Critical Care & Emergencies (all articles)
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.
News Release – FDA Approves First Nasal Spray for Anaphylaxis Treatment: Neffy (Epinephrine Nasal Spray) – U.S. Food and Drug Administration
17 Aug, 2024 | 15:43h | UTCThe U.S. Food and Drug Administration (FDA) has approved Neffy, the first epinephrine nasal spray for the emergency treatment of anaphylaxis and other severe allergic reactions (Type I) in both adults and pediatric patients weighing at least 30 kilograms (approximately 66 pounds). This approval introduces a non-injectable option for the rapid administration of epinephrine, which is critical in managing life-threatening allergic reactions.
Key Points for Healthcare Providers:
– Alternative to Injection: Neffy provides a new option for patients who may delay or avoid epinephrine injections due to needle phobia. This could be particularly beneficial for children and others reluctant to use injectable epinephrine.
– Efficacy and Safety: Neffy’s approval is supported by studies comparing its pharmacokinetics and pharmacodynamics to traditional epinephrine injections. These studies showed comparable blood epinephrine levels and similar physiological effects, such as increased blood pressure and heart rate.
– Administration: Neffy is a single-dose nasal spray, administered into one nostril. If symptoms do not improve or worsen, a second dose may be administered in the same nostril. Patients should still seek emergency medical care to monitor the anaphylactic reaction.
– Warnings: Certain nasal conditions, such as nasal polyps or a history of nasal surgery, may impair Neffy’s absorption. In these cases, injectable epinephrine might be a more reliable option. The product also carries typical warnings for epinephrine use, particularly in patients with coexisting conditions.
– Side Effects: Common side effects include throat irritation, nasal discomfort, headaches, and jitteriness. Healthcare professionals should discuss these with patients to ensure informed use.
Clinical Implications:
Neffy may reduce barriers to the timely treatment of anaphylaxis, potentially improving outcomes by increasing the likelihood of rapid epinephrine administration. Healthcare providers should consider Neffy as an alternative for patients who are needle-averse or have difficulty using injectable epinephrine, while also ensuring patients understand the importance of prompt medical attention following its use.
Approval Background:
Neffy was granted Fast Track designation by the FDA, emphasizing the need for an alternative to injectable epinephrine. The approval was awarded to ARS Pharmaceuticals.
Source: FDA News Release: FDA Approves First Nasal Spray for Treatment of Anaphylaxis
New AHA Guidelines for Managing Elevated Blood Pressure in Acute Care Settings – Hypertension
13 Aug, 2024 | 13:13h | UTCIntroduction:
The American Heart Association (AHA) has released a scientific statement focusing on the management of elevated blood pressure (BP) in acute care settings. This guideline addresses the significant variation in practice due to a lack of robust evidence for managing BP in such environments, particularly in emergencies or when elevated BP is asymptomatic.
Key Points:
1 – Classification of Elevated BP: Elevated BP in acute care settings is categorized into asymptomatic elevated BP and hypertensive emergency, the latter requiring immediate treatment due to acute target-organ damage.
2 – Hypertensive Emergency: Immediate treatment is necessary for patients with BP >180/110–120 mm Hg and evidence of new or worsening target-organ damage, typically using intravenous antihypertensive medications in a closely monitored environment.
3 – Asymptomatic Elevated BP: In cases where elevated BP is present without symptoms or target-organ damage, the use of antihypertensive medications should be approached cautiously. Recent studies suggest potential harm from aggressive treatment, highlighting the importance of verifying BP readings and identifying reversible causes before intervention.
4 – Proper BP Measurement: Accurate BP measurement is crucial. The guidelines stress using recently calibrated devices and following correct measurement techniques to avoid unnecessary treatment due to erroneous readings.
5 – PRN Orders: The use of “as needed” (PRN) antihypertensive medications for asymptomatic elevated BP is discouraged due to the risks of overtreatment and variability in BP control, which can lead to adverse outcomes.
6 – Treatment Thresholds: The guidelines recommend a high threshold for initiating or intensifying antihypertensive treatment in asymptomatic patients, emphasizing the need for repeated measurements and assessment of underlying causes.
7 – Post-Discharge Care: It is crucial to maintain prehospital antihypertensive regimens and avoid intensification at discharge unless clearly indicated. Effective care coordination and patient education are vital for successful transitions from hospital to home care.
