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Critical Care

Meta-Analysis: Effects of extracorporeal CO2 removal on gas exchange and ventilator settings in critically ill adults – Crit Care

27 May, 2024 | 20:28h | UTC

Summary: 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):

Stommel AM et al. (2024). Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis. Critical Care, 28(146). DOI: 10.1186/s13054-024-04927-x.

 


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 | UTC

Study 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):

Connolly SJ, Sharma M, Cohen AT, et al. (2024). Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. New England Journal of Medicine, 390(19), 1745-1755. DOI: 10.1056/NEJMoa2313040.

 


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 | UTC

Study 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):

Ware LB, Files DC, Fowler A, et al. (2024). Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial. JAMA. Published online May 19, 2024. doi:10.1001/jama.2024.8772

 


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

 


RCT: Thrombectomy improves outcomes in acute stroke with large infarcts – N Engl J Med

25 May, 2024 | 19:35h | UTC

Study Design and Population: This randomized clinical trial investigated the efficacy of thrombectomy in combination with standard medical care versus medical care alone in patients with acute stroke and large infarcts. Participants included 333 patients with proximal cerebral vessel occlusion in the anterior circulation, presenting within 6.5 hours of symptom onset. They were randomized in a 1:1 ratio to either undergo thrombectomy or receive only medical care. An Alberta Stroke Program Early Computed Tomographic Score of ≤5 was used to define large infarcts.

Main Findings: The primary outcome, assessed by the modified Rankin scale score at 90 days, showed a median score of 4 in the thrombectomy group compared to 6 in the control group, indicating better functional outcomes with thrombectomy (generalized odds ratio, 1.63; 95% CI, 1.29 to 2.06; P<0.001). Mortality at 90 days was significantly lower in the thrombectomy group (36.1%) compared to the control group (55.5%) with an adjusted relative risk of 0.65. However, thrombectomy was associated with a higher rate of symptomatic intracerebral hemorrhage (9.6% vs. 5.7% in the control group).

Implications for Practice: The findings suggest that thrombectomy, when added to standard medical care, can significantly improve functional outcomes and reduce mortality in patients with large infarct strokes. However, the increased risk of symptomatic intracerebral hemorrhage must be considered when deciding on this intervention. These results support the broader use of thrombectomy in clinical settings with similar patient profiles but underscore the need for careful risk-benefit analysis due to the potential for serious hemorrhagic complications.

 

Reference (link to abstract – $ for full-text):

Costalat, V. et al. (2024). Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size. N Engl J Med, 390(18), 1677-1689. DOI: 10.1056/NEJMoa2314063

 


RCT: Early minimally invasive surgery may improve outcomes in selected patients with intracerebral hemorrhage – N Engl J Med

25 May, 2024 | 18:58h | UTC

Study Design and Population: This multicenter randomized clinical trial investigated the efficacy of early minimally invasive surgical removal of intracerebral hemorrhage compared to medical management alone. The trial enrolled 300 patients within 24 hours of symptom onset, who had either lobar or anterior basal ganglia hemorrhages, with hematoma volumes ranging from 30 to 80 ml. An adaptation rule was applied partway through the trial, resulting in the exclusive enrollment of patients with lobar hemorrhages after 175 patients were initially enrolled.

Main Findings: Patients in the surgery group achieved a significantly higher mean score on the utility-weighted modified Rankin scale at 180 days (0.458) compared to the control group (0.374), with a difference of 0.084 and a posterior probability of superiority of 0.981. Notably, the benefit of surgery was pronounced among patients with lobar hemorrhages (mean difference 0.127), whereas no benefit was observed in patients with anterior basal ganglia hemorrhages. Additionally, the surgery group experienced a lower 30-day mortality rate (9.3%) compared to the control group (18.0%).

Implications for Practice: The results suggest that early minimally invasive surgery for intracerebral hemorrhage, particularly for lobar hemorrhages, offers significant functional benefits over medical management alone. These findings support the selective use of this surgical approach in clinical settings, potentially leading to improved patient outcomes. Further studies could explore the differential impact of hemorrhage location on surgical outcomes to refine treatment guidelines.

 

Reference (link to abstract – $ for full-text):

Pradilla, G. et al. (2024). Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage. N Engl J Med, 390(14), 1277-1289. DOI: 10.1056/NEJMoa2308440.

