Critical Care & Emergencies (all articles)
Cohort Study: Late Ventricular Arrhythmias After Primary PCI for STEMI Are Rare but Increase Mortality
5 Nov, 2024 | 15:24h | UTCBackground: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are critical complications following ST-segment elevation myocardial infarction (STEMI). While early VT/VF typically occurs before or shortly after reperfusion, contemporary data on the incidence of late VT/VF post-primary percutaneous coronary intervention (PCI) are limited. Understanding the risk of late VT/VF is essential for optimizing in-hospital monitoring and discharge timing.
Objective: To assess the risk of late VT and VF after primary PCI in patients with STEMI, identify associated factors, and evaluate their impact on in-hospital mortality.
Methods: This cohort study analyzed data from 174,126 adults with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, using the National Cardiovascular Data Registry Chest Pain–MI Registry. Late VT/VF was defined as events occurring one or more days after PCI. Multivariable logistic regression was employed to identify factors associated with late VT/VF and its association with in-hospital mortality.
Results: Among the patients, 8.9% experienced VT or VF after primary PCI. Late VT/VF occurred in 2.4% of patients overall and 1.7% of those with uncomplicated STEMI. Late VT/VF associated with cardiac arrest was rare, occurring in 0.4% of all patients and 0.1% of patients with uncomplicated STEMI. Decreased left ventricular ejection fraction (LVEF) was the most significant factor associated with late VT/VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54–1.85). Late VT/VF was linked to increased odds of in-hospital mortality (AOR, 6.40; 95% CI, 5.63–7.29).
Conclusions: Late VT/VF after primary PCI for STEMI is infrequent, particularly in patients with uncomplicated presentations. However, when late VT/VF occurs, it is associated with a significantly higher risk of in-hospital mortality.
Implications for Practice: While vigilant monitoring remains crucial, patients with uncomplicated STEMI may be candidates for earlier discharge through shared decision-making. Identifying high-risk patients for late VT/VF can enable tailored monitoring strategies to improve outcomes.
Study Strengths and Limitations: Strengths include a large, contemporary cohort and detailed data on in-hospital VT/VF events. Limitations involve the observational design, potential unmeasured confounders, and the inability to differentiate between VT and VF due to registry definitions.
Future Research: Further studies are warranted to develop precise risk prediction models for late VT/VF and to explore effective out-of-hospital monitoring strategies post-STEMI.
RCT: No Significant Difference Between Intraosseous and Intravenous Vascular Access in Out-of-Hospital Cardiac Arrest Outcomes
3 Nov, 2024 | 12:58h | UTCBackground: Out-of-hospital cardiac arrest (OHCA) is a major global health concern, resulting in high mortality rates despite advancements in emergency care. In Denmark alone, approximately 5,000 cases occur annually, with a 30-day survival rate of only about 14%. Rapid vascular access during cardiopulmonary resuscitation (CPR) is crucial for administering medications like epinephrine, as recommended by international guidelines. Both intraosseous (IO) and intravenous (IV) routes are routinely used, but their comparative effectiveness remains unclear. Current guidelines favor IV access for initial attempts, yet this recommendation is based on very low-certainty evidence, highlighting the need for well-designed clinical trials.
Objective: To compare the effectiveness of initial intraosseous versus intravenous vascular access on sustained return of spontaneous circulation (ROSC) in adults experiencing nontraumatic OHCA.
Methods: This randomized, parallel-group superiority trial was conducted across all five regions of Denmark, covering 5.9 million inhabitants. Adults aged 18 years or older with nontraumatic OHCA requiring vascular access during CPR were randomized to receive either initial IO or IV access. The IO group was further randomized to humeral or tibial access for a secondary comparison. The primary outcome was sustained ROSC, defined as no need for chest compressions for at least 20 minutes. Key secondary outcomes included 30-day survival and survival with favorable neurologic outcome (modified Rankin scale score of 0–3). Procedural outcomes such as success rates of vascular access within two attempts, time to successful access, and time to first epinephrine administration were also assessed.
Results: Among 1,479 patients included in the primary analysis (731 in the IO group and 748 in the IV group), successful vascular access within two attempts was achieved in 92% of the IO group versus 80% of the IV group. Despite the higher success rate with IO access, the time to first successful access and time to first epinephrine dose were similar between groups. Sustained ROSC occurred in 30% of patients in the IO group and 29% in the IV group (risk ratio [RR], 1.06; 95% confidence interval [CI], 0.90–1.24; P=0.49). At 30 days, survival rates were 12% in the IO group and 10% in the IV group (RR, 1.16; 95% CI, 0.87–1.56), with favorable neurologic outcomes observed in 9% and 8% of patients, respectively (RR, 1.16; 95% CI, 0.83–1.62). No significant differences were found in procedural times, adverse events, or quality-of-life measures among survivors.
Conclusions: In adults with nontraumatic OHCA, initial intraosseous vascular access did not result in a significant difference in sustained ROSC compared to intravenous access. Both methods yielded comparable survival rates and neurologic outcomes at 30 days, suggesting that the choice of vascular access route may not critically impact immediate resuscitation success.
Implications for Practice: These findings indicate that emergency medical services can opt for either intraosseous or intravenous vascular access during resuscitation based on provider expertise, patient anatomy, and situational considerations without adversely affecting patient outcomes. Emphasizing flexibility in vascular access approach may facilitate quicker access and streamline resuscitation efforts in the prehospital setting.
Study Strengths and Limitations: Strengths include the randomized design, large sample size, and nationwide implementation, enhancing generalizability. Limitations involve potential crossover between groups, lack of blinding among clinicians, and the study being underpowered to detect small differences in long-term outcomes.
Future Research: Further studies are needed to assess long-term survival and neurologic outcomes, and to explore whether specific patient subgroups may benefit more from one vascular access method over the other during cardiac arrest resuscitation.
Reference: Vallentin MF, Granfeldt A, Klitgaard TL, et al. Intraosseous or Intravenous Vascular Access for Out-of-Hospital Cardiac Arrest. New England Journal of Medicine. 2024 Oct 31; DOI: http://doi.org/10.1056/NEJMoa2407616
RCT: Intraosseous vs. Intravenous Drug Administration in Out-of-Hospital Cardiac Arrest Shows No Difference in 30-Day Survival
3 Nov, 2024 | 12:48h | UTCBackground: Out-of-hospital cardiac arrest requires rapid drug administration, with medications like epinephrine being highly time-dependent. Intravenous access can be challenging prehospital due to environmental and patient factors, potentially delaying treatment. Intraosseous access may offer faster drug delivery, but its impact on clinical outcomes is unclear.
Objective: To compare the effectiveness of an intraosseous-first versus intravenous-first vascular access strategy on 30-day survival in adults experiencing out-of-hospital cardiac arrest requiring drug therapy.
Methods: In this multicenter, open-label, randomized trial across 11 UK emergency medical systems, 6,082 adults were assigned to receive either intraosseous-first or intravenous-first vascular access during resuscitation. The primary outcome was survival at 30 days. Secondary outcomes included return of spontaneous circulation and favorable neurologic function at hospital discharge (modified Rankin scale score ≤3).
Results: At 30 days, survival was 4.5% in the intraosseous group and 5.1% in the intravenous group (adjusted odds ratio [OR], 0.94; 95% confidence interval [CI], 0.68–1.32; P=0.74). Favorable neurologic outcome at discharge was similar between groups (2.7% vs. 2.8%; adjusted OR, 0.91; 95% CI, 0.57–1.47). Return of spontaneous circulation was lower in the intraosseous group (36.0% vs. 39.1%; adjusted OR, 0.86; 95% CI, 0.76–0.97).
Conclusions: An intraosseous-first vascular access strategy did not improve 30-day survival compared to an intravenous-first strategy in adults with out-of-hospital cardiac arrest. The intraosseous route was associated with a lower rate of return of spontaneous circulation.
Implications for Practice: Paramedics should consider that intraosseous access may not offer a survival advantage over intravenous access and may be linked to a reduced return of spontaneous circulation. This finding may influence decisions on vascular access during resuscitation efforts.
Study Strengths and Limitations: Strengths include a large, multicenter randomized design; limitations involve early termination reducing statistical power and inability to blind prehospital providers.
Future Research: Further studies should investigate why intraosseous access is associated with lower return of spontaneous circulation and assess if specific intraosseous techniques or sites affect outcomes.
RCT: ICS-Formoterol and ICS-SABA Reduce Severe Asthma Exacerbations Compared With SABA Alone
28 Oct, 2024 | 18:12h | UTCBackground: Asthma affects millions worldwide and is managed using inhaled relievers to alleviate acute symptoms. While short-acting β agonists (SABA) are commonly used, combining inhaled corticosteroids (ICS) with SABA or formoterol may enhance outcomes. Recent guidelines recommend ICS-formoterol as the preferred reliever, but the optimal choice remains uncertain, especially following the recent FDA approval of ICS-SABA.
Objective: To compare the efficacy and safety of SABA alone, ICS-SABA, and ICS-formoterol as reliever therapies in asthma.
Methods: This systematic review and network meta-analysis included 27 randomized controlled trials involving 50,496 adult and pediatric asthma patients. Trials compared SABA alone, ICS-SABA, and ICS-formoterol as reliever therapies, ensuring similar maintenance treatments across groups. Outcomes assessed were severe asthma exacerbations, asthma symptom control (Asthma Control Questionnaire-5 [ACQ-5]), asthma-related quality of life (Asthma Quality of Life Questionnaire [AQLQ]), adverse events, and mortality.
