The incidence of ventilator-associated pneumonia (VAP) in trauma patients can be decreased with use of the ventilator bundle (VAPB). Our VAP rate remained high despite the adoption of the VAPB. To ...better implement the VAPB, a multidisciplinary team composed of the surgical intensive care unit (SICU) nursing staff, physician, and respiratory therapist reviewed briefly a checklist of VAPB goals for each patient before morning attending rounds. We hypothesized that such daily goal rounds (GR) focused on the VAPB would decrease the VAP rate.
A pre-GR ten-month period (November 2006 to August 2007) was compared with the ten-month period (September 2007 to June 2008) with daily GRs. The occurrence of VAPs was tallied prospectively in all intubated trauma patients using the National Nosocomial Infection Surveillance criteria. Patient characteristics and outcome data were obtained from our trauma registry and medical records. Patient characteristics were similar in the 85 pre-GR patients and the 89 GR patients.
The number of VAPs decreased 67% in the GR patients (15 pre-GR vs. 5 GR; p=0.02); however, the all-cause mortality rate remained similar (16.5% vs. 21.3%; p=0.41). When patients were divided into those with and without VAP, there was a significant increase in mean ventilator, SICU, and hospital days in patients with VAP (p=0.01 for all). There were only two deaths among trauma patients with VAP.
Daily multidisciplinary GRs focused on the VAPB can decrease the incidence of VAP significantly in trauma patients. Ventilator-associated pneumonia correlated with extended mean ventilator, SICU, and hospital days. Interestingly, despite a significant decrease in VAP, a decrease in the mortality rate was not observed. Given the small number of deaths in the VAP cohort, this study has insufficient statistical power to elucidate the true impact of GR intervention or VAP on the mortality rate in trauma patients.
Costameres, structures at the plasma membrane of skeletal muscle, are present in a rectilinear array that parallels the organization of the underlying contractile apparatus. Costameres have three ...major functions: to keep the plasma membrane, or sarcolemma, aligned and in register with nearby contractile structures; to protect the sarcolemma against contraction-induced damage; and to transmit some of the forces of contraction laterally, to the extracellular matrix. These functions require that costameres link the contractile apparatus through the membrane to the extracellular matrix. Mutations to key components of costameres cause these structures to lose their rectilinear organization and can result in muscle weakness or death. This article summarizes the evidence that costameres are composed of large complexes of integral and peripheral membrane proteins that are linked to the contractile apparatus by intermediate filaments and to the extracellular matrix by laminin. They also present evidence that costameres are altered when key costameric components are missing, as in a murine form of muscular dystrophy.
Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics ...to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU).
We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge.
The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time.
In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).
The proliferation of evidence synthesis methods makes it challenging for reviewers to select the ‘‘right’’ method. This study aimed to update the Right Review tool (a web-based decision support tool ...that guides users through a series of questions for recommending evidence synthesis methods) and establish a common set of questions for the synthesis of both quantitative and qualitative studies (https://rightreview.knowledgetranslation.net/).
A 2-round modified international electronic modified Delphi was conducted (2022) with researchers, health-care providers, patients, and policy makers. Panel members rated the importance/clarity of the Right Review tool's guiding questions, evidence synthesis type definitions and tool output. High agreement was defined as at least 70% agreement. Any items not reaching high agreement after round 2 were discussed by the international Project Steering Group.
Twenty-four experts from 9 countries completed round 1, with 12 completing round 2. Of the 46 items presented in round 1, 21 reached high agreement. Twenty-seven items were presented in round 2, with 8 reaching high agreement. The Project Steering Group discussed items not reaching high agreement, including 8 guiding questions, 9 review definitions (predominantly related to qualitative synthesis), and 2 output items. Three items were removed entirely and the remaining 16 revised and edited and/or combined with existing items. The final tool comprises 42 items; 9 guiding questions, 25 evidence synthesis definitions and approaches, and 8 tool outputs.
