Journal of Intensive Care Medicine

Objective To study the impact of dedicated Neuroscience Intensive Care Units (NSU) on clinical outcomes in patients with acute brain injury. Design Retrospective, multicenter cohort study. Setting 172 intensive care units within the United States. Patients Prospectively compiled and maintained a registry of a total of 32,047 brain-injured patients (stroke = AIS, aneurysmal-bleed = SAH, intra-cerebral-hemorrhage = ICH, and traumatic brain injury = TBI) from 2008–2013. Measurements Exposure of interest was the type of intensive care unit (ICU), divided into NSU and non-NSU (medical = MICU, non-neurosurgical = SICU, trauma = TICU, cardiac = CCU, or mixed). Outcomes of interest were the actual and predicted in-hospital mortality, ICU mortality, ICU length of stay, and ventilator-free days. We calculated the actual and predicted in-hospital mortality using the Cerner Corporation Acute Physiology and Chronic Health Evaluation IV (APACHE Clinical Information System, CIS). We then compared the actual in-hospital mortality against the mortality prediction of the APACHE-IV model based on ICU designation (NSU v. non-NSU). The multivariable model was adjusted for within-hospital effects and known predictors of poor outcomes after brain injury. Main Results National APACHE-IV predicted that in-hospital mortality was higher for NSU admissions than non-NSU admissions (21% v. 19%, p < .0001). However, the actual ICU mortality (10% vs 11%, p < 0.01) and in-hospital mortality (15% vs 16%, p = 0.06) were lower in patients admitted to a NSU as compared to non-NSU. We observed lower ventilator-free days (22 vs 24, p < 0.001) in NSU v. non-NSU. In the multivariable regression analysis adjusted for within-hospital effects, known variables of poor outcome, and the severity of illness APACHE-III score, the in-hospital mortality was lower for NSU admissions (OR, 0.8; 95%CI, 0.7-0.9, p = 0.02) as compared to non-NSU. Conclusion Admission of critically ill brain-injured patients to dedicated NSUs is associated with lower actual in-hospital mortality. Future iterations of APACHE-IV modeling may need to incorporate NSU designations for calculations of expected mortality among brain-injured patients.

Sepsis is one of the most prevalent conditions in critical care medicine and is characterized by a high incidence, mortality, and poor prognosis, with no specific treatment currently available. The pathogenesis of sepsis is complex with a dysregulated inflammatory response at its core. If the initial inflammatory response is not promptly controlled, patients often develop multiple organ dysfunction syndrome or die, whereas survivors may experience post-sepsis syndrome. Regulation by the central and autonomic nervous systems is essential for maintaining inflammatory homeostasis. Among these, the cholinergic anti-inflammatory pathway (CAP) has been extensively studied in sepsis owing to its significant role in modulating inflammatory responses. Recent advancements in CAP-related interventions include minimally invasive vagus nerve stimulation, novel α7nAchR-targeting drugs, serum choline acetyltransferase and cholinesterase, acupuncture, and focused ultrasound stimulation therapy. This review primarily discusses the advantages, limitations, and therapeutic prospects of these approaches. Additionally, heart rate variability, which reflects changes in autonomic nervous system function, can serve as an indicator for assessing the functional status of the vagus nerve. In summary, modulation of inflammatory responses through the vagus nerve-mediated CAP represents a potential strategy for achieving precision medicine for sepsis. Future research should focus on conducting high-quality clinical studies on CAP-based therapies in the context of sepsis-induced inflammatory dysregulation. Incorporating indicators to evaluate the autonomic nervous system function may further elucidate the impact of inflammatory dysregulation in the body.

Objectives The objective of this study was to examine the association between admission time and in-hospital mortality in patients with severe community-acquired pneumonia. Research Design The study population consisted of individuals who were enrolled between January 2019 and December 2023. These individuals were divided into two groups based on the time of admission: daytime admission from 8:00 am to 6:00 pm and nighttime admission from 6:00 pm to 8:00 am The primary endpoint of the study was in-hospital mortality. Binary logistic regression was employed to assess the association between admission time and in-hospital mortality. Results A total of 307 patients with severe community-acquired pneumonia were ultimately enrolled in the study. Of the total number of patients, 57% (175 patients) were admitted at night. A comparative analysis of the clinical outcomes in the two groups revealed that the mortality rate for patients admitted at night was 28%, which was not significantly different from that of patients admitted during the day, which was 35.6% ( P = .155). The findings from binary logistic regression analyses revealed no statistically significant correlation between nighttime admissions and in-hospital mortality. Conclusions This study's findings indicate that nighttime admission for patients diagnosed with severe community-acquired pneumonia is not associated with an elevated risk of mortality. Conversely, there may be a reduced mortality rate for patients admitted during nighttime hours. However, further prospective multicenter studies are required in the future to confirm this.

