Critical Care

Review: Enteral Nutrition in Hospitalized Adults

21 Apr, 2025 | 13:23h | UTC

Introduction:
This is a summary of a new review published in the New England Journal of Medicine discussing the rationale, evidence, and practical considerations for administering enteral nutrition to hospitalized adults. The main objective is to provide guidance on identifying patients with disease-related malnutrition, initiating enteral feeding, and differentiating strategies for critically ill versus non–critically ill patients who require nutritional support.

Key Recommendations:

1. Identify Malnutrition Early:

   • Screen all hospitalized patients for malnutrition (e.g., using the Malnutrition Screening Tool) on admission.

   • Confirm high-risk cases with a comprehensive nutrition assessment (e.g., GLIM or AAIM criteria).

2. Optimize Oral Intake First:

   • Whenever possible, use strategies such as dietary modifications and oral nutritional supplements before initiating enteral nutrition.

   • Implement medical nutrition therapy with the goal of meeting at least 75% of estimated energy and protein requirements orally; consider EN/PN if this goal is not reached within approximately 5 days.

3. Initiate Enteral Nutrition if Oral Intake Is Inadequate:

   • Consider enteral feeding for patients who fail to meet energy and protein goals and do not have contraindications (e.g., intestinal obstruction, severe shock, intestinal ischemia, or active gastrointestinal hemorrhage).

   • Dosing considerations differ significantly by patient population and clinical phase:

     • In critical illness (acute phase, first week), evidence suggests potential harm from early full caloric feeding or high protein doses (e.g., ≥2.2 g/kg/day), particularly in patients with shock or organ failure. A more “trophic” or hypocaloric approach (<70% of estimated energy needs) is often appropriate, especially if there is acute kidney injury or multiorgan dysfunction.

     • In contrast, for non–critically ill medical or surgical patients at risk of malnutrition, studies show that underfeeding is associated with worse outcomes, making it important to achieve closer to full nutritional requirements sooner.

4. Select the Appropriate Route and Timing:

   • For short-term use (up to 6 weeks), place a nasoenteric tube.

   • For anticipated long-term support, consider a gastrostomy or jejunostomy tube.

   • Postpyloric feeding (duodenal or jejunal) may reduce aspiration risk in certain patients.

5. Adjust Dose According to Clinical Phase:

   • In the ICU acute phase, avoid early full feeding; consider “trophic” or hypocaloric regimens.

   • As the patient recovers from critical illness, gradually increase caloric and protein delivery to meet estimated needs if tolerated, though exact targets remain under investigation.

   • In non–critically ill patients, aim to meet estimated requirements unless specific clinical issues necessitate lower delivery.

6. Mitigate Complications:

   • Use continuous pump-assisted infusion, though volume-based feeding can improve goal attainment.

   • Monitor regularly for refeeding syndrome (e.g., hypophosphatemia, hypokalemia, hypomagnesemia) and correct electrolyte abnormalities.

   • Employ glucose management strategies to avoid hyperglycemia.

7. Coordinate Interdisciplinary Care:

   • Engage dietitians, nursing staff, pharmacists, and other professionals to tailor therapy and optimize patient acceptance.

   • Involve patients in shared decision-making, particularly regarding personal values and treatment goals.

Conclusion:
These recommendations underscore enteral nutrition’s essential role in preventing and treating disease-related malnutrition. However, the direct impact on major outcomes (e.g., mortality, complications) varies by patient population, feeding strategy, and timing. In critically ill patients, especially during the first week of ICU care, lower-dose or “trophic” enteral feeding may be safer, whereas non–critically ill patients generally benefit from achieving nutritional targets more fully. Our understanding of optimal feeding approaches continues to evolve, particularly with regard to feeding dose during different phases of illness and recovery.

Reference:
Gramlich L, Guenter P. Enteral Nutrition in Hospitalized Adults. New England Journal of Medicine. 2025;392:1518-1530. DOI: https://doi.org/10.1056/NEJMra2406030

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2025 ACC/AHA/ Guideline for the Management of Patients With Acute Coronary Syndromes

3 Mar, 2025 | 18:02h | UTC

Introduction:

This summary highlights the key points from the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Clinical Practice Guideline on the management of acute coronary syndromes (ACS). It covers both ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation ACS (NSTE-ACS), emphasizing timely diagnosis, reperfusion strategies, risk stratification, and secondary prevention. The primary aim is to help clinicians provide evidence-based and up-to-date care to reduce mortality, complications, and long-term adverse outcomes in patients with ACS.

Key Recommendations:

• Early and Accurate Diagnosis

  • Obtain and interpret a 12-lead ECG within 10 minutes of first medical contact in suspected ACS.
  • Use high-sensitivity troponin testing to accelerate ruling in/out myocardial infarction.

• Reperfusion in STEMI

  • Primary percutaneous coronary intervention (PPCI) is the preferred strategy if it can be performed within 90 minutes (or 120 minutes for transfers).
  • In patients with anticipated long delays, fibrinolytic therapy is recommended if there are no contraindications and the patient presents within 12 hours of symptom onset.

• Routine Invasive vs. Selective Invasive Strategy in NSTE-ACS

  • Patients at intermediate or high ischemic risk benefit from an invasive strategy during hospitalization.
  • Low-risk patients may undergo a selective invasive approach, incorporating noninvasive testing to guide the need for angiography.

• Multivessel Coronary Artery Disease Management

  • For hemodynamically stable STEMI patients with nonculprit lesions, complete revascularization (either during the index procedure or staged) lowers future events.
  • In NSTE-ACS, complete revascularization decisions (PCI vs. CABG) depend on anatomical complexity and comorbidities.

• Antithrombotic Therapy

  • Initiate dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor (ticagrelor or prasugrel preferred over clopidogrel for most) for at least 12 months in patients without high bleeding risk.
  • To reduce bleeding risk in patients with ACS several strategies are available:
    a) in patients at risk for gastrointestinal bleeding, a proton pump inhibitor is recommended;
    b) in patients who have tolerated dual antiplatelet therapy with ticagrelor, transition to ticagrelor monotherapy is recommended ≥1 month after PCI;
    c) in patients who require long-term anticoagulation, aspirin discontinuation is recommended 1 to 4 weeks after PCI with continued use of a P2Y12 inhibitor (preferably clopidogrel).

• Parenteral Anticoagulation

  • All ACS patients should receive an anticoagulant (e.g., unfractionated heparin, low-molecular-weight heparin, bivalirudin) depending on the clinical scenario and planned strategy (PCI, CABG, or medical management).

• Lipid Management

  • High-intensity statin therapy is recommended in all ACS patients.
  • Add a nonstatin agent (e.g., ezetimibe, PCSK9 inhibitor) if LDL cholesterol remains ≥70 mg/dL on maximally tolerated statin.

• Heart Failure and Cardiogenic Shock

  • In acute MI with cardiogenic shock, immediate revascularization of the culprit lesion is indicated.
  • Selected patients with STEMI-related cardiogenic shock may benefit from a short-term microaxial flow pump if they fit specific criteria; close attention to vascular complications and renal failure is required.

• In-Hospital Care and Complications

  • Use telemetry for rhythm monitoring in unstable patients and evaluate left ventricular ejection fraction prior to discharge.
  • Mechanical complications (e.g., ventricular septal rupture) require rapid surgical consultation; short-term mechanical circulatory support devices may be a bridge to surgery.

• Secondary Prevention and Discharge

  • Refer all patients to a cardiac rehabilitation program to reduce rehospitalizations and improve functional status. A home-based program is acceptable when center-based options are not feasible.
  • Repeat lipid panel 4 to 8 weeks postdischarge to confirm adequate LDL-lowering.
  • Annual influenza vaccination is recommended to reduce cardiovascular events and mortality.
  • Consider low-dose colchicine in certain post-ACS patients to reduce the risk of recurrent ischemic events if there are no contraindications.
  • Based on one trial, red blood cell transfusion to maintain hemoglobin of 10 g/dL may be reasonable in patients with ACS and acute or chronic anemia who are not actively bleeding.

Conclusion:
Adherence to these recommendations can significantly improve in-hospital and postdischarge outcomes for patients with acute coronary syndromes. By focusing on rapid identification, prompt reperfusion, tailored antithrombotic therapies, aggressive risk factor modification, and ongoing follow-up (including cardiac rehabilitation), clinicians can lower morbidity, mortality, and readmissions. The guideline also underscores the need to balance bleeding and ischemic risks, use high-intensity lipid-lowering strategies, and provide a structured discharge plan for long-term secondary prevention.

Reference:
Rao SV, O’Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology. In Press, Corrected Proof. Available online 27 February 2025. DOI: https://doi.org/10.1016/j.jacc.2024.11.009

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Systematic Review: Shorter Antibiotic Courses Often Prove Non-Inferior for Common Bacterial Infections

3 Feb, 2025 | 10:00h | UTC

Background: The overuse of antibiotics contributes significantly to the global rise in antimicrobial resistance (AMR). Shorter antibiotic treatment courses have gained traction as an important antimicrobial stewardship intervention. They can potentially reduce drug-related side effects, healthcare costs, and selection pressure favoring resistant pathogens. This review synthesizes findings from randomized controlled trials (RCTs) on antibiotic duration across various common bacterial infections—including respiratory tract, genitourinary, skin and soft tissue, bone/joint, and intra-abdominal infections—to inform practical, day-to-day clinical decision-making.

Objective:

1. To assess the comparative efficacy of short- versus long-course antibiotic therapy for frequent bacterial infections.
2. To highlight key evidence gaps, particularly for severe infections, critically ill populations, and low- to middle-income settings.
3. To propose practical treatment durations in light of current guidelines and study outcomes.

Methods:

• Comprehensive search of MEDLINE and Embase through July 2024 (PROSPERO 2021, CRD42021276209).
• Inclusion: RCTs that compared differing antibiotic durations for bacterial infections or perioperative prophylaxis, reporting clinical cure, relapse, or mortality.
• Exclusion: Non-bacterial infections (viral/fungal), pilot studies, non-randomized designs.
• Data extraction: Patient demographics, infection type, interventions, outcomes, adherence, and risk-of-bias assessment per the RoB 2 tool.
• Guideline review: Major international guidelines (e.g., IDSA, NICE, WHO) were examined to contextualize trial findings.

Results:

• A total of 315 RCTs were included; 85% concluded no difference, non-inferiority, or equivalence of shorter compared with longer antibiotic courses.
• Shorter therapy (often 5–7 days) is well-supported for uncomplicated bacterial sinusitis, community-acquired pneumonia (CAP), simple urinary tract infections (UTIs), cellulitis, and intra-abdominal infections with adequate surgical source control.
• Evidence for reducing duration in severe infections (e.g., bloodstream infections, ventilator-associated pneumonia caused by non-fermenting Gram-negative bacilli) or in critically ill populations remains limited.
• Only 7% of RCTs involved intensive care unit (ICU) patients, and 14% were conducted in low- or middle-income countries.
• Methodologically, 15% of trials posed a low risk of bias; however, non-adherence to assigned durations was common (median 11% per study). Very few trials tracked emergence of resistant organisms through follow-up cultures.

Key findings:

1. Acute GAS Pharyngotonsillitis:
   10 days of penicillin V or amoxicillin remains the conventional standard to ensure microbiological eradication and minimize rheumatic fever risk. While 5 days of azithromycin may be used in macrolide-responsive settings, it is not preferred as first-line therapy due to broader-spectrum activity and limited evidence for preventing complications, particularly in high-risk populations.
2. Community-Acquired Pneumonia (CAP):
   • Outpatient adults with mild to moderate CAP typically improve with 5 days of appropriate therapy (e.g., amoxicillin, doxycycline, or a macrolide), provided patients show clinical stability.
   • Severe CAP or complicated presentations (e.g., MRSA, Pseudomonas, multi-lobar involvement) may need 7–10 days or until clinical stability is achieved.
3. Acute Bacterial Sinusitis (Adults):
   • 5–7 days of amoxicillin/clavulanate or other first-line agents usually suffice if the diagnosis is certain.
4. Genitourinary Infections:
   • Uncomplicated Cystitis (Non-Pregnant Women):
     • 3–5 days of nitrofurantoin or trimethoprim/sulfamethoxazole is often adequate, reflecting strong RCT support.
   • Pyelonephritis or Complicated UTIs (e.g., in men, catheter-associated):
     • While some RCTs show 7 days can be as effective as 14 days in afebrile males with mild UTI, a trial in febrile males demonstrated inferior outcomes with shorter courses. Clinicians should exercise caution in febrile or higher-risk cases.
5. Skin and Soft Tissue Infections (e.g., Cellulitis):
   • 5–6 days of effective oral therapy is sufficient for uncomplicated cellulitis if there is marked clinical improvement by Day 5.
   • For recurrent abscesses or complicated scenarios, duration may need to be extended or individualized.
6. Bone and Joint Infections:
   • 6 weeks is often sufficient for vertebral osteomyelitis in stable patients.
   • For prosthetic joint infections with retained hardware, 6 weeks of therapy was inferior to 12 weeks in a key trial, necessitating individualized duration based on surgical management.
7. Intra-Abdominal Infections:
   • With adequate source control, 4–5 days of antibiotics commonly yields outcomes on par with extended courses.
   • Longer therapy (≥7 days) may be needed when abscesses are not fully drained or in immunocompromised patients.
8. Perioperative Prophylaxis:
   • A single preoperative dose (possibly repeated if surgery is prolonged or blood loss is excessive) is sufficient in most procedures.
   • Continuing prophylaxis beyond 24 hours rarely provides additional benefit and may increase adverse events.