The freely accessible Right Review tool supports choosing an appropriate review method. The design and clarity of this tool was enhanced by harnessing the Delphi technique to shape ongoing development. The updated tool is expected to be available in Quarter 1, 2025.
•Right Review assists in identifying appropriate evidence synthesis methods.•Right Review was updated using an international Delphi process.•Right Review now has a single set of guiding questions.
Background
Stimulation of β2‐adrenoceptors can promote muscle hypertrophy and fibre type shift, and it can counteract atrophy and weakness. The underlying mechanisms remain elusive.
Methods
Fed wild ...type (WT), 2‐day fasted WT, muscle‐specific insulin (INS) receptor (IR) knockout (M‐IR−/−), and MKR mice were studied with regard to acute effects of the β2‐agonist formoterol (FOR) on protein metabolism and signalling events. MKR mice express a dominant negative IGF1 receptor, which blocks both INS/IGF1 signalling. All received one injection of FOR (300 μg kg−1 subcutaneously) or saline. Skeletal muscles and serum samples were analysed from 30 to 240 min. For the study of chronic effects of FOR on muscle plasticity and function as well as intracellular signalling pathways, fed WT and MKR mice were treated with formoterol (300 μg kg−1 day−1) for 30 days.
Results
In fed and fasted mice, one injection of FOR inhibited autophagosome formation (LC3‐II content, 65%, P ≤ 0.05) that was paralleled by an increase in serum INS levels (4‐fold to 25‐fold, P ≤ 0.05) and the phosphorylation of Akt (4.4‐fold to 6.5‐fold, P ≤ 0.05) and ERK1/2 (50% to two‐fold, P ≤ 0.05). This led to the suppression (40–70%, P ≤ 0.05) of the master regulators of atrophy, FoxOs, and the mRNA levels of their target genes. FOR enhanced (41%, P ≤ 0.05) protein synthesis only in fed condition and stimulated (4.4‐fold to 35‐fold, P ≤ 0.05) the prosynthetic Akt/mTOR/p70S6K pathway in both fed and fasted states. FOR effects on Akt signalling during fasting were blunted in both M‐IR−/− and MKR mice. Inhibition of proteolysis markers by FOR was prevented only in MKR mice. Blockade of PI3K/Akt axis and mTORC1, but not ERK1/2, in fasted mice also suppressed the acute FOR effects on proteolysis and autophagy. Chronic stimulation of β2‐adrenoceptors in fed WT mice increased body (11%, P ≤ 0.05) and muscle (15%, P ≤ 0.05) growth and downregulated atrophy‐related genes (30–40%, P ≤ 0.05), but these effects were abolished in MKR mice. Increases in muscle force caused by FOR (WT, 24%, P ≤ 0.05) were only partially impaired in MKR mice (12%, P ≤ 0.05), and FOR‐induced slow‐to‐fast fibre type shift was not blocked at all in these animals. In MKR mice, FOR also restored the lower levels of muscle SDH activity to basal WT values and caused a marked reduction (57%, P ≤ 0.05) in the number of centrally nucleated fibers.
Conclusions
NS/IGF1 signalling is necessary for the anti‐proteolytic and hypertrophic effects of in vivo β2‐adrenergic stimulation and appears to mediate FOR‐induced enhancement of protein synthesis. INS/IGF1 signalling only partially contributes to gain in strength and does not mediate fibre type transition induced by FOR.
Severe acute kidney injury (AKI) is associated with a significant risk of mortality and persistent renal replacement therapy (RRT) dependence. The objective of this study was to develop prediction ...models for mortality at 90-day and 1-year following RRT initiation in critically ill patients with AKI.
All patients who commenced RRT in the intensive care unit for AKI at a tertiary care hospital between 2007 and 2014 constituted the development cohort. We evaluated the external validity of our mortality models using data from the multicentre OPTIMAL-AKI study.