Results: Compared with SABA alone, both ICS-containing relievers significantly reduced severe exacerbations:
- ICS-formoterol: Risk ratio (RR) 0.65 (95% CI, 0.60–0.72); risk difference (RD) –10.3% (95% CI, –11.8% to –8.3%).
- ICS-SABA: RR 0.84 (95% CI, 0.73–0.95); RD –4.7% (95% CI, –8.0% to –1.5%).
Compared with ICS-SABA, ICS-formoterol further reduced severe exacerbations (RR 0.78; RD –5.5%). Both ICS-containing relievers modestly improved asthma symptom control compared with SABA alone. No increase in adverse events was observed with either ICS-containing therapy.
Conclusions: Both ICS-formoterol and ICS-SABA as reliever therapies reduce severe asthma exacerbations and improve symptom control compared with SABA alone, without increasing adverse events. ICS-formoterol may offer additional benefits over ICS-SABA in reducing exacerbations.
Implications for Practice: These findings support the use of ICS-containing reliever therapies over SABA alone in asthma management to reduce severe exacerbations and improve control. ICS-formoterol may be preferred when a greater reduction in exacerbations is desired.
Study Strengths and Limitations: High-certainty evidence strengthens these conclusions, but the lack of direct comparisons between ICS-formoterol and ICS-SABA and limited pediatric data are notable limitations.
Future Research: Direct head-to-head trials comparing ICS-formoterol and ICS-SABA, particularly in pediatric populations, are needed to confirm these findings.
RCT: Early DOACs Safe and Non-Inferior to Delayed Initiation Post-Stroke with Atrial Fibrillation
28 Oct, 2024 | 17:52h | UTCBackground: Atrial fibrillation increases ischaemic stroke risk, and patients are prone to recurrence. Prompt anticoagulation post-stroke is critical, but optimal timing is unclear due to bleeding concerns. Guidelines often delay DOAC initiation without strong evidence.
Objective: To determine if early DOAC initiation (≤4 days) is non-inferior to delayed initiation (7–14 days) in preventing recurrent ischaemic events without increasing intracranial haemorrhage risk in patients with acute ischaemic stroke and atrial fibrillation.
Methods: In this multicentre, open-label, blinded-endpoint, phase 4 randomised controlled trial at 100 UK hospitals, 3,621 adults with atrial fibrillation and acute ischaemic stroke were randomised to early or delayed DOAC initiation. Eligibility required physician uncertainty about timing. Participants and clinicians were unmasked; outcomes were adjudicated by a masked committee. The primary outcome was a composite of recurrent ischaemic stroke, symptomatic intracranial haemorrhage, unclassifiable stroke, or systemic embolism within 90 days.
Results: Among 3,621 patients (mean age 78.5; 45% female), the primary outcome occurred in 59 patients (3.3%) in both early and delayed groups (adjusted risk difference 0.0%, 95% CI –1.1 to 1.2%). Upper confidence limit below the 2% non-inferiority margin (p=0.0003) confirmed non-inferiority. Symptomatic intracranial haemorrhage rates were similar (0.6% early vs 0.7% delayed; p=0.78). No significant differences in mortality or heterogeneity across subgroups.
Conclusions: Early DOAC initiation within 4 days is non-inferior to delayed initiation in preventing recurrent events without increasing intracranial haemorrhage risk. Findings challenge guidelines advising delayed anticoagulation and support early initiation regardless of stroke severity.
Implications for Practice: Clinicians should consider starting DOACs within 4 days post-stroke in atrial fibrillation patients. Early initiation is safe and effective, potentially improving outcomes and suggesting guidelines may need revision.
Study Strengths and Limitations: Strengths include large sample size and masked outcome adjudication. Limitations include exclusion of patients with very severe strokes and low event rates, potentially limiting detection of rare adverse events.
Future Research: Further studies should explore optimal DOAC timing within 4 days and assess safety in patients with severe strokes or extensive haemorrhagic transformation.
RCT: Granulocyte Colony-Stimulating Factor (GCSF) Enhances 90-Day Survival and Reduces Complications in Severe Alcohol-Associated Hepatitis
20 Oct, 2024 | 17:23h | UTCStudy Design and Population: This randomized trial evaluated 126 patients with severe alcohol-associated hepatitis (SAH) eligible for steroid treatment, with discriminant function scores between 32 and 90. Patients were randomized into three groups: prednisolone alone, GCSF alone, and combined GCSF plus prednisolone (GPred). Prednisolone was administered at 40 mg/day, while GCSF was given at 150-300 mcg/d for 7 days, then every third day for up to 12 doses over a month.
Main Findings: The GPred group showed significantly higher 90-day survival (88.1%) compared to prednisolone alone (64.3%, P = 0.03) and GCSF alone (78.6%). The 28-day survival was similar across groups. The GPred group also had more steroid responders by day 7 and showed greater improvements in discriminant function and MELDNa scores. Additionally, patients in the GPred group had significantly lower rates of infections, acute kidney injury, hepatic encephalopathy, and rehospitalizations.
Implications for Practice: Adding GCSF to prednisolone improves survival and reduces the risk of infections and complications in patients with severe alcohol-associated hepatitis. This combination therapy could be considered for improving outcomes in steroid-eligible patients with SAH.
Review: Endovascular Management of Acute Stroke
20 Oct, 2024 | 14:43h | UTCIntroduction: Stroke due to large vessel occlusion (LVO) remains a leading cause of disability and mortality worldwide. Endovascular therapy has revolutionized acute ischemic stroke management by enhancing recanalization rates and improving patient outcomes. This review outlines the evolution of endovascular treatments, expansion of therapeutic indications, current best practices, and ongoing research in the endovascular management of acute stroke.
Key Recommendations:
- Early Time Window Therapy (0–6 Hours): Robust evidence from randomized controlled trials demonstrates that mechanical thrombectomy significantly improves functional outcomes in patients with anterior circulation LVO presenting within 6 hours of symptom onset. Patients are selected based on moderate-to-severe neurological deficits and small infarct cores identified via imaging.
- Extended Time Window Therapy (6–24 Hours): Trials such as DAWN and DEFUSE3 have extended thrombectomy benefits to patients up to 24 hours after symptom onset. Advanced imaging techniques, like CT perfusion and MRI, identify patients with substantial penumbral tissue, indicating potential for recovery.
- Large Ischemic Core Infarcts: Recent studies (e.g., SELECT2, ANGEL-ASPECT) suggest that patients with large core infarcts can benefit from endovascular therapy, challenging previous contraindications. Individualized patient selection is crucial to balance risks and benefits.
- Basilar Artery Occlusion: New evidence supports thrombectomy for basilar artery occlusions, especially in patients with moderate-to-severe symptoms. This intervention improves outcomes in a condition historically associated with high morbidity and mortality.
- Bridging Thrombolysis: The necessity of intravenous thrombolysis before thrombectomy in patients directly admitted to endovascular centers is under debate. Meta-analyses indicate that omitting thrombolysis may not adversely affect outcomes, although it remains standard for patients at non-thrombectomy centers.
- Simplified Imaging for Patient Selection: The use of non-contrast CT and CT angiography alone has proven effective for patient selection, reducing treatment delays and expanding access to thrombectomy, particularly in resource-limited settings.
Conclusion: Advancements in endovascular therapy have markedly improved outcomes for patients with acute ischemic stroke due to LVO. Expanded treatment indications and simplified imaging protocols have broadened patient eligibility for thrombectomy. Ongoing research into adjunctive therapies and optimization of management strategies holds promise for further reducing stroke-related disability and mortality.
Cohort Study: Ondansetron Initiation Linked to Increased 10-Day Sudden Cardiac Death Risk in Hemodialysis Patients
20 Oct, 2024 | 14:05h | UTCBackground: Individuals undergoing maintenance hemodialysis have a markedly elevated risk of sudden cardiac death, attributed to structural heart disease, electrolyte imbalances, and polypharmacy. Ondansetron, a commonly used antiemetic known to prolong the QT interval, has been associated with fatal arrhythmias when administered intravenously in the general population. However, its cardiac safety profile in the hemodialysis population remains unclear.
Objective: To assess whether initiation of oral ondansetron, compared to antiemetics with lesser QT-prolonging potential, is associated with a higher 10-day risk of sudden cardiac death among patients receiving maintenance hemodialysis.
Methods: This new-user, active-comparator cohort study analyzed data from the United States Renal Data System between 2012 and 2019. A total of 119,254 patients receiving in-center hemodialysis who initiated either oral ondansetron or comparator antiemetics (promethazine, metoclopramide, or prochlorperazine) were included. Inverse probability of treatment-weighted survival models estimated adjusted hazard ratios (aHR) and risk differences (aRD), using an intention-to-treat approach with non-sudden cardiac death as a competing event.
Results: Among the patients, 64,978 (55%) initiated ondansetron, while 54,276 (45%) initiated comparator antiemetics. Ondansetron initiation was associated with a higher 10-day risk of sudden cardiac death compared to comparator drugs (aHR 1.44; 95% CI, 1.08–1.93; aRD 0.06%; 95% CI, 0.01%–0.11%). The number needed to harm was 1,688. Secondary analyses of additional cardiac outcomes, including ventricular arrhythmias and cardiovascular mortality, yielded consistent findings.
Conclusions: Initiation of oral ondansetron is associated with an increased short-term risk of sudden cardiac death among patients on maintenance hemodialysis compared to initiation of antiemetics with lesser QT-prolonging potential.