Conclusions: Numerous well-conducted RCTs support shorter antibiotic courses for many common bacterial infections. Nonetheless, high-quality data are sparse for severe or complex infections, pediatric populations with significant comorbidities, and low-resource settings. Clinicians should tailor antibiotic duration to the infection type, disease severity, patient factors, and local resistance patterns—while remaining cognizant that shorter courses can safely balance efficacy, safety, and stewardship aims in many cases.

Study Strengths and Limitations:

• Strengths: Large volume of RCTs, broad infection scope, and inclusion of diverse study designs. Substantial evidence supports shortening antibiotic regimens for multiple common infections.
• Limitations: Underrepresentation of severe, ICU-level infections, children with serious comorbidities, and low-resource settings. High variation in diagnostic criteria, antibiotic choices, and adherence monitoring. Many trials reported low event rates, posing potential non-inferiority bias.

Future Research:

• Well-powered RCTs focusing on severe infections (e.g., MDR Gram-negative bloodstream infections, staphylococcal bacteremia, ventilator-associated pneumonia with resistant pathogens).
• Trials in low- and middle-income countries with robust microbiological and economic assessments.
• Studies using adaptive designs and validated biomarkers to refine duration–response relationships and detect shifts in AMR at the population level.

Reference: Mo Y, Tan WC, Cooper BS. Antibiotic duration for common bacterial infections—a systematic review. JAC-Antimicrobial Resistance. 2025;7(1):dlae215. DOI: https://doi.org/10.1093/jacamr/dlae215

 

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Review: Type 2 Myocardial Infarction

29 Jan, 2025 | 10:00h | UTC

Introduction: Type 2 myocardial infarction (MI) is defined by an imbalance in myocardial oxygen supply and demand without atherothrombosis, though it may involve non-atherothrombotic coronary pathologies (e.g., coronary embolism, vasospasm, spontaneous dissection). Challenges in diagnosis and treatment arise from its heterogeneous aetiologies (e.g., sepsis, hypoxia, arrhythmias, or coronary emboli) and frequent overlap with underlying coronary artery disease (CAD). No approaches to investigation or treatments have yet been shown to definitively improve outcomes, and most recommendations remain theoretical strategies in need of validation.

Key Recommendations:

1. Identify and Correct Underlying Triggers:
   • Recognize that Type 2 MI often occurs in the context of acute illness (e.g., sepsis, hypoxia, anemia, or tachyarrhythmias).
   • Address precipitating factors (e.g., treat infection, restore blood pressure, correct anemia) to reduce further myocardial ischemia.
2. Distinguish from Type 1 MI When Uncertain:
   • Use intracoronary imaging (OCT/IVUS) primarily to exclude plaque rupture or thrombosis if clinically indicated, especially when symptoms and ECG changes persist, recognizing that its utility in routine practice for Type 2 MI is not yet proven.
   • Carefully re-evaluate patients who remain unstable or have recurrent symptoms after correction of potential triggers, as up to 5% of cases may be reclassified as Type 1 MI.
3. Risk Stratification and Etiology-Specific Prognosis:
   • Evaluate the likelihood of obstructive coronary artery disease, which is present in ~68% of Type 2 MI cases (e.g., DEMAND-MI study), particularly in older patients or those with risk factors.
   • Perform echocardiography to identify left ventricular dysfunction or valvular abnormalities.
   • Recognize that patients with Type 2 MI due to hypoxia or anemia have approximately double the 1-year mortality risk compared to those with tachyarrhythmia-triggered events.
   • Note that cardiovascular event rates can be similar to those in Type 1 MI, suggesting that future risk is at least as high.
4. Consider Secondary Prevention in the Context of Limited Evidence:
   • If coronary atherosclerosis is confirmed, single antiplatelet therapy and high-intensity lipid-lowering therapy may be considered; however, there are no dedicated trials validating these approaches exclusively in Type 2 MI.
   • For patients with confirmed left ventricular dysfunction and signs of heart failure, adapt guideline-directed medical therapy carefully, paying close attention to hemodynamic stability.
5. Monitor Long-Term Outcomes and Address Comorbidities:
   • Recognize that patients with Type 2 MI have poor overall prognosis and high rates of non-cardiovascular mortality, yet they also face substantial cardiovascular risk.
   • Manage chronic comorbidities aggressively (e.g., hypertension, diabetes, dyslipidemia) to minimize recurrent ischemic events.
   • Follow up with echocardiographic or other imaging evaluations where indicated, particularly for patients whose clinical course suggests underlying structural disease.

Conclusion:
Type 2 MI presents significant challenges due to its heterogeneous subtypes (e.g., coronary embolism, spontaneous coronary artery dissection, systemic hypoxia) and frequent diagnostic reclassification. While evidence-based guidance remains limited and no proven interventions have definitively improved outcomes, thorough clinical assessment, targeted imaging to rule out Type 1 MI, and individualized management of comorbidities can potentially improve patient care in this complex condition.

Reference:
Chapman AR, Taggart C, Boeddinghaus J, Mills NL, Fox KAA. Type 2 myocardial infarction: challenges in diagnosis and treatment. European Heart Journal. Published 10 December 2024. DOI: https://doi.org/10.1093/eurheartj/ehae803

 

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RCT: Sodium Zirconium Cyclosilicate Improves Spironolactone Uptitration in HFrEF but Raises Concern for Increased HF Events

28 Jan, 2025 | 10:00h | UTC

Background: Hyperkalemia remains a major barrier to optimal use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure and reduced ejection fraction (HFrEF). While MRAs significantly reduce morbidity and mortality, real-world data show that fears surrounding hyperkalemia often lead to MRA down-titration or discontinuation. Sodium zirconium cyclosilicate (SZC), a newer oral potassium binder, has shown promise in managing hyperkalemia. However, its impact on MRA optimization and clinical outcomes in HFrEF has not been fully established.

Objective: To determine whether SZC can enable optimal dosing of spironolactone (≥25 mg/day) by preventing hyperkalemia in patients with symptomatic HFrEF, and to assess potential effects on heart failure outcomes.

Methods: This prospective, double-blind, randomized-withdrawal trial (REALIZE-K) enrolled adult patients with left ventricular ejection fraction ≤40% (NYHA class II-IV), on guideline-directed medical therapy but not on a full-dose MRA due to either prevalent hyperkalemia (serum potassium [K⁺] 5.1-5.9 mEq/L) or high hyperkalemia risk. During an open-label run-in, spironolactone was up-titrated (target 50 mg/day), and participants with hyperkalemia received SZC. Only those who achieved normokalemia (3.5-5.0 mEq/L) on spironolactone ≥25 mg/day continued into a 6-month randomized-withdrawal phase (SZC vs placebo). The primary endpoint was maintenance of normokalemia while on ≥25 mg/day spironolactone without rescue therapy for hyperkalemia. Key secondary outcomes included the time to first hyperkalemia event, time to spironolactone dose reduction/discontinuation due to hyperkalemia, and changes in health-related quality of life (Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score).

Results: A total of 203 participants were randomized (SZC: n=102; placebo: n=101). SZC significantly increased the proportion of participants who maintained normokalemia on ≥25 mg/day spironolactone (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; p<0.001). Rates of hyperkalemia were also lower with SZC (HR: 0.51; 95% CI: 0.37-0.71; p<0.001), and fewer patients required spironolactone down-titration or discontinuation (HR: 0.37; 95% CI: 0.17-0.73; p=0.006). There was no difference in KCCQ-Clinical Summary Score between groups (p=0.72). Notably, more participants in the SZC arm had adjudicated heart failure events (10 vs 2 in placebo) over the 6-month period, although the trial was not powered to detect differences in clinical outcomes.

Conclusions: In patients with symptomatic HFrEF and prevalent or incident hyperkalemia, sodium zirconium cyclosilicate (SZC) successfully enabled higher spironolactone doses by maintaining potassium levels in the normal range. However, the increased rate of heart failure (HF) events in the SZC group raises concern, particularly given the study’s limited power for clinical outcomes and baseline imbalances favoring higher HF risk in the SZC group (older age, lower eGFR, higher NT-proBNP). Although these findings do not establish a definitive causal relationship, they underscore a possible risk of fluid retention and the importance of cautious use in higher-risk populations. Larger, event-driven trials are crucial to confirm whether SZC-related sodium exchange may exacerbate HF decompensation despite the benefits of more effective MRA therapy.

Implications for Practice: SZC offers clinicians a means to sustain or escalate spironolactone dosing in hyperkalemia-prone HFrEF patients who would otherwise face MRA discontinuation. Still, the unexpected signal of increased HF events highlights the need for vigilant patient selection, fluid status monitoring, and regular follow-up. Clinicians should balance the advantages of maintaining guideline-recommended MRA doses against potential costs, the patient’s baseline HF severity, and possible sodium retention. Individualized care, particularly in older patients or those with high NT-proBNP levels, remains critical until more robust outcome data are available.

Study Strengths and Limitations: Strengths include strict definitions of hyperkalemia, a rigorous protocol for titrating spironolactone and SZC, and high rates of concurrent guideline-directed therapies. Limitations encompass the modest sample size, short follow-up period, and imbalance in baseline risk factors favoring the placebo group. Also, the study was not powered for major clinical events, limiting interpretability of the heart failure outcome signals.

Future Research: Further large-scale, long-term investigations are needed to clarify whether the higher incidence of HF events seen with SZC reflects underlying population differences or a genuine treatment-related risk. Such studies should prioritize hard clinical endpoints (eg, HF hospitalization, cardiovascular mortality), capture real-world tolerability data, and incorporate cost-effectiveness analyses. Research into the mechanisms of sodium exchange in compromised HF patients may also help identify subgroups that stand to gain the most from potassium-binding strategies or, conversely, experience undue risk.

Reference: Kosiborod MN, Cherney DZI, Desai AS, et al. “Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients With Heart Failure.” Journal of the American College of Cardiology. 2025; DOI: https://doi.org/10.1016/j.jacc.2024.11.014

 

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Multidrug-resistant Gram-negative bacterial infections: Key Updates and Practical Strategies

25 Jan, 2025 | 22:53h | UTC

Introduction: This summary highlights essential points from a recent review in The Lancet addressing multidrug-resistant Gram-negative bacterial (MDR-GNB) infections. It discusses the global epidemiology, diagnostic advances, and therapeutic approaches, aiming to guide clinicians in managing these difficult-to-treat pathogens, which include resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

Key Recommendations:

1. Use Rapid Diagnostics to Guide Therapy
   • Employ molecular tests (e.g., multiplex PCR) to detect resistance genes quickly and facilitate targeted treatment.
   • Consider phenotypic assays (e.g., CarbaNP, carbapenemase inactivation method) and MALDI-TOF for rapid organism identification and mechanism-specific information.
2. Optimize Antibiotic Selection Based on Resistance Mechanisms
   • AmpC-Producing Enterobacterales (e.g., Enterobacter spp.): Use cefepime if in vitro susceptibility is confirmed.
   • ESBL-Producing Enterobacterales: Carbapenems (e.g., meropenem) remain the mainstay for serious infections.
   • Carbapenem-Resistant Enterobacterales (CRE): Use novel β-lactam/β-lactamase inhibitor agents (e.g., ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam) based on specific carbapenemase mechanisms. For metallo-β-lactamase producers, consider aztreonam plus ceftazidime–avibactam or future co-formulations (e.g., aztreonam–avibactam).
   • DTR-Pseudomonas aeruginosa: Ceftolozane–tazobactam is preferred if active in vitro. Ceftazidime–avibactam or imipenem–relebactam may also be options depending on local susceptibility data.
   • Carbapenem-Resistant Acinetobacter baumannii (CRAB): High-dose sulbactam combinations (e.g., sulbactam–durlobactam) were studied in combination with imipenem–cilastatin during trials; further data are needed to clarify optimal clinical use.
3. Consider Non-Antibiotic Modalities for Refractory Cases
   • Investigational therapies—such as bacteriophages and antivirulence agents—are under clinical evaluation.
   • Fecal microbiota transplantation has shown variable decolonization efficacy in small studies, and randomized trials have yielded limited or inconclusive results.
4. Emphasize Antimicrobial Stewardship and Infection Control
   • Restrict newer agents to cases where standard treatments have failed or resistance patterns require them.
   • Maintain rigorous infection control practices (e.g., contact precautions, hand hygiene, isolation measures) to reduce nosocomial spread of MDR-GNB.
   • Observational data suggest shorter antibiotic courses (7–10 days) might be adequate in select cases, but robust clinical trial evidence is still pending.

