METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data.
CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.
MATERIALS AND METHODS: A cross-sectional study was undertaken in 45 public, teaching, and private hospitals in Malaysia that provide ≥ 10 beds in their ICUs. Knowledge, perceived barriers, facilitators, and practice of early mobilization were assessed using a previously validated mobility survey questionnaire.
RESULTS: Only 35% of ICU physiotherapists reported receiving training/courses on early mobilization in the ICU. 100 (86%) physiotherapists underestimated the incidence of ICU-acquired weakness, and 88 (75%) were unfamiliar with the current literature on early mobilization in the ICU. The need for physician orders before mobilization, medical instability, excessive sedation, and risk of dislodgement of devices or lines were the most common barriers to early mobilization. Nearly half (49 [42%]) of the respondents reported physiotherapist as early mobilization clinical champion in their setting, but the most common physiotherapy treatment techniques in the ICU reported by the respondents' were still chest physiotherapy, range of motion exercises, and bed mobility.
CONCLUSION: We observed strong enthusiasm for early mobilization among Malaysian physiotherapists. Most respondents believed that early mobilization is important and beneficial to ICU patients. However, there is still a big gap in knowledge and training of early mobilization in ICU patients among Malaysian physiotherapists.
METHODS: A retrospective cohort study was conducted at Nakornping Hospital on critically ill patients with CRAB infection who received either a short or long course of colistin treatment between 2015 and 2022. The primary outcome was the 30-day mortality rate while secondary outcomes were clinical response, microbiological response, and nephrotoxicity. Propensity score matching with a 1: 1 ratio was performed to reduce potential biases. Furthermore, a logistic regression model was used to estimate the odds ratio (OR).
RESULTS: A total of 374 patients met the inclusion criteria. Two hundred and forty-eight patients were recruited after utilizing propensity scores to match patients at a 1: 1 ratio. The results from the propensity score matching analysis demonstrated that the long-course therapy group had a lower 30-day mortality rate compared to the short-course therapy group (adjusted OR (aOR) = 0.46, 95% CI: 0.26-0.83, p = 0.009). The clinical response and microbiological response rates were higher in patients who received the long course of colistin therapy compared to those receiving the short course (aOR = 3.24, 95% CI: 1.78-5.92, p = 0.001; aOR = 3.01, 95% CI: 1.63-5.57, p = 0.001). There was no significant different in the occurrence of nephrotoxicity (aOR = 1.28, 95% CI: 0.74-2.22, p = 0.368) between the two treatment groups.
CONCLUSION: A long course of colistin therapy resulted in a lower 30-day mortality rate in critically ill patients, and better clinical and microbiological outcomes, but similar nephrotoxicity as compared to a short course of colistin therapy. Therefore, a specific subset of critically ill patients who had CRAB infection needed to be considered for a long course of therapy.
METHODS: RCTs that compared probiotics or synbiotics to usual care or placebo and reported clinical and diarrheal outcomes were searched in 4 electronic databases from inception to March 8, 2022 without language restriction. Four reviewers independently extracted data and assessed the study qualities using the Critical Care Nutrition (CCN) Methodological Quality Scoring System. Random-effect meta-analysis and trial sequential analysis (TSA) were used to synthesize the results. The primary outcome was ventilator-associated pneumonia (VAP). The main subgroup analysis compared the effects of higher versus lower quality studies (based on median CCN score).
RESULTS: Seventy-five studies with 71 unique trials (n = 8551) were included. In the overall analysis, probiotics significantly reduced VAP incidence (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.56-0.88; I2 = 65%; 16 studies). However, such benefits were demonstrated only in lower (RR 0.47, 95% CI 0.32, 0.69; I2 = 44%; 7 studies) but not higher quality studies (RR 0.89, 95% CI 0.73, 1.08; I2 = 43%; 9 studies), with significant test for subgroup differences (p = 0.004). Additionally, TSA showed that the VAP benefits of probiotics in the overall and subgroup analyses were type-1 errors. In higher quality trials, TSA found that future trials are unlikely to demonstrate any benefits of probiotics on infectious complications and diarrhea. Probiotics had higher adverse events than control (pooled risk difference: 0.01, 95% CI 0.01, 0.02; I2 = 0%; 22 studies).
CONCLUSION: High-quality RCTs did not support a beneficial effect of probiotics on clinical or diarrheal outcomes in critically ill patients. Given the lack of benefits and the increased incidence of adverse events, probiotics should not be routinely administered to critically ill patients.
PROSPERO REGISTRATION: CRD42022302278.