Implications for Practice: Clinicians should exercise caution when prescribing ondansetron to hemodialysis patients and consider alternative antiemetics with lower QT-prolonging risks. If ondansetron is necessary, monitoring for cardiac arrhythmias and performing electrocardiograms may be advisable to mitigate potential risks.
Study Strengths and Limitations: Strengths include a large, nationally representative cohort and an active-comparator design that minimizes confounding. Limitations involve potential residual confounding inherent in observational studies, possible misclassification of outcomes, and inability to assess dose-response relationships due to power constraints.
Future Research: Further studies are warranted to confirm these findings, elucidate the underlying mechanisms of increased cardiac risk, and evaluate the safety of ondansetron across different dosages and patient subgroups within the hemodialysis population.
RCT: More Frequent Screening with Pressure-Supported SBTs Delayed Extubation in Mechanically Ventilated Adults
13 Oct, 2024 | 13:15h | UTCBackground: Prompt liberation from mechanical ventilation is crucial to reduce complications associated with prolonged ventilator use. The optimal frequency of weaning readiness screening and the most effective spontaneous breathing trial (SBT) technique are not well established.
Objective: To evaluate whether the frequency of screening for weaning readiness (once-daily vs more frequent) and the SBT technique used (pressure-supported vs T-piece) affect the time to successful extubation in adults receiving invasive mechanical ventilation.
Methods: In a multicenter randomized clinical trial with a 2×2 factorial design, 797 critically ill adults who had been mechanically ventilated for at least 24 hours were enrolled. Participants were randomized to either once-daily or more frequent screening for weaning readiness and to undergo either pressure-supported SBTs (pressure support >0 to ≤8 cm H₂O with PEEP >0 to ≤5 cm H₂O) or T-piece SBTs, each lasting 30–120 minutes. The primary outcome was the time to successful extubation, defined as the time from starting unsupported spontaneous breathing that was sustained for at least 48 hours post-extubation.
Results: Among the 797 patients (mean age 62.4 years; 59.2% male), there was no significant difference in time to successful extubation when comparing screening frequencies (hazard ratio [HR] 0.88; 95% CI, 0.76–1.03; P = .12) or SBT techniques (HR 1.06; 95% CI, 0.91–1.23; P = .45) individually. However, a significant interaction between screening frequency and SBT technique was identified (P = .009). Specifically, in patients undergoing pressure-supported SBTs, more frequent screening *delayed* time to successful extubation compared to once-daily screening (HR 0.70; 95% CI, 0.50–0.96; P = .02). Conversely, when T-piece SBTs were used, the frequency of screening did not significantly affect extubation time. The median time to successful extubation was shortest in the once-daily screening with pressure-supported SBT group (2.0 days) and longest in the more frequent screening with pressure-supported SBT group (3.9 days).
Conclusions: More frequent screening combined with pressure-supported SBTs resulted in a *longer* time to successful extubation, suggesting this combination may delay weaning from mechanical ventilation. Once-daily screening with pressure-supported SBTs showed a trend toward faster extubation compared to other strategies, although this was not statistically significant.
Implications for Practice: Clinicians should be cautious about combining more frequent screening with pressure-supported SBTs, as this may unintentionally prolong mechanical ventilation. Adopting once-daily screening with pressure-supported SBTs might facilitate earlier extubation.
Study Strengths and Limitations: Strengths of the study include its large sample size, multicenter design, and high adherence to the intervention protocols. Limitations involve the unexpected significant interaction between interventions, which may limit the generalizability of the results.
Future Research: Additional studies are warranted to confirm the interaction between screening frequency and SBT technique and to explore the mechanisms underlying the delayed extubation with more frequent screening and pressure-supported SBTs.
Guideline: SCAI Expert Consensus on Management of STEMI Patients Undergoing Primary PCI
13 Oct, 2024 | 12:44h | UTCIntroduction: ST-elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality, requiring rapid diagnosis and timely reperfusion. While primary percutaneous coronary intervention (PCI) is the preferred reperfusion method, existing guidelines lack detailed procedural and technical recommendations for the cardiac catheterization laboratory (CCL). The Society for Cardiovascular Angiography & Interventions (SCAI) presents this expert consensus statement to provide best practices for CCL team readiness, optimal angiography and intervention techniques, management of special circumstances and anatomical subsets, and strategies to improve quality of care in STEMI patients undergoing primary PCI.
Key Recommendations:
- CCL Team Readiness:
- Prehospital notification and ECG transmission expedite care.
- Implement emergency department (ED) bypass when feasible.
- Perform a focused cardiovascular assessment prior to PCI.
- Arterial Access:
- Prefer transradial access over femoral to reduce complications.
- Use ultrasound guidance and contemporary techniques for femoral access when necessary.
- Diagnostic Assessment:
- Conduct complete coronary angiography during the index procedure.
- Measure left ventricular end-diastolic pressure (LVEDP) to guide management.
- Managing Thrombus:
- Assess thrombus burden after wire crossing.
- Use bail-out aspiration thrombectomy selectively for large thrombus burden.
- Consider parenteral or intracoronary antiplatelet agents for refractory thrombus.
- Managing No-Reflow:
- Administer intracoronary vasodilators to the distal bed.
- Enhance coronary perfusion pressure by augmenting mean arterial pressure and reducing LVEDP.
- Intracoronary Imaging:
- Encourage routine use of IVUS or OCT to guide PCI.
- Employ intracoronary imaging to investigate stent thrombosis or suspected nonatherosclerotic causes.
- Special Circumstances:
- In cardiogenic shock, perform right heart catheterization and consider mechanical circulatory support.
- After failed fibrinolysis, proceed with immediate catheterization and rescue PCI.
- In multivessel disease, complete revascularization is recommended.
- Anatomical Subsets:
- Use plaque modification techniques for calcified lesions.
- Prefer a provisional one-stent strategy in bifurcation lesions.
- Focus on restoring flow in coronary aneurysms.
- Nonatherosclerotic STEMI Causes:
- Administer intracoronary nitroglycerin to identify epicardial vasospasm.
- Manage spontaneous coronary artery dissection conservatively if flow is preserved.
- Use thrombectomy for coronary embolism.
- Investigate MINOCA with additional imaging and testing.
- Quality Improvement:
- Track all STEMI cases to assess treatment times and outcomes for continuous improvement.
Conclusion: Adherence to these recommendations is expected to enhance patient outcomes by optimizing procedural strategies, reducing complications, and improving survival in STEMI patients undergoing primary PCI.
Management of Ascites in Cirrhosis: Key Recommendations from the British Society of Gastroenterology Guidelines
12 Oct, 2024 | 18:23h | UTCIntroduction: Ascites, the pathological accumulation of fluid within the peritoneal cavity, is a common and serious complication of cirrhosis, indicating advanced liver disease and portending increased morbidity and mortality. Recognizing the need for updated clinical guidance, the British Society of Gastroenterology (BSG), in collaboration with the British Association for the Study of the Liver (BASL), has issued comprehensive guidelines. These aim to standardize the diagnosis and management of ascites in cirrhotic patients, incorporating recent advances to optimize patient outcomes.
Key Recommendations:
- Diagnostic Paracentesis: It is strongly recommended that all patients with new-onset ascites undergo diagnostic paracentesis to measure total protein concentration and calculate the serum-ascites albumin gradient (SAAG). (Quality of evidence: moderate; Recommendation: strong)
- Spontaneous Bacterial Peritonitis (SBP): Prompt diagnostic paracentesis should be performed in hospitalized patients with ascites, especially those with gastrointestinal bleeding or signs of infection, to rule out SBP. An ascitic neutrophil count >250/mm³ confirms SBP, necessitating immediate empirical antibiotic therapy tailored to local resistance patterns. (Quality of evidence: moderate; Recommendation: strong)
- Dietary Salt Restriction: Patients should restrict dietary sodium intake to no more than 5–6.5 grams per day (87–113 mmol), equivalent to a no-added-salt diet, to manage fluid accumulation effectively. (Quality of evidence: moderate; Recommendation: strong)
- Diuretic Therapy: For initial moderate ascites, spironolactone monotherapy is recommended. In cases of recurrent severe ascites, combination therapy with spironolactone and furosemide is advised. Regular monitoring for adverse events such as electrolyte imbalances and renal impairment is essential. (Quality of evidence: moderate; Recommendation: strong)
- Large Volume Paracentesis (LVP): LVP is a safe and effective treatment for refractory ascites. Informed consent is required, and routine coagulation studies or prophylactic blood product infusions before the procedure are not recommended. (Quality of evidence: moderate; Recommendation: strong)
- Use of Human Albumin Solution (HAS): After LVP exceeding 5 liters, infusion of HAS at 8 grams per liter of ascites removed is strongly recommended to prevent circulatory dysfunction. (Quality of evidence: high; Recommendation: strong)
- Transjugular Intrahepatic Portosystemic Shunt (TIPSS): TIPSS should be considered for patients with refractory ascites not responding to medical therapy, with caution exercised in patients over 70 years or those with significant comorbidities. (Quality of evidence: high; Recommendation: strong)
- Non-Selective Beta-Blockers (NSBBs): The presence of refractory ascites is not a contraindication for NSBB therapy. Patients should be closely monitored, and dose adjustments made in cases of hypotension or renal dysfunction. (Quality of evidence: moderate; Recommendation: strong)
- Palliative Care: Patients unsuitable for liver transplantation should be offered palliative care referral to focus on symptom management and quality of life improvement. Alternative interventions for refractory ascites may also be considered. (Quality of evidence: weak; Recommendation: strong)
Conclusion: Implementation of these evidence-based guidelines is expected to enhance patient care by promoting early diagnosis, preventing complications, and standardizing management strategies for ascites in cirrhosis. Adherence to these recommendations can improve clinical outcomes, reduce hospitalizations, and enhance the quality of life for affected patients.