The development cohort consisted of 594 patients, of whom 320(54%) died and 40 (15% of surviving patients) remained RRT-dependent at 90-day Eleven variables were included in the model to predict 90-day mortality (AUC:0.79, 95%CI:0.76–0.82). The performance of the 90-day mortality model declined upon validation in the OPTIMAL-AKI cohort (AUC:0.61, 95%CI:0.54–0.69) and showed modest calibration. Similar results were obtained for mortality model at 1-year.
Routinely collected variables at the time of RRT initiation have limited ability to predict mortality in critically ill patients with AKI who commence RRT.
•Mortality is frequent after severe acute kidney injury.•Accurate prediction may help with shared decision-making.•Clinical parameters at dialysis initiation would be ideal for this purpose.•The models in this study only resulted in a moderate predictive ability.•Additional information might be necessary for adequate risk prediction.
Sustained low efficiency dialysis (SLED) has emerged as an alternative to continuous renal replacement therapy (CRRT) for the treatment of acute kidney injury (AKI) in critically ill patients. ...However, there is limited information on the short- and long-term outcomes of SLED compared to CRRT.
We conducted a retrospective cohort study of patients with AKI who commenced either SLED or CRRT in ICUs at a tertiary care hospital in Toronto, Canada. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at one year, and dialysis dependence at 90 days and one year. All outcomes were ascertained by linkage to provincial datasets.
We identified 284 patients, of whom 95 and 189 commenced SLED and CRRT, respectively. Compared to SLED recipients, more CRRT recipients were mechanically ventilated (96% vs 86%, p = 0.002) and receiving vasopressors (94% vs 84%, p = 0.01) at the time of RRT initiation. At 90 days following RRT initiation, 52 (55%) and 126 (67%) SLED and CRRT recipients, respectively, died (adjusted risk ratio (RR) 0.91, 95% CI 0.75–1.11). There was no inter-modality difference in time to death through 90 days (adjusted hazard ratio 0.90, 95% CI 0.64–1.27). Among patients surviving to Day 90, a higher proportion of SLED recipients remained RRT dependent (10 (23%) vs 6 (10%) CRRT recipients, adjusted RR 2.82, 95% CI 1.02–7.81). At one year, there was no difference in mortality or dialysis dependence.
Among critically ill patients with acute kidney injury, mortality at 90 days and one year was not different among patients initiating SLED as compared to CRRT.
•This retrospective cohort study of 284 critically ill patients with acute kidney injury compared outcomes among those initiating therapy with SLED or CRRT.•90-day all-cause mortality, adjusted for relevant confounders, did not differ between recipients of sustained low efficiency dialysis and continuous renal replacement therapy.•The receipt of SLED was associated with a higher risk of persistent dialysis dependence at 90 days.
Stimulation of β
-adrenoceptors can promote muscle hypertrophy and fibre type shift, and it can counteract atrophy and weakness. The underlying mechanisms remain elusive.
Fed wild type (WT), 2-day ...fasted WT, muscle-specific insulin (INS) receptor (IR) knockout (M-IR
), and MKR mice were studied with regard to acute effects of the β
-agonist formoterol (FOR) on protein metabolism and signalling events. MKR mice express a dominant negative IGF1 receptor, which blocks both INS/IGF1 signalling. All received one injection of FOR (300 μg kg
subcutaneously) or saline. Skeletal muscles and serum samples were analysed from 30 to 240 min. For the study of chronic effects of FOR on muscle plasticity and function as well as intracellular signalling pathways, fed WT and MKR mice were treated with formoterol (300 μg kg
day
) for 30 days.