Conclusion:
By combining rapid diagnostics, judicious use of existing and novel antibiotics, and robust infection prevention measures, clinicians can significantly improve outcomes for patients with MDR-GNB infections. However, access to advanced diagnostics and new therapies remains limited in many regions, and further clinical trials are needed to determine optimal treatment and duration strategies. Early mechanism-focused detection and targeted therapy enhance clinical success, reduce toxicity, and help preserve the efficacy of newly approved agents.

Reference:
Macesic N, Uhlemann A-C, Peleg AY. Multidrug-resistant Gram-negative bacterial infections. The Lancet. 2025;405(10474):257-272. DOI: https://doi.org/10.1016/S0140-6736(24)02081-6

 

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2024 ACC/AHA Guideline for the Management of Lower Extremity Peripheral Artery Disease

21 Jan, 2025 | 12:44h | UTC

Introduction:
This summary highlights key points from the 2024 ACC/AHA guideline on managing patients with lower extremity peripheral artery disease (PAD). It addresses diagnosis, risk stratification, and treatment strategies to reduce major adverse cardiovascular events (MACE) and major adverse limb events (MALE), focusing on four clinical subsets of PAD—asymptomatic PAD, chronic symptomatic PAD, chronic limb-threatening ischemia (CLTI), and acute limb ischemia (ALI). Its overarching goal is to optimize cardiovascular risk reduction, preserve limb function, and improve quality of life (QOL).

Key Recommendations:

1. Clinical Assessment and Diagnosis
   • Perform a thorough history and physical examination in patients at risk of PAD (e.g., older adults, those with diabetes, hypertension, dyslipidemia, smokers, or known atherosclerosis).
   • Measure the ankle-brachial index (ABI) to establish the diagnosis of PAD; use toe-brachial index (TBI) for patients with noncompressible arteries.
   • Obtain imaging (e.g., duplex ultrasound, CT angiography, MR angiography) when planning revascularization or in cases with inconclusive ABI.
2. Risk Factor Management (Guideline-Directed Medical Therapy)
   • Antiplatelet and Antithrombotic Therapy:
     • Recommend single antiplatelet therapy (e.g., aspirin or clopidogrel) for symptomatic PAD to reduce MACE.
     • Consider low-dose rivaroxaban (2.5 mg twice daily) plus low-dose aspirin in patients at low bleeding risk to reduce MALE.
   • Lipid-Lowering Therapy:
     • Initiate high-intensity statin therapy in all patients with PAD to reduce cardiovascular and limb events.
     • Add ezetimibe or a PCSK9 inhibitor if LDL-C levels remain above target (≥70 mg/dL).
   • Blood Pressure Control:
     • Target a systolic blood pressure <130 mm Hg in patients with PAD; ACE inhibitors or angiotensin-receptor blockers can further reduce cardiovascular risk.
   • Diabetes Management:
     • Optimize glycemic control, especially in CLTI; newer agents (e.g., SGLT2 inhibitors, GLP-1 receptor agonists) can reduce cardiovascular risk in PAD with type 2 diabetes.
   • Smoking Cessation:
     • Strongly advise cessation of all forms of tobacco and nicotine; offer pharmacotherapy (e.g., varenicline, bupropion, nicotine replacement) and behavioral counseling.
3. Exercise Therapy
   • Supervised Exercise Therapy (SET):
     • A cornerstone of care for patients with claudication to improve walking performance and quality of life.
     • Generally performed 3 times per week for at least 12 weeks in a supervised setting (e.g., cardiac rehab facility).
   • Structured Community-Based (Home-Based) Programs:
     • Include regularly prescribed walking regimens, with periodic clinical follow-up and coaching to promote adherence.
4. Revascularization for Chronic Symptomatic PAD
   • Initial Approach:
     • Offer revascularization (endovascular, surgical, or hybrid) if patients have functionally limiting claudication that fails to improve with medical therapy and structured exercise.
   • Endovascular vs. Surgical:
     • Select a strategy based on lesion characteristics, availability of adequate vein conduit, and patient comorbidities.
     • Combining revascularization with supervised exercise generally yields better functional outcomes.
   • Common Femoral Disease:
     • Surgical endarterectomy remains a highly durable option.
     • Endovascular approaches can be considered for select cases, particularly where surgical risk is high or anatomy is favorable.
5. Management of Chronic Limb-Threatening Ischemia (CLTI)
   • Team-Based Care:
     • Collaborate with vascular specialists, podiatrists, wound-care experts, and other clinicians for optimal outcomes.
   • Revascularization Goals:
     • Prevent amputation, heal wounds, and reduce rest pain.
     • Both endovascular and surgical methods can be effective; selection depends on anatomy, available vein conduit, and patient risk profile (e.g., the BEST-CLI and BASIL-2 trials guide decisions).
   • Adjunctive Wound Care:
     • Use local wound management (e.g., debridement, negative pressure therapy, offloading) to facilitate healing.
     • Treat infection aggressively; urgent revascularization plus antibiotics is essential.
   • Pressure Offloading:
     • Custom footwear and casts/shoes reduce plantar pressure and help prevent or heal foot ulcers.
6. Acute Limb Ischemia (ALI)
   • Immediate Recognition:
     • Suspect ALI in patients with sudden onset of pain, pallor, pulselessness, paresthesia, and paralysis.
     • Determine limb viability (categories I–III) rapidly.
   • Treatment:
     • Begin anticoagulation (e.g., IV unfractionated heparin) unless contraindicated.
     • Urgent revascularization (surgical embolectomy, catheter-directed thrombolysis, or mechanical thrombectomy) for salvageable limbs.
     • Monitor for compartment syndrome and consider fasciotomy if needed.
7. Preventive Foot Care
   • Educate patients on self-inspection, daily hygiene, and protective footwear.
   • Screen regularly for high-risk conditions (neuropathy, calluses, deformities, infection).
   • Promptly address any foot lesions to avoid progression to ulceration, infection, or gangrene.
8. Longitudinal Follow-Up
   • Schedule regular visits to monitor:
     • Cardiovascular risk factor control (lipids, blood pressure, glycemic targets, smoking).
     • Lower extremity symptoms, functional status, and foot health.
     • Need for repeat ABI, duplex ultrasound, or imaging after revascularization to detect restenosis.
   • Reinforce adherence to structured exercise, medication regimens, and foot care strategies.

Conclusion:
These recommendations underscore the importance of personalized, multidisciplinary care that addresses both cardiovascular and limb-related outcomes in patients with lower extremity PAD. A combination of comprehensive risk-factor modification, supervised or structured exercise programs, and strategic use of revascularization can significantly reduce the risk of major limb loss, improve symptoms, and enhance QOL. Ongoing follow-up is critical to detect disease progression, optimize therapy, and maintain patient engagement in preventative care.

Reference:
2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024; DOI: https://doi.org/10.1161/CIR.0000000000001251

 

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Management of Cervical Artery Dissection: Key Points From the AHA Scientific Statement

21 Jan, 2025 | 11:05h | UTC

Introduction:
This document summarizes the American Heart Association (AHA) scientific statement on cervical artery dissection (CAD), an important cause of ischemic stroke, especially in younger and middle-aged adults. Cervical artery dissection often presents with nonspecific symptoms—such as headache, neck pain, or partial Horner syndrome—but can lead to serious neurological deficits. Early recognition, targeted imaging, appropriate acute treatment, and well-informed decisions on antithrombotic therapy are essential to optimize patient outcomes.

Key Recommendations:

• Epidemiology and Risk Factors
  • CAD accounts for up to 25% of ischemic strokes in adults under 50 years of age, with a slightly higher incidence in men but lower peak age in women.
  • Risk factors include genetic predispositions (eg, connective tissue disorders), anatomic variants (elongated styloid process, vascular tortuosity), minor cervical trauma, and comorbidities such as hypertension or fibromuscular dysplasia.
• Diagnosis and Imaging
  1. Clinical Suspicion
     • Suspect CAD in younger adults with new or worsening neck pain, headache, pulsatile tinnitus, partial Horner syndrome, or cranial nerve involvement, especially if there is a history of recent minor neck trauma or manipulation.
     • Up to 8%–12% of patients may have isolated neck or head pain with no initial ischemic signs.
  2. Imaging Modalities
     • Magnetic Resonance Imaging (MRI)/Magnetic Resonance Angiography (MRA): High-resolution, fat-suppressed T1-weighted sequences are useful for detecting intramural hematoma.
     • Computed Tomography Angiography (CTA): Good sensitivity and specificity for luminal abnormalities and can detect intraluminal thrombus. Avoid false positives by distinguishing imaging artifacts from true double lumens or intimal flaps.
     • Conventional Digital Subtraction Angiography (DSA): Historically the gold standard but reserved for equivocal cases because of procedure-related risks (eg, iatrogenic dissection).
     • Ultrasound with Color Doppler: Operator-dependent but helpful for serial follow-up of vessel remodeling.
  3. Additional Diagnostic Testing
     • Connective Tissue Disorders: Consider genetic counseling if physical exam, family history, or recurrent dissections suggest a monogenic disorder (eg, vascular Ehlers-Danlos).
     • Screening for Fibromuscular Dysplasia (FMD): Patients with CAD, especially those with hypertension or evidence of FMD in other vascular beds, may warrant renal artery imaging.
     • Aortic and Intracranial Imaging: Aortic root dilation and cerebral aneurysms may be more prevalent in CAD; consider advanced imaging (eg, MRA) based on clinical judgment.
• Hyperacute and Acute Stroke Management
  1. Intravenous Thrombolysis (IVT):
     • IVT (alteplase or tenecteplase) remains reasonable for otherwise eligible acute ischemic stroke patients, with no specific evidence of higher hemorrhagic risk in CAD. Caution is advised if there is intracranial extension of the dissection or other significant bleeding risk factors.
  2. Mechanical Thrombectomy:
     • Recommended for large-vessel occlusion in CAD patients who meet standard thrombectomy criteria. Tandem lesions (extracranial dissection and intracranial occlusion) can be addressed via retrograde (intracranial first) or antegrade (extracranial first) approach, with similar overall outcomes reported.
  3. Acute or Subacute Stenting:
     • May be considered in selected cases of severe flow-limiting stenosis leading to distal hypoperfusion or in persistent ischemia despite optimal medical therapy. Stenting in tandem occlusions can improve reperfusion but carries added risks (in-stent restenosis, stent thrombosis, or need for dual antiplatelet therapy).
• Antithrombotic Therapy for Secondary Stroke Prevention
  1. Rationale for Early Treatment:
     • Artery-to-artery embolization underpins most CAD-related ischemic events. Early initiation of antithrombotics (ideally within the first 24–72 hours) reduces further embolic risk.
  2. Choice of Agent: Antiplatelet vs Anticoagulant
     • When to Prefer Anticoagulation:
       • Patients with high-risk imaging features: severe stenosis (>50%–70%), intraluminal thrombus, occlusion, multiple or early recurrent dissections.
       • Traditional option is heparin bridging to Vitamin K antagonist (target INR ≈2–3), but direct oral anticoagulants (DOACs) can be considered based on patient profile and preference.
     • When to Prefer Antiplatelet Therapy:
       • Patients with lower stroke risk (no significant stenosis, no intraluminal thrombus) or higher bleeding risk (large infarct, hemorrhagic transformation, intradural extension).
       • Aspirin monotherapy is typical; a short course of dual antiplatelet therapy (aspirin + clopidogrel) for 21–90 days can be considered if minor stroke/TIA criteria apply and bleeding risk is acceptable.
  3. Practical Start-Up and Monitoring:
     • Begin therapy as soon as deemed safe, ideally after hemorrhagic complications are excluded.
     • For VKA: bridge with heparin (IV unfractionated or low–molecular-weight) for at least 5 days until INR is therapeutic for ≥24 hours.
     • Regularly monitor clinical response and, if relevant, INR in anticoagulated patients.
  4. Duration of Therapy:
     • Minimum 3–6 months of antithrombotics, with vessel imaging at follow-up (eg, 3 or 6 months) to assess for healing or persistent dissection.
     • Decisions to extend antithrombotic therapy past the 6-month mark may be considered in the context of an individual’s overall vascular risk factor profile and in the context of neuroimaging features as remodeling occurs.
     • Consider extended or indefinite therapy (often antiplatelet) if persistent stenosis, high-risk anatomic factors, or recurrent dissections occur.
• Risk of Recurrent Dissection and Lifestyle Precautions
  • Recurrence rates range from 1% to 2% per year but are higher in the first few months post-dissection. Fibromuscular dysplasia and younger age are associated with increased recurrence risk.
  • It is reasonable to advise patients to avoid high-risk neck activities (eg, contact sports, extreme neck manipulation) for 1–6 months or until imaging confirms vessel healing. In those with a known connective tissue disorder or recurrent dissection, lifelong caution is appropriate.
• Follow-Up Imaging and Management of Dissecting Aneurysms
  • Recanalization most often occurs by 6–12 months; persistent occlusions or stenoses beyond 12 months rarely recanalize further.
  • Dissecting aneurysms form or enlarge in some cases but seldom rupture. Antithrombotic choice does not appear to affect aneurysm resolution rates.
  • Endovascular or surgical interventions are reserved for enlarging or symptomatic aneurysms causing compression or other complications.

