daily) or placebo, and colchicine or placebo. The two primary outcomes were: (1) a composite of death from cardiovascular causes or new or worsening heart failure, assessed as the total number of events; and (2) a composite of the first occurrence of MI, stroke, new or worsening heart failure, or death from cardiovascular causes. Median follow-up was 3 years.
Results: No significant differences were observed between the spironolactone and placebo groups in the primary outcomes. For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group versus 220 events (2.1 per 100 patient-years) in the placebo group (hazard ratio [HR] adjusted for competing risk, 0.91; 95% confidence interval [CI], 0.69–1.21; P=0.51). For the second primary outcome, events occurred in 280 patients (7.9%) in the spironolactone group and 294 patients (8.3%) in the placebo group (HR adjusted for competing risk, 0.96; 95% CI, 0.81–1.13; P=0.60). Serious adverse events were similar between groups.
Conclusions: Routine use of spironolactone after MI did not reduce cardiovascular mortality or new or worsening heart failure compared to placebo.
Implications for Practice: These findings suggest that routine prescription of spironolactone for all patients after MI may not be beneficial and should be reconsidered. Clinicians should carefully evaluate the indication for MRAs post-MI, particularly in patients without heart failure, and remain cautious about routine use without clear evidence of benefit.
Study Strengths and Limitations: Strengths of the study include its large sample size, multicenter international design, and long follow-up period, enhancing the generalizability of the findings. However, limitations include lower-than-expected event rates, potentially reducing statistical power to detect significant differences. The high rate of discontinuation of the trial regimen and underrepresentation of women and certain racial and ethnic groups may also limit the applicability of the results. Additionally, the possibility of a type II error due to reduced power cannot be excluded.
Future Research: Further studies are warranted to identify specific subgroups of patients who may benefit from spironolactone post-MI and to explore alternative therapies that effectively reduce cardiovascular events after MI.
Meta-Analysis: Moderately Rapid Sodium Correction Linked to Better Outcomes in Severe Hyponatremia
20 Nov, 2024 | 16:10h | UTCBackground: Severe hyponatremia is a critical condition that can lead to hyponatremic encephalopathy, necessitating prompt treatment to prevent neurological damage or death. Traditional guidelines recommend limiting sodium correction rates to prevent osmotic demyelination syndrome (ODS). However, emerging evidence suggests that slower correction rates may be associated with increased mortality.
Objective: To evaluate the association between sodium correction rates and mortality among hospitalized adults with severe hyponatremia.
Methods: This systematic review and meta-analysis included 16 cohort studies published between January 2013 and October 2023, involving 11,811 hospitalized adults with severe hyponatremia (serum sodium <120 mEq/L or <125 mEq/L with severe symptoms). Patients were categorized based on sodium correction rates: rapid (≥8-10 mEq/L per 24 hours), slow (<8 or 6-10 mEq/L per 24 hours), and very slow (<4-6 mEq/L per 24 hours). Primary outcomes were in-hospital and 30-day mortality; secondary outcomes included hospital length of stay (LOS) and incidence of ODS.
Results: Rapid correction was associated with significantly lower in-hospital mortality compared to slow correction (odds ratio [OR], 0.67; 95% CI, 0.55-0.82) and very slow correction (OR, 0.29; 95% CI, 0.11-0.79), corresponding to 32 and 221 fewer deaths per 1,000 patients, respectively. At 30 days, rapid correction was associated with 61 and 134 fewer deaths per 1,000 patients compared to slow and very slow correction, respectively. Rapid correction also resulted in shorter hospital LOS by 1.20 days (95% CI, 0.51-1.89) compared to slow correction and 3.09 days (95% CI, 1.21-4.94) compared to very slow correction. There was no statistically significant increase in ODS risk with rapid correction.
Conclusions: In hospitalized adults with severe hyponatremia, rapid sodium correction was associated with reduced mortality and shorter hospital stays without a significant increase in ODS risk.
Implications for Practice: These findings suggest that more aggressive sodium correction may benefit patients with severe hyponatremia, challenging current guidelines that recommend slower correction rates to prevent ODS. Clinicians should weigh the potential benefits of rapid correction against the traditionally emphasized risks, although caution is still warranted given the seriousness of ODS.
Study Strengths and Limitations: Strengths include a large sample size and inclusion of recent studies reflecting current practices. Limitations involve the observational nature of included studies, potential confounding factors, heterogeneity in correction rate definitions, and possible underreporting of ODS due to its rarity and diagnostic challenges.
Future Research: Randomized controlled trials are needed to establish causality and optimal correction rates, as well as to identify patient subgroups that may benefit most from rapid correction while minimizing ODS risk.
RCT: Low-Dose Ketamine Enhances Pain Relief When Added to Morphine in ED Patients
20 Nov, 2024 | 14:42h | UTCBackground: Acute pain is a prevalent complaint among emergency department (ED) patients, yet effective pain management remains suboptimal, especially in individuals with current opioid use due to opioid tolerance and hyperalgesia. Low-dose ketamine (LDK) has been proposed as an adjunct to opioids to enhance analgesia through synergistic or additive effects, but its efficacy in patients with and without current opioid use in the ED setting is not well established.
Objective: This randomized controlled trial aimed to determine the effectiveness of LDK as an adjunct to morphine versus morphine alone for acute pain management in ED patients with and without current opioid use.
Methods: In this single-center, double-blind study, 116 adult patients presenting to the ED with acute pain (numeric rating scale [NRS] ≥5) requiring intravenous opioids were randomized to receive either 0.1 mg/kg ketamine or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain intensity was measured at baseline and at 10, 20, 30, 45, 60, and 120 minutes post-randomization. The primary outcome was pain reduction from baseline to 10 minutes. Secondary outcomes included pain intensity over 120 minutes, need for rescue opioids, side effects, and patient and provider satisfaction.
Results: The study included 116 patients (median age 51 years; 58% male; 36% with current opioid use). Pain reduction from baseline to 10 minutes was significantly greater in the LDK group compared to placebo (median reduction of 4 [IQR 3–6] vs. 1 [IQR 0–2]; p = 0.001). Pain intensity was significantly lower in the LDK group at 10, 20, and 30 minutes post-administration. There was a higher incidence of nausea, vomiting, and dissociation in the LDK group during the first 10 minutes. No significant differences were observed in the need for rescue opioids or in patient and provider satisfaction between groups.
Conclusions: LDK administered as an adjunct to morphine significantly enhances short-term pain relief in ED patients with acute pain, regardless of current opioid use status. However, the increased risk of transient side effects necessitates careful consideration.
Implications for Practice: LDK may be considered as an adjunct to morphine for acute pain management in the ED, particularly when traditional opioid treatments are insufficient. Clinicians should weigh the benefits against the potential for transient side effects, and LDK should not be universally recommended for all patients with moderate to severe pain.
Study Strengths and Limitations: Strengths of the study include its randomized, double-blind design and the inclusion of patients with current opioid use. Limitations include early termination leading to a smaller sample size, potentially underpowering the stratified analysis, and heterogeneity in patient pain conditions. Additionally, assessing the primary outcome at 10 minutes may not capture the peak effect of morphine.
Future Research: Further studies should focus on optimizing LDK administration protocols, such as exploring bolus versus continuous infusion methods, to achieve sustained pain reduction and minimize side effects.
