Journal of the Intensive Care Society最新文献

Aim: Levetiracetam is a widely used anti-epileptic in the critical care setting that is almost exclusively (>90%) renally excreted. The altered pharmacokinetics of levetiracetam have been widely studied in intermittent haemodialysis but the evidence and guidance on dosage in continuous renal replacement therapy is varied and poorly defined. Understanding this is critical as a significant number of critically unwell patients develop renal failure requiring continuous renal replacement therapy. The aim of this systematic review is to investigate the pharmacokinetics of levetiracetam in such patients and to understand the implications on dosing strategies.

Methods: A systematic review of the available literature from 2000 to November 2022 was conducted. Seven articles were identified for inclusion from 54 records. A novel hybrid model was developed to evaluate the quality of pharmacokinetic and haemofiltration data. This data was used to develop a one-compartment model that simulated dosing strategies in 10,000 patients based on an assumed steady state of 72 hr and target trough concentrations of 12-46 mcg/mL.

Results: From the seven articles included, pharmacokinetic data was retrieved for 24 individual patients. Total clearance was 3.49-4.63 L/hr (mean 3.55, S.D. 0.52). Elimination half-life was 5.66-12.88 hr (mean 9.41, S.D. 2.86). Volume of distribution was 0.45-0.73 L/kg. The proportion of total clearance attributable to continuous renal replacement therapy was 52%-73% (mean 54.7%, S.D. 13.5). Our simulations demonstrate that more than half of patients who received twice daily doses of 750 mg or greater without a loading dose achieved therapeutic drug concentrations. The time to achievement of therapeutic drug concentrations was greatly reduced by the addition of a 60 mg/kg loading dose (up to a maximum of 4.5 g). The use of a reduced loading dose or twice daily doses of 500 mg or less without loading were more likely to result in prolonged sub-therapeutic drug concentrations.

Conclusion: Levetiracetam clearance in haemofiltration is similar to healthy adults with normal renal function (GFR > 90 mL/min). The use of reduced doses due to renal failure in critically ill patients may result in sub-therapeutic drug concentrations in a high number of patients. A twice daily dosing of 750-1000 mg with an initial loading dose of 60 mg/kg should be considered in such patients alongside therapeutic drug monitoring.

Hypertonic saline (HTS) may have anti-inflammatory properties. We aimed to investigate the effect of pre-hospital HTS on neutrophil to lymphocyte ratio (NLR), a simple marker of systematic inflammation, in patients with severe traumatic brain injury (TBIs). We included 110 adults with blunt TBIs requiring pre-hospital anaesthesia (median age 57.1 years, 67% male). On hospital admission, median NLR was lower in patients who received pre-hospital HTS (7.9 vs 11.9, p = 0.021), and in multivariable analysis, HTS use remained associated with NLR (p = 0.048). We believe our findings highlight the neuroinflammatory properties of HTS as an area for future research.

Trace elements are required in minute quantities in the diet but play a vital role in a wide variety of functions, such as co-factors in antioxidant reactions and normal immune function to DNA and protein synthesis and skeletal and tissue remodelling and repair. Critically ill patients are at risk of trace element deficiency or excess, due to changes in intake, absorption, metabolism or excretion. Deficiency or excess can lead to a wide range of cellular and organ dysfunction that may be seen in patients with an acute or critical illness, including cardiomyopathy, impaired glucose tolerance and reduced oxygen delivery. In addition, various diseases, such as systemic inflammation and renal and intestinal failure, and intensive care treatments, such as parenteral nutrition, renal replacement therapy and diuretics, can increase the likelihood of deficient or excessive amounts of micronutrient levels. This narrative review discusses sources and normal physiology of trace element handling and how this may be impaired in critically ill patients. It then discusses various conditions seen in critically ill patients that may be caused or exacerbated by abnormal trace element status and the current evidence around whether supplementation is of benefit in particular critical illnesses.

Background: The lighting environment in intensive care units (ICUs) is markedly different from natural light, potentially disrupting patients' circadian rhythms and impacting staff wellbeing. New lighting technologies may mitigate these effects.

Methods: A mixed methods service evaluation was conducted in a London ICU using Dyson Lightcycle™ luminaires (DLs) to evaluate staff wellbeing. Wellbeing assessments and user perceptions of the built environment were conducted using validated questionnaires before, during, and after DL deployment. Existing ambient light usage was measured using HOBO devices installed on the ceiling. Additionally, data on DL usage (including spectral data) were collected continuously using Raspberry Pi™ sensors.