Conclusion: Cervical artery dissection warrants vigilant clinical recognition, prompt imaging, and individualized treatment strategies. Early antithrombotic therapy—whether anticoagulation or antiplatelet—plays a critical role in preventing stroke. Decisions should reflect both the patient’s hemorrhagic risk and the presence of imaging features predictive of stroke. Mechanical thrombectomy and, in selected cases, stenting are viable acute interventions for high-risk presentations. Although recurrences are uncommon, thoughtful follow-up imaging, patient education, and avoidance of high-risk neck activities are central to minimizing future dissections and optimizing outcomes.

Reference: Yaghi S, Engelter S, Del Brutto VJ, Field TS, Jadhav AP, Kicielinski K, Madsen TE, Mistry EA, Salehi Omran S, Pandey A, Raz E, on behalf of the American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Peripheral Vascular Disease. Treatment and Outcomes of Cervical Artery Dissection in Adults: A Scientific Statement From the American Heart Association. Stroke. 2024;55(3). DOI: https://doi.org/10.1161/STR.0000000000000457

 

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Review: Management of Alcohol Withdrawal Syndromes in General Hospital Settings

14 Jan, 2025 | 12:33h | UTC

Introduction:
This summary provides an overview of a state-of-the-art review on identifying, assessing, and treating alcohol withdrawal syndromes among patients in general hospital settings. The rising prevalence of heavy alcohol use—and the sharp increase in hospital admissions for alcohol withdrawal during and after the COVID-19 pandemic—underscores the need for clear, evidence-based guidance. This review addresses the epidemiology, pathophysiology, clinical features, screening tools, and pharmacologic options for managing alcohol withdrawal. It also highlights nutritional considerations and the importance of preventing relapse to reduce readmissions and improve patient outcomes.

Key Recommendations:

1. Screening and Risk Stratification:
   • Use brief, validated questionnaires (eg, Single Alcohol Screening Question or AUDIT-C) to identify at-risk alcohol use.
   • Employ biomarker tests (eg, blood alcohol level, PEth, EtG) when possible to confirm recent intake and evaluate heavy use.
   • Consider standardized risk scales (eg, PAWSS) to identify patients likely to develop severe withdrawal and guide treatment intensity.
2. Symptom Severity Assessment:
   • Select a validated tool to monitor withdrawal progress (eg, CIWA-Ar).
   • For patients with altered mental status or unreliable self-report, consider alternative scales (eg, BAWS or GMAWS) that rely more on objective signs.
3. Benzodiazepine Therapy:
   • Continue to regard benzodiazepines (particularly long-acting agents like diazepam or chlordiazepoxide) as first-line therapy for prevention of seizures and delirium.
   • In patients with liver dysfunction or advanced age, short-acting options (eg, lorazepam, oxazepam) may be safer.
   • Symptom-triggered regimens can reduce total benzodiazepine exposure in lower-risk patients but require trained staff and structured protocols.
   • Fixed-schedule or loading-dose regimens may be warranted in severe withdrawal cases or when symptom-triggered approaches prove insufficient.
4. Alternative and Adjunctive Pharmacotherapies:
   • Phenobarbital: Offers GABA-enhancing and anti-glutamatergic effects, useful in severe or benzodiazepine-resistant withdrawal; consider ICU-level monitoring for high-risk patients.
   • Alpha-2 Adrenergic Agonists (clonidine, dexmedetomidine): Adjunctive benefit for persistent autonomic instability (tachycardia, hypertension), but these agents do not prevent seizures or delirium if used alone.
   • Antiseizure Medications (eg, carbamazepine, gabapentin, valproate): May aid in mild cases or adjunctively, but current evidence does not support them as stand-alone agents in severe withdrawal.
5. Nutritional Repletion and Thiamine Replacement:
   • Aggressively treat thiamine deficiency (eg, IV thiamine 200–500 mg daily) to prevent or halt Wernicke-Korsakoff syndrome.
   • Correct additional deficits (eg, folate, magnesium) for better overall recovery.
6. Relapse Prevention and Post-Acute Care:
   • Initiate FDA-approved medications (eg, naltrexone or acamprosate) during admission to reduce relapse risk after discharge.
   • Provide psychosocial support and referral to continuing addiction services (eg, specialty programs, peer support) to sustain recovery efforts.

Conclusion:
Effective management of alcohol withdrawal in hospital settings requires early recognition of at-risk patients, thoughtful risk stratification, and prompt pharmacologic intervention tailored to withdrawal severity and comorbid conditions. Benzodiazepines remain the mainstay therapy, though phenobarbital shows promise, particularly for resistant or severe cases. Adjunctive alpha-2 agonists help control hyperadrenergic symptoms, but do not replace core GABA-targeted therapies. By integrating nutritional repletion, addressing potential complications, and initiating relapse-prevention strategies, clinicians can reduce both the morbidity of acute withdrawal and the likelihood of future hospitalizations related to alcohol use.

Reference:
Kast KA, Sidelnik SA, Nejad SH, Suzuki J. Management of alcohol withdrawal syndromes in general hospital settings. BMJ 2025;388:e080461. https://doi.org/10.1136/bmj-2024-080461

 

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RCT: High-Flow Nasal Oxygen Noninferior to Noninvasive Ventilation for Most Acute Respiratory Failure Causes

13 Jan, 2025 | 13:11h | UTC

Background: Acute respiratory failure (ARF) arises from diverse etiologies and can manifest as hypoxemic or hypercapnic events. High-flow nasal oxygen (HFNO) and noninvasive ventilation (NIV) are common noninvasive respiratory support modalities, but robust comparative data in various ARF subgroups have been limited. Prior research suggests NIV may benefit chronic obstructive pulmonary disease (COPD) exacerbations and acute cardiogenic pulmonary edema (ACPE), yet for hypoxemic failure (including COVID-19 and immunocompromised populations), HFNO is often favored for its comfort and physiological advantages. The RENOVATE trial was designed to assess whether HFNO is noninferior to NIV for preventing intubation or death among five distinct groups of patients with ARF.

Objective: To determine if HFNO is noninferior to NIV in terms of the composite outcome of endotracheal intubation or death within seven days in patients with ARF, categorized into five subgroups: (1) nonimmunocompromised with hypoxemic ARF, (2) immunocompromised with hypoxemic ARF, (3) COPD exacerbation with respiratory acidosis, (4) ACPE, and (5) hypoxemic COVID-19.

Methods: This multicenter, adaptive, noninferiority randomized clinical trial enrolled 1800 hospitalized adults across 33 Brazilian centers. Patients were stratified by ARF etiology and randomized 1:1 to receive either HFNO or NIV. Treatment protocols allowed HFNO escalation to NIV (particularly for COPD or ACPE) if needed. The primary outcome was defined using a Bayesian hierarchical model with dynamic borrowing across subgroups; noninferiority was met if the posterior probability for an odds ratio (OR) below 1.55 reached ≥0.992. Predefined futility and superiority thresholds guided interim analyses, with a maximum sample size of 2000.

Results: Of 1800 randomized patients, 1766 completed the study (mean age 64 years; 40% women). The primary outcome (intubation or death by day 7) occurred in 39.0% (HFNO) vs 38.1% (NIV). HFNO was noninferior in four subgroups:

• Nonimmunocompromised with hypoxemia: 32.5% vs 33.1% (OR 1.02; posterior probability of noninferiority 0.999).
• COPD exacerbation with respiratory acidosis: 28.6% vs 26.2% (OR 1.05; probability 0.992).
• ACPE: 10.3% vs 21.3% (OR 0.97; probability 0.997).
• Hypoxemic COVID-19: 51.3% vs 47.0% (OR 1.13; probability 0.997).

The immunocompromised subgroup stopped enrollment early for futility; final results there did not confirm noninferiority (57.1% vs 36.4%; OR 1.07; probability 0.989). No significant differences in 28- or 90-day mortality emerged, although mortality rates were generally higher than in some previous trials. Comfort scores favored HFNO, and rates of serious adverse events were similar between groups.

Conclusions: In four of five ARF subgroups, HFNO met predefined noninferiority criteria compared with NIV regarding endotracheal intubation or death at seven days. However, immunocompromised patients with hypoxemic ARF remain an area of uncertainty, as do smaller subgroups (e.g., COPD) under non-borrowing analyses. Clinicians may consider HFNO as an alternative initial approach, recognizing that rescue NIV may still be necessary, particularly in COPD exacerbations.

Implications for Practice: These findings support using HFNO for a broad range of ARF etiologies as a first-line therapy. HFNO’s ease of use, patient comfort, and comparable safety profile may make it especially appealing. Nevertheless, clinicians should remain vigilant in immunocompromised patients and in COPD exacerbations when hypercapnia is pronounced. Potential cost variations between HFNO and NIV may influence real-world adoption, and local resources, staff expertise, and patient tolerance should guide final decisions.

Study Strengths and Limitations: Strengths include a large, diverse sample and a robust Bayesian adaptive design that allowed dynamic borrowing across subgroups. This approach increased precision but also introduced heterogeneity concerns. Some patient groups (particularly immunocompromised and COPD) were relatively small, limiting definitive conclusions in those strata. Additionally, early stopping for futility in immunocompromised patients curtailed full enrollment, and the trial compared HFNO only with face-mask NIV (rather than alternatives such as helmet CPAP).

Future Research: Further large-scale studies should refine whether HFNO can supplant NIV in COPD exacerbations and immunocompromised populations. Investigations on cost-effectiveness, patient-centered outcomes (comfort, quality of life), and comparative models (e.g., helmet NIV) are also warranted.

Reference:
• RENOVATE Investigators and the BRICNet Authors. High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial. JAMA. Published online December 10, 2024. DOI: http://doi.org/10.1001/jama.2024.26244
• Frat JP, Le Pape S, Thille AW. Editorial: Is High-Flow Oxygen the Standard for All Patients With Acute Respiratory Failure? JAMA. Published online December 10, 2024. DOI: http://doi.org/10.1001/jama.2024.25906
• Freund Y, Vromant A. Editorial: Reevaluating Respiratory Support in Acute Respiratory Failure—Insights From the RENOVATE Trial and Implications for Practice. JAMA. Published online December 10, 2024. DOI: http://doi.org/10.1001/jama.2024.25869

 

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Network Meta-Analysis: TMP-SMX May Need Reassessment as First-Line Therapy for PCP in People With HIV

13 Jan, 2025 | 10:25h | UTC

Background: Pneumocystis jirovecii pneumonia (PCP) remains a severe opportunistic infection in people living with HIV (PWH), especially those with low CD4 counts. Trimethoprim–sulfamethoxazole (TMP-SMX) is widely recommended as first-line therapy; however, its toxicity profile can limit use. Alternative regimens such as dapsone–trimethoprim, clindamycin–primaquine, atovaquone, and pentamidine have been explored, but comprehensive comparative data are scarce.

Objective: This systematic review and network meta-analysis aimed to compare the efficacy (treatment failure, mortality) and tolerability (treatment change due to toxicity) of PCP treatment regimens in PWH. The goal was to determine whether TMP-SMX maintains superiority across these outcomes or if alternative regimens offer similar efficacy with improved safety profiles.