In fed and fasted mice, one injection of FOR inhibited autophagosome formation (LC3-II content, 65%, P ≤ 0.05) that was paralleled by an increase in serum INS levels (4-fold to 25-fold, P ≤ 0.05) and the phosphorylation of Akt (4.4-fold to 6.5-fold, P ≤ 0.05) and ERK1/2 (50% to two-fold, P ≤ 0.05). This led to the suppression (40-70%, P ≤ 0.05) of the master regulators of atrophy, FoxOs, and the mRNA levels of their target genes. FOR enhanced (41%, P ≤ 0.05) protein synthesis only in fed condition and stimulated (4.4-fold to 35-fold, P ≤ 0.05) the prosynthetic Akt/mTOR/p70S6K pathway in both fed and fasted states. FOR effects on Akt signalling during fasting were blunted in both M-IR
and MKR mice. Inhibition of proteolysis markers by FOR was prevented only in MKR mice. Blockade of PI3K/Akt axis and mTORC1, but not ERK1/2, in fasted mice also suppressed the acute FOR effects on proteolysis and autophagy. Chronic stimulation of β
-adrenoceptors in fed WT mice increased body (11%, P ≤ 0.05) and muscle (15%, P ≤ 0.05) growth and downregulated atrophy-related genes (30-40%, P ≤ 0.05), but these effects were abolished in MKR mice. Increases in muscle force caused by FOR (WT, 24%, P ≤ 0.05) were only partially impaired in MKR mice (12%, P ≤ 0.05), and FOR-induced slow-to-fast fibre type shift was not blocked at all in these animals. In MKR mice, FOR also restored the lower levels of muscle SDH activity to basal WT values and caused a marked reduction (57%, P ≤ 0.05) in the number of centrally nucleated fibers.
NS/IGF1 signalling is necessary for the anti-proteolytic and hypertrophic effects of in vivo β
-adrenergic stimulation and appears to mediate FOR-induced enhancement of protein synthesis. INS/IGF1 signalling only partially contributes to gain in strength and does not mediate fibre type transition induced by FOR.
Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver ...factors associated with the development of these symptoms.
This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II BDI-II), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay LOS), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months.
BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale P = .28 and Center for Epidemiologic Studies Depression Scale P = .74).
Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders.
Older patients in the intensive care unit are at greater risk of AKI; however, use of kidney replacement therapy in this population is poorly characterized. We describe the triggers and outcomes ...associated with kidney replacement therapy in older patients with AKI in the intensive care unit.
Our study was a prospective cohort study in 16 Canadian hospitals from September 2013 to November 2015. Patients were ≥65 years old, were critically ill, and had severe AKI; exclusion criteria were urgent kidney replacement therapy for a toxin and ESKD. We recorded triggers for kidney replacement therapy (primary exposure), reasons for not receiving kidney replacement therapy, 90-day mortality (primary outcome), and kidney recovery.
Of 499 patients, mean (SD) age was 75 (7) years old, Charlson comorbidity score was 3.0 (2.3), and median (interquartile range) Clinical Frailty Scale score was 4 (3-5). Most were receiving mechanical ventilation (64%;
=319) and vasoactive support (63%;
=314). Clinicians were willing to offer kidney replacement therapy to 361 (72%) patients, and 229 (46%) received kidney replacement therapy. Main triggers for kidney replacement therapy were oligoanuria, fluid overload, and acidemia, whereas main reasons for not receiving therapy were anticipated recovery (67%;
=181) and therapy not consistent with patient preferences for care (24%;
=66). Ninety-day mortality was similar in patients who did and did not receive kidney replacement therapy (50% versus 51%; adjusted hazard ratio, 0.78; 95% confidence interval, 0.58 to 1.06); however, decisions to offer kidney replacement therapy varied significantly by patient mix, acuity, and perceived benefit. There were no differences in health-related quality of life or rehospitalization among survivors.
Most older, critically ill patients with severe AKI were perceived as candidates for kidney replacement therapy, and approximately one half received therapy. Both willingness to offer kidney replacement therapy and reasons for not starting showed heterogeneity due to a range in patient-specific factors and clinician perceptions of benefit.
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