News Release: Seven-Day Antibiotic Regimen Effective for Bloodstream Infections
10 Nov, 2024 | 17:54h | UTCIntroduction: A recent large-scale, multicenter randomized clinical trial has shown that a seven-day course of antibiotics is as effective as the traditional 14-day regimen for treating hospitalized patients with bloodstream infections (BSIs). This finding addresses a critical need in medical practice to optimize antibiotic use amid rising concerns about antimicrobial resistance and healthcare costs.
Highlights: The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial evaluated 3,608 patients with BSIs across 74 hospitals in seven countries, including the United States, Canada, and Australia. Patients were randomized to receive either a seven-day or a 14-day antibiotic course, with the choice of antibiotic, dosage, and administration route determined by their healthcare team.
- Efficacy Results: The 90-day mortality rates were similar between the two groups—14.5% in the seven-day group versus 16.1% in the 14-day group—demonstrating the non-inferiority of the shorter regimen.
- Secondary Outcomes: Rates of relapse, ICU mortality, hospital mortality, and other clinical markers showed no significant differences between the two groups.
- Patient Demographics: The study included a diverse patient population, with 55% in intensive care units at enrollment. Infections originated from various sources, most commonly the urinary tract (42.2%), abdomen (18.8%), and lungs (13.0%).
- Applicability: Exclusion criteria were minimal, enhancing the generalizability of the findings to everyday clinical practice. Patients with extreme immunosuppression or undrained abscesses were excluded, but those with conditions like renal failure were included.
Lead investigator Dr. Nick Daneman emphasized, “These findings underscore the effectiveness of a shorter antibiotic regimen in patients with bloodstream infections, which is welcomed as we look to identify evidence-based prescribing guidelines for serious bacterial infections.”
Conclusion: The BALANCE trial provides robust evidence that a seven-day antibiotic course is sufficient for treating BSIs, potentially transforming current clinical practice. Adopting shorter antibiotic regimens can reduce healthcare costs, minimize adverse effects, and combat antimicrobial resistance without compromising patient outcomes. This aligns with antimicrobial stewardship goals and promotes more efficient use of healthcare resources.
Source: This study was presented at IDWeek 2024, the joint annual meeting of the Infectious Diseases Society of America and other related organizations. The research was conducted by a team from Sunnybrook Health Sciences Centre and the University of Toronto, led by Dr. Nick Daneman and Dr. Robert Fowler. More information can be found at: http://www.idsociety.org/news–publications-new/articles/2024/antibiotic-treatment-regimen-for-bloodstream-infections-can-safely-be-cut-by-half
Guideline: Management of Urinary Tract Infections in Pediatrics and Adults
5 Nov, 2024 | 18:59h | UTCIntroduction: Urinary tract infections (UTIs) are among the most common infections worldwide, significantly impacting patient quality of life and imposing substantial clinical and economic burdens. Despite advancements in diagnosis and treatment, UTIs continue to cause high morbidity and mortality, ranging from simple cystitis to life-threatening sepsis. Addressing the discrepancy between evidence quality and recommendation strength in existing guidelines, the WikiGuidelines Group has developed a consensus statement. This guideline aims to provide evidence-based recommendations for the prevention, diagnosis, and management of UTIs across diverse clinical settings.
Key Recommendations:
- Cranberry Products:
- Recommendation: Cranberry juice or supplements are recommended for preventing symptomatic, culture-verified UTIs in women with recurrent UTIs, children, and individuals susceptible after interventions.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Methenamine Hippurate:
- Recommendation: Methenamine hippurate is recommended as an alternative to prophylactic antibiotics for preventing recurrent UTIs in patients with intact bladder anatomy.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Topical Estrogen:
- Recommendation: Vaginal estrogen therapy is recommended for postmenopausal women to reduce recurrent UTIs by restoring the vaginal microbiome.
- Quality of Evidence: High
- Recommendation Strength: Strong
- Empirical Treatment Regimens:
- Recommendation: For uncomplicated cystitis, nitrofurantoin is recommended as a first-line agent. For pyelonephritis, trimethoprim/sulfamethoxazole or a first-generation cephalosporin are reasonable first-line agents, depending on local resistance rates.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Treatment Duration for Acute Cystitis in Adults:
- Recommendation:
- Nitrofurantoin: 5 days
- Trimethoprim/sulfamethoxazole: 3 days
- Oral fosfomycin: Single dose
- Quality of Evidence: High
- Recommendation Strength: Strong
- Recommendation:
- Treatment Duration for Acute Pyelonephritis in Adults:
- Recommendation:
- Fluoroquinolones: 5–7 days
- Dose-optimized β-lactams: 7 days
- Quality of Evidence: High
- Recommendation Strength: Strong
- Recommendation:
- Antimicrobial Stewardship:
- Recommendation: De-escalation of antibiotics and the use of mostly or all oral treatment regimens are recommended to optimize antimicrobial use and reduce adverse effects.
- Quality of Evidence: High
- Recommendation Strength: Strong
Conclusion: The consensus highlights a significant lack of high-quality prospective data in many areas related to UTIs, limiting the ability to provide clear recommendations. Implementing these evidence-based guidelines can enhance patient care by promoting effective prevention strategies, accurate diagnosis based on clinical symptoms, appropriate treatment durations, and robust antimicrobial stewardship. This approach is expected to improve clinical outcomes, reduce antimicrobial resistance, and preserve the effectiveness of current treatments.
RCT: No Significant Difference Between Intraosseous and Intravenous Vascular Access in Out-of-Hospital Cardiac Arrest Outcomes
3 Nov, 2024 | 12:58h | UTCBackground: Out-of-hospital cardiac arrest (OHCA) is a major global health concern, resulting in high mortality rates despite advancements in emergency care. In Denmark alone, approximately 5,000 cases occur annually, with a 30-day survival rate of only about 14%. Rapid vascular access during cardiopulmonary resuscitation (CPR) is crucial for administering medications like epinephrine, as recommended by international guidelines. Both intraosseous (IO) and intravenous (IV) routes are routinely used, but their comparative effectiveness remains unclear. Current guidelines favor IV access for initial attempts, yet this recommendation is based on very low-certainty evidence, highlighting the need for well-designed clinical trials.
Objective: To compare the effectiveness of initial intraosseous versus intravenous vascular access on sustained return of spontaneous circulation (ROSC) in adults experiencing nontraumatic OHCA.
Methods: This randomized, parallel-group superiority trial was conducted across all five regions of Denmark, covering 5.9 million inhabitants. Adults aged 18 years or older with nontraumatic OHCA requiring vascular access during CPR were randomized to receive either initial IO or IV access. The IO group was further randomized to humeral or tibial access for a secondary comparison. The primary outcome was sustained ROSC, defined as no need for chest compressions for at least 20 minutes. Key secondary outcomes included 30-day survival and survival with favorable neurologic outcome (modified Rankin scale score of 0–3). Procedural outcomes such as success rates of vascular access within two attempts, time to successful access, and time to first epinephrine administration were also assessed.