Methods: Researchers systematically searched Embase, Medline, and CENTRAL (inception through 3 February 2024) for randomized controlled trials (RCTs) comparing at least two PCP treatment regimens in PWH. Independent reviewers screened titles/abstracts and performed full-text reviews. Data extraction included population demographics, treatment arms, outcomes (treatment failure, all-cause mortality, treatment change), and risk-of-bias assessments using the Cochrane Risk-of-Bias 2 tool. A network meta-analysis using a frequentist random-effects model was performed to integrate direct and indirect comparisons, estimating relative treatment effects (risk ratios with 95% confidence intervals) and generating rankings via the surface under the cumulative ranking curve (SUCRA).

Results: Fourteen RCTs (1983–1996) with 1,788 participants across 27 treatment arms were included. No regimen demonstrated significant superiority over TMP-SMX in direct comparisons, although TMP-SMX outperformed atovaquone and trimetrexate plus folinic acid in reducing treatment failure. In the network analysis, clindamycin–primaquine, intravenous pentamidine, and TMP-SMX all had favorable SUCRA values for preventing treatment failure. For all-cause mortality, dapsone–trimethoprim and intravenous pentamidine ranked highest, while TMP-SMX was better than atovaquone in direct comparison. Notably, for tolerability, all alternative regimens tended to be safer than TMP-SMX, which ranked worst for toxicity. Inhaled pentamidine, trimetrexate plus folinic acid, and atovaquone were the best-tolerated therapies.

Conclusions: These findings suggest that TMP-SMX, although commonly used, might not be universally superior to all other regimens when balancing efficacy and safety in PWH with PCP. When the risk of renal or hematologic complications is high, considering clindamycin–primaquine or intravenous pentamidine may provide comparable efficacy with a more favorable safety profile. Inhaled pentamidine or atovaquone may offer good tolerability but should be carefully assessed for efficacy in moderate-to-severe disease.

Implications for Practice: When managing PCP in PWH, TMP-SMX may not always be the ideal standalone first-line choice, especially in patients at high risk for renal or hematologic complications. Clindamycin–primaquine and intravenous pentamidine could represent viable alternatives for clinicians seeking to balance efficacy with improved safety. Inhaled pentamidine or atovaquone may offer strong tolerability but should be carefully evaluated for their effectiveness in moderate-to-severe disease.

Study Strengths and Limitations: Strengths include a robust search strategy, strict inclusion criteria of RCTs, and the use of a network meta-analysis to integrate direct and indirect comparisons. Limitations involve the older timeframe of the included trials (most conducted before the modern ART era) and heterogeneous definitions of treatment failure, which may limit generalizability to broader contemporary clinical settings. Women and other high-risk populations were underrepresented, presenting another limitation.

Future Research: Contemporary RCTs should address the optimal dose and duration of TMP-SMX and alternative agents, include underrepresented groups (women, older adults, patients with renal impairment), and consider modern management of HIV and critical care practices. Ongoing investigations of novel agents like rezafungin may further refine first-line PCP treatment strategies.

Reference: Hatzl S, Posch F, Scholz L, … Bassetti M, Hoenigl M, Krause R. Comparative efficacy and safety of treatment regimens for Pneumocystis jirovecii pneumonia in people living with HIV: a systematic review and network meta-analysis of randomized controlled trials. Clinical Microbiology and Infection, Published online December 26, 2024. DOI: http://doi.org/10.1016/j.cmi.2024.12.024

 

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2024 Focused Guideline Update on Corticosteroid Use in Sepsis, ARDS, and Community-Acquired Pneumonia

13 Jan, 2025 | 11:04h | UTC

Introduction: This summary presents the key points from a 2024 focused update of the guidelines on corticosteroid use for hospitalized adult patients with sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). Developed by a panel of international experts in critical care, endocrinology, and methodology, the update aims to incorporate new evidence into recommendations regarding dosage, duration, and timing of corticosteroid therapy. Pediatric-specific recommendations could not be made due to limited data.

Key Recommendations:

1. Sepsis and Septic Shock
   • Conditional Recommendation: In adult patients with septic shock requiring vasopressor support, the panel suggests administering corticosteroids (typically hydrocortisone 200–300 mg/day IV for about 5–7 days, with or without fludrocortisone).
   • Strong Recommendation Against High Dose/Short Duration: High-dose corticosteroids (> 400 mg/day hydrocortisone equivalent given for fewer than 3 days) are not recommended, as they confer increased risk of adverse effects without demonstrating benefit.
2. Acute Respiratory Distress Syndrome (ARDS)
   • Conditional Recommendation: In adult patients hospitalized with ARDS (including those with COVID-19 ARDS), the panel suggests using corticosteroids (e.g., methylprednisolone, dexamethasone, or hydrocortisone) to lower short-term mortality and potentially reduce duration of mechanical ventilation. No specific agent or dosing regimen is mandated; choices should be guided by clinical judgment and patient context.
3. Community-Acquired Pneumonia (CAP)
   • Strong Recommendation (Severe CAP): In adults hospitalized with severe bacterial CAP, the panel recommends corticosteroids (commonly moderate-dose IV hydrocortisone or methylprednisolone for 5–7 days). Recent data indicate a clear mortality benefit in these high-risk patients.
   • No Recommendation (Less Severe CAP): For adults with less severe bacterial CAP, current evidence is inconclusive regarding mortality benefit. Although some findings suggest improvements in certain outcomes, the panel reached no consensus on whether corticosteroids should be routinely administered.

Conclusion: These updated guidelines emphasize the overall safety and potential survival benefits of corticosteroids in specific populations with critical illness, particularly those with septic shock, ARDS, or severe CAP. For each condition, the recommendations balance desirable effects—such as reduced mortality, organ dysfunction, and length of hospital stay—against possible harms, including hyperglycemia and neuromuscular weakness. Evidence remains insufficient to support pediatric guidance or clarify whether less severe CAP consistently merits treatment. Future research should address optimal dosing strategies, pediatric outcomes, long-term adverse effects, and potential cost-effectiveness across diverse healthcare settings.

Reference:
Chaudhuri, Dipayan MD, MSc, FRCPC, et al. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Critical Care Medicine 52(5): e219–e233, May 2024. DOI: http://dx.doi.org/10.1097/CCM.0000000000006172

 

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Review: Heart Failure with Preserved Ejection Fraction

9 Jan, 2025 | 11:42h | UTC

Introduction: This summary reviews the 2025 New England Journal of Medicine article by Antonio Cannata, M.D., and Theresa A. McDonagh, M.D., which addresses the clinical syndrome of heart failure with preserved ejection fraction (HFpEF). The document describes its heterogeneous nature, diagnostic challenges, and emerging therapeutic approaches. Key objectives include emphasizing the importance of ruling out mimickers (e.g., respiratory disease or amyloidosis) and reviewing the evidence for guideline-directed therapies that reduce hospitalizations and improve quality of life.

Key Recommendations:

• Diagnostic Steps:
  • Confirm an ejection fraction ≥50% and evidence of diastolic dysfunction or raised filling pressures.
  • Exclude confounding conditions (e.g., COPD, hypertrophic cardiomyopathy, cardiac amyloidosis) through imaging (echocardiography, cardiac MRI) and relevant laboratory tests (natriuretic peptides).
  • Consider invasive hemodynamic assessment if the diagnosis remains unclear.
• Initial Management:
  1. Diuretics: Use loop diuretics or thiazides to relieve congestion and peripheral edema. Titrate to the lowest effective dose once euvolemia is achieved.
  2. Blood Pressure and Comorbidity Control: Optimize antihypertensive therapy with agents such as renin–angiotensin–system (RAS) inhibitors or mineralocorticoid receptor antagonists (MRAs) to address underlying hypertension and other cardiovascular risk factors.
• Specific Pharmacotherapies:
  • SGLT2 Inhibitors: Empagliflozin and dapagliflozin reduce the composite risk of cardiovascular death or heart-failure hospitalization, primarily by lowering hospitalization rates.
  • RAS Blockade (ACE Inhibitors/ARBs/ARNIs): Although large trials did not show a clear mortality benefit, some studies indicated fewer hospitalizations.
  • MRAs (e.g., Spironolactone, Finerenone): Evidence for HFpEF is mixed, though a recent trial (FINEARTS-HF) supports the potential role of finerenone in reducing hospitalization in patients with left ventricular ejection fraction ≥40%.
  • GLP-1 Receptor Agonists: Agents like semaglutide (and the dual GIP/GLP-1 agonist tirzepatide) showed improvements in weight reduction, exercise tolerance, and quality of life in patients with HFpEF and obesity, suggesting an emerging cardiometabolic strategy.
  • Beta-Blockers: Widespread use in HFpEF often relates to other comorbidities, but trials have not demonstrated significant outcome benefits specifically for preserved ejection fraction.
• Adjunct Therapies and Devices:
  • Pulmonary Artery Pressure Monitoring (CardioMEMS): Can help guide diuretic adjustments and has shown reductions in hospitalizations for heart failure across ejection-fraction ranges.
  • Interatrial Shunt Devices: Trials so far have not shown conclusive benefits and may pose increased risk in patients with higher ejection fractions.
• Lifestyle and Comorbidity Management:
  • Address obesity, type 2 diabetes, and physical inactivity through dietary and exercise interventions.
  • Evaluate for sleep-disordered breathing, as optimizing respiratory status can improve symptoms and reduce hospitalizations.

Conclusion: HFpEF is a complex syndrome often associated with obesity, hypertension, and other coexisting conditions that contribute to clinical variability. While no single agent has definitively reduced mortality, trials have shown meaningful reductions in hospitalizations and improvements in quality of life, especially with SGLT2 inhibitors and, in obese patients, GLP-1 receptor agonists. Ongoing research into pathophysiology-driven therapies may enhance future outcomes. For now, clinicians should employ a multimodal approach targeting volume status, cardiometabolic health, and comorbidity control to optimize management.

Reference:
Cannata A, McDonagh TA. Heart Failure with Preserved Ejection Fraction. New England Journal of Medicine. 2025;392:173–184.
DOI: https://doi.org/10.1056/NEJMcp2305181

 

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ATS Guidelines on Invasive Pulmonary Aspergillosis and Antifungal Strategies in Critically Ill Adults

7 Jan, 2025 | 12:29h | UTC

Introduction: This summary provides an overview of a recent American Thoracic Society clinical practice guideline addressing two core questions in adult pulmonary and critical care practice. First, it examines whether combination therapy with a mold-active triazole (most data concern voriconazole, though newer agents such as isavuconazole or posaconazole may also be considered) plus an echinocandin (specifically caspofungin, micafungin, or anidulafungin) offers added benefit over mold-active triazole monotherapy for patients with proven or probable invasive pulmonary aspergillosis (IPA). Second, it evaluates whether routine use of prophylactic or empiric antifungal agents against Candida species is advisable in critically ill, nonneutropenic, nontransplant patients at risk of invasive candidiasis (IC). By synthesizing available evidence using the GRADE approach, this guideline aims to support clinicians in optimizing therapeutic strategies and improving patient outcomes in these complex infections.

Key Recommendations:

Initial Combination Therapy vs. Monotherapy for IPA

• For patients with proven or probable IPA, the guideline makes a conditional recommendation, meaning the best choice isn’t entirely clear. Both initial combination therapy (mold-active triazole + echinocandin) and monotherapy (mold-active triazole alone) are considered reasonable options.
• Evidence stems primarily from studies in hematologic malignancy (HM) or hematopoietic stem cell transplant (HSCT) recipients, with mixed findings in observational cohorts and a key randomized trial favoring combination therapy, particularly in a subgroup diagnosed by positive galactomannan assays.
• When critical illness or triazole resistance is a concern, combination therapy may be considered, but there is insufficient evidence to categorically endorse one approach over the other.

Prophylactic or Empiric Antifungal Therapy for Candida in Critically Ill Patients

• In nonneutropenic, nontransplant adult ICU patients at risk for IC, the guideline makes a conditional recommendation against routinely using prophylactic or empiric antifungal therapy. This means the benefits of withholding these treatments likely outweigh the risks, but there’s still some uncertainty.
• Low-quality evidence from multiple randomized controlled trials showed no significant mortality benefit in administering antifungals prophylactically or empirically compared with placebo.
• Although IC carries substantial morbidity and mortality, its overall incidence in this population remains low, and ongoing surveillance or targeted diagnostics may be preferable to universal antifungal administration.