Conclusion:
These guidelines represent a significant step toward standardizing BP management in acute care settings. By focusing on accurate measurement, cautious treatment of asymptomatic elevated BP, and proper follow-up, clinicians can reduce unnecessary interventions and improve patient outcomes.
Guideline Reference: Bress, A.P., et al. (2024). “The Management of Elevated Blood Pressure in the Acute Care Setting: A Scientific Statement from the American Heart Association.” Hypertension, 81–e106.
Meta-Analysis: Daily Sedation Interruption Shortens PICU Stay Without Impacting Mortality or Ventilation Duration in Pediatric MV Patients – JAMA Netw Open
11 Aug, 2024 | 13:19h | UTCStudy Design and Population: This systematic review and meta-analysis included six randomized clinical trials (RCTs) involving 2,810 pediatric patients receiving mechanical ventilation (MV) in the pediatric intensive care unit (PICU). The trials compared the effects of daily sedation interruption (DSI) with continuous intravenous (IV) sedation on clinical outcomes such as MV duration and PICU length of stay.
Main Findings: The analysis found that DSI was associated with a significant reduction in the length of PICU stay (mean difference of -1.45 days, p = 0.03). However, there was no significant difference in the duration of MV between DSI and continuous sedation (mean difference of -0.93 days, p = 0.06). Additionally, there were no significant differences in total sedative doses, adverse events, or mortality between the two groups.
Implications for Practice: The findings suggest that DSI may reduce the length of PICU stay without increasing the risk of adverse events, making it a potentially valuable strategy in managing sedation for pediatric patients on MV. However, further research is needed to explore the long-term neurodevelopmental outcomes associated with DSI.
IDSA 2024 Guidelines for Managing Complicated Intra-abdominal Infections – Clin Infect Dis
10 Aug, 2024 | 22:10h | UTCIntroduction: The Infectious Diseases Society of America (IDSA) has updated its clinical practice guidelines for managing complicated intra-abdominal infections in adults, children, and pregnant individuals. The update focuses on risk assessment, diagnostic imaging, and microbiological evaluation, with recommendations grounded in systematic literature reviews and the GRADE approach for rating evidence.
Key Points:
1 – Risk Stratification:
– For adults with complicated intra-abdominal infections, the APACHE II score is recommended for risk stratification within 24 hours of hospital or ICU admission. The WSES Sepsis Severity Score is an acceptable alternative.
– No specific severity scoring system is recommended for pediatric patients.
2 – Diagnostic Imaging for Appendicitis:
– In non-pregnant adults, CT is suggested as the initial imaging modality for suspected acute appendicitis.
– For children, an abdominal ultrasound (US) is preferred initially, with MRI or CT recommended if the US is inconclusive.
– In pregnant individuals, US or MRI can be considered, with MRI suggested if initial US results are inconclusive.
3 – Imaging for Acute Cholecystitis and Cholangitis:
– For non-pregnant adults, US is recommended initially. If inconclusive, a CT scan is suggested.
– For pregnant individuals, US or MRI can be used, but the guidelines do not specify a preferred modality due to a knowledge gap.
4 – Blood Cultures:
– Blood cultures are recommended in adults and children with suspected intra-abdominal infections presenting with severe symptoms such as hypotension or tachypnea, especially when antibiotic-resistant organisms are a concern.
– Routine blood cultures are not recommended for patients without these risk factors.
5 – Intra-abdominal Fluid Cultures:
– In complicated intra-abdominal infections requiring source control procedures, obtaining intra-abdominal cultures is advised to guide antimicrobial therapy.
– In uncomplicated appendicitis cases, routine cultures are not recommended unless the patient is immunocompromised or complicated disease is suspected during surgery.
Conclusion: These guidelines provide evidence-based recommendations to improve the management of complicated intra-abdominal infections, emphasizing appropriate risk stratification, targeted diagnostic imaging, and the selective use of cultures to guide therapy.