 


Guidelines on the use of intravenous albumin in various clinical settings – CHEST

25 May, 2024 | 18:49h | UTC

The International Collaboration for Transfusion Medicine Guidelines provides comprehensive guidelines on the use of intravenous albumin across various clinical settings, including critical care, cardiovascular surgery, kidney replacement therapy, and complications of cirrhosis. The guideline emphasizes that there are few evidence-based indications supporting the routine use of albumin to improve patient outcomes. Key findings include:

 

1 – Critical Care: Limited recommendations for using albumin in adult, pediatric, and neonatal critical care, primarily advising against its routine use for volume replacement or managing hypoalbuminemia due to low or very low certainty of evidence.

2 – Cardiovascular Surgery: No recommendations for using albumin to prime cardiovascular bypass circuits or for volume replacement due to moderate to very low certainty of evidence.

3 – Kidney Replacement Therapy: Albumin is not suggested for preventing or managing intradialytic hypotension or improving ultrafiltration due to very low certainty of evidence.

4 – Cirrhosis Complications: Some conditional recommendations for using albumin in specific scenarios like large-volume paracentesis and spontaneous bacterial peritonitis due to low certainty of evidence; however, it is generally not suggested for other complications of cirrhosis.

 

Overall, the guidelines advise a cautious approach to albumin use, highlighting the need for more robust evidence to support its broader application in clinical practice.

 

Reference (link to free full-text):

Callum J et al. (2024). Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines. CHEST, 2024. DOI: https://doi.org/10.1016/j.chest.2024.02.049.

 


Cohort Study: Late ventricular arrhythmias are rare in STEMI patients without left ventricular dysfunction post-primary PCI – JAMA Netw Open

11 May, 2024 | 14:15h | UTC

Study Design and Population: This cohort study analyzed data from the US National Cardiovascular Data Registry Chest Pain–MI Registry, involving 174,126 adults with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2015 to 2018. The population included a broad demographic with a focus on those experiencing late ventricular tachycardia (VT) or ventricular fibrillation (VF) post-PCI, specifically examining occurrences one day or more after the intervention.

Main Findings: The study found that 8.9% of the patients developed VT or VF after PCI, with 2.4% experiencing these arrhythmias late in the hospitalization period. Among patients with uncomplicated STEMI, late VT or VF with cardiac arrest was exceedingly rare, occurring in only 0.1%. Notably, reduced left ventricular ejection fraction was strongly associated with an increased risk of late VT or VF with cardiac arrest. The presence of late VT or VF significantly correlated with higher in-hospital mortality rates.

Implications for Practice: The findings suggest that late VT or VF after primary PCI in STEMI patients is infrequent, particularly among those without complications. This data supports the potential for safe earlier hospital discharge in uncomplicated cases. However, vigilance is advised due to the significant mortality risk associated with late VT or VF events. Clinicians should consider patient-specific risk factors such as left ventricular function when making discharge decisions.

 

Reference (link to free full-text):

Rymer JA et al. (2024). Ventricular Arrhythmias After Primary Percutaneous Coronary Intervention for STEMI. JAMA Network Open, 7(5), e2410288. DOI: 10.1001/jamanetworkopen.2024.10288.

 


Cluster Randomized Trial: Hyperangulated video laryngoscopy reduces intubation attempts in surgical patients – JAMA

11 May, 2024 | 13:39h | UTC

Study Design and Population: This cluster randomized multiple crossover clinical trial was conducted at a single U.S. academic hospital to compare the effectiveness of hyperangulated video laryngoscopy versus direct laryngoscopy in reducing the number of intubation attempts during surgery. The study involved 7,736 adult patients, aged 18 years or older, undergoing elective or emergent cardiac, thoracic, or vascular surgical procedures that required single-lumen endotracheal intubation for general anesthesia. The trial randomized two sets of 11 operating rooms on a weekly basis to use either video laryngoscopy or direct laryngoscopy for the initial intubation attempt from March 2021 to December 2022.