Conclusion: The panel emphasizes that these recommendations should be applied with clinical judgment, especially in patients with severe disease, likely high fungal burden, or concerns for antifungal resistance. Combination therapy for IPA may be particularly relevant when critical illness or limited triazole efficacy is suspected. Meanwhile, prophylactic or empiric anti-Candida therapy in the broader ICU setting does not appear to substantially reduce mortality. Continued advances in rapid diagnostics, close monitoring of local resistance patterns, and new antifungal agents may further refine best practices. Future research should focus on validating these findings in diverse patient populations, exploring novel combination regimens, and establishing more precise risk assessments for IC in the ICU.

Reference: Epelbaum O, Marinelli T, Haydour Q, Pennington KM, Evans SE, Carmona EM, Husain S, Knox KS, Jarrett BJ, Azoulay E, Hope WW, and others. “Treatment of Invasive Pulmonary Aspergillosis and Preventive and Empirical Therapy for Invasive Candidiasis in Adult Pulmonary and Critical Care Patients: An Official American Thoracic Society Clinical Practice Guideline.” American Journal of Respiratory and Critical Care Medicine (2025). https://doi.org/10.1164/rccm.202410-2045ST

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RCT: Assessing Procalcitonin-Based Antibiotic Management in Critically Ill Patients With Sepsis

7 Jan, 2025 | 14:00h | UTC

Background: Optimal antibiotic duration for sepsis remains uncertain. Procalcitonin (PCT) and C-reactive protein (CRP) are thought to support shorter courses, but prior research was small-scale or at risk of bias. This multicenter, randomized trial (ADAPT-Sepsis) evaluated whether daily PCT- or CRP-guided protocols could reduce antibiotic use without increasing 28-day all-cause mortality in critically ill adults with suspected sepsis.

Objective: To determine if daily biomarker-guided (PCT or CRP) strategies decrease total antibiotic days among critically ill adults while maintaining acceptable 28-day mortality, compared with standard care.

Methods: From 2018 to 2024 (with enrollment paused March–August 2020 due to COVID-19), 2760 adults (≥18 years) on intravenous antibiotics for suspected sepsis (acute organ dysfunction and presumed infection) and likely to continue antibiotics for at least 72 hours were randomized across 41 UK NHS ICUs within 24 hours of antibiotic initiation. They were assigned in a 1:1:1 ratio to (1) daily PCT-guided advice (n=918), (2) daily CRP-guided advice (n=924), or (3) standard care (n=918). Biomarker results were concealed; clinicians received automated daily prompts recommending continuation or discontinuation. The co-primary outcomes were (1) total antibiotic duration (randomization to day 28) and (2) 28-day all-cause mortality. Secondary measures included antibiotic duration for the initial sepsis episode, 90-day mortality, readmissions, and length of stay.

Results: Among 2760 participants (mean age, 60.2 years; 60.3% men; ~50% with septic shock), over 96% provided 28-day data. Patients in the PCT-guided arm had a statistically significant mean reduction in total antibiotic duration vs standard care (9.8 vs 10.7 days; difference, 0.88 days; 95% CI, 0.19–1.58; p=0.01). The PCT strategy met the prespecified 5.4% noninferiority margin for 28-day mortality (20.9% vs 19.4%; absolute difference, 1.57; 95% CI, –2.18 to 5.32; p=0.02), implying noninferiority but not fully excluding a small risk of excess mortality. CRP-guided protocols did not shorten total antibiotic use (10.6 vs 10.7 days; p=0.79) and were inconclusive for noninferiority regarding mortality (21.1% vs 19.4%; difference, 1.69; 95% CI, –2.07 to 5.45; p=0.03). Notably, 90-day mortality also showed no significant differences. A post-trial commentary (PulmCCM) emphasized that some uncertainty remains with the 5.4% margin and warned that patient-level randomization could subtly discourage earlier antibiotic discontinuation in standard care, which received no explicit “stop” prompts.

Conclusions: In critically ill patients with suspected sepsis, a PCT-guided antibiotic discontinuation protocol shortened overall antibiotic use by nearly one day without exceeding the predefined noninferiority threshold for 28-day mortality. However, the chosen 5.4% margin allows for the possibility of clinically relevant harm. A CRP-guided protocol did not reduce total antibiotic use and showed inconclusive mortality findings.

Implications for Practice: Adopting PCT-based stewardship may modestly decrease antibiotic exposure without a clear short-term mortality penalty, potentially limiting antibiotic resistance. Clinicians should remain vigilant, recognizing the risk tolerance implied by the 5.4% margin. PCT results should complement, not replace, comprehensive clinical judgment.

Study Strengths and Limitations: Strengths include the large sample size, multi-center design, blinded biomarker allocation, and distinct emphasis on both effectiveness and safety outcomes. Limitations include the acceptance of a 5.4% potential excess mortality as the noninferiority threshold, uncertainty about rare but significant harms, and the possibility of bias introduced by patient-level randomization. Generalizability to lower-resource settings may also be limited.

Future Research: Further randomized trials with lower noninferiority margins or cluster-level allocation are needed to better define the safety and efficacy of PCT-guided strategies for reducing antibiotic duration in sepsis. Additional investigations are needed for long-term patient-centered outcomes, cost-effectiveness, and the role of alternative biomarkers or combined strategies in sepsis care.

Reference:

Dark P, Hossain A, McAuley DF, et al. Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial. JAMA. 2024; published online December 9. DOI: http://doi.org/10.1001/jama.2024.26458

PulmCCM Commentary: “Is procalcitonin ‘safe’ to guide antibiotic use in patients with sepsis? ADAPT-Sepsis tests the strategy in the U.K., with global ambitions.” Jan 02, 2025. https://www.pulmccm.org/p/is-procalcitonin-safe-to-guide-antibiotic

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Meta-Analysis: Tailored Hydration Strategies Decrease CI-AKI and MACE in Coronary Angiography

6 Jan, 2025 | 13:00h | UTC

Background: Contrast-induced acute kidney injury (CI-AKI) poses a considerable burden on patients undergoing coronary angiography or percutaneous coronary intervention (PCI). Beyond the direct tubular toxicity of iodine contrast, several risk factors, including chronic kidney disease (CKD) and hemodynamic instability, further increase the likelihood of renal damage. Although guideline-based prevention strategies recommend peri-procedural intravenous hydration, the optimal volume and method remain unclear.

Objective: This meta-analysis aimed to determine whether patient-tailored intravenous fluid administration (using parameters other than body weight alone) can reduce the incidence of CI-AKI, as well as major adverse cardiovascular events (MACE), compared with conventional non-tailored hydration protocols in patients undergoing coronary angiography and/or PCI.

Methods: A systematic review of randomized controlled trials (RCTs) was performed, including 13 studies and 4,458 participants. Tailored hydration strategies encompassed left ventricular end-diastolic pressure (LVEDP)-guided infusion, diuresis-driven matched replacement (RenalGuard®), bioimpedance vector analysis, central venous pressure, or inferior vena cava ultrasound measurements. These were compared against standard non-tailored fluid protocols. The primary outcome was CI-AKI (variously defined but measured within 7 days), and secondary outcomes included MACE, all-cause mortality, and renal replacement therapy (RRT).

Results: Across 12 RCTs (n=3,669), tailored hydration significantly reduced CI-AKI rates (risk ratio 0.56, 95% CI [0.46–0.69], p<0.00001; I²=26%). Ten studies (n=3,377) revealed lower MACE incidence in the tailored hydration arm (RR=0.57, 95% CI [0.42–0.78], p=0.0005; I²=12%). A significant reduction in all-cause mortality (RR=0.57, 95% CI [0.35–0.94], p=0.03) and RRT requirement (RR=0.51, 95% CI [0.29–0.89], p=0.02) was also observed, with no significant increase in pulmonary edema. Subgroup analyses (e.g., CKD) supported the overall benefit of individualizing fluid regimens.

Conclusions: Tailored hydration strategies appear superior to standard approaches in lowering the risk of CI-AKI, MACE, mortality, and RRT after coronary angiography or PCI. Although LVEDP-guided protocols are simple to implement and effective, the RenalGuard® system may offer additional benefits in selected populations, albeit at higher cost and complexity.

Implications for Practice: Clinicians should consider personalized hydration based on physiological or hemodynamic parameters to optimize fluid volume, reduce renal injury, and potentially improve clinical outcomes. Nevertheless, practical challenges include access to specialized equipment and the need for close monitoring in some techniques.

Study Strengths and Limitations: This systematic review highlights consistent treatment effects across diverse RCTs and methods. However, potential biases due to lack of blinding, varying CI-AKI definitions, and limited head-to-head comparisons among tailored approaches constrain definitive conclusions. The small sample size of certain studies and underpowered subgroup analyses also limit the generalizability of findings.

Future Research: Further large-scale trials are warranted to compare various tailored protocols directly, focusing on cost-effectiveness, ease of implementation, and patient-centered endpoints. Ongoing investigations, such as the NEPTUNE trial, aim to clarify whether combining multiple parameters (like LVEDP and contrast volume/eGFR ratio) yields optimal renal protection.

Reference: Cossette F, Trifan A, Prévost-Marcotte G, et al. Tailored Hydration for the Prevention of Contrast-Induced Acute Kidney Injury After Coronary Angiogram or PCI: A Systematic Review and Meta-Analysis. American Heart Journal. Published online January 4, 2025. DOI: http://doi.org/10.1016/j.ahj.2025.01.002

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Meta-analysis: Therapeutic-Dose Heparin Improves 28-Day Mortality in COVID-19 Hospitalized Patients

6 Jan, 2025 | 12:00h | UTC

Background: High rates of thrombotic events and systemic inflammation among COVID-19 hospitalized patients led researchers to test whether intensified anticoagulation strategies could reduce morbidity and mortality. Previous trials yielded conflicting results, partly due to varying doses of anticoagulants—prophylactic, intermediate, or therapeutic—and heterogeneous patient severity. This comprehensive investigation, conducted by the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, aimed to clarify the benefits and risks of escalated anticoagulation dosing in patients hospitalized for COVID-19.

Objective: To estimate whether higher-dose anticoagulation (therapeutic or intermediate) improves 28-day all-cause mortality compared with lower-dose anticoagulation (prophylactic or intermediate), and to evaluate secondary outcomes, including progression to mechanical ventilation, thromboembolic events, and major bleeding.

Methods: This prospective meta-analysis included randomized trials comparing higher- versus lower-dose anticoagulation for hospitalized COVID-19 patients. Investigators collected trial-level summary data, focusing primarily on heparins. Dosing categories—therapeutic, intermediate, and prophylactic—were predefined. The main outcome was 28-day mortality; secondary outcomes included progression to invasive mechanical ventilation (IMV), venous or arterial thrombotic events, and major hemorrhage. Data were analyzed using a fixed-effects model, with odds ratios (ORs) pooled across trials.

Results: Overall, 22 trials (over 11 000 total participants) contributed data, primarily evaluating heparins. For therapeutic versus prophylactic-dose heparin, 28-day mortality was significantly reduced (OR, 0.77; 95% CI, 0.64–0.93), especially among patients requiring low-flow oxygen or no supplemental oxygen. Therapeutic dose reduced thromboembolic events (OR 0.48; 95% CI, 0.36-0.64) but increased major bleeding (OR 1.90; 95% CI, 1.19-3.05) compared to prophylactic dose. In contrast, when therapeutic was compared to intermediate-dose heparin, the summary OR for 28-day mortality was 1.21 (CI, 0.93–1.58), suggesting a potential trend toward higher mortality that did not reach statistical significance. Intermediate versus prophylactic-dose comparisons revealed no conclusive mortality difference (OR, 0.95; CI, 0.76–1.19). Across all higher-dose arms, thromboembolic events decreased, while the risk of major bleeding increased, underscoring the delicate risk–benefit balance. Subgroup analyses by respiratory support level, D-dimer, and baseline severity did not indicate strong interaction effects, although sample sizes were limited in more severe illness subgroups.

Conclusions: Therapeutic-dose heparin reduces 28-day mortality relative to prophylactic-dose in hospitalized patients with COVID-19, mainly among those not requiring invasive ventilation. Mortality was similar or potentially worse when therapeutic was compared to intermediate-dose. Clinicians must weigh the lower rate of thrombotic complications against the higher bleeding risk, particularly in critically ill patients.

Implications for Practice: Although higher anticoagulant dosing appears beneficial for certain hospitalized COVID-19 patients, especially those with mild to moderate respiratory compromise, individualized assessment remains key. Current guidelines broadly recommend prophylactic dosing for the critically ill and suggest considering higher doses only in carefully selected patients. Evolving viral variants and changes in standard of care further complicate direct application of these findings to present-day hospital settings.

