Journal of Intensive Care最新文献

Background: Sepsis-associated encephalopathy (SAE) may be worsened by early systemic insults. We aimed to investigate the association of early systemic insults with outcomes of critically ill patients with severe SAE.

Methods: We performed a retrospective analysis using data from the French OUTCOMEREA prospective multicenter database. We included patients hospitalized in intensive care unit (ICU) for at least 48 h with severe SAE (defined by a score on the Glasgow Coma Scale (GCS) ≤ 13 and severe sepsis or septic shock (SEPSIS 2.0 criteria)) requiring invasive ventilation and who had no primary brain injury. We analyzed early systemic insults (abnormal glycemia (< 3 mmol/L or ≥ 11 mmol/L), hypotension (diastolic blood pressure ≤ 50 mmHg), temperature abnormalities (< 36 °C or ≥ 38.3 °C), anemia (hematocrit < 21%), dysnatremia (< 135 mmol/L or ≥ 145 mmol/L), oxygenation abnormalities (PaO₂ < 60 or > 200 mmHg), carbon dioxide abnormalities (< 35 mmHg or ≥ 45 mmHg), and the impact of their correction at day 3 on day-28 mortality and awakening, defined as a recovery of GCS > 13.

Results: We included 995 patients with severe SAE, of whom 883 (89%) exhibited at least one early systemic insult that persisted through day 3. Compared to non-survivors, survivors had significantly less early systemic insults (hypoglycemia, hypotension, hypothermia, and anemia) within the first 48 h of ICU admission. The absence of correction of the following systemic insults at day 3 was independently associated with mortality: blood pressure (adjusted hazard ratio (aHR) = 1.77, 95% confidence interval (CI) 1.34-2.34), oxygenation (aHR = 1.78, 95% CI 1.20-2.63), temperature (aHR = 1.46, 95% CI 1.12-1.91) and glycemia (aHR = 1.41, 95% CI 1.10-1.80). Persistent abnormal blood pressure, temperature and glycemia at day 3 were associated with decreased chances of awakening.

Conclusions: In patients with severe SAE, the persistence of systemic insults within the first three days of ICU admission is associated with increased mortality and decreased chances of awakening.

Background: Interleukin-6 (IL-6) is a cytokine that predicts clinical outcomes in critically ill patients, including those with sepsis. Elderly patients have blunted and easily dysregulated host responses to infection, which may influence IL-6 kinetics and alter the association between IL-6 levels and clinical outcomes.

Methods: This retrospective observational study included patients aged ≥ 16 years who were admitted to the intensive care unit at Chiba University Hospital. The patients were categorized into two groups: non-elderly (< 70 years) and elderly (≥ 70 years). Associations between log-transformed blood IL-6 levels and 28-day in-hospital mortality (primary outcome) and multiple organ dysfunction (MOD) on days 3 and 7 (secondary outcomes) were examined.

Results: The non-elderly and elderly groups included 272 and 247 patients, respectively. There were no significant differences in the Sequential Organ Failure Assessment score, components of the APACHE II score (Acute physiology score and Chronic health points), MOD at baseline, or any of the outcome measures between the groups. In the non-elderly group, univariate Cox regression analysis showed a significant association between IL-6 levels and mortality (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.25-2.37, P < 0.001). This association remained significant after adjusting for sex, body mass index, steroid use prior to sepsis onset, and number of chronic organ dysfunctions (HR 1.66, 95% CI 1.20-2.32, P = 0.002). However, no significant association was observed in the elderly group in either the univariate (P = 0.69) or multivariable analyses (P = 0.77). Multivariable logistic regression analysis of MOD on days 3 and 7 revealed significant associations between MOD and IL-6 levels in both groups.

Conclusions: Blood IL-6 levels were significantly associated with mortality in non-elderly patients with sepsis, but not in elderly patients. IL-6 levels were associated with MOD in both groups. Therefore, IL-6 levels should be interpreted with caution when predicting mortality in elderly patients with sepsis.