Background Cerebral venous thrombosis (CVT) is a rare but serious complication of traumatic brain injury (TBI), yet the implications of this association remain poorly understood. This study explores the demographics, risk factors, and clinical outcomes of patients with both TBI and CVT (CVT-TBI). Methods The National Inpatient Sample (NIS) was queried from 2016–2020 for adult patients with a primary diagnosis of TBI and concurrent CVT. Chi-squared tests and logistic regression were used to compare demographic, clinical, and outcome variables of CVT-TBI and TBI-only patients. Results Of the 1,583,915 TBI patients identified between 2016–2020, 640 (0.04%) had concurrent CVT. CVT-TBI patients were younger (47.94 vs 61.81; p < 0.001), more likely to have Medicaid (30.5% vs 14.1%; p < 0.001), less likely to be female (31.3% vs 39.0%; p < 0.001), and less likely to be Caucasian (60.9% vs 68.1%; p < 0.001). Multivariate analysis demonstrated age (OR = 0.98; p < 0.001), skull fracture (OR = 3.741; p < 0.001), epidural hematoma (OR = 1.407; p = 0.012), subdural hematoma (OR = 2.395; p < 0.001), and subarachnoid hemorrhage (OR = 1.415; p < 0.001) as CVT risk factors. CVT-TBI patients experienced more severe clinical courses involving mechanical ventilation (21.9% vs 10.4%; p < 0.001), cerebral herniation (6.3% vs 3.7%; p = 0.001), and being comatose (45.3% vs 30.7%; p < 0.001) and were more likely to undergo decompressive hemicraniectomy (4.7% vs 1.1%; p < 0.001), tracheostomy or percutaneous endoscopic gastrostomy tube placement (3.9% vs 1.5%; p < 0.001), and develop long-term sequelae, including seizures (10.9% vs 4.2%; p < 0.001) and hydrocephalus (7.0% vs 1.7%; p < 0.001). After matching, there was a significant difference in discharge home (OR = 1.806; p = 0.018), but no significant difference in discharge to a skilled nursing home (OR = 1.068; p = 0.449), short term rehabilitation facility (OR = 0.850; p = 0.500), or inpatient mortality (OR = 1.134; p = 0.500). Conclusions This population-based retrospective analysis unveils distinctive demographic and clinical features of CVT-TBI patients, emphasizing the need for tailored risk assessment and management strategies to improve outcomes for this subset of TBI patients.

Background Hemoadsorption is currently employed to treat septic shock and other clinical conditions involving massive inflammatory mediator release. CytoSorb ® , a device utilizing synthetic resin microbeads, provides a large adsorption surface for blood purification. This study aimed to review the clinical course of patients with septic shock treated with CytoSorb ® in our hospital's intensive care unit (ICU). Patients and Methods This study retrospectively analyzed the clinical course of patients with septic shock treated with CytoSorb ® , focusing on treatment timing and the volume of blood processed. Results Between July 1, 2016, and December 31, 2023, 175 patients (106 men, 69 women; median age: 67 years, interquartile [IQR]: 58-85) received CytoSorb ® therapy. Survivors exhibited a significantly lower simplified acute physiology score at admission than nonsurvivors. CytoSorb ® was initiated within 24 h of shock onset in 102 patients (58%, early starters) and between 25 and 48 h in 73 patients (42%, late starters). Hemodynamic improvements elevated mean arterial pressure and reduced lactate, procalcitonin, C-reactive protein, sequential organ failure assessment scores, and noradrenaline doses in survivors. These effects were more pronounced in early starters receiving intensive treatment, who also demonstrated significantly lower lactate levels and higher mean arterial pressure at the end of therapy. Overall, 86 patients (49%) died in the ICU. Survivors underwent longer treatment durations and processed greater blood volumes than nonsurvivors. Conclusions In patients with septic shock treated with CytoSorb ® within 48 h of onset, treatment intensity–rather than timing–was associated with lower ICU mortality rates.

Purpose This study aimed to investigate in-patient mortality and predictors of death associated with convulsive status epilepticus (CSE) in a large nationwide cohort and create a simplified predictive score for in-hospital mortality. Methods Retrospective data from the National Inpatient Sample (NIS) database between 2007 and 2014 were analyzed, including 123,082 adults with CSE. Univariate logistic testing identified admission variables, neurological and medical complications associated with mortality. A simplified clinical prediction score, called M ³ A ² S ² H, was generated using variables that were frequent (>1%) and had a significant impact on mortality. Results The overall hospital mortality rate was 3.5%. Univariate analysis revealed that older age, female gender, past medical history, and acute hospital conditions were related to mortality. After reclassification, a final multivariable model with 27 clinical variables was constructed, and the eight strongest predictors were included in the M ³ A ² S ² H score: hypoxic-ischemic encephalopathy/cardiac arrest (2 points); age >60 years, acute symptomatic CSE, invasive mechanical ventilation, sepsis, metastases, and chronic liver failure (all 1 point); and medication nonadherence (−1 point). The mortality rate among patients with ≤0, 1, 2, 3, 4, or ≥5 of these risk factors progressively increased from 0.2%, 2.1%, 7.8%, 20.3%, 31.9%, to 50.0% (P < 0.0001). Additionally, a similar stepwise trend was observed regarding discharge to a facility versus home without services (P < 0.0001). Conclusions This study demonstrates that mortality in CSE cases occurs in 3.5% of adult hospital admissions. Identification of specific acute and chronic conditions using the standardized M ³ A ² S ² H score can help predict the risk of death or disability even in hospitals without advanced brain monitoring.