Cluster RCT: AI-ECG Shows Potential to Reduce Door-to-Balloon Time and Cardiac Deaths in STEMI Patients – NEJM AI
10 Aug, 2024 | 21:57h | UTCStudy Design and Population: This open-label, cluster randomized controlled trial assessed the impact of AI-powered electrocardiogram (AI-ECG) on reducing treatment delays for ST-elevation myocardial infarction (STEMI). The study involved 43,234 patients, with an average age of 60 years, at Tri-Service General Hospital in Taiwan. Patients were randomized 1:1 into an intervention group (AI-ECG-assisted STEMI detection) or a control group receiving standard care.
Main Findings: AI-ECG significantly reduced the median door-to-balloon time for emergency department patients (82.0 vs. 96.0 minutes, P=0.002) and the ECG-to-balloon time across all settings (78.0 vs. 83.6 minutes, P=0.011). While the AI-ECG intervention did not significantly affect all-cause mortality or new-onset heart failure, it led to a notable reduction in cardiac death rates (85 vs. 116 cases; odds ratio, 0.73; P=0.029).
Implications for Practice: AI-ECG can expedite the critical time to treatment for STEMI patients, potentially reducing cardiac death. Although overall mortality remained unchanged, the reduction in cardiac deaths suggests that AI-ECG could be a valuable tool in emergency and inpatient settings to improve outcomes for STEMI patients.
IDSA 2024 Guidelines for Treatment of Antimicrobial-Resistant Gram-Negative Infections – Clin Infect Dis
10 Aug, 2024 | 20:16h | UTCIntroduction:
The Infectious Diseases Society of America (IDSA) has released updated guidelines in 2024 addressing the treatment of infections caused by antimicrobial-resistant (AMR) Gram-negative bacteria. These guidelines cover pathogens including extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia.
Key Points:
1 – ESBL-E Infections:
– Preferred treatment for uncomplicated cystitis includes nitrofurantoin and TMP-SMX. Fluoroquinolones and carbapenems are alternatives but should be reserved to prevent resistance.
– For pyelonephritis or complicated urinary tract infections (cUTI), TMP-SMX, ciprofloxacin, or levofloxacin are preferred. Carbapenems are recommended when resistance precludes other options.
2 – AmpC-E Infections:
– Cefepime is suggested for treating infections caused by organisms at moderate risk of significant AmpC production (e.g., Enterobacter cloacae complex, Klebsiella aerogenes, and Citrobacter freundii).
– The use of cephamycins (e.g., cefoxitin, cefotetan) for treating ESBL-E infections is not recommended due to insufficient clinical outcome data.
3 – CRE Infections:
– Acknowledgement of increased prevalence of metallo-beta-lactamase (MBL)-producing CRE in the U.S.
– The combination of ceftazidime-avibactam and aztreonam is suggested for MBL-producing CRE, with updated dosing recommendations provided.
4 – DTR Pseudomonas aeruginosa:
– Traditional β-lactams (e.g., cefepime) with high-dose extended-infusion therapy are recommended.
– Tobramycin or amikacin, administered once daily, are alternatives for pyelonephritis or cUTI.
5 – CRAB and Stenotrophomonas maltophilia Infections:
– Sulbactam-durlobactam with meropenem or imipenem-cilastatin is the preferred treatment for CRAB.
– The order of preference for agents treating S. maltophilia includes cefiderocol, ceftazidime-avibactam, and aztreonam, among others.
Conclusion:
The 2024 IDSA guidelines provide critical updates on managing AMR Gram-negative infections, emphasizing the importance of selecting the appropriate antibiotic based on susceptibility, resistance mechanisms, and patient-specific factors. These guidelines are essential for optimizing treatment outcomes in the face of increasing antimicrobial resistance.
Reference:
RCT: Dapagliflozin Does Not Improve Outcomes in Critically Ill Patients With Acute Organ Dysfunction – JAMA
10 Aug, 2024 | 19:58h | UTCStudy Design and Population: This multicenter, open-label, randomized clinical trial conducted across 22 ICUs in Brazil evaluated the effect of adding dapagliflozin to standard care in 507 critically ill patients with at least one acute organ dysfunction (respiratory, cardiovascular, or kidney). The study took place between November 2022 and September 2023, with participants randomly assigned to either 10 mg of dapagliflozin plus standard care or standard care alone for up to 14 days or until ICU discharge.
Main Findings: The primary outcome, a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay, showed no significant difference between the dapagliflozin and control groups (win ratio, 1.01; 95% CI, 0.90 to 1.13; P = .89). Secondary outcomes also did not demonstrate significant benefits, although dapagliflozin had a slightly higher probability of reducing the need for kidney replacement therapy.