Trial registration: Not applicable.

The incidence of heat-related illnesses and heatstroke continues to rise amidst global warming. Hyperthermia triggers inflammation, coagulation, and progressive multiorgan dysfunction, and, at levels above 40 °C, can even lead to cell death. Blood cells, particularly granulocytes and platelets, are highly sensitive to heat, which promotes proinflammatory and procoagulant changes. Key factors in heatstroke pathophysiology involve mitochondrial thermal damage and excessive oxidative stress, which drive apoptosis and necrosis. While the kinetics of cellular damage from heat have been extensively studied, the mechanisms driving heat-induced organ damage and death are not yet fully understood. Converse to hyperthermia, hypothermia is generally protective, as seen in therapeutic hypothermia. However, accidental hypothermia presents another environmental threat due to arrhythmias, cardiac arrest, and coagulopathy. From a cellular physiology perspective, hypothermia generally supports mitochondrial homeostasis and enhances cell preservation, aiding whole-body recovery following resuscitation. This review summarizes recent findings on temperature-related cellular damage and preservation and suggests future research directions for understanding the tempo-physiologic axis.

Background: Hepatic encephalopathy (HE) is a severe complication of acute hepatic failure requiring urgent critical care management. Branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine have been investigated as potential treatments to improve outcomes in patients with acute HE. However, the effectiveness of BCAA administration during the acute phase remains unclear. This study aimed to evaluate the effect of intravenous BCAA (IV-BCAA) treatment on clinical outcomes in patients with acute HE by systematically reviewing and analyzing randomized controlled trials (RCTs).

Methods: We conducted a comprehensive literature search of MEDLINE, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI), a Japanese database for medical literature. We included RCTs involving adult patients with acute HE who received IV-BCAA or placebo during the acute phase after admission (< 7 days). Two reviewers independently screened the citations and extracted data. The primary "critical" outcomes were mortality from any cause and improvement in disturbance of consciousness. The secondary "important" outcome included the incidence of complications such as nausea and diarrhea. Risk ratios (RRs) were calculated using random effects models with inverse variance weighting.

Results: Among the 2073 screened records, four met the criteria for quantitative analysis. The analysis included 219 patients: 109 received IV-BCAA, and 110 received placebo. Improvement in the disturbance of consciousness and mortality were not significantly different between the two groups (RR, 1.26; 95% confidence interval [CI], 0.96-1.66; RR, 0.90; 95% CI 0.70-1.16, respectively). Following IV-BCAA administration, the absolute differences of improvement in the disturbance of consciousness and mortality were 118 more per 1000 (95% CI 18 fewer-300 more) and 55 fewer per 1000 (95% CI 165 fewer-88 more), respectively. No significant differences were observed in the incidence of nausea or diarrhea between the two groups.

Conclusions: Our meta-analysis demonstrates that all outcomes were not significantly different between IV-BCAA treatment and placebo for acute HE. Further RCTs are required to better understand IV-BCAA treatment potential in patients with HE.