Results: DL usage was high (>70% per 24 h), primarily as supplementary lighting. Users found DLs easy to control and beneficial for clinical and administrative tasks. Participants assigned a 12.5% higher satisfaction score rated from 0 to 8 of lighting overall during deployment compared to pre-deployment (6.06 ± 0.29 and 5.06 ± 0.60, respectively; p = 0.20). Control variables for the built environment (noise, temperature and air quality) remained unchanged. Staff reported improvements in mood (38%, p < 0.001), fatigue (17.7%, p < 0.001), and sleep quality (21.2%, p = 0.01) during DL use.

Discussion: In the first pilot feasibility service evaluation of its kind, the relationship between ICU lighting quality and staff wellbeing was investigated using DLs. We show that it is feasible to equip an ICU with a novel mode of lighting to evaluate both illuminance and user-centred outcomes. The study suggests a positive association between DL use and staff wellbeing, with notable improvements in mood, fatigue and sleep quality. The nature of the emitted light may enhance the space rather than simply illuminate, thus further adding to a feeling of wellbeing. These findings support data from studies which report effects of light brightness and colour on mood. Additionally, there appears to be a signal towards benefit to the user when additional lighting is provided, compared to the current overhead fluorescent luminaires prevalent in most ICUs. In this service evaluation these benefits were demonstrated in ICU staff operating the device. However, it is conceivable that effects such as improved mood and reduced sleep disturbance may have patient benefits too.

Conclusion: Local lighting systems like DLs show promise in enhancing ICU staff wellbeing. Their impact on patient outcomes and the potential for broader implementation deserve further investigation in appropriately designed and powered larger-scale trials.

Background: Community acquired pneumonia (CAP) is a common cause of hospital admission. CAP carries significant risk of adverse outcomes including organ dysfunction, intensive care unit (ICU) admission and death. Earlier admission to ICU for those with severe CAP is associated with better outcomes. Traditional prediction models are used in clinical practice to predict the severity of CAP. However, accuracy of predicting severity may be improved by using machine learning (ML) based models with added advantages of automation and speed. This systematic review evaluates the evidence base of ML-prediction tools in predicting CAP severity.

Methods: MEDLINE, EMBASE and PubMed were systematically searched for studies that used ML-based models to predict mortality and/or ICU admission in CAP patients, where a performance metric was reported.

Results: 11 papers including a total of 351,365 CAP patients were included. All papers predicted severity and four predicted ICU admission. Most papers applied multiple ML algorithms to datasets and derived area under the receiver operator characteristic curve (AUROC) of 0.98 at best performance and 0.57 at worst, with a mixed performance against traditional prediction tools.

Conclusion: Although ML models showed good performance at predicting CAP severity, the variables selected for inclusion in each model varied significantly which limited comparisons between models and there was a lack of reproducible data, limiting validity. Future research should focus on validating ML predication models in multiple cohorts to derive robust, reproducible performance measures, and to demonstrate a benefit in terms of patient outcomes and resource use.

Introduction: Antiplatelet and anticoagulation therapies are frequently required in acutely unwell patients and confer an increased propensity for procedural bleeding. During percutaneous tracheostomy insertion, the decision to stop these therapies is left to clinical decision-makers. This meta-analysis summarises the risk of bleeding associated with antiplatelet and anticoagulation therapy during percutaneous tracheostomy insertion.

Method: We conducted a systematic review and meta-analysis of studies which reported intraoperative bleeding during percutaneous tracheostomy while on single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT), as well as therapeutic anticoagulation (TAC). Groups were compared against those with prophylactic or no anticoagulation. Studies were pooled using random effects via the inverse variance method.

Results: Four databases found 22 eligible studies, of which 14 studies presented data for meta-analysis representing 3,485 percutaneous tracheostomy insertion procedures. These included six studies that reported intraoperative bleeding outcome SAPT, six for DAPT and five for TAC. Overall, methodological quality was poor. No significant association was found for SAPT (Odds ratio 1.58; 95% confidence interval 0.72-4.41); P = 0.25; I ² = 81%) and TAC (OR 1.79; 95% CI 0.58-5.56; P = 0.35; I² = 35%). The DAPT group was associated with increased bleeding with an OR of 2.05 (95% CI 1.18-3.56; P = 0.01; I ² = 0%).

Conclusion: Our study supports temporarily withholding DAPT or TAC (if clinically feasible) to minimize bleeding risks associated with percutaneous dilatational tracheostomy.

Background: Identifying women at highest or lowest risk of perinatal intensive care unit (ICU) admission may enable clinicians to risk stratify women antenatally so that enhanced care or elective admission to ICU may be considered or excluded in birthing plans. We aimed to develop a statistical model to predict the risk of maternal ICU admission.