Main Findings: Hyperangulated video laryngoscopy significantly decreased the number of intubation attempts compared to direct laryngoscopy. Specifically, 1.7% of surgical procedures using video laryngoscopy required more than one intubation attempt versus 7.6% for direct laryngoscopy, with an estimated proportional odds ratio of 0.20 (95% CI, 0.14-0.28; P < .001). Furthermore, intubation failure was markedly lower with video laryngoscopy (0.27%) compared to direct laryngoscopy (4.0%). However, there was no significant difference in the rates of airway and dental injuries between the two methods.

Implications for Practice: The findings indicate that hyperangulated video laryngoscopy enhances initial intubation success and reduces the need for multiple intubation attempts in a variety of surgical settings. This suggests that video laryngoscopy could be considered a preferable technique for endotracheal intubation in the operating room, potentially improving patient outcomes and efficiency. Further research might explore the generalizability of these results to other medical centers and different patient populations.

 

Reference (link to abstract – $ for full-text):

Ruetzler, K. et al. (2024). Cluster Randomized Trial: Hyperangulated Video Laryngoscopy Reduces Intubation Attempts in Surgical Patients. JAMA, 331(15), 1279-1286. DOI: 10.1001/jama.2024.0762

 


RCT: Video laryngoscopy improves first-attempt intubation success in neonates compared to direct laryngoscopy – N Engl J Med

11 May, 2024 | 13:37h | UTC

Study Design and Population: This single-center randomized clinical trial investigated the efficacy of video laryngoscopy versus direct laryngoscopy for urgent intubation in neonates. A total of 226 neonates requiring intubation either in the delivery room or neonatal intensive care unit (NICU) were enrolled and stratified by gestational age into two groups: less than 32 weeks and 32 weeks or more. The study primarily focused on the success rate of the first intubation attempt, monitored through exhaled carbon dioxide detection.

Main Findings: The trial included 214 neonates, analyzing the success of intubation on the first attempt. Video laryngoscopy significantly outperformed direct laryngoscopy, achieving a first-attempt success rate of 74% (95% confidence interval [CI], 66 to 82) compared to 45% (95% CI, 35 to 54) in the direct laryngoscopy group. Moreover, the median number of attempts for successful intubation was lower in the video-laryngoscopy group (1 attempt, 95% CI, 1 to 1) versus the direct-laryngoscopy group (2 attempts, 95% CI, 1 to 2). Additionally, neonates in the video laryngoscopy group experienced higher median lowest oxygen saturations and heart rates during intubation.

Implications for Practice: The findings suggest that video laryngoscopy could be more effective than direct laryngoscopy for urgent neonatal intubation, particularly in increasing the likelihood of success on the first attempt. These results recommend reconsidering current intubation techniques in neonatal care settings to incorporate video laryngoscopy, potentially leading to safer and more efficient intubation processes in this vulnerable population.

 

Reference (link to abstract – $ for full-text):

Geraghty, L.E. et al. (2024). Video versus Direct Laryngoscopy for Urgent Intubation of Newborn Infants. The New England Journal of Medicine. DOI: 10.1056/NEJMoa2402785.

 


Review: Acute and complicated inflammatory pericarditis – Mayo Clin Proc

6 May, 2024 | 18:03h | UTC

The article provides a comprehensive review of current approaches to the diagnosis and management of inflammatory pericardial disease, with a particular focus on acute and complicated cases of pericarditis. Here’s a summary tailored for a medical audience:

Key Points:

1 – Epidemiology and Presentation:

– Acute pericarditis is relatively common, particularly among younger populations.

– It can be effectively managed in most cases but poses a significant risk of recurrence and morbidity if not properly treated.

– Presentations can vary, with chest pain being a predominant symptom, which improves upon leaning forward and worsens in the supine position.

2 – Diagnostic Evaluation:

– Diagnosis hinges on a combination of clinical signs (e.g., chest pain, pericardial rub), ECG changes, imaging findings, and laboratory markers (elevated CRP and white blood cell count).

– Multimodality imaging plays a critical role in diagnosis and management, including echocardiography, CT, and MRI to evaluate pericardial effusion and inflammation.

3 – Management Strategies:

– The treatment landscape has evolved with the introduction of targeted anti-inflammatory therapies and a more systematic approach to care.

– Management includes NSAIDs as first-line therapy, colchicine to reduce recurrence rates, and corticosteroids for severe cases. Recent advancements include the use of interleukin-1 receptor blockers for complicated cases.