Results: Among 1,479 patients included in the primary analysis (731 in the IO group and 748 in the IV group), successful vascular access within two attempts was achieved in 92% of the IO group versus 80% of the IV group. Despite the higher success rate with IO access, the time to first successful access and time to first epinephrine dose were similar between groups. Sustained ROSC occurred in 30% of patients in the IO group and 29% in the IV group (risk ratio [RR], 1.06; 95% confidence interval [CI], 0.90–1.24; P=0.49). At 30 days, survival rates were 12% in the IO group and 10% in the IV group (RR, 1.16; 95% CI, 0.87–1.56), with favorable neurologic outcomes observed in 9% and 8% of patients, respectively (RR, 1.16; 95% CI, 0.83–1.62). No significant differences were found in procedural times, adverse events, or quality-of-life measures among survivors.
Conclusions: In adults with nontraumatic OHCA, initial intraosseous vascular access did not result in a significant difference in sustained ROSC compared to intravenous access. Both methods yielded comparable survival rates and neurologic outcomes at 30 days, suggesting that the choice of vascular access route may not critically impact immediate resuscitation success.
Implications for Practice: These findings indicate that emergency medical services can opt for either intraosseous or intravenous vascular access during resuscitation based on provider expertise, patient anatomy, and situational considerations without adversely affecting patient outcomes. Emphasizing flexibility in vascular access approach may facilitate quicker access and streamline resuscitation efforts in the prehospital setting.
Study Strengths and Limitations: Strengths include the randomized design, large sample size, and nationwide implementation, enhancing generalizability. Limitations involve potential crossover between groups, lack of blinding among clinicians, and the study being underpowered to detect small differences in long-term outcomes.
Future Research: Further studies are needed to assess long-term survival and neurologic outcomes, and to explore whether specific patient subgroups may benefit more from one vascular access method over the other during cardiac arrest resuscitation.
Reference: Vallentin MF, Granfeldt A, Klitgaard TL, et al. Intraosseous or Intravenous Vascular Access for Out-of-Hospital Cardiac Arrest. New England Journal of Medicine. 2024 Oct 31; DOI: http://doi.org/10.1056/NEJMoa2407616
RCT: Intraosseous vs. Intravenous Drug Administration in Out-of-Hospital Cardiac Arrest Shows No Difference in 30-Day Survival
3 Nov, 2024 | 12:48h | UTCBackground: Out-of-hospital cardiac arrest requires rapid drug administration, with medications like epinephrine being highly time-dependent. Intravenous access can be challenging prehospital due to environmental and patient factors, potentially delaying treatment. Intraosseous access may offer faster drug delivery, but its impact on clinical outcomes is unclear.
Objective: To compare the effectiveness of an intraosseous-first versus intravenous-first vascular access strategy on 30-day survival in adults experiencing out-of-hospital cardiac arrest requiring drug therapy.
Methods: In this multicenter, open-label, randomized trial across 11 UK emergency medical systems, 6,082 adults were assigned to receive either intraosseous-first or intravenous-first vascular access during resuscitation. The primary outcome was survival at 30 days. Secondary outcomes included return of spontaneous circulation and favorable neurologic function at hospital discharge (modified Rankin scale score ≤3).
Results: At 30 days, survival was 4.5% in the intraosseous group and 5.1% in the intravenous group (adjusted odds ratio [OR], 0.94; 95% confidence interval [CI], 0.68–1.32; P=0.74). Favorable neurologic outcome at discharge was similar between groups (2.7% vs. 2.8%; adjusted OR, 0.91; 95% CI, 0.57–1.47). Return of spontaneous circulation was lower in the intraosseous group (36.0% vs. 39.1%; adjusted OR, 0.86; 95% CI, 0.76–0.97).
Conclusions: An intraosseous-first vascular access strategy did not improve 30-day survival compared to an intravenous-first strategy in adults with out-of-hospital cardiac arrest. The intraosseous route was associated with a lower rate of return of spontaneous circulation.
Implications for Practice: Paramedics should consider that intraosseous access may not offer a survival advantage over intravenous access and may be linked to a reduced return of spontaneous circulation. This finding may influence decisions on vascular access during resuscitation efforts.
Study Strengths and Limitations: Strengths include a large, multicenter randomized design; limitations involve early termination reducing statistical power and inability to blind prehospital providers.
Future Research: Further studies should investigate why intraosseous access is associated with lower return of spontaneous circulation and assess if specific intraosseous techniques or sites affect outcomes.
RCT: ICS-Formoterol and ICS-SABA Reduce Severe Asthma Exacerbations Compared With SABA Alone
28 Oct, 2024 | 18:12h | UTCBackground: Asthma affects millions worldwide and is managed using inhaled relievers to alleviate acute symptoms. While short-acting β agonists (SABA) are commonly used, combining inhaled corticosteroids (ICS) with SABA or formoterol may enhance outcomes. Recent guidelines recommend ICS-formoterol as the preferred reliever, but the optimal choice remains uncertain, especially following the recent FDA approval of ICS-SABA.
Objective: To compare the efficacy and safety of SABA alone, ICS-SABA, and ICS-formoterol as reliever therapies in asthma.
Methods: This systematic review and network meta-analysis included 27 randomized controlled trials involving 50,496 adult and pediatric asthma patients. Trials compared SABA alone, ICS-SABA, and ICS-formoterol as reliever therapies, ensuring similar maintenance treatments across groups. Outcomes assessed were severe asthma exacerbations, asthma symptom control (Asthma Control Questionnaire-5 [ACQ-5]), asthma-related quality of life (Asthma Quality of Life Questionnaire [AQLQ]), adverse events, and mortality.
Results: Compared with SABA alone, both ICS-containing relievers significantly reduced severe exacerbations:
- ICS-formoterol: Risk ratio (RR) 0.65 (95% CI, 0.60–0.72); risk difference (RD) –10.3% (95% CI, –11.8% to –8.3%).
- ICS-SABA: RR 0.84 (95% CI, 0.73–0.95); RD –4.7% (95% CI, –8.0% to –1.5%).
Compared with ICS-SABA, ICS-formoterol further reduced severe exacerbations (RR 0.78; RD –5.5%). Both ICS-containing relievers modestly improved asthma symptom control compared with SABA alone. No increase in adverse events was observed with either ICS-containing therapy.
Conclusions: Both ICS-formoterol and ICS-SABA as reliever therapies reduce severe asthma exacerbations and improve symptom control compared with SABA alone, without increasing adverse events. ICS-formoterol may offer additional benefits over ICS-SABA in reducing exacerbations.
Implications for Practice: These findings support the use of ICS-containing reliever therapies over SABA alone in asthma management to reduce severe exacerbations and improve control. ICS-formoterol may be preferred when a greater reduction in exacerbations is desired.
Study Strengths and Limitations: High-certainty evidence strengthens these conclusions, but the lack of direct comparisons between ICS-formoterol and ICS-SABA and limited pediatric data are notable limitations.
Future Research: Direct head-to-head trials comparing ICS-formoterol and ICS-SABA, particularly in pediatric populations, are needed to confirm these findings.
RCT: Early DOACs Safe and Non-Inferior to Delayed Initiation Post-Stroke with Atrial Fibrillation
28 Oct, 2024 | 17:52h | UTCBackground: Atrial fibrillation increases ischaemic stroke risk, and patients are prone to recurrence. Prompt anticoagulation post-stroke is critical, but optimal timing is unclear due to bleeding concerns. Guidelines often delay DOAC initiation without strong evidence.