RCT: Liberal Transfusion Strategy Reduced Unfavorable Neurological Outcomes in Acute Brain Injury
12 Oct, 2024 | 11:01h | UTCBackground: Patients with acute brain injury frequently develop anemia, and the optimal hemoglobin threshold for red blood cell transfusion in this population remains uncertain. Previous studies have shown conflicting results regarding the benefits of liberal versus restrictive transfusion strategies on neurological outcomes.
Objective: To determine whether a liberal transfusion strategy (hemoglobin threshold <9 g/dL) reduces the occurrence of unfavorable neurological outcomes at 180 days compared to a restrictive strategy (hemoglobin threshold <7 g/dL) in patients with acute brain injury.
Methods: The TRAIN trial, a multicenter, phase 3, randomized clinical trial, was conducted across 72 ICUs in 22 countries. It included patients with traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage, who had hemoglobin levels below 9 g/dL within the first 10 days post-injury. Participants were randomized to a liberal strategy (transfusion triggered by hemoglobin <9 g/dL) or a restrictive strategy (transfusion triggered by hemoglobin <7 g/dL), with primary outcomes measured by the occurrence of an unfavorable neurological outcome, defined by a Glasgow Outcome Scale Extended score of 1-5 at 180 days.
Results: Among 820 patients who completed the trial (mean age 51 years; 45.9% women), 806 had data on the primary outcome (393 liberal, 413 restrictive). The liberal group received a median of 2 units of blood (IQR, 1–3), while the restrictive group received a median of 0 units (IQR, 0–1), with an absolute mean difference of 1.0 unit (95% CI, 0.87–1.12 units). At 180 days, 62.6% of patients in the liberal group had an unfavorable neurological outcome compared to 72.6% in the restrictive group (absolute difference –10.0%; 95% CI, –16.5% to –3.6%; adjusted relative risk 0.86; P = .002). The effect was consistent across prespecified subgroups. Cerebral ischemic events were lower in the liberal group (8.8% vs 13.5%; relative risk 0.65; 95% CI, 0.44–0.97). No significant differences were observed in 28-day survival or other secondary outcomes.
Conclusions: In patients with acute brain injury and anemia, a liberal transfusion strategy resulted in a lower rate of unfavorable neurological outcomes at 180 days compared to a restrictive strategy.
Implications for Practice: A liberal transfusion threshold of 9 g/dL may improve neurological outcomes in patients with acute brain injury by reducing cerebral ischemic events. Clinicians should consider adopting a higher hemoglobin threshold for transfusion in this population, weighing the benefits against potential risks associated with transfusions, such as infection or lung injury.
Study Strengths and Limitations: Strengths include the large, multicenter international design and blinding of outcome assessors. Limitations involve the open-label nature, potential detection bias in assessing cerebral ischemic events, lack of standardized neuroprognostication, and incomplete assessment of concomitant interventions.
Future Research: Further studies are needed to confirm these findings in specific subgroups of acute brain injury, to explore optimal transfusion strategies, and to assess long-term outcomes and potential risks associated with liberal transfusion thresholds.
RCT: Tele-ICU Intervention Did Not Significantly Reduce ICU Length of Stay in Critically Ill Patients
10 Oct, 2024 | 17:40h | UTCBackground: Telemedicine in critical care, particularly through tele-ICU interventions, has gained traction as a potential solution to the global shortage of intensivists. These systems, which include remote intensivist-led care, have shown promise in improving outcomes, but robust evidence from randomized clinical trials is lacking. The TELESCOPE trial was conducted to assess whether daily remote multidisciplinary rounds combined with monthly audit and feedback meetings could reduce ICU length of stay (LOS) compared with standard care.
Objective: The primary objective of the TELESCOPE trial was to determine if a tele-ICU intervention, involving remote daily multidisciplinary rounds and monthly performance audits led by a board-certified intensivist, could reduce ICU LOS compared to usual care.
Methods: This was a cluster randomized clinical trial involving 30 general ICUs in Brazil, enrolling all consecutive adult patients admitted between June 2019 and April 2021. A total of 17,024 patients were included, with 15 ICUs receiving the tele-ICU intervention and 15 receiving standard care. The intervention consisted of daily remote rounds led by an intensivist, monthly audit meetings, and the provision of evidence-based protocols. The primary outcome was ICU LOS, and secondary outcomes included hospital mortality, ICU efficiency, and various infection rates.
Results: There was no statistically significant difference in ICU LOS between the intervention and control groups (mean LOS: 8.1 days in the tele-ICU group vs. 7.1 days in the usual care group; percentage change, 8.2%; 95% CI, −5.4% to 23.8%; P = .24). Hospital mortality was also similar (41.6% vs. 40.2%; odds ratio, 0.93; 95% CI, 0.78-1.12). No significant differences were found in secondary outcomes, including rates of central line-associated bloodstream infections, ventilator-associated events, or ventilator-free days at 28 days.
Conclusions: The tele-ICU intervention did not reduce ICU LOS in critically ill patients. The lack of observed benefit may be due to suboptimal implementation, variable adherence by local teams, and the high severity of illness in the patient population.
Implications for Practice: While tele-ICU models hold potential, this study suggests that remote intensivist-led care, as implemented in the TELESCOPE trial, may not be sufficient to improve outcomes in high-resource ICU settings with critically ill patients.
Study Strengths and Limitations: The study’s strengths include its pragmatic design, the large number of patients enrolled, and its reflection of real-world ICU settings. However, limitations include the unblinded nature of the trial, suboptimal adherence to the tele-ICU protocol in some centers, and the strain on ICU resources during the COVID-19 pandemic, which may have affected the trial’s outcomes.
Future Research: Further studies should explore how tele-ICU interventions can be optimized, with a focus on identifying the ICU environments and patient populations most likely to benefit. Trials should also address potential barriers to effective implementation, such as staff engagement and local resource constraints.
Umbrella Review: 5-Day Antibiotic Courses Effective for Non-ICU Community-Acquired Pneumonia or Exacerbations of COPD
6 Oct, 2024 | 17:12h | UTCBackground: Respiratory tract infections (RTIs) significantly contribute to global disease burden and antibiotic usage. Optimizing antibiotic treatment duration is crucial for antimicrobial stewardship to minimize resistance. Despite evidence supporting shorter antibiotic courses for RTIs, prolonged treatment durations persist in clinical practice.
Objective: To evaluate the current evidence base for optimal antibiotic treatment durations in RTIs and determine whether shorter courses are supported.
Methods: An umbrella review was conducted by searching Ovid MEDLINE, Embase, and Web of Science up to May 1, 2024, without language restrictions. Systematic reviews comparing antibiotic treatment durations for community-acquired pneumonia (CAP), acute exacerbations of chronic obstructive pulmonary disease (AECOPD), hospital-acquired pneumonia (HAP), acute sinusitis, and streptococcal pharyngitis, tonsillitis, or pharyngotonsillitis in adults were included. Pediatric-focused reviews were excluded. Quality assessments utilized the AMSTAR 2 tool for reviews and the Cochrane risk-of-bias tool (version 1) for randomized controlled trials (RCTs). The GRADE approach determined the overall quality of evidence.
Results: Thirty systematic reviews were included, generally of low to critically low quality. For non-ICU CAP (14 reviews), moderate-quality evidence supports a 5-day antibiotic course, with insufficient data for shorter durations. In AECOPD (eight reviews), a 5-day treatment was non-inferior to longer courses regarding clinical and microbiological cure, with similar or fewer adverse events. Evidence for non-ventilator-associated HAP is lacking. In acute sinusitis, shorter regimens appear effective, but further research is needed for patients requiring antibiotics. For pharyngotonsillitis (eight reviews), evidence supports short-course cephalosporin therapy but not short-course penicillin when dosed three times daily.
Conclusions: Evidence supports a 5-day antibiotic treatment duration for non-ICU CAP and AECOPD in clinically improving patients. Implementing this evidence in practice is essential. High-quality RCTs are needed to assess shorter durations for CAP and AECOPD, establish optimal durations for HAP and acute sinusitis, and evaluate short-course penicillin with optimal dosing in pharyngotonsillitis.
Implications for Practice: Clinicians should adopt 5-day antibiotic courses for non-ICU CAP and AECOPD in patients showing clinical improvement, aligning with antimicrobial stewardship objectives to reduce unnecessary antibiotic exposure and resistance development.
Study Strengths and Limitations: Strengths include a comprehensive search and assessment of systematic reviews and meta-analyses. Limitations involve the generally low quality of included reviews and RCTs, with many studies exhibiting unclear or high risk of bias. Heterogeneity in definitions of short-course treatment and variability in patient populations and settings were also noted.
Future Research: High-quality RCTs are required to investigate antibiotic durations shorter than 5 days for CAP and AECOPD, determine optimal treatment lengths for HAP and acute sinusitis, and assess short-course penicillin therapy with optimal dosing schedules in pharyngotonsillitis.