Study Strengths and Limitations: Strengths include prospective planning, collaboration with multiple trials, and a large pooled sample. Limitations encompass heterogeneity in dose definitions, partial reliance on published data where individual-level parameters could not be fully harmonized, and potential temporal changes in COVID-19 clinical profiles. Moreover, bleeding severity beyond major hemorrhage was not universally reported, limiting robust safety assessments.

Future Research: Further studies should focus on individualized anticoagulant strategies that consider biomarkers (for example, D-dimer) and evolving treatment protocols. Investigations examining optimal timing, duration, and post-discharge management will help refine anticoagulation practices.

Reference:

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Anticoagulation Among Patients Hospitalized for COVID-19: A Systematic Review and Prospective Meta-analysis. Annals of Internal Medicine. DOI: https://doi.org/10.7326/ANNALS-24-00800

Shappell CN, Anesi GL. Anticoagulation for COVID-19: Seeking Clarity and Finding Yet More Gray. Annals of Internal Medicine. DOI: https://doi.org/10.7326/ANNALS-24-03244

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Review: Nutritional Support in Critically Ill Patients

6 Jan, 2025 | 11:00h | UTC

Introduction: This summary is derived from a state-of-the-art review on nutritional support in the intensive care unit (ICU) published in The BMJ. Critically ill patients experience metabolic disturbances, inflammation, and profound muscle wasting. Nutritional therapy aims to mitigate these effects, though recent randomized controlled trials (RCTs) challenge the dogma of early, aggressive provision of high-calorie and high-protein diets for all ICU patients. Instead, emerging evidence indicates that moderate energy and protein restriction, particularly during the first week, may enhance recovery and reduce complications such as hospital-acquired infections, muscle weakness, and ICU-acquired morbidity. Nonetheless, identifying ideal feeding strategies remains complex, given the dynamic nature of critical illness and the interplay with other interventions such as sedation and physical rehabilitation.

Key Recommendations:

1. Individualized Timing and Dose: Limit caloric and protein loads during the acute phase (roughly the first seven days), especially in patients with hemodynamic instability or shock. Later, as patients transition to recovery, gradually increase macronutrient delivery to meet evolving metabolic needs.
2. Preferred Feeding Route: Enteral nutrition is generally recommended when the gastrointestinal tract is functional, particularly after shock resolution. Parenteral nutrition can be reserved for prolonged gut dysfunction or inability to meet needs enterally. Studies comparing enteral versus parenteral feeding have shown no clear outcome differences, but early enteral feeding is often favored for physiological and cost reasons.
3. Avoid Overfeeding and Overzealous Protein Provision: Several large RCTs (including EFFORT-Protein, EDEN, and NUTRIREA-3) observed no mortality benefit—and in some instances, worse outcomes—when patients received full or high doses of energy and protein in the first week. Metabolic “resistance” and inhibition of protective processes such as autophagy might explain why restricted early feeding sometimes confers advantages.
4. Monitoring and Assessment: Traditional tools (NUTRIC, NRS-2002) and biomarkers (albumin, prealbumin) do not reliably predict who benefits from higher or lower feeding levels. Ultrasound or computed tomography to assess muscle mass may hold promise, but no validated approach exists to guide individualized macronutrient targets.
5. Micronutrients and Specialized Formulations: Broad-spectrum pharmaconutrients (glutamine, antioxidants, etc.) have not improved outcomes in well-powered trials. Instead, standard vitamin and trace element supplementation consistent with recommended daily allowances appears sufficient in most cases.
6. Long-term Rehabilitation: Combined nutritional support and physical exercise are critical for mitigating long-term impacts of ICU-acquired weakness and functional decline. Evidence increasingly highlights the need for prolonged, structured rehabilitation to optimize muscle recovery and quality of life.

Conclusion: Although nutritional support remains central to critical care, it is most effective when carefully adapted to disease phase, patient comorbidities, and evolving organ dysfunction. Key evidence suggests a more conservative approach to energy and protein during the acute phase, followed by gradual escalation and integration with rehabilitation. Ongoing research seeks to identify physiological markers that distinguish when to intensify nutritional therapy and how best to align macronutrient delivery with other therapies to promote muscle function and reduce complications.

Reference: Reignier J, Rice TW, Arabi YM, Casaer M. Nutritional Support in the ICU. BMJ. 2025;388:e077979. DOI: https://doi.org/10.1136/bmj-2023-077979

 

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AGA Clinical Practice Update on Managing Portal Vein Thrombosis in Cirrhotic Patients: Expert Review

3 Jan, 2025 | 10:00h | UTC

Introduction: This summary highlights key recommendations from an AGA expert review on portal vein thrombosis (PVT) in cirrhotic patients. PVT is common in cirrhosis, with an estimated five-year incidence of around 11%, and may worsen portal hypertension and elevate mortality. Management is challenging because of limited evidence, the potential complications of both PVT and anticoagulation, and significant heterogeneity regarding clot characteristics, host factors, and cirrhosis severity. This review presents the latest guidance on identifying clinically relevant PVT, selecting anticoagulation, and considering endovascular interventions, including TIPS (transjugular intrahepatic portosystemic shunt).

Key Recommendations:

1. No Routine Screening: Asymptomatic patients with compensated cirrhosis do not require regular screening for PVT in the absence of suggestive clinical changes.
2. Imaging Confirmation: When Doppler ultrasound reveals suspected PVT, contrast-enhanced CT or MRI is recommended to confirm the diagnosis, exclude malignancy, and characterize clot extent and occlusion.
3. Hypercoagulability Testing: Extensive thrombophilia workup is not indicated unless there is family or personal history of thrombotic events, or associated laboratory abnormalities.
4. Intestinal Ischemia Management: Patients who develop PVT with evidence of intestinal ischemia should receive prompt anticoagulation and, ideally, multidisciplinary team care involving gastroenterology, hepatology, interventional radiology, hematology, and surgery.
5. Observation of Minor or Recent Thrombi: In cirrhotic patients without ischemia, with recent (<6 months) thrombi that are <50% occlusive, close imaging follow-up every three months is a reasonable option to track potential spontaneous clot regression.
6. Anticoagulation for Significant PVT: Consider anticoagulation for more extensive or obstructive (>50%) recent PVT, especially if the main portal vein or mesenteric vessels are involved. Candidates for liver transplantation and those with inherited thrombophilia may derive additional benefit.
7. Chronic Cavernous PVT: Anticoagulation is generally not advised in patients with long-standing (>6 months) complete occlusion and well-formed collateral channels.
8. Variceal Screening: Perform endoscopic screening or ensure prophylaxis for varices. Avoid delays in initiating anticoagulation, as timeliness is essential for better recanalization outcomes.
9. Choice of Anticoagulant: Vitamin K antagonists, low-molecular-weight heparin, and direct oral anticoagulants (DOACs) are all viable options in cirrhosis. DOACs may be appropriate in well-compensated (Child-Turcotte-Pugh class A or certain class B) cirrhosis but should be avoided in class C. Treatment selection should consider patient preferences, monitoring feasibility, and risk of bleeding.
10. Duration of Therapy: Reassess clot status with cross-sectional imaging every three months. Continue anticoagulation for transplant-eligible individuals who show partial or complete recanalization, and consider discontinuation in nonresponders after six months if futility is evident.
11. TIPS Revascularization: Portal vein revascularization using TIPS may be pursued in patients who have other TIPS indications (like refractory ascites or variceal bleeding) or to improve transplant feasibility by recanalizing portal flow.

Conclusion: PVT in cirrhosis remains a complex clinical issue requiring careful evaluation of clot extent, timing, and the potential need for transplantation. The recommendations presented here underscore prompt imaging, timely anticoagulation for high-risk thrombi, and individualized therapy based on Child-Turcotte-Pugh classification and bleeding risk. When necessary, multidisciplinary collaboration is key to achieving optimal patient outcomes. Prospective randomized trials and standardized classifications of PVT will be instrumental in refining future guidelines.

Reference:
Davis JPE, Lim JK, Francis FF, Ahn J. AGA Clinical Practice Update on Management of Portal Vein Thrombosis in Patients With Cirrhosis: Expert Review. Gastroenterology. 2024. DOI: http://doi.org/10.1053/j.gastro.2024.10.038

 

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Cohort Study: One in Four Patients Demonstrates Covert Cognition Despite Behavioral Unresponsiveness

3 Jan, 2025 | 08:30h | UTC

Background: Cognitive motor dissociation (CMD) refers to the presence of specific neuroimaging or electrophysiological responses to commands in patients otherwise incapable of voluntary behavioral output. Detecting CMD is clinically relevant because its underdiagnosis may lead to premature decisions regarding goals of care, life-sustaining treatment, and rehabilitation efforts. Although several single-center studies have suggested that CMD may exist in 10–20% of patients with disorders of consciousness, larger multinational data were lacking, particularly using both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG).

Objective: To determine how often CMD occurs in a large, multinational cohort of adults with impaired consciousness and to evaluate the clinical variables potentially associated with this phenomenon.

Methods: This prospective cohort study included 353 adults with disorders of consciousness recruited from six international centers between 2006 and 2023. Enrolled participants had at least one behavioral assessment using the Coma Recovery Scale–Revised (CRS-R) and underwent task-based fMRI, EEG, or both. Sites utilized validated analytic pipelines and automated data processing to minimize false positives. Participants were divided into two groups: those without observable responses to verbal commands (coma, vegetative state, or minimally conscious state–minus) and those with observable responses (minimally conscious state–plus or emerged). CMD was defined as the absence of any observable behavioral response to commands, combined with a positive command-following signal on fMRI or EEG.

Results: Among 241 participants with no overt command-following, 25% showed CMD through either fMRI alone, EEG alone, or both. CMD was more common in younger patients, those assessed later after injury, and those with traumatic brain injury. Interestingly, in 112 participants who did exhibit command-following on bedside exams, only 38% demonstrated confirmatory responses on fMRI or EEG. These findings support the notion that the tasks used for neuroimaging and electrophysiological assessments may require more sustained cognitive engagement than typical bedside evaluations.

Conclusions: CMD was identified in about one in four patients who lacked behavioral command-following. Combining fMRI with EEG likely increases detection rates compared to either modality alone. The results highlight the need for increased awareness of covert cognitive activity in this population, given potential ramifications for prognosis, family counseling, and clinical care.

Implications for Practice: Clinicians should consider the possibility of CMD in patients who appear unresponsive at the bedside. When feasible, employing both fMRI and EEG might reveal hidden cognitive capacities that can guide patient-centered decisions, encourage targeted therapies, and allow healthcare teams to respect potential consciousness and autonomy. However, such technologies remain limited to specialized centers.

Study Strengths and Limitations: Strengths include a diverse sample from multiple international sites and the integration of two complementary neurodiagnostic techniques. Limitations involve heterogeneous recruitment practices, variations in local data acquisition methods, and potential selection biases toward patients who survived until advanced testing was available. Additionally, the absence of standardized paradigms across sites reduced consistency of results.

Future Research: Further large-scale investigations should standardize fMRI and EEG protocols and determine whether earlier and more consistent identification of CMD affects functional outcomes. Efforts to refine and validate automated analytic pipelines could facilitate widespread adoption of these techniques in routine clinical settings.

Reference: Bodien YG, Allanson J, Cardone P, et al. Cognitive Motor Dissociation in Disorders of Consciousness. New England Journal of Medicine. 2024;391:598-608. DOI: http://doi.org/10.1056/NEJMoa2400645

 

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Systematic Review and Bayesian Meta-Analysis: Higher Protein Delivery May Increase Mortality in Critically Ill Patients

2 Jan, 2025 | 08:30h | UTC

Background: Nutritional guidelines often recommend higher protein doses (approximately 1.2–2.0 g/kg/d) to mitigate muscle loss in critically ill patients. However, recent multicenter trials have raised concerns that elevated protein targets might increase mortality and adversely affect patient-centered outcomes. This study applied a Bayesian approach to synthesize current evidence regarding the effect of higher versus lower protein delivery on mortality, infections, mechanical ventilation duration, and health-related quality of life in critically ill adults.

Objective: To estimate the probability of beneficial or harmful effects of increased protein delivery on clinically important outcomes, with emphasis on quantifying the likelihood of mortality benefit versus risk.

Methods: A systematic review and Bayesian meta-analysis were conducted according to a preregistered protocol (PROSPERO CRD42024546387) and PRISMA 2020 guidelines. Twenty-two randomized controlled trials comparing higher (mean 1.5 g/kg/d) versus lower (mean 0.9 g/kg/d) protein delivery in adult ICU patients were included, ensuring similar energy intake in both groups. A hierarchical random-effects Bayesian model was applied, using vague priors to estimate relative risks for mortality and infections, mean differences for ventilator days, and standardized mean differences for quality of life.