Objective: To determine if early DOAC initiation (≤4 days) is non-inferior to delayed initiation (7–14 days) in preventing recurrent ischaemic events without increasing intracranial haemorrhage risk in patients with acute ischaemic stroke and atrial fibrillation.
Methods: In this multicentre, open-label, blinded-endpoint, phase 4 randomised controlled trial at 100 UK hospitals, 3,621 adults with atrial fibrillation and acute ischaemic stroke were randomised to early or delayed DOAC initiation. Eligibility required physician uncertainty about timing. Participants and clinicians were unmasked; outcomes were adjudicated by a masked committee. The primary outcome was a composite of recurrent ischaemic stroke, symptomatic intracranial haemorrhage, unclassifiable stroke, or systemic embolism within 90 days.
Results: Among 3,621 patients (mean age 78.5; 45% female), the primary outcome occurred in 59 patients (3.3%) in both early and delayed groups (adjusted risk difference 0.0%, 95% CI –1.1 to 1.2%). Upper confidence limit below the 2% non-inferiority margin (p=0.0003) confirmed non-inferiority. Symptomatic intracranial haemorrhage rates were similar (0.6% early vs 0.7% delayed; p=0.78). No significant differences in mortality or heterogeneity across subgroups.
Conclusions: Early DOAC initiation within 4 days is non-inferior to delayed initiation in preventing recurrent events without increasing intracranial haemorrhage risk. Findings challenge guidelines advising delayed anticoagulation and support early initiation regardless of stroke severity.
Implications for Practice: Clinicians should consider starting DOACs within 4 days post-stroke in atrial fibrillation patients. Early initiation is safe and effective, potentially improving outcomes and suggesting guidelines may need revision.
Study Strengths and Limitations: Strengths include large sample size and masked outcome adjudication. Limitations include exclusion of patients with very severe strokes and low event rates, potentially limiting detection of rare adverse events.
Future Research: Further studies should explore optimal DOAC timing within 4 days and assess safety in patients with severe strokes or extensive haemorrhagic transformation.
RCT: Granulocyte Colony-Stimulating Factor (GCSF) Enhances 90-Day Survival and Reduces Complications in Severe Alcohol-Associated Hepatitis
20 Oct, 2024 | 17:23h | UTCStudy Design and Population: This randomized trial evaluated 126 patients with severe alcohol-associated hepatitis (SAH) eligible for steroid treatment, with discriminant function scores between 32 and 90. Patients were randomized into three groups: prednisolone alone, GCSF alone, and combined GCSF plus prednisolone (GPred). Prednisolone was administered at 40 mg/day, while GCSF was given at 150-300 mcg/d for 7 days, then every third day for up to 12 doses over a month.
Main Findings: The GPred group showed significantly higher 90-day survival (88.1%) compared to prednisolone alone (64.3%, P = 0.03) and GCSF alone (78.6%). The 28-day survival was similar across groups. The GPred group also had more steroid responders by day 7 and showed greater improvements in discriminant function and MELDNa scores. Additionally, patients in the GPred group had significantly lower rates of infections, acute kidney injury, hepatic encephalopathy, and rehospitalizations.
Implications for Practice: Adding GCSF to prednisolone improves survival and reduces the risk of infections and complications in patients with severe alcohol-associated hepatitis. This combination therapy could be considered for improving outcomes in steroid-eligible patients with SAH.
Review: Endovascular Management of Acute Stroke
20 Oct, 2024 | 14:43h | UTCIntroduction: Stroke due to large vessel occlusion (LVO) remains a leading cause of disability and mortality worldwide. Endovascular therapy has revolutionized acute ischemic stroke management by enhancing recanalization rates and improving patient outcomes. This review outlines the evolution of endovascular treatments, expansion of therapeutic indications, current best practices, and ongoing research in the endovascular management of acute stroke.
Key Recommendations:
- Early Time Window Therapy (0–6 Hours): Robust evidence from randomized controlled trials demonstrates that mechanical thrombectomy significantly improves functional outcomes in patients with anterior circulation LVO presenting within 6 hours of symptom onset. Patients are selected based on moderate-to-severe neurological deficits and small infarct cores identified via imaging.
- Extended Time Window Therapy (6–24 Hours): Trials such as DAWN and DEFUSE3 have extended thrombectomy benefits to patients up to 24 hours after symptom onset. Advanced imaging techniques, like CT perfusion and MRI, identify patients with substantial penumbral tissue, indicating potential for recovery.
- Large Ischemic Core Infarcts: Recent studies (e.g., SELECT2, ANGEL-ASPECT) suggest that patients with large core infarcts can benefit from endovascular therapy, challenging previous contraindications. Individualized patient selection is crucial to balance risks and benefits.
- Basilar Artery Occlusion: New evidence supports thrombectomy for basilar artery occlusions, especially in patients with moderate-to-severe symptoms. This intervention improves outcomes in a condition historically associated with high morbidity and mortality.
- Bridging Thrombolysis: The necessity of intravenous thrombolysis before thrombectomy in patients directly admitted to endovascular centers is under debate. Meta-analyses indicate that omitting thrombolysis may not adversely affect outcomes, although it remains standard for patients at non-thrombectomy centers.
- Simplified Imaging for Patient Selection: The use of non-contrast CT and CT angiography alone has proven effective for patient selection, reducing treatment delays and expanding access to thrombectomy, particularly in resource-limited settings.
Conclusion: Advancements in endovascular therapy have markedly improved outcomes for patients with acute ischemic stroke due to LVO. Expanded treatment indications and simplified imaging protocols have broadened patient eligibility for thrombectomy. Ongoing research into adjunctive therapies and optimization of management strategies holds promise for further reducing stroke-related disability and mortality.
Cohort Study: Ondansetron Initiation Linked to Increased 10-Day Sudden Cardiac Death Risk in Hemodialysis Patients
20 Oct, 2024 | 14:05h | UTCBackground: Individuals undergoing maintenance hemodialysis have a markedly elevated risk of sudden cardiac death, attributed to structural heart disease, electrolyte imbalances, and polypharmacy. Ondansetron, a commonly used antiemetic known to prolong the QT interval, has been associated with fatal arrhythmias when administered intravenously in the general population. However, its cardiac safety profile in the hemodialysis population remains unclear.
Objective: To assess whether initiation of oral ondansetron, compared to antiemetics with lesser QT-prolonging potential, is associated with a higher 10-day risk of sudden cardiac death among patients receiving maintenance hemodialysis.
Methods: This new-user, active-comparator cohort study analyzed data from the United States Renal Data System between 2012 and 2019. A total of 119,254 patients receiving in-center hemodialysis who initiated either oral ondansetron or comparator antiemetics (promethazine, metoclopramide, or prochlorperazine) were included. Inverse probability of treatment-weighted survival models estimated adjusted hazard ratios (aHR) and risk differences (aRD), using an intention-to-treat approach with non-sudden cardiac death as a competing event.
Results: Among the patients, 64,978 (55%) initiated ondansetron, while 54,276 (45%) initiated comparator antiemetics. Ondansetron initiation was associated with a higher 10-day risk of sudden cardiac death compared to comparator drugs (aHR 1.44; 95% CI, 1.08–1.93; aRD 0.06%; 95% CI, 0.01%–0.11%). The number needed to harm was 1,688. Secondary analyses of additional cardiac outcomes, including ventricular arrhythmias and cardiovascular mortality, yielded consistent findings.