Summary of the review “Neuroleptic Malignant Syndrome”
6 Oct, 2024 | 16:20h | UTCIn a comprehensive review published in the New England Journal of Medicine, Wijdicks and Ropper discuss neuroleptic malignant syndrome (NMS), a rare but potentially fatal complication of antipsychotic therapy characterized by fever, muscle rigidity, and autonomic dysfunction. Given the widespread use of dopamine-blocking agents across various medical specialties, it is crucial for practicing physicians to recognize and manage this syndrome promptly to improve patient outcomes.
Key Aspects Influencing Patient Care:
- Epidemiology and Risk Factors:
- NMS occurs in approximately 0.02 to 3% of patients exposed to dopamine-blocking agents.
- Risk factors include dehydration, high doses of antipsychotics, rapid dose escalation, intramuscular administration, and prior episodes of NMS.
- Both first-generation (typical) and second-generation (atypical) antipsychotics can cause NMS, though it may be less severe with atypical agents.
- Clinical Presentation:
- Hyperthermia: Elevated temperatures often exceeding 40°C.
- Muscle Rigidity: Lead-pipe rigidity leading to rhabdomyolysis and elevated creatine kinase levels.
- Autonomic Dysfunction: Tachycardia, fluctuating blood pressure, diaphoresis.
- Altered Mental Status: Ranges from agitation to stupor or catatonia.
- Laboratory Findings: Leukocytosis, electrolyte imbalances, and signs of renal impairment.
- Diagnosis:
- Based on clinical criteria including recent exposure to dopamine antagonists and presence of key symptoms.
- Important to differentiate from serotonin syndrome, malignant hyperthermia, heat stroke, and severe catatonia.
- Management:
- Immediate Discontinuation of the offending agent.
- Supportive Care in ICU:
- Stabilize vital signs and manage autonomic instability.
- Aggressive hydration to prevent renal failure from rhabdomyolysis.
- Cooling measures for hyperthermia.
- Pharmacologic Interventions:
- Dantrolene: Reduces muscle rigidity and hyperthermia.
- Dopamine Agonists: Bromocriptine or amantadine may reverse dopamine blockade.
- Benzodiazepines: Lorazepam for sedation and muscle relaxation.
- Monitoring for Complications:
- Watch for respiratory failure, renal dysfunction, electrolyte disturbances, and cardiac arrhythmias.
- Electroconvulsive Therapy (ECT):
- Considered in refractory cases unresponsive to medical management.
- Outcome and Prognosis:
- Recovery typically occurs within 7 to 11 days with appropriate treatment.
- Mortality rates have decreased but can reach up to 15% within one year due to complications.
- Rechallenge with Antipsychotics:
- If necessary, reintroduce antipsychotics cautiously after full recovery, using low doses and slow titration.
- Prefer atypical agents and monitor closely for recurrence.
Clinical Implications:
- Early Recognition: Timely identification of NMS is critical for initiating life-saving interventions.
- Interdisciplinary Approach: Collaboration among psychiatrists, intensivists, neurologists, and other specialists enhances patient care.
- Education and Prevention:
- Educate healthcare providers about the signs and risk factors of NMS.
- Monitor patients on antipsychotics closely, especially during dose changes or when using high-potency agents.
Summary of “Dialysis for Chronic Kidney Failure: A Review”
3 Oct, 2024 | 22:46h | UTCIn their comprehensive review published in JAMA on October 2, 2024, Dr. Jennifer E. Flythe and Dr. Suzanne Watnick discuss current evidence regarding the pathophysiology, diagnosis, and management of dialysis-dependent chronic kidney failure. The article emphasizes clinical considerations that directly impact patient care, particularly in the initiation and management of dialysis therapy.
Key Aspects Influencing Patient Care
- Initiation of Dialysis
- No Specific eGFR Threshold: There is no recommended estimated glomerular filtration rate (eGFR) for starting dialysis. Decisions should be individualized, focusing on persistent uremic symptoms (e.g., nausea, fatigue), volume overload (e.g., dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia.
- Shared Decision-Making: The timing of dialysis initiation should involve a collaborative approach between clinicians and patients, considering symptoms, laboratory trends, and patient preferences.
- No Mortality Benefit from Early Initiation: A randomized clinical trial found no mortality advantage in starting dialysis at higher eGFR levels (10–14 mL/min/1.73 m²) compared to lower levels (5–7 mL/min/1.73 m²).
- Dialysis Modalities
- Hemodialysis vs. Peritoneal Dialysis: Observational data indicate no significant difference in 5-year mortality rates between the two modalities.
- Modality Selection Factors: Decisions should consider patient lifestyle, comorbid conditions, availability of home support, and resource accessibility.
- Common Complications
- Cardiovascular Risks: Cardiovascular complications, such as arrhythmias and cardiac arrest, are leading causes of death among dialysis patients.
- Infections:
- Hemodialysis: Catheter-related bloodstream infections occur at rates of 1.1 to 5.5 episodes per 1000 catheter-days.
- Peritoneal Dialysis: Peritonitis occurs at a rate of 0.26 episodes per patient-year.
- Systemic Complications: Anemia, hyperphosphatemia, hypocalcemia, and hypertension are prevalent and often require pharmacologic intervention.
- Dialysis-Related Issues: Hypotension during dialysis, muscle cramps, itching, and vascular access malfunction can hinder effective treatment.
- Management Strategies
- Anemia: Initiate intravenous iron and/or erythropoietin-stimulating agents when hemoglobin is below 10 g/dL, aiming to maintain levels between 10 and 11.5 g/dL.
- Mineral and Bone Disorders: Use dietary phosphorus restrictions and phosphorus binders; monitor and manage parathyroid hormone levels to mitigate fracture risk.
- Hypertension: Implement dietary salt restriction, adjust ultrafiltration, and prescribe antihypertensive medications, recognizing there’s no specific BP target in dialysis patients.
- Practical Considerations for Clinicians
- Medication Management: Avoid nephrotoxic agents like NSAIDs and iodinated contrast media in patients with residual kidney function. Adjust dosages for medications excreted renally.
- Symptom Control: Address common symptoms such as pruritus with appropriate therapies such as oral antihistamines and moisturizers. Difelikefalin is a new agent that can also be used.
- Patient Education: Counsel on dietary restrictions (salt, fluid, potassium) and ensure vaccinations are up to date, including hepatitis B, pneumococcal, COVID-19, and RSV vaccines.
Conclusion
For the over 540,000 patients in the U.S. receiving maintenance dialysis, individualized care plans that involve shared decision-making are crucial. Understanding when to initiate dialysis, selecting the appropriate modality, managing complications, and addressing patient-specific needs can significantly influence outcomes and quality of life.
Network Meta-Analysis: Eletriptan, Rizatriptan, Sumatriptan, and Zolmitriptan Most Effective for Acute Migraine Episodes
23 Sep, 2024 | 22:34h | UTCBackground: Migraine, a highly prevalent neurological disorder, is a leading cause of disability, especially among women aged 15 to 49. Effective acute management is critical, with current guidelines recommending non-steroidal anti-inflammatory drugs (NSAIDs) and triptans for moderate to severe episodes. However, the relative efficacy of various drug interventions remains unclear, especially with newer treatments like lasmiditan and gepants entering the market.
Objective: To evaluate and compare the efficacy and tolerability of all licensed oral drugs for the acute treatment of migraine episodes in adults.
Methods: A systematic review and network meta-analysis was conducted, including 137 randomized controlled trials (RCTs) involving 89,445 participants. The study analyzed 17 drug interventions, including NSAIDs, triptans, ditans, and gepants, and compared them with placebo. Primary outcomes included pain freedom at two hours post-dose and sustained pain freedom from two to 24 hours post-dose. Certainty of evidence was assessed using the CINeMA framework, and sensitivity analyses were conducted to confirm the robustness of the findings.
Results: All active interventions outperformed placebo for pain freedom at two hours, with odds ratios ranging from 1.73 (95% CI 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan. The most effective drugs for sustained pain freedom were eletriptan and ibuprofen. Among head-to-head comparisons, eletriptan was the most effective for pain freedom at two hours, followed by rizatriptan, sumatriptan, and zolmitriptan. Newer drugs like lasmiditan, rimegepant, and ubrogepant were less effective than the triptans and showed adverse effects like dizziness and nausea.
Conclusions: Triptans—specifically eletriptan, rizatriptan, sumatriptan, and zolmitriptan—demonstrated superior efficacy and tolerability profiles compared to newer treatments like lasmiditan and gepants. Given their efficacy, these triptans should be prioritized in acute migraine management. However, triptans are underused, and barriers to access should be addressed to ensure broader utilization. Lasmiditan and gepants may still serve as alternatives for patients contraindicated for triptans due to cardiovascular risks.
Implications for Practice: Clinicians should prioritize triptans, particularly eletriptan, rizatriptan, sumatriptan, and zolmitriptan, in managing acute migraine episodes due to their superior efficacy. Careful consideration is needed when selecting newer drugs like lasmiditan and gepants, as they may be less effective and have higher costs and adverse event risks. Cost-effectiveness and patient cardiovascular profiles should guide decision-making.
Study Strengths and Limitations: Strengths include the comprehensive inclusion of both published and unpublished data, as well as the large sample size and robust methodological framework. Limitations include moderate heterogeneity and low confidence in some comparisons due to reporting biases and imprecise treatment effects in older studies.
Future Research: Future studies should focus on re-evaluating the cardiovascular contraindications of triptans to ensure broader access. Additional research is also needed to assess the cost-effectiveness of newer treatments like lasmiditan and gepants, particularly in patients for whom triptans are unsuitable.
