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: 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.
DATA SOURCES: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic reviews were searched from their inception until June 2017.
REVIEW METHODS: All randomized controlled trials, observational studies, and case-control studies were included. Case reports, case series, nonsystematic reviews, and studies that involved children were excluded.
RESULTS: Nine studies (n = 464) were eligible in the data synthesis. Both continuous and bolus furosemide resulted in no difference in all-cause mortality (7 studies; n = 396; I2 = 0%; fixed-effect model [FEM]: odds ratio [OR] 1.15 [95% confidence interval (CI) 0.67-1.96]; p = 0.64). Continuous furosemide was associated with significant greater total urine output (n = 132; I2 = 70%; random-effect model: OR 811.19 [95% CI 99.84-1,522.53]; p = 0.03), but longer length of hospital stay (n = 290; I2 = 40%; FEM: OR 2.84 [95% CI 1.74-3.94]; p < 0.01) in comparison to the bolus group. No statistical significance was found in the changes of creatinine and estimated glomerular filtration rate between both groups.
CONCLUSIONS: In this meta-analysis, continuous furosemide was associated with greater diuretic effect in total urine output as compared with bolus. Neither had any differences in mortality and changes of renal function tests. However, a large adequately powered randomized clinical trial is required to fill this knowledge gap.
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: This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation.
RESULTS: A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p MIC than the IB arm on day 1 (97 versus 70 %, p
METHODS: The Asia-Pacific and Middle East Working Group on Nutrition in the ICU has identified major areas of uncertainty in clinical practice for healthcare professionals providing nutrition therapy in Asia-Pacific and the Middle East and developed a series of consensus statements to guide nutrition therapy in the ICU in these regions.
RESULTS: Accordingly, consensus statements have been provided on nutrition risk assessment and parenteral and enteral feeding strategies in the ICU, monitoring adequacy of, and tolerance to, nutrition in the ICU and institutional processes for nutrition therapy in the ICU. Furthermore, the Working Group has noted areas requiring additional research, including the most appropriate use of hypocaloric feeding in the ICU.
CONCLUSIONS: The objective of the Working Group in formulating these statements is to guide healthcare professionals in practicing appropriate clinical nutrition in the ICU, with a focus on improving quality of care, which will translate into improved patient outcomes.
DESIGN: A systematic review of the literature followed by a consensus-based voting process.
SETTING: A web-based international consensus conference.
PARTICIPANTS: Two hundred fifty-one physicians from 46 countries.
INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines.
MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed.
CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.
METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days.
RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group.
CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).