Implications for Practice: The addition of dapagliflozin to standard care in critically ill patients with acute organ dysfunction did not improve overall clinical outcomes. Although the study did not find significant benefits, the wide confidence intervals suggest that further research could be warranted to explore potential effects more definitively.
RCT: Intravenous Amino Acids Reduce AKI Incidence in Cardiac Surgery Patients – N Engl J Med
3 Aug, 2024 | 19:12h | UTCStudy Design and Population: In this multinational, double-blind, randomized clinical trial, 3511 adult patients scheduled for cardiac surgery with cardiopulmonary bypass were recruited from 22 centers across three countries. Patients were randomly assigned to receive an intravenous infusion of either a balanced mixture of amino acids (2 g/kg/day) or a placebo (Ringer’s solution) for up to three days.
Main Findings: The primary outcome, occurrence of acute kidney injury (AKI), was significantly lower in the amino acid group (26.9%) compared to the placebo group (31.7%) with a relative risk of 0.85 (95% CI, 0.77 to 0.94; P=0.002). The incidence of severe AKI (stage 3) was also reduced in the amino acid group (1.6% vs. 3.0%; relative risk, 0.56; 95% CI, 0.35 to 0.87). There were no substantial differences between the groups regarding secondary outcomes such as the use and duration of kidney-replacement therapy or all-cause 30-day mortality.
Implications for Practice: The infusion of amino acids in adult patients undergoing cardiac surgery appears to reduce the incidence of AKI, indicating a potential protective renal effect. However, this intervention did not significantly impact other secondary outcomes, including mortality and the use of kidney-replacement therapy. These findings suggest that amino acids could be considered as a strategy to mitigate AKI risk in this patient population, although further research is needed to explore long-term benefits and other clinical outcomes.
RCT: Liberal vs. Restrictive Transfusion Strategy Shows No Significant Difference in Neurologic Outcomes for Traumatic Brain Injury Patients – N Engl J Med
3 Aug, 2024 | 19:06h | UTCStudy Design and Population: This randomized clinical trial evaluated the effects of liberal versus restrictive red cell transfusion strategies in 742 adults with moderate to severe traumatic brain injury (TBI) and anemia. Participants were randomized to either a liberal transfusion strategy (initiated at hemoglobin ≤10 g/dL) or a restrictive strategy (initiated at hemoglobin ≤7 g/dL). The primary outcome was an unfavorable neurologic outcome at 6 months, assessed using the Glasgow Outcome Scale–Extended.
Main Findings: The study found that 68.4% of patients in the liberal-strategy group and 73.5% in the restrictive-strategy group experienced an unfavorable outcome (adjusted absolute difference of 5.4 percentage points; 95% CI, −2.9 to 13.7). No significant difference in mortality or depression was observed between the two groups. Although some functional independence and quality of life measures were better in the liberal group among survivors, venous thromboembolic events and acute respiratory distress syndrome rates were comparable.
Implications for Practice: The findings indicate that a liberal transfusion strategy does not significantly improve neurologic outcomes at 6 months in critically ill TBI patients compared to a restrictive strategy. Clinicians may consider maintaining a restrictive transfusion strategy, given the similar outcomes and potential for fewer transfusions. Further research is needed to explore specific subgroups that might benefit from different transfusion strategies.
RCT: Tenecteplase Reduces Disability but Not Mortality in Ischemic Stroke 4.5 to 24 Hours Post-Onset – N Engl J Med
3 Aug, 2024 | 19:03h | UTCStudy Design and Population: This randomized clinical trial was conducted in China to assess the efficacy and safety of tenecteplase in patients with ischemic stroke caused by large-vessel occlusion. The study included 516 patients who were randomly assigned to receive either tenecteplase (264 patients) or standard medical treatment (252 patients) within 4.5 to 24 hours after stroke onset. All patients had salvageable brain tissue confirmed by perfusion imaging and did not have access to endovascular thrombectomy.