Summary: Perioperative Management of Patients Taking Direct Oral Anticoagulants
19 Sep, 2024 | 21:12h | UTCDirect oral anticoagulants (DOACs)—including apixaban, rivaroxaban, edoxaban, and dabigatran—are increasingly used for stroke prevention in atrial fibrillation and for treating venous thromboembolism. Effective perioperative management of DOACs is essential to minimize bleeding and thromboembolic risks during surgical and nonsurgical procedures. Below are practical recommendations focused on the perioperative management of patients taking DOACs, based on a recent JAMA review article.
Elective Surgical or Nonsurgical Procedures
Classify Bleeding Risk of Procedures:
- Minimal Risk:
- Minor dental procedures (e.g., cleaning, extractions)
- Minor dermatologic procedures (e.g., skin lesion removal)
- Cataract surgery
- Low to Moderate Risk:
- Endoscopic procedures without high-risk interventions
- Cholecystectomy
- Inguinal hernia repair
- High Risk:
- Major surgery (e.g., cancer surgery, joint replacement)
- Procedures involving neuraxial anesthesia
- Endoscopic procedures with high-risk interventions (e.g., large polyp removal)
DOAC Management Strategies:
- Minimal Bleeding Risk Procedures:
- Option 1: Continue DOACs without interruption.
- Option 2: For added safety, withhold the morning dose on the day of the procedure (especially for twice-daily DOACs like apixaban and dabigatran).
- Low to Moderate Bleeding Risk Procedures:
- Preoperative:
- Discontinue DOACs 1 day before the procedure.
- This allows approximately 2 half-lives for drug clearance.
- Postoperative:
- Resume DOACs 1 day after the procedure, ensuring adequate hemostasis.
- Preoperative:
- High Bleeding Risk Procedures:
- Preoperative:
- Discontinue DOACs 2 days before the procedure.
- This allows approximately 4-5 half-lives for drug clearance.
- Postoperative:
- Resume DOACs 2-3 days after the procedure, based on bleeding risk and hemostasis.
- Preoperative:
Evidence Supporting These Strategies:
- The PAUSE study demonstrated that standardized interruption protocols without heparin bridging result in low rates of:
- Thromboembolism: 0.2%–0.4%
- Major Bleeding: 1%–2%
Postoperative DOAC Resumption:
- Assess surgical-site hemostasis before resuming DOACs.
- Delay resumption if there is ongoing bleeding or concerns about hemostasis.
- For high bleeding risk procedures, consider a longer delay (2–3 days).
Perioperative Heparin Bridging:
- Not recommended for patients on DOACs.
- Bridging increases bleeding risk without reducing thromboembolism.
- DOACs have rapid offset and onset, making bridging unnecessary.
Special Considerations
Patients with Impaired Renal Function:
- For CrCl 30–50 mL/min:
- Dabigatran: Extend preoperative discontinuation by an additional day.
- For CrCl <30 mL/min:
- Dabigatran is contraindicated.
- For other DOACs, consider extending discontinuation to 3–4 days before surgery.
Patients Undergoing Neuraxial Anesthesia:
- Discontinue DOACs for 3 days (apixaban, edoxaban, rivaroxaban) or 4 days (dabigatran) before the procedure.
- Minimizes risk of spinal or epidural hematoma.
Dental Procedures:
- Generally safe to continue DOACs.
- For added safety:
- Omit or delay the dose on the day of the procedure.
- Employ local hemostatic measures (e.g., tranexamic acid mouthwash).
Endoscopic Procedures:
- Low-risk procedures (e.g., diagnostic endoscopy without biopsy):
- Follow standard DOAC interruption for low to moderate bleeding risk.
- High-risk procedures (e.g., polypectomy of large polyps):
- Extend DOAC discontinuation by an additional day pre- and post-procedure.
Patients Unable to Resume Oral Medications Postoperatively:
- Use prophylactic low-molecular-weight heparin (LMWH) until oral intake is possible.
- Avoid therapeutic-dose LMWH due to bleeding risk.
Emergent, Urgent, or Semiurgent Procedures
Risks:
- Higher bleeding risk: Up to 23%
- Thromboembolism risk: Up to 11%
Management Strategies:
- Assess Time Since Last DOAC Dose:
- If within 48 hours, consider that significant anticoagulant effect may persist.
- Laboratory Testing (if available):
- DOAC Level Testing:
- ≥50 ng/mL: Consider using reversal agents.
- <50 ng/mL: May proceed without reversal agents.
- DOAC Level Testing:
- Use of Reversal Agents:
- For Dabigatran:
- Idarucizumab (5 g IV)
- For Factor Xa Inhibitors (apixaban, rivaroxaban, edoxaban):
- Andexanet alfa (dosing based on last dose timing and amount)
- Prothrombin Complex Concentrates (PCCs): If andexanet alfa is unavailable or contraindicated.
- For Dabigatran:
- Proceeding Without Testing:
- If testing is unavailable and last DOAC dose was within 48 hours, consider reversal agents.
- If >48 hours since last dose, may proceed without reversal.
Considerations:
- Reversal agents are expensive and may carry thrombotic risks.
- Use should be judicious, weighing risks and benefits.
- Consult hematology or thrombosis experts when possible.
Key Takeaways
- Elective Procedures:
- Utilize standardized protocols based on procedural bleeding risk.
- Routine preoperative DOAC level testing is unnecessary.
- Avoid heparin bridging.
- Emergent/Urgent Procedures:
- Reversal agents may be appropriate when significant DOAC levels are present.
- Decision to use reversal agents should consider bleeding risk, time since last dose, and availability of DOAC level testing.
- Patient Communication:
- Ensure patients understand the plan for DOAC interruption and resumption.
- Provide clear instructions regarding timing and dosing.
- Interdisciplinary Coordination:
- Collaborate with surgical teams, anesthesiologists, and pharmacists.
- Use electronic medical records and clinical decision support tools to enhance communication.
Conclusion
By applying standardized perioperative management protocols, clinicians can effectively balance the risks of bleeding and thromboembolism in patients taking DOACs who require surgical or nonsurgical procedures. These strategies simplify decision-making, avoid unnecessary interventions like heparin bridging, and promote patient safety.
Summary: Community-Acquired Pneumonia
19 Sep, 2024 | 17:21h | UTCIntroduction
Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, accounting for approximately 1.4 million emergency department visits, 740,000 hospitalizations, and 41,000 deaths annually in the United States. Effective management of CAP requires prompt and accurate diagnosis, appropriate antimicrobial therapy, and consideration of adjunctive treatments. This summary highlights key practice points from a review article in JAMA related to the diagnosis and treatment of CAP for medical professionals.
Diagnosis of CAP
Clinical Presentation
- Signs and Symptoms: Suspect CAP in patients presenting with two or more of the following:
- Fever (>38 °C) or hypothermia (≤36 °C)
- Leukocytosis (>10,000/μL) or leukopenia (<4,000/μL)
- New or increased cough
- Dyspnea
Radiographic Confirmation
- Chest Imaging: Obtain a chest radiograph for all patients with suspected CAP to identify air space opacities or infiltrates.
- Chest CT: Consider if the chest radiograph is inconclusive but clinical suspicion remains high.
- Differential Diagnosis: Rule out other causes of symptoms and radiographic findings, such as pulmonary embolism, heart failure, or malignancy.
Microbiological Testing
- Viral Testing:
- SARS-CoV-2 and Influenza: Test all patients for COVID-19 and influenza during periods of community transmission, as results influence treatment decisions and infection control measures.
- Bacterial Testing:
- Indications: Reserve sputum and blood cultures for patients with severe CAP or risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa.
- Risk Factors:
- Previous infection or colonization with MRSA or P. aeruginosa.
- Hospitalization with parenteral antibiotics within the past 90 days.
Treatment of CAP
Empirical Antimicrobial Therapy
- Hospitalized Patients without Risk Factors for Resistant Bacteria:
- First-Line Therapy: β-lactam plus macrolide combination.
- Example: Ceftriaxone (1-2 g IV daily) plus azithromycin (500 mg IV or orally daily).
- Alternative: Respiratory fluoroquinolone monotherapy (e.g., levofloxacin) if β-lactam/macrolide therapy is contraindicated.
- First-Line Therapy: β-lactam plus macrolide combination.
- Patients with Severe CAP:
- Similar to non-severe CAP but ensure coverage for atypical pathogens.
- Consider Corticosteroids: Early administration (within 24 hours) of systemic corticosteroids may reduce mortality.
- Outpatients without Comorbidities:
- First-Line Therapy: Amoxicillin (1 g orally three times daily) or doxycycline (100 mg orally twice daily).
- Outpatients with Comorbidities:
- Combination Therapy: Amoxicillin/clavulanate (500 mg/125 mg orally three times daily) plus azithromycin (500 mg on day 1, then 250 mg daily).
Duration of Therapy
- Minimum Duration: Treat for a minimum of 3 days if the patient achieves clinical stability (normal vital signs) within 72 hours.
- Extended Duration: Extend to 5 days or more if the patient does not meet stability criteria by day 3 or has complications.
- Transition to Oral Therapy: Switch from intravenous to oral antibiotics when the patient can tolerate oral intake.
Antimicrobial Stewardship
- Avoid Unnecessary Antibiotics: Do not initiate antibiotics for confirmed viral CAP without evidence of bacterial coinfection.
- De-escalation: Narrow antibiotic coverage based on culture results and clinical improvement.
- Monitor for Adverse Effects: Be vigilant for antibiotic-associated complications, such as Clostridioides difficile infection.