– Pericardiectomy may be considered in chronic or recurrent cases that are refractory to medical management.

4 – Future Directions:

– Ongoing research is directed at improving diagnostic accuracy through advanced imaging techniques and refining treatment protocols to minimize recurrence and manage complicated cases effectively.

– The integration of novel biological agents and personalized medicine approaches is anticipated to enhance outcomes for patients with pericardial disease.

This article emphasizes the importance of a protocol-driven approach to the initial care, the use of targeted therapeutics based on individual patient profiles, and the integration of care pathways to manage acute and complicated pericarditis effectively.

 

Reference (link to free full-text):
Malik, A. A., Lloyd, J. W., Anavekar, N. S., & Luis, S. A. (2024). Acute and Complicated Inflammatory Pericarditis: A Guide to Contemporary Practice. Mayo Clinic Proceedings, 99(5), 795-811. https://doi.org/10.1016/j.mayocp.2024.01.012

 


SCCM/IDSA Updated guidelines for evaluating new fever in adult ICU patients – Crit Care Med

5 May, 2024 | 15:12h | UTC

The 2023 revision of the guidelines for assessing new-onset fever in adult ICU patients stresses rigorous diagnostic processes using the GRADE methodology. These guidelines, developed without industry funding, offer 12 recommendations and nine best-practice statements focused primarily on the accurate measurement of core body temperature and initial diagnostic evaluations geared towards identifying potential infectious causes. Central temperature monitoring is recommended when possible; otherwise, oral or rectal measurements are preferred. The utility of imaging studies and rapid diagnostic tests is highlighted, along with the selective use of biomarkers to guide the cessation of antimicrobial therapy. The guidelines underscore that most recommendations are based on weak evidence, thus highlighting the need for continued research in diagnostic methodologies and fever management in the ICU setting.

 

Reference (link to free full-text):

O’Grady NP, Alexander E, Alhazzani W, et al. (2023). Society of Critical Care Medicine and the Infectious Diseases Society of America Guidelines for Evaluating New Fever in Adult Patients in the ICU. Critical Care Medicine, 51(11), 1570-1586. DOI: 10.1097/CCM.0000000000006022.

 


RCT: Empagliflozin does not reduce heart failure hospitalization or death post-myocardial infarction

29 Apr, 2024 | 12:39h | UTC

This randomized, placebo-controlled trial assessed empagliflozin in preventing heart failure or death in patients recently hospitalized for acute myocardial infarction. Among 6,522 patients divided evenly into empagliflozin and placebo groups, there was no significant difference in the primary outcome—a composite of heart failure hospitalization or death—after 17.9 months. The empagliflozin group saw 8.2% experiencing the primary outcome versus 9.1% in the placebo group, yielding a non-significant hazard ratio of 0.90 (95% CI, 0.76 to 1.06; P=0.21). The results indicate that empagliflozin does not effectively reduce the risk of heart failure or mortality compared to placebo in this setting.

 

Reference (link to abstract – $ for full-text):

Butler, J. et al. (2024). Empagliflozin after Acute Myocardial Infarction. N Engl J Med, 390(16), 1455-1466. DOI: 10.1056/NEJMoa2314051

 


RCT: Efficacy and safety of microaxial flow pump in STEMI-related cardiogenic shock

28 Apr, 2024 | 20:17h | UTC

This randomized clinical trial assessed the impact of a microaxial flow pump (Impella CP) on mortality in 355 patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock. Patients were randomly assigned to receive either the microaxial flow pump plus standard care or standard care alone. The primary outcome was mortality at 180 days. Results showed a significant reduction in death rates in the microaxial flow pump group (45.8%) compared to the standard care group (58.5%) with a hazard ratio of 0.74 (95% CI, 0.55 to 0.99; P=0.04). However, the incidence of severe adverse events was notably higher in the microaxial flow pump group, including severe bleeding and device-related complications.

