Critical Care
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.
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.
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.
Phase 2b Trial: Nicardipine Implants Show Promise in Reducing Vasospasm After Aneurysmal Subarachnoid Hemorrhage – JAMA Neurology
25 Aug, 2024 | 11:29h | UTCStudy Design and Population: This single-masked, multicenter, randomized clinical trial involved 41 patients with World Federation of Neurological Surgeons grade 3 or 4 aneurysmal subarachnoid hemorrhage (aSAH) from six neurovascular centers in Germany and Austria. The patients were randomized to either receive localized nicardipine release implants during microsurgical aneurysm repair plus standard care or standard care alone.
Main Findings: The incidence of moderate to severe angiographic vasospasm (aVS) between days 7 and 9 after aSAH was significantly lower in the implant group (20%) compared to the control group (58%; P = .02). Additionally, fewer patients in the implant group required vasospasm rescue therapy (10% vs. 58%; P = .002). However, at 52 weeks, no significant difference was observed in favorable outcomes between the groups (84% in the implant group vs. 67% in the control group; P = .27).
Implications for Practice: Nicardipine implants show promise in reducing vasospasm-related complications following aSAH, suggesting a potential benefit for early postoperative management. However, their impact on long-term clinical outcomes requires further investigation in larger phase 3 trials to determine the overall benefit and cost-effectiveness of this intervention.
Meta-Analysis: ERAS Protocols Improve Recovery and Reduce Complications After Emergency Laparotomy – Am J Surg
18 Aug, 2024 | 19:32h | UTCStudy Design and Population: This systematic review and meta-analysis assessed the effects of Enhanced Recovery After Surgery (ERAS) protocols compared to standard care (SC) in patients undergoing emergency laparotomy. The analysis included six randomized clinical trials (RCTs) with a total of 509 patients.
Main Findings: The ERAS group showed a reduction in length of hospital stay (mean difference: -2.92 days) and quicker recovery milestones, such as time to ambulation (mean difference: -1.67 days) and first bowel opening (mean difference: -1.26 days). The ERAS protocols were also associated with lower rates of pulmonary complications (odds ratio [OR]: 0.43) and surgical site infections (OR: 0.33). Mortality rates were similar between the ERAS and SC groups.
Implications for Practice: These findings suggest that ERAS protocols may enhance recovery and reduce complications in patients undergoing emergency laparotomy. Implementation of these protocols could be beneficial in emergency surgical settings, where feasible.
Systematic Review: Nasogastric Feeding Increases Diarrhea and Pain Compared to Nasojejunal Feeding in Acute Pancreatitis – BMC Gastroenterol
18 Aug, 2024 | 19:23h | UTCStudy Design and Population: This systematic review and meta-analysis compared the safety and efficacy of nasogastric (NG) versus nasojejunal (NJ) feeding initiated within 48 hours of hospital admission in patients with moderate to severe acute pancreatitis. The analysis included four randomized controlled trials (RCTs) involving a total of 217 patients.
Main Findings: The review found no significant difference in mortality between NG and NJ feeding groups. However, NG feeding was associated with a higher incidence of diarrhea (RR 2.75, P = 0.02) and pain (RR 2.91, P = 0.002). The risk of infection was also higher in the NG group (6.67% vs. 3.33%, P = 0.027). No significant differences were observed in the need for surgical intervention, the requirement for parenteral nutrition, or the success rates of feeding procedures.
Implications for Practice: The findings suggest that while NG feeding does not increase mortality in acute pancreatitis, it is associated with higher rates of certain complications, particularly diarrhea and pain. Clinicians should consider these risks when choosing a feeding strategy for patients with acute pancreatitis, especially within the critical early 48-hour period post-admission.
Randomized Noninferiority Trial: Oral Vonoprazan Noninferior to IV Proton Pump Inhibitors in Preventing Rebleeding of High-Risk Peptic Ulcers – Gastroenterology
18 Aug, 2024 | 18:32h | UTCStudy Design and Population: This multicenter, randomized, open-label, noninferiority trial was conducted in Thailand across six centers, including both university and community hospitals. A total of 194 patients with high-risk peptic ulcer (PU) bleeding who had achieved successful endoscopic hemostasis were randomized to receive either vonoprazan or intravenous proton pump inhibitors (PPI). The study aimed to compare the efficacy of vonoprazan, a potassium-competitive acid blocker, with that of high-dose PPIs in preventing rebleeding.