Sepsis often leads to vasoplegia and a hyperdynamic cardiac state, with treatment focused on restoring vascular tone. However, sepsis can also cause reversible myocardial dysfunction, particularly in the elderly with pre-existing heart conditions. The Surviving Sepsis Campaign Guidelines recommend using dobutamine with norepinephrine or epinephrine alone for patients with septic shock with cardiac dysfunction and persistent hypoperfusion despite adequate fluid resuscitation and stable blood pressure. However, the definition of cardiac dysfunction and hypoperfusion in these guidelines remains controversial, leading to varied clinical interpretations. Cardiac dysfunction with persistent hypoperfusion despite restoring adequate preload and afterload is often considered a cardiogenic shock. Therefore, sepsis complicated by new-onset myocardial dysfunction or worsening of underlying myocardial dysfunction due to sepsis-induced cardiomyopathy, resulting in cardiogenic shock, can be defined as "Sepsis-induced cardiogenic shock (SICS)". SICS is known to be associated with significantly higher mortality. A history of cardiac dysfunction is a strong predictor of SICS, highlighting the need for precise diagnosis and management given the aging population and rising cardiovascular disease prevalence. Therefore, SICS might benefit from early invasive hemodynamic monitoring with a pulmonary artery catheter (PAC), unlike those with septic shock alone. While routine PAC monitoring for all septic patients is impractical, echocardiography could be a useful screening tool for high-risk individuals. If echocardiography indicates cardiogenic shock, PAC might be warranted for continuous monitoring. The role of inotropes in SICS remains uncertain. Mechanical circulatory support (MCS) might be considered for severe cases, as high-dose vasopressors and inotropes are associated with worse outcomes. Correct patient selection is the key to improving outcomes with MCS. Engaging a cardiogenic shock team for a multidisciplinary approach can be beneficial. In summary, addressing the evidence gaps in SICS diagnosis and management is crucial. Echocardiography for screening, advanced monitoring with PAC, and careful patient selection for MCS are important for optimal patient care.

Background: Fluid balance gap (FBgap-prescribed vs. achieved) is associated with hospital mortality. Downtime is an important quality indicator for the delivery of continuous renal replacement therapy (CRRT). We examined the association of CRRT downtime with FBgap and clinical outcomes including mortality.

Methods: This is a retrospective cohort study of critically ill adults receiving CRRT utilizing both electronic health records (EHR) and CRRT machine data. FBgap was calculated as achieved minus prescribed fluid balance. Downtime, or percent treatment time loss (%TTL), was defined as CRRT downtime in relation to the total CRRT time. Data collection stopped upon transition to intermittent hemodialysis when applicable. Linear and logistic regression models were used to analyze the association of %TTL with FBgap and hospital mortality, respectively. Covariates included demographics, Sequential Organ Failure Assessment (SOFA) score at CRRT initiation, use of organ support devices, and the interaction between %TTL and machine alarms.

Results: We included 3630 CRRT patient-days from 500 patients with a median age of 59.5 years (IQR 50-67). Patients had a median SOFA score at CRRT initiation of 13 (IQR 10-16). Median %TTL was 8.1% (IQR 4.3-12.5) and median FBgap was 17.4 mL/kg/day (IQR 8.2-30.4). In adjusted models, there was a significant positive relationship between FBgap and %TTL only in the subgroup with higher alarm frequency (6 + alarms per CRRT-day) (β = 0.87 per 1% increase, 95%CI 0.48-1.26). No association was found in the subgroups with lower alarm frequency (0-2 and 3-5 alarms). There was no statistical evidence for an association between %TTL and hospital mortality in the adjusted model with the interaction term of alarm frequency.

Conclusions: In critically ill adult patients undergoing CRRT, %TTL was associated with FBgap only in the subgroup with higher alarm frequency, but not in the other subgroups with lower alarms. No association between %TTL and mortality was observed. More frequent alarms, possibly indicating unexpected downtime, may suggest compromised CRRT delivery and could negatively impact FBgap.

Background: Patients with severe respiratory failure have high mortality and need various interventions. However, the impact of intensivists on treatment choices, patient outcomes, and optimal intensivist staffing patterns is unknown. In this study, we aimed to evaluate treatments and clinical outcomes for patients at board-certified intensive care training facilities compared with those at non-certified facilities.

Methods: This retrospective cohort study used Japan's nationwide in-patient database from 2016 to 2019 and included patients with non-operative severe respiratory failure who required mechanical ventilation for over 4 days. Treatments and in-hospital mortality were compared between board-certified intensive care facilities requiring at least one intensivist and non-certified facilities using propensity score matching.