Introduction: Endotracheal intubation in the emergency department can be challenging due to difficult airways. The Cormack-Lehane score helps assess intubation difficulty based on laryngoscopic views, with higher scores indicating poorer visibility. This study examines whether point-of-care ultrasound measurements of anterior neck soft tissue thickness at the vocal cords and hyoid bone can predict difficult intubations with Macintosh blade. Methodology: Prospective observational study included 100 patients over 18 years old who required rapid sequence intubation in emergency department at a tertiary care hospital in India, from March to December 2023. Patients with cervical spine pathology and pregnant women were excluded. Ultrasound measurements of anterior neck soft tissue thickness were taken at the vocal cords and hyoid bone. Direct laryngoscopy with a Macintosh blade was then performed, and the CL grade was recorded. Intubation difficulty was categorized based on CL grades 1-2 (easy) and 3-4 (difficult). Diagnostic performance metrics, including sensitivity, specificity, and Area under the Receiver Operating Characteristic Curve (AUROC), were calculated. Results: The study found that increased anterior neck soft tissue thickness at both the hyoid bone and vocal cords was significantly associated with higher CL grades ( P < .001). The AUROC values were 0.961 for hyoid bone measurements and 0.970 for vocal cords measurements, indicating high diagnostic accuracy. The sensitivity and specificity of these measurements suggest they are effective predictors of difficult intubation. Notably, higher ANS measurements correlated with a higher likelihood of requiring multiple intubation attempts. Conclusion: This study supports the use of ultrasound-measured anterior neck soft tissue thickness at the hyoid bone and vocal cords as effective predictors of difficult intubation. The high accuracy and statistical significance of these measurements suggest they can improve pre-intubation assessments and guide clinical decisions. Using these ultrasound measurements in routine practice could help better predict intubation challenges and improve patient outcome.

Background: Nephrotoxicity remains a significant concern in the management of critically ill patients receiving antibiotic therapy. The combination of Vancomycin and Piperacillin-Tazobactam (VPT) is frequently employed to combat multidrug-resistant infections. However, emerging evidence suggests a potential increase in the risk of acute kidney injury (AKI) associated with this combination. This study aims to systematically review and analyze the nephrotoxic risk of the VPT combination in comparison to Vancomycin with Cefepime (VC) combination therapy. Methodology: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed in databases including PubMed and Google Scholar for studies published until 2024. Studies that reported AKI incidence in patients treated with VPT, or VC were included. The data were analyzed using random-effects models to estimate pooled incidence rates of AKI. Subgroup analyses were performed based on patient demographics and baseline renal function. Results: A total of six studies involving 23 794 patients were included in the analysis. The pooled incidence of AKI in the VPT group was found to be 29.9% (95% CI: 25.3%-38.4%), significantly higher than that of the VC (22.7%) ( P < .05). A comparative analysis demonstrated a significantly higher risk of AKI in patients on VPT compared to VC (1.503; 95% CI: 1.221-1.849 P < .001). Conclusion: The findings of this study underscore a significant increase in the risk of AKI associated with the Vancomycin and Piperacillin-Tazobactam combination in critically ill patients. Clinicians should exercise caution when prescribing this combination, particularly for patients with pre-existing renal dysfunction.

Telemedicine in the intensive care unit (tele-ICU) is an increasingly significant field that leverages advanced technology to provide remote critical care services for patients in the ICU. The primary goal of tele-ICU is to enhance access to expert intensive care specialists, improve clinical outcomes, and optimize the management of critical care capacity and resources. Numerous studies have demonstrated that telemedicine can improve the efficiency of resource utilization, foster adherence to clinical best practices, and directly enhance both the quality of care and patient outcomes in the ICU setting. Moreover, telemedicine facilitates greater access to critical care knowledge, strengthens collaboration between healthcare providers across different institutions, and supports the development of specialized training programs for critical care professionals. Currently, the most widely adopted tele-ICU model is the centralized hub-and-spoke model, where a central monitoring station oversees multiple ICUs at geographically distant locations. While this model has proven effective in many contexts, there remains significant potential for further advancements in tele-ICU practices. In this article, we propose two novel theoretical models of tele-ICU that aim to address current limitations, improve quality of care, optimize personnel deployment, and maximize resource utilization. These proposed models are intended to offer a more flexible, scalable, and efficient approach to delivering critical care in diverse healthcare settings, ultimately contributing to better patient outcomes and more sustainable healthcare practices.