METHODS: Using indirect calorimetry, REE was measured at acute (≤5 days; n = 294) and late (≥6 days; n = 180) phases of intensive care unit admission. PEs were developed by multiple linear regression. A multi-fold cross-validation approach was used to validate the PEs. The best PEs were selected based on the highest coefficient of determination (R2), the lowest root mean square error (RMSE) and the lowest standard error of estimate (SEE). Two PEs developed from paired 168-patient data were compared with measured REE using mean absolute percentage difference.
RESULTS: Mean absolute percentage difference between predicted and measured REE was <20%, which is not clinically significant. Thus, a single PE was developed and validated from data of the larger sample size measured in the acute phase. The best PE for REE (kcal/day) was 891.6(Height) + 9.0(Weight) + 39.7(Minute Ventilation)-5.6(Age) - 354, with R2 = 0.442, RMSE = 348.3, SEE = 325.6 and mean absolute percentage difference with measured REE was: 15.1 ± 14.2% [acute], 15.0 ± 13.1% [late].
CONCLUSIONS: Separate PEs for acute and late phases may not be necessary. Thus, we have developed and validated a PE from acute phase data and demonstrated that it can provide optimal estimates of REE for patients in both acute and late phases.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03319329.
METHODS: This is a retrospective review of all mechanically ventilated surgical patients in the wards, in a tertiary hospital, in 2020. Sixty-two patients out of 116 patients ventilated in surgical wards fulfilled the inclusion criteria. Demography, surgical diagnosis and procedures and physiologic, biochemical and survival data were analyzed to explore the outcomes and predictors of mortality.
RESULTS: Twenty-two out of 62 patients eventually gained ICU admission. Mean time from intubation to ICU entry and mean length of ICU stay were 48 h (0 to 312) and 10 days (1 to 33), respectively. Survival for patients admitted to ICU compared to ventilation in the acute surgery wards was 54.5% (12/22) vs 17.5% (7/40). Thirty-four patients underwent surgery, and the majority were bowel-related emergency operations. SAPS2 score validation revealed AUC of 0.701. More than half of patients with mortality risk
BACKGROUND: Having a loved one in the ICU is a stressful experience, which may cause psychological distress for family members. Depression, anxiety and stress are the common forms of psychological distress associated with ICU patient's family members. Directly or indirectly, psychological distress may have behavioural or physiological impacts on the family members and ICU patient's recovery.
DESIGN: The study was based on the five-stage methodological framework by Arksey and O'Malley (International Journal of Social Research Methodology, 2005, 8, 19) and were guided by the PRISMA-ScR Checklist.
METHODS: A comprehensive and systematic search was performed in five electronic databases, namely the Scopus, Web of Sciences, CINAHL® Complete @EBSCOhost, ScienceDirect and MEDLINE. Reference lists from the screened full-text articles were reviewed.
RESULTS: From a total of 1252 literature screened, 22 studies published between 2010-2019 were included in the review. From those articles, four key themes were identified: (a) Prevalence of psychological distress; (b) Factors affecting family members; (c) Symptoms of psychological distress; and (d) Impact of psychological distress.
CONCLUSIONS: Family members with a critically ill patient in ICU show high levels of anxiety, depression and stress. They had moderate to major symptoms of psychological distress that negatively impacted both the patient and family members.
RELEVANCE TO CLINICAL PRACTICE: The review contributed further insights on psychological distress among ICU patient's family members and proposed psychological interventions that could positively impact the family well-being and improve the patients' recovery.
DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials.
STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients.
DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes.
DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C.
CONCLUSIONS: IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.
METHODS: We conducted a retrospective observational study in our multi-disciplinary Pediatric Intensive Care Unit (ICU) from January 2015 to December 2018. All patients from birth to 16 years of age who were admitted to the pediatric ICU were included. The Kidney Disease Improving Global Outcomes (KDIGO) definition was considered as the reference standard. We compared the incidence data assessed by KDIGO, pediatric risk, injury, failure, loss of kidney function and end- stage renal disease (pRIFLE) and pediatric reference change value optimised for AKI (pROCK).
RESULTS: Out of 7505 patients, 9.2% developed AKI by KDIGO criteria. The majority (59.8%) presented with stage 1 AKI. Recovery from AKI was observed in 70.4% of patients within 7 days from diagnosis. Both pRIFLE and pROCK were less sensitive compared to KDIGO criteria for the classification of AKI. Patients who met all three-KDIGO, pRIFLE and pROCK criteria had a high mortality rate (35.0%).
CONCLUSION: Close to one in ten patients admitted to the pediatric ICU met AKI criteria according to KDIGO. In about 30% of patients, AKI persisted beyond 7 days. Follow-up of patients with persistent kidney function reduction at hospital discharge is needed to reveal the long-term morbidity due to AKI in the pediatric ICU.
OBJECTIVE: This study analyses the effect of estimating EGP for ICU patients with very low SI (severe insulin resistance) and its impact on identified, model-based insulin sensitivity identification, modeling accuracy, and model-based glycemic clinical control.