Adjunctive Therapies
- Corticosteroids:
- Severe CAP: Administer systemic corticosteroids (e.g., hydrocortisone 200 mg/day) within 24 hours of diagnosis to reduce mortality and complications.
- Non-severe CAP: Routine use is not recommended due to lack of benefit and potential harm.
Secondary Prevention
- Vaccinations:
- Pneumococcal Conjugate Vaccine: Recommend for eligible patients to prevent future pneumococcal infections.
- Influenza Vaccine: Annual vaccination to reduce the risk of influenza-associated pneumonia.
- COVID-19 and RSV Vaccines: Encourage vaccination per current guidelines.
- Lifestyle Modifications:
- Smoking Cessation: Strongly advise quitting smoking to reduce the risk of CAP and improve respiratory health.
- Alcohol Moderation: Counsel patients on reducing excessive alcohol intake.
- Management of Comorbidities:
- Optimize treatment for chronic conditions such as chronic obstructive pulmonary disease (COPD), heart failure, and diabetes.
Key Practice Points
- Diagnostic Evaluation:
- Use a combination of clinical signs, symptoms, and radiographic findings to diagnose CAP.
- Test all patients for SARS-CoV-2 and influenza during times of community prevalence.
- Reserve extensive pathogen testing for severe cases or those at risk for resistant organisms.
- Antimicrobial Therapy:
- Initiate empirical antibiotics promptly based on disease severity and risk factors.
- Prefer β-lactam/macrolide combination therapy for most hospitalized patients.
- Limit the duration of antibiotics to the shortest effective course to reduce resistance and adverse effects.
- Use of Corticosteroids:
- Consider early corticosteroid therapy in patients with severe CAP to improve outcomes.
- Avoid routine corticosteroid use in non-severe CAP due to potential risks.
- Antimicrobial Stewardship:
- Reassess antibiotic therapy daily and de-escalate based on clinical response and microbiological data.
- Transition to oral antibiotics when appropriate.
- Preventive Measures:
- Promote vaccinations and lifestyle changes to prevent recurrent CAP.
- Address and manage underlying health conditions that may predispose to CAP.
Conclusion
Effective management of CAP involves prompt diagnosis using clinical and radiographic criteria, appropriate empirical antimicrobial therapy tailored to disease severity and risk factors, and consideration of adjunctive treatments such as corticosteroids in severe cases. Antimicrobial stewardship principles should guide therapy duration and de-escalation to minimize resistance and adverse effects. Preventive strategies, including vaccinations and lifestyle modifications, are essential to reduce the incidence of CAP and improve patient outcomes.
RCT: Preoxygenation with Noninvasive Ventilation Reduced Hypoxemia during Emergency Intubation
19 Sep, 2024 | 12:53h | UTCBackground: Hypoxemia during tracheal intubation in critically ill adults increases the risk of cardiac arrest and death. Preoxygenation aims to mitigate this risk, but the optimal method remains uncertain. Noninvasive ventilation (NIV) may offer advantages over oxygen masks by providing positive pressure and higher inspired oxygen fractions, but evidence is limited.
Objective: To determine whether preoxygenation with noninvasive ventilation reduces the incidence of hypoxemia during tracheal intubation compared to preoxygenation with an oxygen mask among critically ill adults.
Methods: In a multicenter, pragmatic, unblinded, randomized trial conducted at 24 emergency departments and intensive care units in the United States, 1301 critically ill adults (age ≥18 years) undergoing tracheal intubation were randomized 1:1 to receive preoxygenation with either noninvasive ventilation (n=645) or an oxygen mask (n=656). Patients already receiving positive-pressure ventilation or at high risk of aspiration were excluded. In the NIV group, preoxygenation was administered using a tight-fitting mask connected to a ventilator, with an FiO₂ of 100%, expiratory pressure ≥5 cm H₂O, and inspiratory pressure ≥10 cm H₂O. In the oxygen-mask group, preoxygenation was provided using a nonrebreather mask or bag-mask device without manual ventilation, with oxygen flow ≥15 liters per minute. The primary outcome was hypoxemia during intubation, defined as oxygen saturation <85% between induction of anesthesia and 2 minutes after tracheal intubation.
Results: Hypoxemia occurred in 9.1% of patients in the NIV group versus 18.5% in the oxygen-mask group (difference –9.4 percentage points; 95% CI, –13.2 to –5.6; P<0.001). Cardiac arrest during intubation occurred in 0.2% of patients in the NIV group and 1.1% in the oxygen-mask group (difference –0.9 percentage points; 95% CI, –1.8 to –0.1). Aspiration occurred in 0.9% of patients in the NIV group and 1.4% in the oxygen-mask group (difference –0.4 percentage points; 95% CI, –1.6 to 0.7). No significant differences were observed in other adverse events.
Conclusions: Preoxygenation with noninvasive ventilation significantly reduced the incidence of hypoxemia during tracheal intubation among critically ill adults compared to preoxygenation with an oxygen mask, without increasing the risk of aspiration.
Implications for Practice: Preoxygenation with noninvasive ventilation should be considered for critically ill adults undergoing emergency tracheal intubation to reduce the risk of hypoxemia and potential cardiac arrest. Clinicians should ensure appropriate equipment and training are available for the use of NIV during preoxygenation.
Study Strengths and Limitations: Strengths include a large sample size, multicenter design across diverse emergency departments and ICUs, and pragmatic approach enhancing generalizability. Limitations include exclusion of patients already receiving positive-pressure ventilation or at high risk of aspiration, potentially limiting applicability to these populations. The unblinded design may introduce bias, although outcome data were collected by independent observers.
Future Research: Further studies are needed to evaluate the effectiveness of noninvasive ventilation for preoxygenation in patients at high risk of aspiration and to compare its efficacy with high-flow nasal cannula. Research should also assess long-term clinical outcomes and cost-effectiveness of implementing NIV for preoxygenation.
RCT: High-Intensity NPPV Reduced Criteria for Intubation in Acute COPD Exacerbations
16 Sep, 2024 | 16:50h | UTCBackground: Acute exacerbations of chronic obstructive pulmonary disease (COPD) often lead to hypercapnic respiratory failure requiring ventilatory support. Noninvasive positive pressure ventilation (NPPV) is standard care, commonly delivered at low intensity with lower inspiratory pressures. However, approximately 15% of patients still require endotracheal intubation despite low-intensity NPPV. High-intensity NPPV, using higher inspiratory pressures to achieve greater reductions in PaCO₂, has shown benefits in stable hypercapnic COPD patients, but its effect during acute exacerbations is unclear.
Objective: To determine whether high-intensity NPPV reduces the need for endotracheal intubation in patients with acute COPD exacerbations and persistent hypercapnia compared to low-intensity NPPV.
Methods: In a multicenter, randomized clinical trial conducted at 30 respiratory wards in China from January 2019 to January 2022, 300 patients with acute COPD exacerbations and PaCO₂ greater than 45 mm Hg after 6 hours of low-intensity NPPV were enrolled. Participants were randomized 1:1 to receive either high-intensity NPPV (inspiratory positive airway pressure [IPAP] adjusted to achieve tidal volumes of 10–15 mL/kg predicted body weight, typically IPAP 20–30 cm H₂O) or to continue low-intensity NPPV (IPAP adjusted for tidal volumes of 6–10 mL/kg, maximum IPAP 20 cm H₂O). Patients in the low-intensity group meeting prespecified criteria for intubation were allowed to crossover to high-intensity NPPV. The primary outcome was the need for endotracheal intubation during hospitalization, defined by prespecified clinical and gas exchange criteria. Secondary outcomes included actual endotracheal intubation rates, mortality, length of hospital stay, and adverse events.
Results: Of the 300 patients (mean age 73 years; 68% male), the primary outcome occurred in 4.8% of the high-intensity group versus 13.7% of the low-intensity group (absolute difference –9.0%; 95% CI, –15.4% to –2.5%; one-sided P = .004; adjusted risk ratio [RR], 0.35; 95% CI, 0.14–0.76). However, actual endotracheal intubation rates did not differ significantly between groups (3.4% vs 3.9%; absolute difference –0.5%; 95% CI, –4.8% to 3.7%; P = .81). The high-intensity group had greater reductions in PaCO₂ levels over 72 hours (mean PaCO₂ at 72 hours: 53 mm Hg vs 64 mm Hg; P < .001) and higher rates of achieving normocapnia (21.8% vs 4.6%; P < .001). Abdominal distension occurred more frequently in the high-intensity group (37.4% vs 25.5%; absolute difference 11.9%; 95% CI, 1.5%–22.4%; P = .03), but other adverse events and serious adverse events were similar between groups.
Conclusions: High-intensity NPPV reduced the proportion of patients meeting criteria for endotracheal intubation compared to low-intensity NPPV in patients with acute COPD exacerbations and persistent hypercapnia. However, actual intubation rates did not differ, possibly due to crossover from low- to high-intensity NPPV in patients meeting intubation criteria.
Implications for Practice: High-intensity NPPV may be considered for patients with acute COPD exacerbations who remain hypercapnic after initial low-intensity NPPV, as it may reduce progression to severe respiratory failure requiring intubation criteria. Clinicians should monitor for abdominal distension and potential alkalosis, although these did not significantly affect overall tolerance or safety.
Study Strengths and Limitations: Strengths include the multicenter randomized design, clear enrollment criteria, and standardized protocols. Limitations include early trial termination, unblinded interventions, potential bias due to allowed crossover, and lack of power to detect differences in mortality or actual intubation rates.