Objetives Extracorporeal membrane oxygenation (ECMO) after surgery for congenital heart disease (CHD) provides hemodynamic support to patients when their myocardial function is temporarily affected. Postoperative infections in children with CHD on ECMO are a significant challenge, as they complicate recovery and affect outcomes during this critical period of hemodynamic support. The objective of this study was to analyze the mortality related to the micro-organism isolated in children with ECMO after surgery for CHD. Methods Retrospective cohort study from January 2014 to December 2021 at a university hospital in Colombia. The primary outcome was the infection-related inpatient mortality of children undergoing surgery for CHD who received ECMO support, according to the type of microorganisms isolated in cultures. Results A total of 3307 surgeries for CHD were performed during the study period. Of these, 108 (3.3%) required veno-arterial ECMO after surgery. We found positive cultures in 35% of these patients. The incidence of infection was 14.5 cases per 1000 days of ECMO. The overall mortality of infected patients was 54.1%. Isolation of Gram-negative bacteria in cultures was associated with higher odds of dying compared with other isolations, regardless of age and type of CHD (aOR 6.92 95% CI 1.91-25.02; p < .01). We found no differences in hospital length of stay or PICU stay based on the type of bacteria isolated. The most commonly isolated Gram-negative bacteria was Klebsiella pneumoniae , which was associated with longer mechanical ventilation [26 (IQR 18.2-31.0) versus 11 (IQR 8.0-15.0) days; p < .01]. Conclusions The presence of a Gram-negative bacterium as the cause of infection in any sample was associated with increased odds of mortality in children receiving ECMO support in the postoperative period following corrective surgery for congenital heart disease. Infections occurred in 1 out of 3 children on ECMO following surgery for CHD.

Background Extracorporeal membrane oxygenation (ECMO) serves as a critical intervention for patients with severe cardiac and pulmonary dysfunction. Given the high rates of mortality and morbidity, as well as the impact on families, palliative care (PC) integration is recommended. We aimed to examine the indications and outcomes of ECMO patients at a tertiary care hospital and evaluate the impact of PC consultation on patient outcomes. Methods We conducted a retrospective cohort study of 306 patients cannulated for venovenous (VV) or venoarterial (VA) ECMO from January 2020 to December 2022. We analyzed demographics, ECMO indications, and outcomes, comparing those who received PC consultations with those who did not. Results Of the 306 patients analyzed, 220 were on VA-ECMO and 86 on VV-ECMO. The overall in-hospital mortality rate was 49%. Patients on VV-ECMO had longer ECMO durations (8 vs 4 days) and hospital stays (31 vs 16 days, P < 0.001) than patients on VA-ECMO. PC consultations were associated with increased ECMO duration and hospital stay in both groups (P < 0.001). Mortality among patients who received PC consultations was not statistically different from those who did not (P = 0.68). Notably, patients with obesity on VA-ECMO had 2.3 times higher odds of in-hospital death (P = 0.027). Conclusion PC consultation is integral in managing patients on ECMO, focusing on holistic support for patients and their families. Further prospective studies are warranted to explore the psychosocial benefits of PC for patients on ECMO and their family members.

Background Over half of ICU survivors experience post intensive care syndrome (PICS). Few PICS clinics were operational in the United States at the onset of the COVID-19 pandemic. Here we describe early experience of such a clinic at a large academic medical center. Our objective was to describe the (a) model of care (b) clinic interventions (c) short-term cognitive, psychiatric, and functional outcomes (d) one-year outcomes of COVID-19 ICU survivors at the Cleveland Clinic post-ICU recovery clinic (PIRC). Methods We conducted a retrospective cohort study through a chart review of all patients seen in PIRC from April 2020 – December 2020. A total of 59 patients completed the visit with 49% being virtual, and 51% being in-person. The cohort was predominantly white (50.8%), and male (57.6%) with a median age of 58.2 years. We screened for cognitive and psychiatric impairments using several different validated questionnaires. Functional impairments were self-reported and detected after assessment by a physical therapist. Quantifiable clinic interventions were referrals, pharmacy medication reconciliation, and vaccine administration. One-year outcomes were health care utilization, and death. Results In our cohort, 36%, 39.6%, and 17% of patients screened positive for cognitive impairment, anxiety and/or depression, and PTSD respectively. 42.3% of patients had lower extremity mobility impairment. 57.6% of patients required at least one referral after clinic. Of the 67.9% of patients who were working and 93.9% driving prior to hospitalization, only 24.6% and 73.2% had returned to those activities, respectively. The most common pharmacy intervention was discontinuation of a medication no longer in use. By one year, 34% of patients had hospital re-admissions with 5% requiring the ICU. There were no deaths. Conclusions Adult survivors of COVID-19 critical illness have impairments in all PICS domains as well as high health care utilization in the first year after hospital discharge. MeSH Terms Post intensive care syndrome, COVID-19 Key Points/Summary Adult survivors of COVID-19 critical illness have impairments in all PICS domains as well as high health care utilization in the first year after hospital discharge. Post-ICU recovery clinics can help survivors with recovery.