Results: Of the 66,905 patients in this study, 30,588 were treated at board-certified facilities, and 36,317 were not. The following differed between board-certified and non-certified facilities: propofol (35% vs. 18%), dexmedetomidine (37% vs. 19%), fentanyl (50% vs. 20%), rocuronium (8.5% vs. 2.6%), vecuronium (1.9% vs. 0.6%), noradrenaline (35% vs. 19%), arginine vasopressin (8.1% vs. 2.0%), adrenaline (2.3% vs. 1.0%), dobutamine (8.7% vs. 4.8%), phosphodiesterase inhibitors (1.0% vs. 0.3%), early enteral nutrition (29% vs. 14%), early rehabilitation (34% vs. 30%), renal replace therapy (15% vs. 6.7%), extracorporeal membrane oxygenation (1.6% vs. 0.3%), critical care unit admission (74% vs. 30%), dopamine (9.0% vs. 15%), sivelestat (4.1% vs. 7.0%), and high-dose methylprednisolone (13% vs. 15%). After 1:1 propensity score matching, the board-certified group had lower in-hospital mortality than the non-certified group (31% vs. 38%; odds ratio, 0.75; 95% confidence interval, 0.72-0.77; P < 0.001). Subgroup analyses showed greater benefits in the board-certified group for older patients, those who required vasopressors on the first day of mechanical ventilation, and those treated in critical care units.

Conclusions: Board-certified intensive care training facilities implemented several different adjunctive treatments for severe respiratory failure compared to non-board-certified facilities, and board-certified facilities were associated with lower in-hospital mortality. Because various factors may contribute to the outcome, the causal relationship remains uncertain. Further research is warranted to determine how best to strengthen patient outcomes in the critical care system through the certification of intensive care training facilities.

The guideline entitled "Japanese Clinical Practice Guidelines for Rehabilitation in Critically Ill Patients 2023" was published by the Japanese Society of Intensive Care Medicine in 2023. However, there is an issue with the clinical question and recommendation for respiratory physiotherapy in mechanically ventilated children. Although the evidence was based on two randomized controlled trials regarding prone positioning, the recommendation may have risk of misunderstanding as a recommendation for all respiratory physiotherapy. There are abundant evidence-based recommendations against chest physiotherapy for infants with bronchiolitis with no benefit and possible adverse events. Revising the recommendation for respiratory physiotherapy in critically ill, mechanically ventilated children should be considered.

Background: Experiencing a loved one's stay in the intensive care unit (ICU) can profoundly affect families, often leading to post-intensive care syndrome-family (PICS-F), a condition particularly exacerbated during the COVID-19 pandemic. While PICS-F significantly impacts the mental health of families of ICU patients, especially in the context of COVID-19, the long-term effects beyond 12 months remain understudied. This study aims to explore the prevalence of PTSD-related symptoms and health-related quality of life (HRQOL) in family members up to 18 months after ICU discharge.

Methods: This prospective study, conducted in a tertiary university hospital in Tokyo, enrolled family members of severe COVID-19 ICU patients (July 2020 to June 2022 with final follow-up ending in December 2023). The primary outcome was family member symptoms of PTSD at 6, 12 and 18 months after ICU discharge, measured by the Impact of Events Scale-Revised (presence of PTSD symptoms defined by score > 24). Secondary outcomes were family member symptoms of anxiety and depression, sleep disorders, and health-related quality of life (HRQOL) at the same timepoint.

Results: Among 97 enrolled family members, 68 participated. At least one PTSD-related symptom was reported by 26% of family members, persisting over 18 months post-discharge (16% at 6 months, 23% at 12 months, and 25% at 18 months). A subgroup (15%) exhibited delayed-onset PTSD symptoms. Family members with PTSD-related symptoms reported lower HRQOL, especially in mental and social components.

Conclusions: The study underscores the importance of long-term support for family members post-ICU discharge, given the sustained prevalence of PTSD-related symptoms among family members of severe COVID-19 patients.