Future Research: Further large-scale trials are needed to confirm these findings, assess the impact on actual intubation rates and mortality, and explore the efficacy of high-intensity NPPV in different clinical settings and patient populations, including those without prior NPPV exposure or with more severe respiratory distress.
RCT: Tenecteplase Noninferior to Alteplase in Acute Ischemic Stroke
14 Sep, 2024 | 20:03h | UTCBackground: Acute ischemic stroke (AIS) is a leading cause of morbidity and mortality globally, with a particularly high burden in China. Intravenous thrombolysis with alteplase, administered within 4.5 hours of symptom onset, is the current standard of care. Tenecteplase, a genetically modified variant of alteplase with greater fibrin specificity and a longer half-life, allows for single-bolus administration, potentially simplifying and expediting treatment. Prior studies suggest tenecteplase may be as effective as alteplase in AIS, but data specific to Chinese patients are limited.
Objective: To determine whether tenecteplase is noninferior to alteplase in achieving excellent functional outcomes in Chinese patients with AIS treated within 4.5 hours of symptom onset.
Methods:
- Design: Multicenter, randomized, open-label, blinded-endpoint, noninferiority trial conducted at 55 centers in China between July 2021 and July 2023.
- Participants: 1,489 Chinese adults aged ≥18 years with AIS, National Institutes of Health Stroke Scale (NIHSS) scores of 1–25, measurable neurological deficits, and symptom onset within 4.5 hours.
- Interventions: Patients were randomized 1:1 to receive either:
- Tenecteplase: 0.25 mg/kg intravenous single bolus (maximum 25 mg).
- Alteplase: 0.9 mg/kg intravenous (maximum 90 mg), with 10% as an initial bolus and the remainder infused over 1 hour.
- Outcomes:
- Primary Outcome: Proportion of patients achieving a modified Rankin Scale (mRS) score of 0 or 1 at 90 days (indicating no symptoms or no significant disability).
- Secondary Outcomes: Major neurological improvement at 24 hours, mRS scores of 0–2 at 90 days, change in NIHSS score at 90 days, Barthel Index score ≥95 at 90 days.
- Safety Outcomes: Symptomatic intracerebral hemorrhage (sICH) per ECASS III definition and all-cause mortality at 90 days.
Results:
- Participants: 1,465 patients were included in the full analysis set (732 tenecteplase; 733 alteplase). Median age was 66 years, median NIHSS score was 6, and 30.4% were female.
- Primary Outcome:
- 72.7% in the tenecteplase group achieved mRS 0 or 1 at 90 days compared to 70.3% in the alteplase group.
- Adjusted risk ratio (RR): 1.03 (95% CI, 0.97–1.09), meeting the predefined noninferiority margin (RR ≥0.937).
- Secondary Outcomes:
- Major Neurological Improvement at 24 Hours: 48.0% (tenecteplase) vs. 45.0% (alteplase); RR, 1.07 (95% CI, 0.96–1.19).
- mRS 0–2 at 90 Days: 80.9% (tenecteplase) vs. 79.9% (alteplase); RR, 1.01 (95% CI, 0.96–1.06).
- Change in NIHSS Score at 90 Days: Mean change of –3.70 (tenecteplase) vs. –3.02 (alteplase); adjusted difference, –0.45 (95% CI, –1.40 to 0.50).
- Barthel Index ≥95 at 90 Days: 75.7% (tenecteplase) vs. 73.9% (alteplase); RR, 1.02 (95% CI, 0.96–1.08).
- Safety Outcomes:
- sICH: Occurred in 1.2% of patients in both groups; RR, 1.01 (95% CI, 0.37–2.70).
- 90-Day Mortality: 4.6% (tenecteplase) vs. 5.8% (alteplase); RR, 0.80 (95% CI, 0.51–1.23).
Conclusions: Tenecteplase was noninferior to alteplase in achieving excellent functional outcomes (mRS 0 or 1) at 90 days in Chinese patients with AIS treated within 4.5 hours of symptom onset. Safety profiles, including rates of sICH and mortality, were similar between the two treatments. These findings support tenecteplase as a suitable alternative to alteplase for intravenous thrombolysis in AIS.
Implications for Practice:
- Administration Advantage: Tenecteplase’s single-bolus administration could streamline treatment workflows and reduce door-to-needle times.
- Efficacy and Safety: Comparable efficacy and safety profiles suggest tenecteplase can be confidently used in place of alteplase.
- Patient Selection: Results are applicable to a broad range of AIS patients, including those with varying stroke severities and ages.
Study Strengths and Limitations:
- Strengths: Large sample size, multicenter design, and inclusion of a real-world patient population enhance the generalizability of findings.
- Limitations: Open-label design may introduce bias despite blinded endpoint assessments. The relatively low proportion of patients undergoing thrombectomy limits conclusions about combined therapy.
Future Research:
- Further studies could explore the effectiveness of tenecteplase in specific subgroups, such as patients with large vessel occlusions or those requiring endovascular interventions.
- Investigations into long-term outcomes beyond 90 days and real-world implementation strategies may provide additional insights.
RCT: Invasive Strategy Does Not Significantly Improve Cardiovascular Outcomes Over Conservative Management in Older Adults with NSTEMI
7 Sep, 2024 | 13:25h | UTCStudy Design and Population: This was a prospective, multicenter, randomized trial conducted across 48 sites in the UK, enrolling 1,518 patients aged 75 years or older with non-ST-segment elevation myocardial infarction (NSTEMI). Patients were randomly assigned to receive either the best available medical therapy alone (conservative strategy) or in combination with invasive treatment (coronary angiography and revascularization). The population included individuals who were frail or had high comorbidities, with a mean age of 82 years.
Main Findings: Over a median follow-up of 4.1 years, the primary outcome (a composite of cardiovascular death or nonfatal myocardial infarction) occurred in 25.6% of the invasive-strategy group and 26.3% of the conservative-strategy group (HR, 0.94; 95% CI, 0.77–1.14; P=0.53), showing no significant difference. Cardiovascular death rates were similar between the two groups, but nonfatal myocardial infarction was lower in the invasive group (11.7% vs. 15.0%; HR, 0.75; 95% CI, 0.57–0.99). Procedural complications were rare, affecting less than 1% of patients.
Implications for Practice: This trial suggests that in older adults with NSTEMI, an invasive strategy does not significantly reduce the risk of cardiovascular death or nonfatal myocardial infarction compared to a conservative approach. The findings support the consideration of conservative management in frail elderly patients or those with significant comorbidities, given the minimal additional benefit of invasive treatment.
Reference: Kunadian, V., Mossop, H., Shields, C., Bardgett, M., Watts, P., Teare, M. D., Pritchard, J., et al. (2024). Invasive treatment strategy for older patients with myocardial infarction. New England Journal of Medicine. http://doi.org/10.1056/NEJMoa2407791
Link: https://www.nejm.org/doi/10.1056/NEJMoa2407791
RCT: Interruption of Oral Anticoagulation during TAVI Reduces Bleeding Without Increasing Thromboembolic Events
7 Sep, 2024 | 12:43h | UTCStudy Design and Population: This international, open-label, randomized noninferiority trial examined 858 patients undergoing transcatheter aortic-valve implantation (TAVI) who had an indication for oral anticoagulation due to concomitant diseases. Patients were randomized 1:1 to either continue or interrupt their oral anticoagulation during the procedure, with the primary outcome being a composite of cardiovascular death, stroke, myocardial infarction, major vascular complications, or major bleeding within 30 days.
Main Findings: Primary outcome events occurred in 16.5% of the continuation group and 14.8% of the interruption group, showing a non-significant risk difference of 1.7 percentage points (95% CI, -3.1 to 6.6). Thromboembolic events were similar between groups (8.8% in continuation vs. 8.2% in interruption). However, bleeding events were significantly higher in the continuation group (31.1% vs. 21.3%; risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6).
Implications for Practice: Interrupting oral anticoagulation during TAVI significantly reduces bleeding without increasing thromboembolic risks, suggesting it may be a safer strategy for patients undergoing TAVI. These findings could influence clinical decision-making regarding anticoagulation management in this population.
Reference: van Ginkel, D.J. et al. (2024). Continuation versus Interruption of Oral Anticoagulation during TAVI. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2407794
RCT: No Difference in Postoperative Complications Between Continuation and Discontinuation of Renin-Angiotensin System Inhibitors Before Major Surgery – JAMA
31 Aug, 2024 | 19:12h | UTCStudy Design and Population: This multicenter randomized clinical trial included 2,222 patients who had been treated with renin-angiotensin system inhibitors (RASIs) for at least 3 months and were scheduled for major noncardiac surgery at 40 hospitals in France between January 2018 and April 2023. The participants were randomly assigned to either continue RASIs until the day of surgery or to discontinue them 48 hours before surgery.
Main Findings: The trial found no significant difference in the primary outcome—a composite of all-cause mortality and major postoperative complications within 28 days—between the continuation and discontinuation groups (22% in both groups, RR 1.02, 95% CI 0.87-1.19). However, the continuation group experienced a higher incidence of intraoperative hypotension (54% vs. 41%, RR 1.31, 95% CI 1.19-1.44).
Implications for Practice: Continuation of RASIs before major noncardiac surgery does not increase the risk of postoperative mortality or major complications, but it does elevate the risk of intraoperative hypotension. Clinicians should weigh these risks when deciding whether to continue or discontinue RASIs before surgery.