Main Findings: The trial found that the 30-day rebleeding rate in the vonoprazan group was 7.1%, compared to 10.4% in the PPI group. This demonstrated noninferiority of vonoprazan within a 10% margin (risk difference: -3.3%, 95% CI: -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates were also noninferior. Secondary outcomes, including mortality rates, the need for rescue therapy, blood transfusion requirements, and length of hospital stay, were comparable between the two groups. Adverse events were similar in both groups.
Implications for Practice: Vonoprazan presents a viable alternative to intravenous PPIs for preventing rebleeding in patients with high-risk PU after endoscopic hemostasis. The availability of vonoprazan in oral form could potentially reduce hospital stays. However, further studies in multiethnic populations are needed to confirm these findings and assess the cost-effectiveness of vonoprazan in this setting.
Non-Inferiority Trial: Burr-Hole Drainage Without Irrigation Results in Higher Reoperation Rate in Chronic Subdural Hematoma – The Lancet
18 Aug, 2024 | 18:17h | UTCStudy Design and Population: This Finnish, nationwide, multicentre, randomised, controlled non-inferiority trial (FINISH) evaluated whether subdural irrigation during burr-hole drainage for chronic subdural haematoma could be omitted without compromising outcomes. The trial enrolled 589 adults (165 women, 424 men) requiring burr-hole drainage, randomly assigned to receive drainage with or without irrigation.
Main Findings: The study found a 6.0 percentage point higher reoperation rate within 6 months in the non-irrigation group (18.3%) compared to the irrigation group (12.6%). There were no significant differences in secondary outcomes, including the proportion of patients with an unfavorable functional outcome (13.1% vs. 12.6%) or mortality (6.1% vs. 7.1%). Adverse events were comparable between the groups.
Implications for Practice: The trial results suggest that omitting subdural irrigation during burr-hole drainage increases the risk of reoperation, without improving functional outcomes or reducing mortality. The findings support the continued use of subdural irrigation in this procedure.
Updated Guidelines on Perioperative Management of Anticoagulant and Antiplatelet Therapy for Interventional Techniques – Pain Physician
18 Aug, 2024 | 14:52h | UTCIntroduction: The American Society of Interventional Pain Physicians (ASIPP) has published updated guidelines for the perioperative management of patients undergoing interventional techniques while receiving antiplatelet and anticoagulant therapy. These guidelines are essential for clinicians to balance the risk of thromboembolism against the risk of bleeding during interventional procedures.
Key Points:
1 – Risk of Thromboembolic Events:
– Thromboembolic events have a higher risk of morbidity and mortality compared to the risk of epidural hematoma. Thus, interruption of antithrombotic therapy should be carefully considered.
2 – Risk Stratification of Procedures:
– Interventional techniques are classified into three categories based on risk: low, moderate, or high. For high-risk procedures, cessation of anticoagulant or antiplatelet therapy is recommended, whereas for low to moderate-risk procedures, therapy may continue under certain conditions.
3 – Management of Direct Oral Anticoagulants (DOACs):
– DOACs such as dabigatran, apixaban, rivaroxaban, and edoxaban should generally be discontinued for 2 days before high-risk procedures and one day for moderate-risk procedures. Adjustments are needed based on renal function, specially for dabigatran.
4 – Discontinuation of Aspirin:
– For high-risk interventional procedures, discontinuation of aspirin (81 or 325 mg) is recommended 6 days before the procedure. However, for low to moderate-risk procedures, aspirin therapy may be continued or stopped for 3 days depending on individual risk factors and clinical judgment.
5 – Discontinuation of Other Antiplatelet Agents:
– Clopidogrel (Plavix) and Prasugrel (Effient): These agents should be discontinued 6 days before high-risk procedures. For low-risk procedures, these medications can be continued.
– Ticagrelor (Brilinta): Discontinue for 5 days before high-risk procedures, with consideration of patient-specific risk factors.
6 – Timing for Restarting Therapy:
– Antithrombotic therapy should typically be resumed within 12-24 hours after low to moderate-risk procedures and within 24-48 hours after high-risk procedures, depending on bleeding risk and patient status.
7 – Shared Decision-Making:
– Decisions on whether to continue or discontinue antithrombotic therapy should involve shared decision-making between the patient, the interventional pain specialist, and other treating physicians, considering all associated risks.