Main Findings: The primary outcome, absence of disability (modified Rankin scale score of 0 or 1) at 90 days, was achieved by 33.0% of patients in the tenecteplase group compared to 24.2% in the standard treatment group (relative rate, 1.37; 95% CI, 1.04 to 1.81; P=0.03). Mortality at 90 days was similar between the two groups (13.3% for tenecteplase vs. 13.1% for standard treatment). Symptomatic intracranial hemorrhage within 36 hours occurred in 3.0% of tenecteplase-treated patients compared to 0.8% of those receiving standard treatment.
Implications for Practice: The study suggests that tenecteplase administered 4.5 to 24 hours post-stroke onset can reduce disability in patients with large-vessel occlusion who do not have access to endovascular thrombectomy. However, the increased risk of symptomatic intracranial hemorrhage warrants cautious consideration. Further research may be needed to optimize patient selection and timing of administration to balance benefits and risks.
RCT: Reteplase More Likely to Achieve Excellent Functional Outcome Than Alteplase in Acute Ischemic Stroke – N Engl J Med
3 Aug, 2024 | 19:00h | UTCStudy Design and Population: This randomized clinical trial compared the efficacy and safety of reteplase versus alteplase in patients with acute ischemic stroke. The study involved 1,412 patients who presented within 4.5 hours of symptom onset. Patients were randomly assigned in a 1:1 ratio to receive either intravenous reteplase or intravenous alteplase.
Main Findings: The primary efficacy outcome, an excellent functional outcome (modified Rankin scale score of 0 or 1) at 90 days, was achieved in 79.5% of the reteplase group compared to 70.4% of the alteplase group (risk ratio, 1.13; 95% CI, 1.05 to 1.21; P<0.001 for noninferiority and P=0.002 for superiority). The primary safety outcome, symptomatic intracranial hemorrhage within 36 hours, was similar between groups (2.4% for reteplase vs. 2.0% for alteplase; risk ratio, 1.21; 95% CI, 0.54 to 2.75). However, reteplase was associated with a higher incidence of any intracranial hemorrhage at 90 days (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51) and more adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20).
Implications for Practice: Reteplase shows superior efficacy in achieving excellent functional outcomes compared to alteplase in acute ischemic stroke, making it a viable alternative thrombolytic agent. However, the higher risk of intracranial hemorrhage and adverse events necessitates careful patient selection and monitoring. Further research may be needed to refine dosage and administration protocols to mitigate these risks.
RCT: Pantoprazole Reduces GI Bleeding in Mechanically Ventilated ICU Patients – N Engl J Med
3 Aug, 2024 | 18:57h | UTCStudy Design and Population: This international, randomized, double-blind trial involved 4,821 critically ill adults undergoing invasive mechanical ventilation across 68 intensive care units (ICUs). Participants were assigned to receive either intravenous pantoprazole (40 mg daily) or a matching placebo. The primary efficacy outcome was the incidence of clinically significant upper gastrointestinal bleeding within 90 days, and the primary safety outcome was mortality from any cause within the same period.
Main Findings: The trial found that upper gastrointestinal bleeding occurred in 1.0% of patients treated with pantoprazole compared to 3.5% in the placebo group (hazard ratio, 0.30; 95% CI, 0.19 to 0.47; P<0.001). Mortality at 90 days was 29.1% in the pantoprazole group and 30.9% in the placebo group, showing no significant difference (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P=0.25). There were no significant differences in the rates of ventilator-associated pneumonia or Clostridioides difficile infection between the groups.
Implications for Practice: The study demonstrates that pantoprazole significantly reduces the risk of upper gastrointestinal bleeding in critically ill patients on mechanical ventilation without affecting overall mortality. This suggests that pantoprazole can be considered a safe and effective option for stress ulcer prophylaxis in this high-risk population, potentially improving patient outcomes in the ICU.
Meta-Analysis: Effects of extracorporeal CO2 removal on gas exchange and ventilator settings in critically ill adults – Crit Care
27 May, 2024 | 20:28h | UTCSummary: Study Design and Population: This systematic review and meta-analysis included 49 studies (3 RCTs, 46 observational studies) involving 1672 critically ill adults undergoing extracorporeal carbon dioxide removal (ECCO2R) for respiratory failure between January 2000 and March 2022.
Main Findings: ECCO2R significantly reduced PaCO2, plateau pressure, and tidal volume, while increasing pH across all patient groups. Adverse event rate was 19%. The three RCTs did not show mortality benefits but indicated longer ICU and hospital stays.