Results: A total of 4,164 patients were analyzed. The posterior probability that higher protein intake increases mortality was 56.4%, compared with a 43.6% probability of any mortality benefit. Probabilities for a clinically relevant (≥5%) mortality decrease were low (22.9%), while the probability of at least a 5% increase reached 32.4%. Infections were slightly more likely with higher protein, although the likelihood of a major detrimental effect remained modest. The probability of a clinically meaningful difference in ventilator days was negligible, suggesting near equivalence for that endpoint. Conversely, quality of life might be negatively impacted by higher protein dosing, although few trials measured this outcome.

Conclusions: Under a Bayesian framework, current evidence suggests that high protein delivery in critically ill patients might pose a meaningful risk of increased mortality. Although a beneficial effect cannot be fully excluded, its probability appears comparatively small. These findings challenge the longstanding assumption that more protein universally translates to better outcomes.

Implications for Practice: Clinicians should exercise caution when aiming for higher protein targets. Individual patient characteristics, such as severity of illness, renal function, and underlying comorbidities, may modulate outcomes. The data support considering a personalized protein prescription rather than routinely pushing intake beyond conventional targets.

Study Strengths and Limitations: Strengths include a robust Bayesian analysis that evaluates probabilities of both benefit and harm across multiple thresholds, as well as the inclusion of recently published large trials. Limitations involve heterogeneity in protein dosing strategies, potential publication bias (indicated by Egger’s test), and limited data on quality of life.

Future Research: Ongoing trials, such as TARGET Protein and REPLENISH, will provide valuable insights into optimal protein dosing, particularly in specific subgroups. Further investigation should explore mechanistic underpinnings of how high protein intake could adversely affect recovery in critically ill patients.

Reference: Heuts S, Lee ZY, Lew CCH, et al. Higher Versus Lower Protein Delivery in Critically Ill Patients: A Systematic Review and Bayesian Meta-Analysis. Critical Care Medicine. December 27, 2024. DOI: http://doi.org/10.1097/CCM.0000000000006562

 

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Management of Adult Sepsis in Resource-Limited Settings: A Global Delphi-Based Consensus

26 Dec, 2024 | 02:06h | UTC

Introduction: 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:

1. 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.
2. 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.
3. 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.
4. 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.
5. 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

 

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2025 ASA Practice Advisory for the Perioperative Care of Older Adults Undergoing Inpatient Surgery

23 Dec, 2024 | 20:27h | UTC

Introduction: This summary outlines the American Society of Anesthesiologists (ASA) 2025 advisory on optimizing perioperative care for older adults (age 65 years or older) undergoing inpatient surgery. It focuses on preoperative, intraoperative, and postoperative measures to mitigate cognitive complications, especially delirium and longer-term cognitive decline, in a population that is highly vulnerable to functional deterioration and loss of independence. The recommendations are based on systematic reviews and meta-analyses, supplemented by expert consensus where evidence is limited. Although not intended as strict standards of care, these advisory statements provide practical guidance that can be adapted to local contexts and patient-specific needs.

Key Recommendations:

1. Expanded Preoperative Evaluation:
   • Incorporate frailty assessment, cognitive screening, and psychosocial or nutritional evaluations into routine preoperative workups for older patients.
   • Patients identified with frailty or cognitive deficits should receive targeted interventions, such as geriatric co-management, deprescribing when indicated, and early family education about delirium risks.
   • Evidence suggests a modest decrease in postoperative delirium when such evaluations are included.
2. Choice of Primary Anesthetic (Neuraxial vs. General):
   • Current studies do not demonstrate a clear advantage of neuraxial over general anesthesia in reducing postoperative delirium risk.
   • Both approaches are acceptable; individualize decisions based on patient factors, surgical requirements, and preference-sensitive discussions.
3. Maintenance of General Anesthesia (Total Intravenous vs. Inhaled Agents):
   • Data are inconclusive regarding delirium prevention, with no significant difference between total intravenous anesthesia (TIVA) and inhaled volatile agents.
   • Some low-level evidence indicates TIVA might reduce short-term cognitive decline, but this effect is inconsistent over longer follow-up.
4. Dexmedetomidine for Delirium Prophylaxis:
   • Moderate-level evidence supports dexmedetomidine for reducing delirium incidence in older patients, yet its use may increase bradycardia and hypotension.
   • Optimal dosing and timing remain uncertain, and baseline patient vulnerability should inform decisions.
5. Medications with Potential Central Nervous System Effects:
   • Drugs such as benzodiazepines, antipsychotics, anticholinergics, ketamine, and gabapentinoids warrant careful risk-benefit analysis.
   • Current findings are inconclusive, suggesting neither a firm endorsement nor outright disapproval; preexisting conditions and polypharmacy should guide individualized treatment plans.

Conclusion: Preserving cognitive function and independence in older adults undergoing inpatient surgery is a growing priority. These recommendations highlight the importance of comprehensive preoperative screenings (frailty, cognition, and psychosocial domains), shared decision-making when choosing anesthetic techniques, and thoughtful use of pharmacologic agents. While dexmedetomidine shows promise in mitigating delirium, vigilance regarding hypotension and bradycardia is essential. Ultimately, these strategies aim to reduce anesthesia-related complications in older patients by addressing the multifaceted determinants of postoperative cognitive outcomes.

Reference: Sieber F, McIsaac DI, Deiner S, et al. 2025 American Society of Anesthesiologists Practice Advisory for Perioperative Care of Older Adults Scheduled for Inpatient Surgery. Anesthesiology. 2025;142(1):22–51. https://doi.org/10.1097/ALN.0000000000005172

 

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RCT: Early Restrictive vs Liberal Oxygen Strategy in Severe Trauma – No Significant Outcome Difference

22 Dec, 2024 | 17:21h | UTC

Background: The Advanced Trauma Life Support (ATLS) guidelines recommend providing supplemental oxygen to severely injured patients in the early phase after trauma, although the evidence base is limited. Observational research suggests that liberal oxygen administration may raise the risk of death and respiratory complications. Therefore, the TRAUMOX2 trial examined whether an 8-hour restrictive oxygen strategy (targeting an SpO₂ of 94%) could improve outcomes compared with a liberal strategy (12–15 L/min or FiO₂ 0.6–1.0) initiated prehospital or upon trauma center admission.

Objective: To determine whether an early restrictive oxygen approach, as compared with a liberal approach, reduces the composite outcome of death and/or major respiratory complications (pneumonia or ARDS) within 30 days in severely injured adults.

Methods: This investigator-initiated, international, multicenter, open-label, randomized controlled trial enrolled patients aged 18 years or older with blunt or penetrating trauma requiring full trauma team activation and anticipated hospital stay of at least 24 hours. Randomization occurred either prehospital or upon trauma center arrival in a 1:1 ratio to restrictive (lowest dose of oxygen to maintain SpO₂ at 94%) versus liberal therapy (12–15 L/min via nonrebreather mask or FiO₂ 0.6–1.0). The intervention lasted 8 hours, with all other management per standard care. The primary outcome—death or major respiratory complications (pneumonia per CDC criteria or ARDS per the Berlin definition)—was evaluated by blinded assessors within 30 days. Statistical analyses employed logistic regression, adjusted for stratification variables.

Results: Among 1979 randomized patients, 1508 completed the study (median age, 50 years; Injury Severity Score [ISS], 14). The composite primary outcome occurred in 16.1% (118/733) of restrictive-group patients and 16.7% (121/724) of liberal-group patients (odds ratio, 1.01; 95% CI, 0.75–1.37; p=0.94). Mortality alone (8.6% vs 7.3%) and major respiratory complications alone (8.9% vs 10.8%) showed no significant differences between groups. Adverse and serious adverse events were similar, except atelectasis was less frequent in the restrictive group (27.6% vs 34.7%).

Conclusions: In severely injured trauma patients, an 8-hour restrictive oxygen strategy did not significantly reduce death or major respiratory complications compared with a liberal strategy. Both approaches produced similar 30-day outcomes. Nevertheless, restricting oxygen may limit atelectasis and could be a reasonable alternative to giving high-flow oxygen to all trauma patients.

Implications for Practice: Clinicians may choose to target approximately 94% SpO₂ in the early trauma phase without compromising major outcomes. This approach potentially avoids the risks of hyperoxia, though no definitive survival benefit was identified. Pragmatic implementation of a conservative oxygen strategy seems feasible in diverse prehospital and hospital settings.

Study Strengths and Limitations: Notable strengths include multicenter design, randomized enrollment in prehospital and in-hospital settings, and blinded outcome assessment. Limitations include postrandomization exclusions of patients with minor injuries, a relatively short intervention period (8 hours), and an overall open-label design. These factors, along with lower-than-expected event rates, may have limited the power to detect differences in mortality. Commentary from https://bit.ly/bottomline_traumox2 also highlights that the median ISS of 14 indicates moderate rather than extremely severe trauma, possibly contributing to the modest event rates.

Future Research: Large-scale studies with extended intervention durations and targeted subgroups (e.g., severe traumatic brain injury) could clarify optimal oxygen thresholds in trauma care. Ongoing trials with larger sample sizes may better capture smaller but clinically meaningful differences in mortality or complications.

Reference: Arleth T, Baekgaard J, Siersma V, et al. Early Restrictive vs Liberal Oxygen for Trauma Patients: The TRAUMOX2 Randomized Clinical Trial. JAMA. Published online December 10, 2024. DOI: http://doi.org/10.1001/jama.2024.25786

 

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Meta-Analysis: Endovascular Therapy for Vertebrobasilar Occlusion Improves Functional Outcomes

19 Dec, 2024 | 22:56h | UTC

Background: Acute vertebrobasilar artery occlusion (VBAO) is associated with high mortality and severe neurological deficits. Previous randomized trials of endovascular therapy (EVT) for VBAO have shown inconsistent results, leaving uncertainty about its efficacy across different patient subgroups.

Objective: To determine whether EVT confers improved 90-day functional outcomes compared with standard medical therapy alone in patients with acute VBAO and to explore treatment effect heterogeneity in prespecified subgroups.

Methods: This individual patient data meta-analysis included all four major randomized controlled trials (ATTENTION, BAOCHE, BASICS, BEST) that enrolled patients with VBAO treated within 24 hours of estimated onset. Participants received either EVT or best medical therapy. The primary outcome was a favorable functional status at 90 days (modified Rankin Scale [mRS] score 0–3). Secondary outcomes included functional independence (mRS 0–2), distribution of mRS scores (shift analysis), symptomatic intracranial hemorrhage (sICH), and all-cause mortality at 90 days.

Results: Among 988 patients (556 EVT; 432 control), median age 67 years, EVT significantly increased the proportion achieving mRS 0–3 (45% vs 30%; adjusted odds ratio [aOR] 2.41, 95% CI 1.78–3.26) and mRS 0–2 (35% vs 21%; aOR 2.52, 95% CI 1.82–3.48). EVT improved the overall distribution of functional outcomes (aOR for mRS shift 2.09, 95% CI 1.61–2.71) and reduced 90-day mortality (36% vs 45%; aOR 0.60, 95% CI 0.45–0.80). Although sICH was more common with EVT (5% vs <1%; aOR 11.98, 95% CI 2.82–50.81), the net clinical benefit remained strongly in favor of EVT. Subgroup analyses showed broadly consistent benefit, though the advantage was uncertain for patients with mild baseline severity (NIHSS <10).

Conclusions: EVT for acute VBAO significantly improves functional outcomes and reduces mortality despite a higher sICH risk. These results support EVT as a standard consideration in appropriately selected patients with moderate-to-severe VBAO. The benefit’s magnitude is comparable to that seen in anterior circulation large vessel occlusions, although caution is advised in mild cases and those with extensive baseline infarction.

Implications for Practice: Clinicians should consider EVT for most patients presenting with acute VBAO. While sICH risk is increased, the substantial improvements in function and survival justify its use in suitable candidates. Careful imaging and clinical assessment remain critical for optimal patient selection.

Study Strengths and Limitations: Strengths include a pooled individual patient dataset from all major VBAO EVT trials, allowing detailed subgroup analyses. Limitations involve early trial termination, underrepresentation of women, predominance of Asian populations, and exclusion of patients with very mild symptoms or large baseline infarcts, potentially limiting generalizability.

Future Research: Further trials are needed to define EVT’s role in patients with mild symptoms, isolated vertebral occlusion, large infarcts, or those presenting beyond 24 hours. Additional studies should assess real-world applicability and diverse patient populations.

Reference: Nogueira RG, et al. Endovascular therapy for acute vertebrobasilar occlusion (VERITAS): a systematic review and individual patient data meta-analysis. DOI: http://doi.org/10.1016/S0140-6736(24)01820-8

 

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