Conclusion: These guidelines provide a comprehensive framework for managing the delicate balance between thromboembolic and bleeding risks in patients on anticoagulant or antiplatelet therapy undergoing interventional procedures. They emphasize the importance of personalized care and multidisciplinary collaboration.
Innovative Antimicrobial Susceptibility Testing Bypasses Blood Culture, Promising Faster Sepsis Diagnosis – Nature
18 Aug, 2024 | 14:09h | UTCStudy Design and Population: This study introduces a novel ultra-rapid antimicrobial susceptibility testing (AST) method that bypasses the traditional blood culture process, potentially reducing diagnostic time by 40-60 hours. The method was evaluated using a cohort of 190 hospitalized patients in Korea with suspected sepsis, including those with blood cancers.
Main Findings: The new AST method identified bacterial species in all patients with positive blood infections, achieving a 100% match in species identification. For antimicrobial susceptibility, the method demonstrated a 94.9% categorical agreement with conventional AST methods, with a theoretical turnaround time of 13 ± 2.53 hours, significantly faster than current workflows.
Implications for Practice: This method could improve sepsis treatment by providing same-day results, potentially reducing sepsis-related mortality and the use of broad-spectrum antibiotics. However, further validation in a more diverse patient population is necessary to confirm its clinical efficacy and value.
Review: Prevention and Management of Device-Associated Complications in the Intensive Care Unit – The BMJ
17 Aug, 2024 | 20:04h | UTCIntroduction:
This review article, published by experts from the David Geffen School of Medicine at UCLA, focuses on the complications associated with invasive devices commonly used in the Intensive Care Unit (ICU). While these devices are essential for managing critically ill patients, they also pose significant risks, necessitating a thorough understanding of their potential complications and strategies for prevention and management.
Key Points:
1 – Central Venous Catheters (CVCs):
– CVCs are widely used in ICU patients but carry risks like vascular injury, pneumothorax, thrombosis, and infection.
– Use of real-time ultrasound guidance and careful operator technique are crucial for minimizing these risks.
– Prompt removal of unnecessary CVCs is essential to reduce the risk of complications.
2 – Arterial Catheters:
– Commonly used for hemodynamic monitoring, these catheters can lead to complications such as vascular occlusion, nerve injury, and infection.
– Ultrasound guidance is recommended to reduce the risk of complications, and catheters should be discontinued as soon as clinically feasible.
3 – Airway Devices (Endotracheal Tubes and Tracheostomies):
– Complications include laryngeal injury, tracheal stenosis, and tracheomalacia.
– Strategies to reduce these risks include minimizing intubation attempts, ensuring proper tube placement, and managing cuff pressures carefully.
4 – Extracorporeal Membrane Oxygenation (ECMO):
– ECMO is associated with significant complications, including bleeding, thromboembolic events, and neurologic injuries.
– Proper cannulation technique and vigilant monitoring are essential to mitigate these risks.
5 – Infection Control:
– Strict adherence to aseptic techniques and the use of chlorhexidine-impregnated dressings are recommended to prevent device-associated infections.
Conclusion:
This review underscores the importance of judicious use and timely removal of invasive devices in the ICU to minimize complications. Healthcare professionals must remain vigilant and employ best practices to prevent and manage these complications effectively.
Study: Novel Point-of-Care hs-cTnI Test Shows High Diagnostic Accuracy and Predictive Values for Myocardial Infarction – J Am Coll Cardiol
17 Aug, 2024 | 19:00h | UTCStudy Design and Population: This international, multicenter diagnostic study assessed the clinical and analytical performance of the new high-sensitivity cardiac troponin I (hs-cTnI)-SPINCHIP point-of-care (POC) test. The study involved 1,102 adult patients presenting with acute chest discomfort in emergency departments, with myocardial infarction (MI) diagnoses adjudicated by two independent cardiologists.
Main Findings: The hs-cTnI-SPINCHIP test exhibited strong diagnostic accuracy with an area under the receiver-operating characteristic curve of 0.94, similar to established central laboratory assays. The 0/1-hour algorithm of the test identified 51% of patients as low risk for MI with a sensitivity and negative predictive value of 100%, while it confirmed MI in 27% of patients with a specificity of 90.9% and a positive predictive value of 72.9%. Consistency was observed across different sample types.
Implications for Practice: The SPINCHIP hs-cTnI POC test provides a rapid and accurate option for diagnosing MI in emergency settings, aiding quicker decision-making for ruling out or confirming MI.