 

Reference (link to abstract – $ for full-text):

Jacob E. Møller et al. (2024). Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock. N Engl J Med, 390(15), 1382-1393. DOI: 10.1056/NEJMoa2312572

 


RCT: Reduction in cardiac events through preventive PCI in vulnerable atherosclerotic coronary plaques

28 Apr, 2024 | 17:39h | UTC

This multicenter, open-label, randomized controlled trial assessed the effectiveness of preventive percutaneous coronary intervention (PCI) versus optimal medical therapy alone in treating patients with non-flow-limiting vulnerable coronary plaques identified by intracoronary imaging. Conducted across 15 research hospitals in four countries, the trial enrolled 1,606 patients, with 803 in each treatment group. After 2 years, major adverse cardiac events were significantly lower in the PCI group (0.4%) compared to the medical therapy group (3.4%), with a p-value of 0.0003. These results suggest that preventive PCI can effectively reduce cardiac events in patients with high-risk vulnerable plaques, supporting the expansion of PCI indications to these patients.

 

Reference (link to abstract – $ for full-text):

Prof Seung-Jung Park et al. (2024). Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial. The Lancet, Volume Not Specified (Issue Not Specified), Pages Not Specified. DOI: https://doi.org/10.1016/S0140-6736(24)00413-6

 


RCT: Intravascular ultrasound guidance improves outcomes in percutaneous coronary intervention for acute coronary syndrome

28 Apr, 2024 | 17:22h | UTC

This randomized clinical trial evaluated 3505 acute coronary syndrome (ACS) patients across 58 centers in China, Italy, Pakistan, and the UK, comparing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) with angiography-guided PCI. The study’s primary endpoint was target vessel failure—comprising cardiac death, myocardial infarction, or revascularisation—after 1 year. The IVUS-guided group showed significantly lower rates of the primary endpoint (4.0%) compared to the angiography-guided group (7.3%), with a hazard ratio of 0.55. This outcome was primarily driven by reductions in myocardial infarction and revascularisation, with similar safety profiles between the two groups.

 

Reference (link to abstract – $ for full-text):

Xiaobo Li et al. (2024). Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicentre, randomised trial. The Lancet, Volume (Issue), Pages. DOI: https://doi.org/10.1016/S0140-6736(24)00282-4

 


RCT: Lack of significant effect of Paxlovid (nirmatrelvir–ritonavir) on symptom alleviation in Covid-19

26 Apr, 2024 | 11:49h | UTC

Study Design and Population:

This phase 2–3 randomized clinical trial investigated the efficacy of nirmatrelvir in combination with ritonavir for treating mild-to-moderate Covid-19 in adults. Participants, both vaccinated and unvaccinated, were enrolled based on their risk factors for severe Covid-19. The study included 1296 adults who had confirmed Covid-19 with symptom onset within the past 5 days. They were randomly assigned to receive either nirmatrelvir–ritonavir or placebo every 12 hours for 5 days.

 

Main Findings:

The primary endpoint was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Results showed that the median time to alleviation was 12 days for the treatment group and 13 days for the placebo group, a difference that was not statistically significant (P=0.60). Hospitalizations and deaths were slightly lower in the treatment group (0.8%) compared to the placebo group (1.6%), but this difference was also not statistically significant. Adverse events were similar across both groups, with dysgeusia and diarrhea being the most common in the treatment group.

 

Implications for Practice:

The findings indicate that nirmatrelvir–ritonavir treatment does not significantly reduce the time to symptom alleviation for Covid-19 compared to placebo among vaccinated or unvaccinated adults. These results suggest that further research is needed to explore the potential benefits of this treatment in specific subpopulations or in combination with other interventions.

 

Reference (free full-text):

Reference: Hammond J. et al. (2024). Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19. N Engl J Med, 390(13), 1186-1195. DOI: 10.1056/NEJMoa2309003


RCT: Clarithromycin improves early clinical and inflammatory responses in hospitalized community-acquired pneumonia patients

23 Mar, 2024 | 20:25h | UTC

Study Design and Population: The ACCESS trial was a phase 3, prospective, double-blind, randomized controlled trial conducted in 18 Greek hospitals, involving adults hospitalized with community-acquired pneumonia who displayed systemic inflammatory response syndrome, had a Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin levels of 0.25 ng/mL or more. Participants were randomly assigned to receive either standard of care with intravenous cephalosporins or β-lactam/β-lactamase inhibitor combinations plus oral clarithromycin (500 mg twice daily for 7 days) or placebo. The trial aimed to evaluate the impact of clarithromycin on early clinical and inflammatory responses.