Objective Observational studies suggest links between inflammatory factors, metabolites, and sepsis, yet their causality is uncertain. This study employs Mendelian Randomization (MR) to investigate the causality between these factors and sepsis, aiming to uncover the precise relationship and identify novel treatment approaches. Methods We used summary data from genome-wide association studies (GWAS) involving 91 inflammatory factors, 1400 metabolites as exposure, and STREPTO SEPSIS as outcome. Inverse variance weighting (IVW) and MR-Egger were used to evaluate the causal effect between exposure and outcome. Sensitivity analyses were performed using Cochrane's Q test, MR-Egger intercept method, MR-PRESSO method and leave-one-out method. Results Thymic stromal lymphopoietin levels (TSLP) (OR = 1.269; 95%CI = 1.016-1.585; P = .036) and Interleukin 15 receptor subunit alpha levels (IL-15Rα) (OR = 0.894; 95%CI = 0.801-0.998; P = .046) had a significant causal relationship with sepsis. Forty-four metabolites were associated with sepsis, including Spermidine to choline ratio (OR = 1.447; 95%CI = 1.104-1.977; P = .009), 4-hydroxyhippurate levels (OR = 1.448; 95%CI = 1.117-1.877; P = .005), and Sphingomyelin (d18:1/20:1, d18:2/20:0) levels (OR = 1.371; 95%CI = 1.139-1.651; P < .001). TSLP was associated with 19 metabolites, and IL-15Rα was associated with 30 metabolites. Conclusions This study uncovers the causal link between sepsis and two inflammatory factors, TSLP and IL-15Rα, and suggests metabolites’ potential in intervention. It also identifies 44 metabolites associated with sepsis, indicating possible biomarkers or therapeutic targets. The findings offer new perspectives on sepsis pathogenesis and could inform future treatment strategies.

Multisystem Inflammatory Syndrome in Children: A Comprehensive Review over the Past Five Years This review explores many facets of Multisystem Inflammatory Syndrome in Children (MIS-C) over the previous 5 years. In the time since the COVID 19 pandemic gripped our medical systems, we can now explore the data that has been collected from the previous years. The literature has allowed us to better understand the impact of COVID 19 and the post illness occurrence of a severe systemic inflammatory disease on our youngest patient populations. This paper will outline the pathophysiology of MIS-C, the treatments utilized, short and long-term patient outcomes including epidemiological factors.

The use of focused critical care echocardiography, diagnostic modality aimed to provide immediate and actionable information, represents a core competency of contemporary intensive care medicine. Resuscitative transesophageal echocardiography (TEE) is a focused, goal-directed examination performed at the point of care, for the rapid evaluation of critically ill patients in whom transthoracic images are either logistically untenable, inadequate, or unobtainable. Some of the applications of TEE in the management of critically ill patients include the evaluation of patients in shock and cardiac arrest, the assessment of trauma patients, and the guidance of several endovascular procedures. Due to the indwelling nature of the transducer, TEE can provide consistently high-quality images and allows for continuous monitoring during hemodynamic interventions, making it ideally suited for the evaluation of critically ill patients. In this article, we review the evolving landscape of resuscitative TEE, discuss the rationale, supporting evidence, safety, and training for the use of this modality in critical care settings. We address the transdisciplinary evolution of TEE and the practical aspects of its implementation in emergency and critical care settings.

Background: Airway Pressure Release Ventilation (APRV) is an alternate mode of ventilation in acute respiratory failure (ARF), but there is inconsistent data to support its use over other modes of ventilation. Because of increased intrathoracic pressure for most of the respiratory cycle, a negative impact of APRV on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) has been hypothesized. We evaluated the effects of APRV ventilation, with particular attention to ICP, CPP and ICP-directed therapy, in a real-world cohort of neuro-ICU patients. Methods: Retrospective single-center analysis from January 2021 to December 2023 of neurosurgical ICU patients with ICP monitoring. APRV was used as a rescue mode at the physician's discretion when the Horovitz index (PaO 2 /FIO 2 ratio) fell below 150 despite optimized conventional ventilation. Results: Between 2021 and 2023, APRV was utilized in 29 patients undergoing a total of 60 episodes. Forty patients (66.7%) were female, median age was 49.5 (Q1 34; Q3 61.25) years. After transition to APRV, mean FiO2 decreased by 4.3% (t = 3.5, p < .001) and mean PaO2 increased by 22.7 mm Hg (t = 4.2, p < .001). The Horovitz index improved by 44.6 mm Hg (t = 4.9, p < .001). Mean compliance did not differ after transition to APRV (−1.5 ml/mbar, t = −0.9, p = .4). During the APRV episode, mean ICP was 1.2 mm Hg lower (t = 2.6, p = .01), while mean CPP was 1.6 mm Hg higher (t = −0.9, p = .4) and the intensity of ICP-directed therapy (TIL) was significantly lower (X 2 = 92.771, p < .001). Conclusion: APRV was hemodynamically tolerated in 29 out of 33 patients, and was safe with regard to ICP, CPP, and the intensity of ICP-directed therapy. Oxygenation was increased by APRV. 4 out of 33 patients would not tolerate APRV for hemodynamic reasons, APRV therefore was stopped immediately.