METHODS: Using clinical data from 717 STAR patients in 3 independent cohorts (Hungary, New Zealand, and Malaysia), insulin sensitivity, time of insulin resistance, and EGP values are analyzed. A method is presented to estimate EGP in the presence of non-physiologically low SI. Performance is assessed via model accuracy.
RESULTS: Results show 22%-62% of patients experience 1+ episodes of severe insulin resistance, representing 0.87%-9.00% of hours. Episodes primarily occur in the first 24 h, matching clinical expectations. The Malaysian cohort is most affected. In this subset of hours, constant model-based EGP values can bias identified SI and increase blood glucose (BG) fitting error. Using the EGP estimation method presented in these constrained hours significantly reduced BG fitting errors.
CONCLUSIONS: Patients early in ICU stay may have significantly increased EGP. Increasing modeled EGP in model-based glycemic control can improve control accuracy in these hours. The results provide new insight into the frequency and level of significantly increased EGP in critical illness.
METHODS: This single-centre prospective study, involved children aged from birth to 3 years old, admitted to PICU longer than 72 hours. They received either enteral nutrition (EN) or combination of EN and partial parenteral nutrition (PPN). Clinical and nutrition delivery characteristics were recorded from admission until transferred out of PICU. Multiple regression analysis at significant level p
METHODS: This is a retrospective analysis of a single-center prospective observational study that enrolled mechanically ventilated adults with expected ≥96 hours ICU stay. SARC-F and CFS questionnaires were administered to patient's next-of-kin and mNUTRIC were calculated. Calf-circumference was measured at the right calf. Nutrition data was collected from nursing record. The high-risk scores (mNUTRIC ≥5, SARC-CALF >10 or CFS ≥4) of these variables were combined to become the NUTRIC-SF score (range: 0-3).
RESULTS: Eighty-eight patients were analyzed. Multiple logistic model demonstrated increasing mNUTRIC score was independently associated with 60-day mortality while increasing SARC-CALF and CFS showed a strong trend towards higher 60-day mortality. Discriminative ability of NUTRIC-SF for 60-day mortality is better than it's component (AUROC 0.722, 95% confidence interval [CI] 0.677-0.868). Every increment of 300 kcal/day and 30 g/day is associated with a trend towards higher rate of discharge alive for high [≥2; Adjusted Hazard Ratio 1.453 (95% CI 0.991-2.130) for energy, 1.503 (95% CI 0.936-2.413) for protein] but not low (<2) NUTRIC-SF score.
CONCLUSION: NUTRIC-SF score may be a clinically relevant risk stratification tool in the ICU. This article is protected by copyright. All rights reserved.
METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations.
RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively.
CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
METHODS: Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation.
RESULTS: HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2.
CONCLUSION: In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.
METHODS: This single-center prospective observational study was conducted in a general ICU. Mechanically ventilated critically ill adult patients (age ≥18 years) without pre-existing systemic neuromuscular diseases and expected to stay for ≥96 h in the ICU were included. US measurements were performed within 48 h of ICU admission (baseline), at day 7, day 14 of ICU stay and at ICU discharge (if stay >14 days). Quadriceps muscle layer thickness (QMLT), rectus femoris cross sectional area (RFCSA), vastus intermedius pennation angle (PA) and fascicle length (FL), and rectus femoris echogenicity (mean and standard deviation [SD]) were measured. Patients' next-of-kin were interviewed by using established questionnaires for their pre-hospitalization nutritional risk (nutrition risk screening-2002) and functional status (SARC-F, clinical frailty scale [CFS], Katz activities of daily living [ADL] and Lawton Instrumental ADL).
RESULTS: Ninety patients were recruited. A total of 86, 53, 24 and 10 US measures were analyzed, which were performed at a median of 1, 7, 14 and 22 days from ICU admission, respectively. QMLT, RFCSA and PA reduced significantly over time. The overall trend of change of FL was not significant. The only independent predictor of 60-day mortality was the change of QMLT from baseline to day 7 (adjusted odds ratio 0.95 for every 1% less QMLT loss, 95% confidence interval 0.91-0.99; p = 0.02). Baseline measures of high nutrition risk (modified nutrition risk in critically ill ≥5), sarcopenia (SARC-F ≥4) and frailty (CFS ≥5) were associated with lower baseline QMLT, RFCSA and PA and higher 60-day mortality.
CONCLUSIONS: Every 1% loss of QMLT over the first week of critical illness was associated with 5% higher odds of 60-day mortality. SARC-F, CFS and mNUTRIC are associated with quadriceps muscle status and 60-day mortality and may serve as a potential simple and indirect measures of premorbid muscle status at ICU admission.