Main Findings: Among 278 participants allocated to clarithromycin (n=139) or placebo (n=139), the primary composite endpoint—indicating early clinical response and inflammatory burden reduction within 72 hours—was met by 68% of patients in the clarithromycin group compared to 38% in the placebo group, showcasing a significant difference (29.6%, odds ratio 3.40, p<0.0001). Serious treatment-emergent adverse events were slightly lower in the clarithromycin group than in the placebo group, although not statistically significant.

Implications for Practice: The addition of clarithromycin to the standard of care for hospitalized patients with community-acquired pneumonia significantly improves early clinical response and reduces inflammatory burden, potentially through modulation of the immune response. These results support the use of clarithromycin alongside β-lactam antibiotics in the treatment of community-acquired pneumonia, highlighting its role in enhancing patient outcomes by targeting early clinical and inflammatory indicators.

Reference

Prof Evangelos J Giamarellos-Bourboulis, MD et al. (2024). Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine, Volume(Issue), Pages. DOI: https://doi.org/10.1016/S2213-2600(23)00412-5. Access the study here: Link


PCI vs. CABG in left main coronary disease patients with and without diabetes—a pooled analysis of 4 trials

22 Mar, 2024 | 11:41h | UTC

Study Design and Population: This research pooled individual patient data from four randomized clinical trials (SYNTAX, PRECOMBAT, NOBLE, and EXCEL), comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in 4393 patients with left main coronary artery disease. The trials included both patients with and without diabetes, allowing for a comparative analysis of outcomes based on the revascularization method and the presence of diabetes.

Main Findings: Patients with diabetes exhibited higher rates of 5-year mortality, spontaneous myocardial infarction (MI), and repeat revascularization compared to those without diabetes. However, mortality rates following PCI vs. CABG were similar in diabetic (15.3% vs. 14.1%, respectively) and non-diabetic patients (9.7% vs. 8.9%, respectively). PCI was associated with a lower risk of stroke within the first year post-operation across all patients. Notably, diabetic patients underwent higher rates of spontaneous MI and repeat revascularization after PCI compared to CABG, with a more significant absolute excess risk observed beyond the first year compared to non-diabetic patients.

Implications for Practice: For patients with left main disease deemed suitable for either PCI or CABG, diabetes status significantly influences long-term outcomes, including death and cardiovascular events. While PCI offers a lower early risk of stroke, it is associated with increased risks of spontaneous MI and repeat revascularization, particularly in diabetic patients. These findings underscore the importance of considering patient-specific factors, such as diabetes status, in choosing between PCI and CABG for left main coronary artery disease revascularization.

Reference

Prakriti Gaba et al. (2024). Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With or Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials. Circulation, 0. DOI: 10.1161/CIRCULATIONAHA.123.065571. Access the study here: Link


RCT: Lower oxygenation target improves days alive without life support in severe COVID-19 hypoxemia

21 Mar, 2024 | 13:46h | UTC

Study Design and Population: This multicenter randomized clinical trial investigated the impact of different oxygenation targets on the survival of adult patients with COVID-19 and severe hypoxemia in the ICU. Conducted across 11 European ICUs from August 2020 to March 2023, the study involved 726 patients requiring at least 10 L/min of oxygen or mechanical ventilation. Participants were randomly assigned to receive an oxygenation target of either 60 mm Hg (lower oxygenation group, n=365) or 90 mm Hg (higher oxygenation group, n=361) for up to 90 days.

Main Findings: The primary outcome was the number of days alive without life support at 90 days post-intervention. Patients in the lower oxygenation group achieved a median of 80.0 days alive without life support compared to 72.0 days in the higher oxygenation group, a difference that was statistically significant (P=0.009). Although there was a slight reduction in mortality at 90 days in the lower oxygenation group (30.2% vs 34.7% in the higher group), this was not statistically significant. No significant differences were observed in the proportion of patients with serious adverse events or the number of days alive and out of hospital.

Implications for Practice: Targeting a lower Pao2 of 60 mm Hg in ICU patients with COVID-19 and severe hypoxemia appears to increase the days alive without life support compared to a higher target of 90 mm Hg, without increasing serious adverse events. This finding suggests that a lower oxygenation target could be more beneficial for this patient population, potentially guiding clinical practice in managing oxygen therapy for severe COVID-19 cases.