Implications for Practice: ECCO2R improves gas exchange and reduces ventilation invasiveness, especially in ARDS and lung transplant patients. However, due to the lack of mortality benefits and increased adverse events, further studies are needed to identify patient groups that could benefit most from ECCO2R.
Reference (link to free full-text):
Randomized Controlled Trial: Mixed results with Andexanet Alfa for Factor Xa inhibitor-associated acute intracerebral hemorrhage – N Engl J Med
27 May, 2024 | 20:26h | UTCStudy Design and Population: This randomized controlled trial involved 530 patients with acute intracerebral hemorrhage who had taken factor Xa inhibitors within 15 hours before the event. They were randomly assigned to receive either andexanet alfa or usual care.
Main Findings: Hemostatic efficacy was achieved in 67% of patients receiving andexanet compared to 53.1% receiving usual care. Andexanet significantly reduced anti-factor Xa activity by 94.5%, compared to 26.9% with usual care. However, thrombotic events were more frequent in the andexanet group, including ischemic stroke.
Implications for Practice: Andexanet alfa is effective in controlling hematoma expansion in patients with factor Xa inhibitor-associated intracerebral hemorrhage but has an increased risk of thrombotic events. Further research is needed to balance efficacy and safety.
Reference (link to abstract – $ for full-text):
Randomized Clinical Trial: Intravenous acetaminophen in critically ill sepsis patients shows no significant improvement in organ support-free days – JAMA
27 May, 2024 | 20:19h | UTCStudy Design and Population: The ASTER trial was a phase 2b randomized, double-blind, clinical trial conducted between October 2021 and April 2023 across 40 US academic hospitals. The study enrolled 447 adults with sepsis and respiratory or circulatory organ dysfunction within 36 hours of presentation in emergency departments or intensive care units. Participants were randomized to receive either 1 g of acetaminophen intravenously every 6 hours or a placebo for 5 days.
Main Findings: The primary endpoint, days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) up to day 28, showed no significant difference between the acetaminophen group (20.2 days) and the placebo group (19.6 days). Secondary outcomes revealed that the acetaminophen group had significantly lower total, respiratory, and coagulation SOFA scores on days 2 through 4 and a lower rate of acute respiratory distress syndrome within 7 days (2.2% vs 8.5%). No significant interaction was observed between cell-free hemoglobin levels and acetaminophen.
Implications for Practice: While intravenous acetaminophen was safe, it did not significantly enhance the number of days alive and free of organ support in critically ill sepsis patients. The findings suggest that acetaminophen may not be effective in improving organ dysfunction outcomes in this patient population, although certain secondary benefits were noted. Further research might be necessary to explore these secondary findings and potential subgroups that could benefit from acetaminophen treatment.
Reference (free for a limited period):
Cohort Study: Thick liquids not linked to better outcomes in hospitalized patients with dementia—further studies required – JAMA Intern Med
25 May, 2024 | 19:41h | UTC– This matched cohort study evaluated the impact of thick vs. thin liquids on clinical outcomes in 8916 hospitalized patients aged 65 and older with Alzheimer Disease and Related Dementias (ADRD) and oropharyngeal dysphagia. Conducted across 11 diverse hospitals in New York from January 2017 to September 2022, the study utilized propensity score matching to ensure comparability between the two diet groups based on demographic and clinical characteristics.
– The study found no significant difference in mortality rates between the thick and thin liquid groups (hazard ratio, 0.92; 95% CI, 0.75-1.14; P = .46). Patients on a thick liquid diet were less likely to require intubation (odds ratio [OR], 0.66; 95% CI, 0.54-0.80) but exhibited a higher incidence of respiratory complications such as pneumonia (OR, 1.73; 95% CI, 1.56-1.91).
– The findings suggest that while thick liquids may reduce the need for intubation, they may increase the risk of respiratory complications. These results underscore the necessity for future prospective studies to more definitively ascertain the effectiveness of thick liquids in improving clinical outcomes for this patient population.
Reference (link to abstract – $ for full-text):
Makhnevich, A. et al. (2024). Thick Liquids and Clinical Outcomes in Hospitalized Patients With Alzheimer Disease and Related Dementias and Dysphagia. JAMA Intern Med. Published online May 6, 2024. doi:10.1001/jamainternmed.2024.0736