Objectives Ventilator-associated pneumonia (VAP) and delirium are major complications among patients in the intensive care unit (ICU). The impact of oral bacterial count on these conditions is not well understood. This study aimed to explore the association between oral bacterial load and the incidence of VAP and delirium in ICU patients. Methods In this single-center longitudinal study, 130 patients admitted to the ICU from September 2022 to May 2023 were included. Oral bacteria counts on the tongue were quantified, and assessments of oral health using the Oral Health Assessment Tool (OHAT) and oral moisture levels were also conducted. We examined the associations between oral bacterial count, OHAT scores, and oral moisture with the incidence of VAP and delirium. Results The incidence rates of VAP and delirium were 31.4% and 35.4%, respectively. Patients with a high oral bacterial load (≥5.0 × 10 ⁷ CFU/mL) at ICU admission had a higher likelihood of developing VAP (odds ratio [OR] 7.43, 95% confidence interval [CI] 1.68-32.87) and delirium (OR 3.30, 95% CI 1.04-10.44) compared with those with lower bacterial counts (<1.0 × 10 ⁷ CFU/mL). No significant associations were found between OHAT scores and oral moisture and the occurrence of VAP or delirium. Conclusion A higher oral bacterial count at ICU admission was associated with increased incidences of VAP and delirium.

Objectives There is substantial practice variation in the management strategies for atrial fibrillation (AF) with rapid ventricular rate (RVR) and hemodynamic instability in critically ill patients. This study aimed to evaluate the use and effectiveness of direct current cardioversion (DCCV) for unstable AF RVR in the intensive care unit (ICU). Design Multicenter retrospective cohort study. Setting Non-cardiac/cardiovascular surgery ICUs of the Mayo Clinic Hospitals in Minnesota, Wisconsin, Florida, and Arizona. Patients Adult patients who developed paroxysmal AF RVR with hemodynamic instability (heart rate ≥ 130 beats per minute and a documented SBP ≤ 90 mmHg or the need for vasopressors) during ICU stay. Interventions Emergency DCCV. Measurements and Main Results Primary outcomes were in-hospital mortality, hospital-, ICU-, and organ support-free days. Secondary outcomes were return to sinus rhythm rate before and after discharge. Among 691 patients eligible for inclusion, 47 (6.8%) received emergent DCCV in the ICU. The frequency of DCCV was higher for patients located in surgical ICUs (14.5% vs 6.1%, P = .04). Patients were 1:2 propensity-score matched. The comparative analyses were conducted on 141 patients. Those who underwent DCCV were more likely to restore sinus rhythm (odds ratio [95% confidence interval], 5.2 [1.30 20.8]). However, DCCV was not associated with increased odds of having sinus rhythm at discharge, lower mortality, or higher number of ICU-, or hospital-free days. The number of organ support-free days was significantly lower in the DCCV group (estimate ± standard error, −5.0 ± 2.0, P = .012). Conclusions Emergency DCCV is rarely used to treat unstable AF in non-cardiac ICUs. Despite increased likelihood of immediate sinus rhythm restoration, DCCV was not associated with improvement in patient-centered outcomes. Prospective studies are warranted to evaluate harms and benefits of DCCV in non-cardiac critically ill patients with unstable AF where the driver of hemodynamic instability is often an underlying condition rather than arrhythmia per se.

Objective Fluid resuscitation is an important intervention in children with septic shock. The composition of resuscitation fluid is a matter of debate. Our aim was to study the effects of balanced salt solution (BSS) versus normal saline (NS) for resuscitation in pediatric septic shock. Data sources We searched MEDLINE, Embase, LILAC, Cochrane Collaboration, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. Study selection Two independent authors screened title and abstracts and then full papers of included studies. Data extraction Two authors extracted data from full papers independently. Random-effects model was used for analysis of RCTs. We used Cochrane's risk of bias tool for assessing the quality of studies. Primary outcome was mortality and secondary outcomes were rates of acute kidney injury (AKI), need for renal replacement therapy (RRT), and adverse effects (hyperchloremia, metabolic acidosis, and fluid overload); and duration of PICU and hospital stay. Data synthesis Five RCTs with 992 children were included. Resuscitation with BSS versus NS was not associated with reduction in mortality (RR 0.82, 95% CI 0.45-1.50, p = 0.52; RCTs = 5); with similar results on sensitivity analysis (RR 0.76, 95% CI 0.41-1.41, p = 0.52; 4 RCTs = 4). However, resuscitation with BSS was associated with lower rates of AKI (sensitivity analysis RR 0.64, 95% CI 0.50-0.82, p = 0.0004; RCTs = 3); lesser need for RRT (RR 0.52, 95% CI 0.35-0.76, p = 0.0008; RCTs = 2); and lower rate of hyperchloremia (RR 0.74, 95% CI 0.62-0.87, p = 0.0002; RCTs = 3). The data is scant for other secondary outcomes (metabolic acidosis, fluid overload, and duration of PICU and hospital stay) to make any suggestions. The overall ‘risk of bias’ was low and unclear in most domains. Conclusion Use of BSS as resuscitation fluid in pediatric septic shock was not associated with reduction in mortality. However, BSS was associated with decreased risk of AKI, need of RRT and hyperchloremia. Clinical Trial Registration (if any) PROSPERO (CRD42022332208).