Reference

Reference: Nielsen FM et al. (2024). Randomized Clinical Trial: Effect of Oxygenation Targets on Survival Without Life Support in COVID-19 Patients with Severe Hypoxemia. JAMA, Published online March 19, 2024. DOI: 10.1001/jama.2024.2934. Access the study here: [Link]


Meta-Analysis: No mortality benefit of early vs. delayed/selective coronary angiography in out-of-hospital cardiac arrest without ST-elevation

21 Mar, 2024 | 11:40h | UTC

Study Design and Population: This article presents a systematic review and meta-analysis of five randomized controlled trials comparing early/immediate versus delayed/selective coronary angiography (CAG) in 1512 patients who experienced out-of-hospital cardiac arrest (OHCA) without ST-segment elevation. The population had a mean age of 67 years, with 26% female and 23% having a prior myocardial infarction. Follow-up duration was at least 30 days across included studies.

Main Findings: The analysis revealed no significant difference in the odds of all-cause death between early/immediate and delayed/selective CAG strategies (Odds Ratio [OR] 1.12, 95% CI 0.91–1.38). Similar results were found for the composite outcome of all-cause death or neurological deficit (OR 1.10, 95% CI 0.89–1.36). Subgroup analysis showed no significant effect modification based on age, initial cardiac rhythm, history of coronary artery disease, the presumed ischemic cause of arrest, or time to return of spontaneous circulation. Interestingly, a trend toward increased odds of death was observed in women receiving early CAG compared to men, although this finding approached but did not reach statistical significance.

Implications for Practice: The findings suggest that for OHCA patients without ST-segment elevation, an early/immediate CAG strategy does not confer a mortality benefit over a delayed/selective approach across major subgroups. Notably, the potential for increased mortality risk in women with early CAG warrants further investigation. Clinicians should consider these results when deciding on the timing of CAG in this patient population, keeping in mind the overall lack of mortality benefit and the nuanced differences among subgroups.

Reference: Fardin Hamidi et al. (2023). Early versus delayed coronary angiography in patients with out-of-hospital cardiac arrest and no ST-segment elevation: a systematic review and meta-analysis of randomized controlled trials. Clinical Research in Cardiology, 113(561–569). Access the study here: [Link]


ACG Guideline: Management of Acute Pancreatitis

20 Mar, 2024 | 21:49h | UTC

This guideline, crafted by the American College of Gastroenterology, provides essential strategies for managing acute pancreatitis, offering a concise overview of diagnosis, treatment, and prevention recommendations for healthcare professionals. Here is a summary of the key information contained in the document:

 

  1. Introduction and Epidemiology: Acute pancreatitis (AP) is one of the most common gastrointestinal diseases leading to hospitalization in the United States, with about 300,000 admissions annually and a cost of over 2.5 billion dollars. The incidence of AP has been increasing annually, although the mortality rate has remained stable due to advancements in management.
  2. Etiology and Diagnosis: AP is typically caused by gallstones and alcohol consumption. Diagnosis is made based on the presence of two of the following three criteria: characteristic abdominal pain, serum amylase and/or lipase levels more than three times the upper limit of normal, and/or characteristic findings on abdominal imaging.
  3. Initial Management and Hydration: Initial management emphasizes the importance of moderate to aggressive intravenous hydration, preferably with lactated Ringer’s solution over normal saline, due to its potential benefit in reducing systemic inflammation and preventing complications.
  4. Nutrition: Patients with mild AP are encouraged to start early oral feeding within 24 to 48 hours as tolerated, preferring a low-fat solid diet over a progressive approach from liquids to solids.
  5. Management of Complications: The document addresses the management of complications such as pancreatic necrosis, suggesting the use of antibiotics only in cases of infected necrosis and highlighting a preference for minimally invasive methods of debridement and necrosectomy.
  6. Prevention of Recurrence and Role of ERCP: To prevent recurrences in biliary pancreatitis, cholecystectomy is recommended. In selected cases of acute biliary pancreatitis without cholangitis, medical therapy is preferred over early ERCP.
  7. Use of Antibiotics: The guidelines discourage the prophylactic use of antibiotics in cases of severe AP without evidence of infection, due to the lack of demonstrated benefit and potential risks.

