Critical Care
RCT: Lack of significant effect of Paxlovid (nirmatrelvir–ritonavir) on symptom alleviation in Covid-19
26 Apr, 2024 | 11:49h | UTCStudy 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):
RCT: Clarithromycin improves early clinical and inflammatory responses in hospitalized community-acquired pneumonia patients
23 Mar, 2024 | 20:25h | UTCStudy 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 | UTCStudy 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 | UTCStudy 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 | UTCStudy 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 | UTCThis 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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 | UTCStudy 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.
RCT: Propafenone leads to quicker sinus rhythm restoration than amiodarone in supraventricular arrhythmias related to septic shock
1 Oct, 2023 | 15:19h | UTCStudy 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.
Commentary on Twitter:
Propafenone?70 mg bolus+ 400-840 mg/24h vs amiodarone?300 mg + by 600-1800 mg/24h for SVA in septic shock, RCT
?propafenone not better for rhythm control at 24h but excellent hemodynamic safety profile, cardioverting faster & fewer recurrences#FOAMCc
?https://t.co/GVuoxPD7Hy pic.twitter.com/rRlj00x71p— Intensive Care Medicine (@yourICM) September 13, 2023
RCT | Restrictive vs. liberal red blood cell transfusion strategy for critically injured patients
11 Aug, 2023 | 15:08h | UTC
Pictorial Review | Watch out for the early killers: imaging diagnosis of thoracic trauma
9 Aug, 2023 | 15:02h | UTCWatch Out for the Early Killers: Imaging Diagnosis of Thoracic Trauma – Korean Journal of Radiology
Proposed algorithm for appropriate fluid management in acute pancreatitis
8 Aug, 2023 | 13:33h | UTCFluid treatment in acute pancreatitis: a careful balancing act – British Journal of Surgery
Related:
Update on the management of acute pancreatitis – Current Opinion in Critical Care
Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis – New England Journal of Medicine
Acute Pancreatitis: Diagnosis and Treatment – Drugs
Evidence-Based Disposition of Acute Pancreatitis – emDocs
Pancreatitis – National Institute for Health and Care Excellence
Research: Endoscopic or Surgical Step-up Approach for Infected Necrotising Pancreatitis
Evidence-Based Approach to the Surgical Management of Acute Pancreatitis – The Surgery Journal
Review | Management of hypocalcemia in the critically ill
8 Aug, 2023 | 13:19h | UTCManagement of hypocalcaemia in the critically ill – Current Opinion in Critical Care
Nationwide Study | Examining survival rates and risk factors in 237 drowned patients receiving ECMO
8 Aug, 2023 | 13:13h | UTC
M-A | Efficacy and safety of supraclavicular versus infraclavicular approach for subclavian vein catheterization
7 Aug, 2023 | 14:49h | UTC
Review | Cardiorenal syndrome in the hospital
7 Aug, 2023 | 14:36h | UTCCardiorenal Syndrome in the Hospital – Clinical Journal of the American Society of Nephrology
Commentary on Twitter
The cardiorenal syndrome refers to a group of complex, bidirectional pathophysiological pathways involving dysfunction in both the heart and kidney. This Review focuses on the cardiorenal syndrome encountered in the hospital setting https://t.co/f05vpOPzCx pic.twitter.com/4Is5A2F1km
— CJASN (@CJASN) July 31, 2023
Caring for two in the ICU: pharmacologic management of pregnancy-related complications
7 Aug, 2023 | 14:31h | UTCCaring for two in the ICU: Pharmacologic management of pregnancy-related complications – Pharmacotherapy (free for a limited period)
Review | Diagnosis and management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome
4 Aug, 2023 | 11:50h | UTC
M-A | Supine vs. nonsupine endotracheal intubation
4 Aug, 2023 | 11:45h | UTC
M-A | Uncertain benefits of blood purification techniques in severe infection or sepsis
4 Aug, 2023 | 11:41h | UTC
RCT | Recombinant human prourokinase demonstrates noninferiority to alteplase in acute ischemic stroke treatment
3 Aug, 2023 | 13:46h | UTCSee also: Visual Abstract
Position Paper | Management of complicated diaphragmatic hernia in the acute setting
3 Aug, 2023 | 13:42h | UTC
Registry Analysis | Takotsubo syndrome outcomes influenced by trigger type and patient characteristics
3 Aug, 2023 | 13:14h | UTCCommentary: Takotsubo Trigger Type Matters, With Physical Shocks Linked to Worse Outcomes – TCTMD
Review | Diagnosing delirium in perioperative and intensive care medicine
3 Aug, 2023 | 13:09h | UTCDiagnosing delirium in perioperative and intensive care medicine – Current Opinion in Anesthesiology
Guideline on multimodal rehabilitation for patients with post-intensive care syndrome
2 Aug, 2023 | 14:04h | UTC
Commentary from the author on Twitter
Very proud to announce our new publication:
Guideline on multimodal rehabilitation for patients with post-intensive care syndrome
Incl. 1 statement, 12 recommendations, and 4 therapy options for prevention & rehab of patients with PICShttps://t.co/NbjIx7zcwR pic.twitter.com/X63epI7ec7
— Peter Nydahl (@NydahlPeter) July 31, 2023
Case Report | Post-myocardial infarction free-wall rupture: rapid diagnosis and management
2 Aug, 2023 | 13:52h | UTCPost-Myocardial Infarction Free-Wall Rupture: Rapid Diagnosis and Management – JACC: Case Reports
Commentary on Twitter
Learn how to evaluate, diagnose and manage #cvMI wall rupture to improve survival in #JACCCaseReports' latest issue: https://t.co/aGPJ1rZ8eu#CardioTwitter #cvSurg #CathLab pic.twitter.com/bPTtJownNf
— JACC Journals (@JACCJournals) July 31, 2023