Conclusions: Initiation of oral ondansetron is associated with an increased short-term risk of sudden cardiac death among patients on maintenance hemodialysis compared to initiation of antiemetics with lesser QT-prolonging potential.
Implications for Practice: Clinicians should exercise caution when prescribing ondansetron to hemodialysis patients and consider alternative antiemetics with lower QT-prolonging risks. If ondansetron is necessary, monitoring for cardiac arrhythmias and performing electrocardiograms may be advisable to mitigate potential risks.
Study Strengths and Limitations: Strengths include a large, nationally representative cohort and an active-comparator design that minimizes confounding. Limitations involve potential residual confounding inherent in observational studies, possible misclassification of outcomes, and inability to assess dose-response relationships due to power constraints.
Future Research: Further studies are warranted to confirm these findings, elucidate the underlying mechanisms of increased cardiac risk, and evaluate the safety of ondansetron across different dosages and patient subgroups within the hemodialysis population.
Guideline: SCAI Expert Consensus on Management of STEMI Patients Undergoing Primary PCI
13 Oct, 2024 | 12:44h | UTCIntroduction: ST-elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality, requiring rapid diagnosis and timely reperfusion. While primary percutaneous coronary intervention (PCI) is the preferred reperfusion method, existing guidelines lack detailed procedural and technical recommendations for the cardiac catheterization laboratory (CCL). The Society for Cardiovascular Angiography & Interventions (SCAI) presents this expert consensus statement to provide best practices for CCL team readiness, optimal angiography and intervention techniques, management of special circumstances and anatomical subsets, and strategies to improve quality of care in STEMI patients undergoing primary PCI.
Key Recommendations:
- CCL Team Readiness:
- Prehospital notification and ECG transmission expedite care.
- Implement emergency department (ED) bypass when feasible.
- Perform a focused cardiovascular assessment prior to PCI.
- Arterial Access:
- Prefer transradial access over femoral to reduce complications.
- Use ultrasound guidance and contemporary techniques for femoral access when necessary.
- Diagnostic Assessment:
- Conduct complete coronary angiography during the index procedure.
- Measure left ventricular end-diastolic pressure (LVEDP) to guide management.
- Managing Thrombus:
- Assess thrombus burden after wire crossing.
- Use bail-out aspiration thrombectomy selectively for large thrombus burden.
- Consider parenteral or intracoronary antiplatelet agents for refractory thrombus.
- Managing No-Reflow:
- Administer intracoronary vasodilators to the distal bed.
- Enhance coronary perfusion pressure by augmenting mean arterial pressure and reducing LVEDP.
- Intracoronary Imaging:
- Encourage routine use of IVUS or OCT to guide PCI.
- Employ intracoronary imaging to investigate stent thrombosis or suspected nonatherosclerotic causes.
- Special Circumstances:
- In cardiogenic shock, perform right heart catheterization and consider mechanical circulatory support.
- After failed fibrinolysis, proceed with immediate catheterization and rescue PCI.
- In multivessel disease, complete revascularization is recommended.
- Anatomical Subsets:
- Use plaque modification techniques for calcified lesions.
- Prefer a provisional one-stent strategy in bifurcation lesions.
- Focus on restoring flow in coronary aneurysms.
- Nonatherosclerotic STEMI Causes:
- Administer intracoronary nitroglycerin to identify epicardial vasospasm.
- Manage spontaneous coronary artery dissection conservatively if flow is preserved.
- Use thrombectomy for coronary embolism.
- Investigate MINOCA with additional imaging and testing.
- Quality Improvement:
- Track all STEMI cases to assess treatment times and outcomes for continuous improvement.
Conclusion: Adherence to these recommendations is expected to enhance patient outcomes by optimizing procedural strategies, reducing complications, and improving survival in STEMI patients undergoing primary PCI.
Management of Ascites in Cirrhosis: Key Recommendations from the British Society of Gastroenterology Guidelines
12 Oct, 2024 | 18:23h | UTCIntroduction: Ascites, the pathological accumulation of fluid within the peritoneal cavity, is a common and serious complication of cirrhosis, indicating advanced liver disease and portending increased morbidity and mortality. Recognizing the need for updated clinical guidance, the British Society of Gastroenterology (BSG), in collaboration with the British Association for the Study of the Liver (BASL), has issued comprehensive guidelines. These aim to standardize the diagnosis and management of ascites in cirrhotic patients, incorporating recent advances to optimize patient outcomes.
Key Recommendations:
- Diagnostic Paracentesis: It is strongly recommended that all patients with new-onset ascites undergo diagnostic paracentesis to measure total protein concentration and calculate the serum-ascites albumin gradient (SAAG). (Quality of evidence: moderate; Recommendation: strong)
- Spontaneous Bacterial Peritonitis (SBP): Prompt diagnostic paracentesis should be performed in hospitalized patients with ascites, especially those with gastrointestinal bleeding or signs of infection, to rule out SBP. An ascitic neutrophil count >250/mm³ confirms SBP, necessitating immediate empirical antibiotic therapy tailored to local resistance patterns. (Quality of evidence: moderate; Recommendation: strong)
- Dietary Salt Restriction: Patients should restrict dietary sodium intake to no more than 5–6.5 grams per day (87–113 mmol), equivalent to a no-added-salt diet, to manage fluid accumulation effectively. (Quality of evidence: moderate; Recommendation: strong)
- Diuretic Therapy: For initial moderate ascites, spironolactone monotherapy is recommended. In cases of recurrent severe ascites, combination therapy with spironolactone and furosemide is advised. Regular monitoring for adverse events such as electrolyte imbalances and renal impairment is essential. (Quality of evidence: moderate; Recommendation: strong)
- Large Volume Paracentesis (LVP): LVP is a safe and effective treatment for refractory ascites. Informed consent is required, and routine coagulation studies or prophylactic blood product infusions before the procedure are not recommended. (Quality of evidence: moderate; Recommendation: strong)
- Use of Human Albumin Solution (HAS): After LVP exceeding 5 liters, infusion of HAS at 8 grams per liter of ascites removed is strongly recommended to prevent circulatory dysfunction. (Quality of evidence: high; Recommendation: strong)
- Transjugular Intrahepatic Portosystemic Shunt (TIPSS): TIPSS should be considered for patients with refractory ascites not responding to medical therapy, with caution exercised in patients over 70 years or those with significant comorbidities. (Quality of evidence: high; Recommendation: strong)
- Non-Selective Beta-Blockers (NSBBs): The presence of refractory ascites is not a contraindication for NSBB therapy. Patients should be closely monitored, and dose adjustments made in cases of hypotension or renal dysfunction. (Quality of evidence: moderate; Recommendation: strong)
- Palliative Care: Patients unsuitable for liver transplantation should be offered palliative care referral to focus on symptom management and quality of life improvement. Alternative interventions for refractory ascites may also be considered. (Quality of evidence: weak; Recommendation: strong)
Conclusion: Implementation of these evidence-based guidelines is expected to enhance patient care by promoting early diagnosis, preventing complications, and standardizing management strategies for ascites in cirrhosis. Adherence to these recommendations can improve clinical outcomes, reduce hospitalizations, and enhance the quality of life for affected patients.