 

Tenner, S. et al (2024). American College of Gastroenterology Guidelines: Management of Acute Pancreatitis. The American Journal of Gastroenterology, 119(3), 419-437. https://doi.org/10.14309/ajg.0000000000002645


RCT: No difference in ICU length of stay or 90-day mortality between tight and liberal glucose control

2 Oct, 2023 | 11:25h | UTC

Study Design and Population: This randomized controlled trial assessed the effects of tight versus liberal glucose control on the length of ICU stay in critically ill patients. A total of 9,230 patients were included, with 4,622 in the liberal-control group (insulin initiation when blood glucose levels exceeded 215 mg/dL) and 4,608 in the tight-control group (blood glucose targeted between 80 and 110 mg/dL). In both groups, parenteral nutrition was withheld during the first week of ICU admission. The primary endpoint was the duration of ICU stay, and 90-day mortality served as a key safety outcome.

Main Findings: No significant differences were observed in the primary endpoint, the length of ICU stay, between the two groups (hazard ratio 1.00; 95% CI, 0.96 to 1.04; P=0.94). The 90-day mortality rates were also similar (10.1% in the liberal-control group vs. 10.5% in the tight-control group, P=0.51). Incidences of severe hypoglycemia were low and statistically similar in both groups (1.0% in the tight-control group vs. 0.7% in the liberal-control group). Secondary outcomes, including new infections and the duration of respiratory and hemodynamic support, showed no significant differences. However, lower incidences of severe acute kidney injury and cholestatic liver dysfunction were observed in the tight-control group.

Implications & Limitations: The study supports existing evidence that tight glucose control doesn’t provide substantial benefits in reducing ICU stay duration or mortality. This suggests that a more liberal approach to glucose control may be preferable in most ICU settings, especially to minimize hypoglycemia risk. Key limitations of the study include its narrow focus on the absence of early parenteral nutrition, which could limit generalizability, and the inability to blind caregivers to treatment assignments. Future research should investigate the impact of tight glucose control in various patient subgroups and under different nutritional conditions.

Article: Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU – New England Journal of Medicine

 


RCT: Propafenone leads to quicker sinus rhythm restoration than amiodarone in supraventricular arrhythmias related to septic shock

1 Oct, 2023 | 15:19h | UTC

Study Design & Population: The research was a two-center, prospective, controlled parallel-group, double-blind trial involving 209 septic shock patients who had new-onset supraventricular arrhythmia and a left ventricular ejection fraction above 35%. Patients were randomized to receive either intravenous propafenone (70 mg bolus followed by 400–840 mg/24 h) or amiodarone (300 mg bolus followed by 600–1800 mg/24 h).

Main Findings: The primary outcomes focused on the proportion of patients in sinus rhythm 24 hours post-infusion, time to the first sinus rhythm restoration, and arrhythmia recurrence rates. No significant difference was observed in 24-hour sinus rhythm rates between the propafenone (72.8%) and amiodarone (67.3%) groups (p=0.4). Time to the first rhythm restoration was significantly shorter for the propafenone group (median 3.7 hours) compared to the amiodarone group (median 7.3 hours, p=0.02). Recurrence of arrhythmia was notably lower in the propafenone group (52%) than in the amiodarone group (76%, p<0.001). In the subgroup of patients with a dilated left atrium, amiodarone appeared to be more effective.

Implications & Limitations: The study suggests that while propafenone doesn’t offer better rhythm control at 24 hours compared to amiodarone, it does provide faster cardioversion and fewer arrhythmia recurrences, especially in patients with a non-dilated left atrium. No significant differences were observed in clinical outcomes, such as ICU or long-term mortality, between propafenone and amiodarone in the trial. Limitations include potential underpowering of the study and the inability to fully account for the impact of multiple covariates involved in the complex therapy of septic shock.

Article: Balik, M., Maly, M., Brozek, T. et al. Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: a randomised controlled trial. Intensive Care Med (2023)

 

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RCT | Restrictive vs. liberal red blood cell transfusion strategy for critically injured patients

11 Aug, 2023 | 15:08h | UTC

The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma – Journal of Intensive Care

 


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