Introduction Biostatistics is an increasing focus in both the United States Medical Licensing exams (USMLE) and medical school curricula. Nonetheless, literature has documented that it is poorly understood among both practicing physicians and physician trainees. Our purpose is to narrow this knowledge gap by offering readers a “how-to” guide that both supplements essential biostatistics knowledge and assists in constructing research projects. Methods In Part II of our tandem manuscripts, we expand our Part I biostatistics analysis of research articles in the Journal of Intensive Care Medicine (JICM) with explanations and practical use of biostatistics, addressing the most common statistical terms and tests used in the JICM. Results Understanding biostatistics requires interpreting the type of study, type of data collected, statistical tests available for all types of data, and results of the statistical tests. Conclusion Gaining proficiency in biostatistics will improve the precision of evidence-based medical outcomes, helping close the current knowledge gap among practicing physicians and trainees.

Background Sepsis complicates acute pancreatitis (AP), increasing mortality risk. Few studies have examined how sepsis and its onset timing affect mortality in AP. This study evaluates the association between sepsis occurrence and all-cause mortality in AP, focusing specifically on the impact of sepsis onset timing. Methods This multicenter retrospective cohort study included 494 ICU-admitted AP patients from the MIMIC-IV database and 91 from our center. Patients were grouped by sepsis occurrence and onset timing. Clinical outcomes were in-hospital and 90-day all-cause mortality. Machine learning identified key variables associated with mortality. Multivariable regression analyzed the impact of sepsis and its onset timing on mortality. To reduce baseline differences, propensity score matching (PSM) based on time to sepsis was conducted. After PSM, Kaplan-Meier survival analyses incorporated data from our center for validation. Restricted cubic spline analysis examined any nonlinear relationship between sepsis onset timing and mortality. Results Patients with sepsis had significantly higher in-hospital and 90-day mortality rates than those without sepsis ( p < 0.05). Sepsis was identified as a significant risk factor for in-hospital mortality and remained significantly associated after adjusting for key variables ( p < 0.05). However, sepsis onset timing did not significantly impact in-hospital or 90-day mortality. These findings were validated after PSM and with our center's data. No nonlinear relationship between sepsis onset timing and mortality was found. Conclusion Sepsis significantly increases all-cause mortality in AP patients, but the timing of its onset has limited impact. Continuous monitoring and intervention for sepsis during hospitalization are recommended to improve prognosis.

Background Blood lactate is commonly used in clinical medicine as a diagnostic, therapeutic and prognostic guide. Lactate's growing importance in many disciplines of clinical medicine and academic enquiry is underscored by the tenfold increase in publications over the past 10 years. Lactate monitoring is presently shifting from single to serial measurements, offering a means of assessing response to therapy and to guide treatment decisions. With the promise of wearable lactate sensors and their potential integration in electronic patient records and early warning scores, the utility of serial lactate measurement deserves closer scrutiny. Methods Articles included in this review were identified by searching MEDLINE, PubMed and EMBASE using the term “lactate” alone and in combination with “serial”, “point of care”, “clearance”, “prognosis” and “clinical”. Authors were assigned vetting of publications according to their specialty (anesthesiology, intensive care, trauma, emergency medicine, obstetrics, pediatrics and general hospital medicine). The manuscript was assembled in multidisciplinary groups guided by underlying pathology rather than hospital area. Findings Lactate's clinical utility as a dynamic parameter is increasingly recognized. Several publications in the last year highlight the value of serial measurements in guiding therapy. Outside acute clinical areas like the emergency room, operating room or intensive care, obtaining lactate levels is often fraught with difficulty and delays. Interpretation Measuring serial lactate and lactate clearance offers regular feedback on response to therapy and patient status. Particularly on the ward, wearable devices integrated in early warning scores via the hospital IT system are likely to identify deteriorating patients earlier than having to rely on observations by an often-overstretched nursing workforce.