RCT: Liberal Transfusion Strategy Reduced Unfavorable Neurological Outcomes in Acute Brain Injury
12 Oct, 2024 | 11:01h | UTCBackground: Patients with acute brain injury frequently develop anemia, and the optimal hemoglobin threshold for red blood cell transfusion in this population remains uncertain. Previous studies have shown conflicting results regarding the benefits of liberal versus restrictive transfusion strategies on neurological outcomes.
Objective: To determine whether a liberal transfusion strategy (hemoglobin threshold <9 g/dL) reduces the occurrence of unfavorable neurological outcomes at 180 days compared to a restrictive strategy (hemoglobin threshold <7 g/dL) in patients with acute brain injury.
Methods: The TRAIN trial, a multicenter, phase 3, randomized clinical trial, was conducted across 72 ICUs in 22 countries. It included patients with traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage, who had hemoglobin levels below 9 g/dL within the first 10 days post-injury. Participants were randomized to a liberal strategy (transfusion triggered by hemoglobin <9 g/dL) or a restrictive strategy (transfusion triggered by hemoglobin <7 g/dL), with primary outcomes measured by the occurrence of an unfavorable neurological outcome, defined by a Glasgow Outcome Scale Extended score of 1-5 at 180 days.
Results: Among 820 patients who completed the trial (mean age 51 years; 45.9% women), 806 had data on the primary outcome (393 liberal, 413 restrictive). The liberal group received a median of 2 units of blood (IQR, 1–3), while the restrictive group received a median of 0 units (IQR, 0–1), with an absolute mean difference of 1.0 unit (95% CI, 0.87–1.12 units). At 180 days, 62.6% of patients in the liberal group had an unfavorable neurological outcome compared to 72.6% in the restrictive group (absolute difference –10.0%; 95% CI, –16.5% to –3.6%; adjusted relative risk 0.86; P = .002). The effect was consistent across prespecified subgroups. Cerebral ischemic events were lower in the liberal group (8.8% vs 13.5%; relative risk 0.65; 95% CI, 0.44–0.97). No significant differences were observed in 28-day survival or other secondary outcomes.
Conclusions: In patients with acute brain injury and anemia, a liberal transfusion strategy resulted in a lower rate of unfavorable neurological outcomes at 180 days compared to a restrictive strategy.
Implications for Practice: A liberal transfusion threshold of 9 g/dL may improve neurological outcomes in patients with acute brain injury by reducing cerebral ischemic events. Clinicians should consider adopting a higher hemoglobin threshold for transfusion in this population, weighing the benefits against potential risks associated with transfusions, such as infection or lung injury.
Study Strengths and Limitations: Strengths include the large, multicenter international design and blinding of outcome assessors. Limitations involve the open-label nature, potential detection bias in assessing cerebral ischemic events, lack of standardized neuroprognostication, and incomplete assessment of concomitant interventions.
Future Research: Further studies are needed to confirm these findings in specific subgroups of acute brain injury, to explore optimal transfusion strategies, and to assess long-term outcomes and potential risks associated with liberal transfusion thresholds.
Umbrella Review: 5-Day Antibiotic Courses Effective for Non-ICU Community-Acquired Pneumonia or Exacerbations of COPD
6 Oct, 2024 | 17:12h | UTCBackground: Respiratory tract infections (RTIs) significantly contribute to global disease burden and antibiotic usage. Optimizing antibiotic treatment duration is crucial for antimicrobial stewardship to minimize resistance. Despite evidence supporting shorter antibiotic courses for RTIs, prolonged treatment durations persist in clinical practice.
Objective: To evaluate the current evidence base for optimal antibiotic treatment durations in RTIs and determine whether shorter courses are supported.
Methods: An umbrella review was conducted by searching Ovid MEDLINE, Embase, and Web of Science up to May 1, 2024, without language restrictions. Systematic reviews comparing antibiotic treatment durations for community-acquired pneumonia (CAP), acute exacerbations of chronic obstructive pulmonary disease (AECOPD), hospital-acquired pneumonia (HAP), acute sinusitis, and streptococcal pharyngitis, tonsillitis, or pharyngotonsillitis in adults were included. Pediatric-focused reviews were excluded. Quality assessments utilized the AMSTAR 2 tool for reviews and the Cochrane risk-of-bias tool (version 1) for randomized controlled trials (RCTs). The GRADE approach determined the overall quality of evidence.
Results: Thirty systematic reviews were included, generally of low to critically low quality. For non-ICU CAP (14 reviews), moderate-quality evidence supports a 5-day antibiotic course, with insufficient data for shorter durations. In AECOPD (eight reviews), a 5-day treatment was non-inferior to longer courses regarding clinical and microbiological cure, with similar or fewer adverse events. Evidence for non-ventilator-associated HAP is lacking. In acute sinusitis, shorter regimens appear effective, but further research is needed for patients requiring antibiotics. For pharyngotonsillitis (eight reviews), evidence supports short-course cephalosporin therapy but not short-course penicillin when dosed three times daily.
Conclusions: Evidence supports a 5-day antibiotic treatment duration for non-ICU CAP and AECOPD in clinically improving patients. Implementing this evidence in practice is essential. High-quality RCTs are needed to assess shorter durations for CAP and AECOPD, establish optimal durations for HAP and acute sinusitis, and evaluate short-course penicillin with optimal dosing in pharyngotonsillitis.
Implications for Practice: Clinicians should adopt 5-day antibiotic courses for non-ICU CAP and AECOPD in patients showing clinical improvement, aligning with antimicrobial stewardship objectives to reduce unnecessary antibiotic exposure and resistance development.
Study Strengths and Limitations: Strengths include a comprehensive search and assessment of systematic reviews and meta-analyses. Limitations involve the generally low quality of included reviews and RCTs, with many studies exhibiting unclear or high risk of bias. Heterogeneity in definitions of short-course treatment and variability in patient populations and settings were also noted.
Future Research: High-quality RCTs are required to investigate antibiotic durations shorter than 5 days for CAP and AECOPD, determine optimal treatment lengths for HAP and acute sinusitis, and assess short-course penicillin therapy with optimal dosing schedules in pharyngotonsillitis.
Summary of the review “Neuroleptic Malignant Syndrome”
6 Oct, 2024 | 16:20h | UTCIn a comprehensive review published in the New England Journal of Medicine, Wijdicks and Ropper discuss neuroleptic malignant syndrome (NMS), a rare but potentially fatal complication of antipsychotic therapy characterized by fever, muscle rigidity, and autonomic dysfunction. Given the widespread use of dopamine-blocking agents across various medical specialties, it is crucial for practicing physicians to recognize and manage this syndrome promptly to improve patient outcomes.
Key Aspects Influencing Patient Care:
- Epidemiology and Risk Factors:
- NMS occurs in approximately 0.02 to 3% of patients exposed to dopamine-blocking agents.
- Risk factors include dehydration, high doses of antipsychotics, rapid dose escalation, intramuscular administration, and prior episodes of NMS.
- Both first-generation (typical) and second-generation (atypical) antipsychotics can cause NMS, though it may be less severe with atypical agents.
- Clinical Presentation:
- Hyperthermia: Elevated temperatures often exceeding 40°C.
- Muscle Rigidity: Lead-pipe rigidity leading to rhabdomyolysis and elevated creatine kinase levels.
- Autonomic Dysfunction: Tachycardia, fluctuating blood pressure, diaphoresis.