Methods: We studied 762,918 pregnancies between 2005 and 2018. Predictive models were constructed using multivariable logistic regression. The primary outcome was ICU admission. Additional analyses were performed to allow inclusion of delivery-related factors. Predictors were selected following expert consultation and reviewing literature, resulting in 13 variables being included in the primary analysis: demographics, prior health status, obstetric history and pregnancy-related factors. A complete case analysis was performed. K-fold cross validation was used to mitigate against overfitting.

Results: Complete data were available for 578,310 pregnancies, of whom 1087 were admitted to ICU (0.19%). Model performance was fair (area under the ROC curve = 0.66). A comparatively high cut-point of ⩾0.6% for ICU admission risk resulted in a negative predictive value (NPV) of 99.8% (specificity 97.8%) but positive predictive value (PPV) of 0.8% (sensitivity 9.1%). Models including delivery-related factors demonstrated superior discriminative performance.

Conclusions: Our model for maternal ICU admission has an acceptable discriminative performance. The low frequency of ICU admission and resulting low PPV indicates that the model would be unlikely to be useful as a 'rule-in' test for pre-emptive consideration of ICU admission. Its potential for improving efficiency in screening as a 'rule-out' test remains uncertain.

Introduction: Up to 20% of patients with traumatic brain injury (TBI) develop acute respiratory distress syndrome (ARDS), which is associated with increased odds of mortality. Guideline-based treatment for ARDS includes "lung protective" ventilation strategies, some of which are in opposition to "brain protective" strategies used for ventilation with patients with TBI. We conducted a scoping review of ventilation management strategies with clinical outcomes among patients with TBI and ARDS.

Methods: We searched three databases (MEDLINE, Embase, Web of Science) using a systematic search strategy. We included any studies of patients with TBI and ARDS with ventilation strategies including PEEP, oxygenation, prone positioning, recruitment maneuvers, pulmonary vasodilators (e.g., nitric oxide), high frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation (ECMO). All clinical outcomes were included. Extracted data included details about sample (age, gender), study design, inclusion/exclusion criteria, intervention details, and outcomes.

Results: The search returned 10,514 articles, 35 of which met final inclusion criteria. Interventions studied included ECMO (n = 13 articles), HFOV (n = 4), PEEP interventions (n = 3), prone positioning (n = 3), vasodilators (n = 4), and other lung recruitment maneuvers (n = 9). No randomized controlled trials were identified; studies were mostly case reports (n = 18/35, 51%) and series (n = 7/35, 20%), with some cohort studies (n = 5/35, 14%) and non-randomized experimental trials (n = 5/35, 14%), all at single institutions. Outcomes included physiologic changes (e.g., change in cerebrodynamics or hemodynamics with intervention) and clinical outcomes such as mortality, complications, or neurologic recovery. Five studies (14%) included pediatric patients.

Discussion: In this scoping review of ventilatory strategies for patients with concurrent TBI and ARDS, we found variation in heterogeneity of study design, interventions, and outcomes. Studies were mostly case report/series and observational studies, seriously limiting our ability to draw conclusions about effectiveness of interventions. Targeted areas of further research are discussed.

Background: The psychological impact of surviving an admission to an intensive care unit (ICU) with COVID-19 is uncertain. The objective of the study was to assess the prevalence of anxiety, depression and post-traumatic stress disorder (PTSD) symptoms in ICU survivors treated for COVID-19 infection, and identify risk factors for psychological distress.

Methods: This observational study was conducted at 52 ICUs in the United Kingdom. Participants, treated for COVID-19 infection during an ICU admission of ⩾24 h, were recruited post-ICU discharge. Self-report questionnaires were completed at 3, 6 and/or 12 months. Symptoms of anxiety and depression were identified using the Hospital Anxiety and Depression Scale. PTSD was assessed using the Impact of Events Scale-6. Demographic, clinical, physical and psychosocial factors were considered as putative predictors of psychological distress.

Results: 1620 patients provided consent and 1258 (77.7%) responded to at least one questionnaire, with responses at 3 months (N = 426), 6 months (N = 656) and 12 months (N = 1050) following ICU admission. The following prevalence rates were found at 3, 6 and 12 months, respectively: anxiety in 28.8% (95% CI 24.6-33.1), 30.4% (95% CI 27.0-33.8) and 29.3% (95% CI 26.5-32.1); depression in 25.1% (21.0-29.3), 25.9% (22.7-29.3) and 24.0% (21.5-26.6); and PTSD in 43.5% (38.8-48.2), 44.3% (40.6-48.0) and 43.2% (40.2-46.1) of patients. Risk factors for psychological distress included a previous mental health diagnosis, unemployment or being on sick leave, and a history of asthma or COPD.

Conclusion: Clinically significant symptoms of anxiety, depression and PTSD were common and persisted up to 12 months post-ICU discharge.