Background Distinguishing surgical intensive care unit (ICU) patients with ongoing bleeding who require hemorrhage control interventions (HCI) can be challenging. Guidelines recommend risk-stratification with clinical variables and prediction tools, however supporting evidence remains mixed. Methods This retrospective study evaluated adult patients admitted to the surgical ICU with concern for ongoing hemorrhage under our institution's “Hemorrhage Watch” (HW) protocol and aimed to derive a clinical prediction model identifying those needing HCI with serial vital signs (VS) and serum biomarkers. The HW protocol included ICU admission followed by a 3-h observation period with VS monitoring every 15 min and hourly biomarkers. The primary outcome was the need for HCI (operative and endovascular interventions) within nine hours of ICU arrival. Secondary outcomes included in-hospital mortality, blood transfusions, and ICU and hospital length-of-stay. A clinical prediction model was developed by utilizing the variables most associated with HCI in a best subsets regression, which was subsequently internally validated using a Bootstrap algorithm. Results 305 patients were identified for inclusion and 18 (5.9%) required HCI (3 operative, 15 endovascular). The median age was 70 years (IQR 54, 83), 60% had traumatic injuries, and 73% were enrolled from the emergency department. Blood product transfusion and mortality were similar between the HCI and no-HCI groups. Our analysis demonstrated that a model based on the minimum hemoglobin (9.9 vs 8.1 g/dL), minimum diastolic (57 vs 53 mm Hg) and systolic blood pressures (105 vs 90 mm Hg), and minimum respiratory rate (15 vs 18) could predict HCI with an area under the Receiver Operating Characteristics curve (AUROC) of 0.87, outperforming the Shock Index (SI) (AUROC = 0.64). Conclusions In this study of surgical ICU patients with concern for ongoing bleeding, a prediction model using serial VS and biomarkers outperformed the SI and may help identify those requiring HCI.

Purpose The onset of diaphragmatic weakness begins within hours of commencing invasive mechanical ventilation (IMV), which may contribute to the physical disability that can persist at five years after intensive care unit (ICU) discharge. Inspiratory muscle training (IMT) has the potential to alleviate the negative effects of IMV. Methods We conducted a systematic review and meta-analysis with an approach consistent with Cochrane methods. We registered our review a priori (PROSPERO: CRD 42023451809) and published our protocol. Randomized controlled trials (RCTs) which enrolled adults (≥18 years) admitted to ICU who required IMV for ≥24 h were eligible if they delivered an IMT intervention using an external device that provided airway resistance (eg, threshold device, tapered flow resistive device) compared to usual care. Our primary outcome was physical function. Secondary outcomes included respiratory muscle strength, mortality, length of stay, IMV weaning time, reintubation rate, dyspnea and endurance. We searched Medline, Embase, Emcare, AMED, CINAHL, CENTRAL and clinicaltrials.gov from inception and used the Covidence platform for study selection and data extraction. We reported results as standardized mean difference (SMD) if outcome measures were similar. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to assess the certainty of evidence. Results We screened 12 945 studies and 18 met the inclusion criteria. Three studies reported the effects of IMT on physical function. IMT may have no effect on physical function (SMD = −0.05, 95% confidence interval: −0.46 to 0.36) however results are very uncertain. Conclusion Our results suggest physical function is not impacted by IMT; however, our results are based on a limited number of studies with small samples sizes. High quality, appropriately powered RCTs are needed to improve the precision of the effect estimate.

Introduction During extracorporeal membrane oxygenation (ECMO) systemic anticoagulation with unfractionated heparin (UFH) is standard-of-care. However, there is uncertainty regarding optimal anticoagulation monitoring strategies. Methods We retrospectively investigated venovenous and venoarterial ECMO patients at the medical ICUs at the Medical University of Graz, Austria. We analyzed the correlation and concordance of R-time in thromboelastography (TEG), activated partial thromboplastin time (aPTT), and anti-Xa activity. The proportion within target range, the association of coagulation parameters above or below target range (aPTT 54–72 s; equals 1.5–2× upper limit of normal (ULN), anti-Xa activity 0.2–0.5 U/mL, and R-time in assays without heparinase 675–900 s; equals 1.5–2× ULN) with mortality, bleeding events and thrombotic complications were investigated. Results We analyzed 671 clusters of simultaneously performed coagulation tests in 85 ECMO cases that fulfilled inclusion criteria. Median age of patients was 57 years and 32% were female. There were poor correlations between the three coagulation tests and the proportion of discordance was 46%. Within the target range were 21% of R-time, 15% of aPTT, and 44% of anti-Xa activity measurements. Singular and multiple bleeding events occurred in 25 and 32 patients, respectively. The most common bleeding locations were catheter and cannula insertion sites followed by pulmonary hemorrhage. In VA-ECMO, anti-Xa activity was associated (OR 1.03 [1.01–1.06], p = 0.005) and correlated with bleeding events (spearman rho 0.49, p = 0.002; point biserial 0.49, p = 0.001). aPTT level below target range was associated with reduced mortality (OR 0.98 [0.97–0.99], p = 0.024). Thrombotic events occurred in six patients with no association of coagulation tests. Conclusion There was a high rate of discordance and poor correlation between aPTT, anti-Xa activity and R-time in TEG in ECMO patients. We found high rates of bleeding events and in VA-ECMO an association with elevated anti-Xa activity levels.