- Altered Mental Status: Ranges from agitation to stupor or catatonia.
- Laboratory Findings: Leukocytosis, electrolyte imbalances, and signs of renal impairment.
- Diagnosis:
- Based on clinical criteria including recent exposure to dopamine antagonists and presence of key symptoms.
- Important to differentiate from serotonin syndrome, malignant hyperthermia, heat stroke, and severe catatonia.
- Management:
- Immediate Discontinuation of the offending agent.
- Supportive Care in ICU:
- Stabilize vital signs and manage autonomic instability.
- Aggressive hydration to prevent renal failure from rhabdomyolysis.
- Cooling measures for hyperthermia.
- Pharmacologic Interventions:
- Dantrolene: Reduces muscle rigidity and hyperthermia.
- Dopamine Agonists: Bromocriptine or amantadine may reverse dopamine blockade.
- Benzodiazepines: Lorazepam for sedation and muscle relaxation.
- Monitoring for Complications:
- Watch for respiratory failure, renal dysfunction, electrolyte disturbances, and cardiac arrhythmias.
- Electroconvulsive Therapy (ECT):
- Considered in refractory cases unresponsive to medical management.
- Outcome and Prognosis:
- Recovery typically occurs within 7 to 11 days with appropriate treatment.
- Mortality rates have decreased but can reach up to 15% within one year due to complications.
- Rechallenge with Antipsychotics:
- If necessary, reintroduce antipsychotics cautiously after full recovery, using low doses and slow titration.
- Prefer atypical agents and monitor closely for recurrence.
Clinical Implications:
- Early Recognition: Timely identification of NMS is critical for initiating life-saving interventions.
- Interdisciplinary Approach: Collaboration among psychiatrists, intensivists, neurologists, and other specialists enhances patient care.
- Education and Prevention:
- Educate healthcare providers about the signs and risk factors of NMS.
- Monitor patients on antipsychotics closely, especially during dose changes or when using high-potency agents.
Summary of “Dialysis for Chronic Kidney Failure: A Review”
3 Oct, 2024 | 22:46h | UTCIn their comprehensive review published in JAMA on October 2, 2024, Dr. Jennifer E. Flythe and Dr. Suzanne Watnick discuss current evidence regarding the pathophysiology, diagnosis, and management of dialysis-dependent chronic kidney failure. The article emphasizes clinical considerations that directly impact patient care, particularly in the initiation and management of dialysis therapy.
Key Aspects Influencing Patient Care
- Initiation of Dialysis
- No Specific eGFR Threshold: There is no recommended estimated glomerular filtration rate (eGFR) for starting dialysis. Decisions should be individualized, focusing on persistent uremic symptoms (e.g., nausea, fatigue), volume overload (e.g., dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia.
- Shared Decision-Making: The timing of dialysis initiation should involve a collaborative approach between clinicians and patients, considering symptoms, laboratory trends, and patient preferences.
- No Mortality Benefit from Early Initiation: A randomized clinical trial found no mortality advantage in starting dialysis at higher eGFR levels (10–14 mL/min/1.73 m²) compared to lower levels (5–7 mL/min/1.73 m²).
- Dialysis Modalities
- Hemodialysis vs. Peritoneal Dialysis: Observational data indicate no significant difference in 5-year mortality rates between the two modalities.
- Modality Selection Factors: Decisions should consider patient lifestyle, comorbid conditions, availability of home support, and resource accessibility.
- Common Complications
- Cardiovascular Risks: Cardiovascular complications, such as arrhythmias and cardiac arrest, are leading causes of death among dialysis patients.
- Infections:
- Hemodialysis: Catheter-related bloodstream infections occur at rates of 1.1 to 5.5 episodes per 1000 catheter-days.
- Peritoneal Dialysis: Peritonitis occurs at a rate of 0.26 episodes per patient-year.
- Systemic Complications: Anemia, hyperphosphatemia, hypocalcemia, and hypertension are prevalent and often require pharmacologic intervention.
- Dialysis-Related Issues: Hypotension during dialysis, muscle cramps, itching, and vascular access malfunction can hinder effective treatment.
- Management Strategies
- Anemia: Initiate intravenous iron and/or erythropoietin-stimulating agents when hemoglobin is below 10 g/dL, aiming to maintain levels between 10 and 11.5 g/dL.
- Mineral and Bone Disorders: Use dietary phosphorus restrictions and phosphorus binders; monitor and manage parathyroid hormone levels to mitigate fracture risk.
- Hypertension: Implement dietary salt restriction, adjust ultrafiltration, and prescribe antihypertensive medications, recognizing there’s no specific BP target in dialysis patients.
- Practical Considerations for Clinicians
- Medication Management: Avoid nephrotoxic agents like NSAIDs and iodinated contrast media in patients with residual kidney function. Adjust dosages for medications excreted renally.
- Symptom Control: Address common symptoms such as pruritus with appropriate therapies such as oral antihistamines and moisturizers. Difelikefalin is a new agent that can also be used.
- Patient Education: Counsel on dietary restrictions (salt, fluid, potassium) and ensure vaccinations are up to date, including hepatitis B, pneumococcal, COVID-19, and RSV vaccines.
Conclusion
For the over 540,000 patients in the U.S. receiving maintenance dialysis, individualized care plans that involve shared decision-making are crucial. Understanding when to initiate dialysis, selecting the appropriate modality, managing complications, and addressing patient-specific needs can significantly influence outcomes and quality of life.
Network Meta-Analysis: Eletriptan, Rizatriptan, Sumatriptan, and Zolmitriptan Most Effective for Acute Migraine Episodes
23 Sep, 2024 | 22:34h | UTCBackground: Migraine, a highly prevalent neurological disorder, is a leading cause of disability, especially among women aged 15 to 49. Effective acute management is critical, with current guidelines recommending non-steroidal anti-inflammatory drugs (NSAIDs) and triptans for moderate to severe episodes. However, the relative efficacy of various drug interventions remains unclear, especially with newer treatments like lasmiditan and gepants entering the market.
Objective: To evaluate and compare the efficacy and tolerability of all licensed oral drugs for the acute treatment of migraine episodes in adults.
Methods: A systematic review and network meta-analysis was conducted, including 137 randomized controlled trials (RCTs) involving 89,445 participants. The study analyzed 17 drug interventions, including NSAIDs, triptans, ditans, and gepants, and compared them with placebo. Primary outcomes included pain freedom at two hours post-dose and sustained pain freedom from two to 24 hours post-dose. Certainty of evidence was assessed using the CINeMA framework, and sensitivity analyses were conducted to confirm the robustness of the findings.
Results: All active interventions outperformed placebo for pain freedom at two hours, with odds ratios ranging from 1.73 (95% CI 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan. The most effective drugs for sustained pain freedom were eletriptan and ibuprofen. Among head-to-head comparisons, eletriptan was the most effective for pain freedom at two hours, followed by rizatriptan, sumatriptan, and zolmitriptan. Newer drugs like lasmiditan, rimegepant, and ubrogepant were less effective than the triptans and showed adverse effects like dizziness and nausea.
Conclusions: Triptans—specifically eletriptan, rizatriptan, sumatriptan, and zolmitriptan—demonstrated superior efficacy and tolerability profiles compared to newer treatments like lasmiditan and gepants. Given their efficacy, these triptans should be prioritized in acute migraine management. However, triptans are underused, and barriers to access should be addressed to ensure broader utilization. Lasmiditan and gepants may still serve as alternatives for patients contraindicated for triptans due to cardiovascular risks.
Implications for Practice: Clinicians should prioritize triptans, particularly eletriptan, rizatriptan, sumatriptan, and zolmitriptan, in managing acute migraine episodes due to their superior efficacy. Careful consideration is needed when selecting newer drugs like lasmiditan and gepants, as they may be less effective and have higher costs and adverse event risks. Cost-effectiveness and patient cardiovascular profiles should guide decision-making.
Study Strengths and Limitations: Strengths include the comprehensive inclusion of both published and unpublished data, as well as the large sample size and robust methodological framework. Limitations include moderate heterogeneity and low confidence in some comparisons due to reporting biases and imprecise treatment effects in older studies.
Future Research: Future studies should focus on re-evaluating the cardiovascular contraindications of triptans to ensure broader access. Additional research is also needed to assess the cost-effectiveness of newer treatments like lasmiditan and gepants, particularly in patients for whom triptans are unsuitable.
Summary: Perioperative Management of Patients Taking Direct Oral Anticoagulants
19 Sep, 2024 | 21:12h | UTCDirect oral anticoagulants (DOACs)—including apixaban, rivaroxaban, edoxaban, and dabigatran—are increasingly used for stroke prevention in atrial fibrillation and for treating venous thromboembolism. Effective perioperative management of DOACs is essential to minimize bleeding and thromboembolic risks during surgical and nonsurgical procedures. Below are practical recommendations focused on the perioperative management of patients taking DOACs, based on a recent JAMA review article.
Elective Surgical or Nonsurgical Procedures
Classify Bleeding Risk of Procedures:
- Minimal Risk:
- Minor dental procedures (e.g., cleaning, extractions)
- Minor dermatologic procedures (e.g., skin lesion removal)
- Cataract surgery
- Low to Moderate Risk:
- Endoscopic procedures without high-risk interventions
- Cholecystectomy
- Inguinal hernia repair
- High Risk:
- Major surgery (e.g., cancer surgery, joint replacement)
- Procedures involving neuraxial anesthesia
- Endoscopic procedures with high-risk interventions (e.g., large polyp removal)
DOAC Management Strategies:
- Minimal Bleeding Risk Procedures:
- Option 1: Continue DOACs without interruption.
- Option 2: For added safety, withhold the morning dose on the day of the procedure (especially for twice-daily DOACs like apixaban and dabigatran).
- Low to Moderate Bleeding Risk Procedures:
- Preoperative:
- Discontinue DOACs 1 day before the procedure.
- This allows approximately 2 half-lives for drug clearance.
- Postoperative:
- Resume DOACs 1 day after the procedure, ensuring adequate hemostasis.
- Preoperative:
- High Bleeding Risk Procedures:
- Preoperative:
- Discontinue DOACs 2 days before the procedure.
- This allows approximately 4-5 half-lives for drug clearance.
- Postoperative:
- Resume DOACs 2-3 days after the procedure, based on bleeding risk and hemostasis.
- Preoperative:
Evidence Supporting These Strategies:
- The PAUSE study demonstrated that standardized interruption protocols without heparin bridging result in low rates of:
- Thromboembolism: 0.2%–0.4%
- Major Bleeding: 1%–2%
Postoperative DOAC Resumption:
- Assess surgical-site hemostasis before resuming DOACs.
- Delay resumption if there is ongoing bleeding or concerns about hemostasis.
- For high bleeding risk procedures, consider a longer delay (2–3 days).
Perioperative Heparin Bridging:
- Not recommended for patients on DOACs.
- Bridging increases bleeding risk without reducing thromboembolism.
- DOACs have rapid offset and onset, making bridging unnecessary.
Special Considerations
Patients with Impaired Renal Function:
- For CrCl 30–50 mL/min:
- Dabigatran: Extend preoperative discontinuation by an additional day.
- For CrCl <30 mL/min:
- Dabigatran is contraindicated.
- For other DOACs, consider extending discontinuation to 3–4 days before surgery.
Patients Undergoing Neuraxial Anesthesia:
- Discontinue DOACs for 3 days (apixaban, edoxaban, rivaroxaban) or 4 days (dabigatran) before the procedure.
- Minimizes risk of spinal or epidural hematoma.
Dental Procedures:
- Generally safe to continue DOACs.
- For added safety:
- Omit or delay the dose on the day of the procedure.
- Employ local hemostatic measures (e.g., tranexamic acid mouthwash).
Endoscopic Procedures:
- Low-risk procedures (e.g., diagnostic endoscopy without biopsy):
- Follow standard DOAC interruption for low to moderate bleeding risk.
- High-risk procedures (e.g., polypectomy of large polyps):
- Extend DOAC discontinuation by an additional day pre- and post-procedure.
Patients Unable to Resume Oral Medications Postoperatively:
- Use prophylactic low-molecular-weight heparin (LMWH) until oral intake is possible.
- Avoid therapeutic-dose LMWH due to bleeding risk.
Emergent, Urgent, or Semiurgent Procedures
Risks:
- Higher bleeding risk: Up to 23%
- Thromboembolism risk: Up to 11%
Management Strategies:
- Assess Time Since Last DOAC Dose:
- If within 48 hours, consider that significant anticoagulant effect may persist.
- Laboratory Testing (if available):
- DOAC Level Testing:
- ≥50 ng/mL: Consider using reversal agents.
- <50 ng/mL: May proceed without reversal agents.
- DOAC Level Testing:
- Use of Reversal Agents:
- For Dabigatran:
- Idarucizumab (5 g IV)
- For Factor Xa Inhibitors (apixaban, rivaroxaban, edoxaban):
- Andexanet alfa (dosing based on last dose timing and amount)
- Prothrombin Complex Concentrates (PCCs): If andexanet alfa is unavailable or contraindicated.
- For Dabigatran:
- Proceeding Without Testing:
- If testing is unavailable and last DOAC dose was within 48 hours, consider reversal agents.
- If >48 hours since last dose, may proceed without reversal.
Considerations:
- Reversal agents are expensive and may carry thrombotic risks.
- Use should be judicious, weighing risks and benefits.
- Consult hematology or thrombosis experts when possible.
Key Takeaways
- Elective Procedures:
- Utilize standardized protocols based on procedural bleeding risk.
- Routine preoperative DOAC level testing is unnecessary.
- Avoid heparin bridging.
- Emergent/Urgent Procedures:
- Reversal agents may be appropriate when significant DOAC levels are present.
- Decision to use reversal agents should consider bleeding risk, time since last dose, and availability of DOAC level testing.
- Patient Communication:
- Ensure patients understand the plan for DOAC interruption and resumption.
- Provide clear instructions regarding timing and dosing.
- Interdisciplinary Coordination:
- Collaborate with surgical teams, anesthesiologists, and pharmacists.
- Use electronic medical records and clinical decision support tools to enhance communication.
Conclusion
By applying standardized perioperative management protocols, clinicians can effectively balance the risks of bleeding and thromboembolism in patients taking DOACs who require surgical or nonsurgical procedures. These strategies simplify decision-making, avoid unnecessary interventions like heparin bridging, and promote patient safety.