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Vitamin C Administration to the Critically Ill: A Systematic Review and Meta-Analysis.
Langlois, PL, Manzanares, W, Adhikari, NKJ, Lamontagne, F, Stoppe, C, Hill, A, Heyland, DK
JPEN. Journal of parenteral and enteral nutrition. 2019;(3):335-346
Abstract
Vitamin C, an enzyme cofactor and antioxidant, could hasten the resolution of inflammation, oxidative stress, and microvascular dysfunction. While observational studies have demonstrated that critical illness is associated with low levels of vitamin C, randomized controlled trials (RCTs) of vitamin C, alone or in combination with other antioxidants, have yielded contradicting results. We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (inception to December 2017) for RCTs comparing vitamin C, by enteral or parenteral routes, with placebo or none, in intensive care unit (ICU) patients. Two independent reviewers assessed study eligibility without language restrictions and abstracted data. Overall mortality was the primary outcome; secondary outcomes were incident infections, ICU length of stay (LOS), hospital LOS, and duration of mechanical ventilation (MV). We prespecified 5 subgroups hypothesized to benefit more from vitamin C. Eleven randomized trials were included. When 9 RCTs (n = 1322) reporting mortality were pooled, vitamin C was not associated with reduced risk of mortality (risk ratio [RR] 0.72, 95% confidence interval [CI]: 0.43-1.20, P = .21). No effect was found on infections, ICU or hospital LOS, or duration of MV. In multiple subgroup comparison, no statistically significant subgroup effects were observed. However, we did observe a tendency towards a mortality reduction (RR 0.21; 95% CI: 0.04-1.05; P = .06) when intravenous high-dose vitamin C monotherapy was administered. Current evidence does not support supplementing critically ill patients with vitamin C. A moderately large treatment effect may exist, but further studies, particularly of monotherapy administration, are warranted.
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Medical treatment for botulism.
Chalk, CH, Benstead, TJ, Pound, JD, Keezer, MR
The Cochrane database of systematic reviews. 2019;(4):CD008123
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Abstract
BACKGROUND Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key, but the role of other medical treatments is unclear. This is an update of a review first published in 2011. OBJECTIVES To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding, and risk of adverse events in botulism. SEARCH METHODS We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase on 23 January 2018. We reviewed bibliographies and contacted authors and experts. We searched two clinical trials registers, WHO ICTRP and clinicaltrials.gov, on 21 February 2019. SELECTION CRITERIA Randomized controlled trials (RCTs) and quasi-RCTs examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism, and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin intravenous (BIG-IV), plasma exchange, 3,4-diaminopyridine, and guanidine. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology.Our primary outcome was in-hospital death from any cause occurring within four weeks from randomization or the beginning of treatment. Secondary outcomes were death from any cause occurring within 12 weeks, duration of hospitalization, duration of mechanical ventilation, duration of tube or parenteral feeding, and proportion of participants with adverse events or complications of treatment. MAIN RESULTS A single RCT met the inclusion criteria. Our 2018 search update identified no additional trials. The included trial evaluated BIG-IV for the treatment of infant botulism and included 59 treatment participants and 63 control participants. The control group received a control immune globulin that did not have an effect on botulinum toxin. Participants were followed during the length of their hospitalization to measure the outcomes of interest. There was some violation of intention-to-treat principles, and possibly some between-treatment group imbalances among participants admitted to the intensive care unit and mechanically ventilated, but otherwise the risk of bias was low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a benefit in the treatment group on mean duration of hospitalization (BIG-IV: 2.60 weeks, 95% confidence interval (CI) 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) -3.10 weeks, 95% CI -4.52 to -1.68; moderate-certainty evidence); mechanical ventilation (BIG-IV: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD -2.60 weeks, 95% CI -4.06 to -1.14; low-certainty evidence); and tube or parenteral feeding (BIG-IV: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD -6.40 weeks, 95% CI -10.00 to -2.80; moderate-certainty evidence), but not on proportion of participants with adverse events or complications (BIG-IV: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11; moderate-certainty evidence). AUTHORS' CONCLUSIONS We found low- and moderate-certainty evidence supporting the use of BIG-IV in infant intestinal botulism. A single RCT demonstrated that BIG-IV probably decreases the duration of hospitalization; may decrease the duration of mechanical ventilation; and probably decreases the duration of tube or parenteral feeding. Adverse events were probably no more frequent with immune globulin than with placebo. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.
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Is discard better than return gastric residual aspirates: a systematic review and meta-analysis.
Wen, Z, Xie, A, Peng, M, Bian, L, Wei, L, Li, M
BMC gastroenterology. 2019;(1):113
Abstract
BACKGROUND The assessment of residual gastric volume is common practice in critical care units. However, the effects and safety of discarding or returning gastric aspirates remain uncertain. Therefore, we aimed to evaluate the role of discarding or returning gastric aspirates on the gastric residual volumes in critically ill patients. METHODS A comprehensive, systematic meta-analysis of randomized controlled trials (RCTs) on the efficacy and safety of discarding or returning gastric aspirates in critical ill patients was performed. Studies were identified by searching Pubmed and other databases (from inception to 31 Sept 2018). Summary odd ratios (ORs) or mean differences (MDs) with 95% confidence intervals were calculated using fixed- or random-effects model for outcome assessment. RESULTS Four RCTs, with a total number of 314 adult patients, were included in the analysis. No significant differences were found in the 48th hour residual volume (MD = 8.89, 95% CI: 11.97 to 29.74), the average potassium level (MD = 0.00, 95% CI: - 0.16 to 0.16), the episodes of gastric emptying delay (OR = 0.98, 95% CI: 0.35 to 2.80), the incidence of aspiration pneumonia (OR = 0.93, 95% CI: 0.14 to 6.17), the episodes of nausea or vomiting (OR = 0.53, 95% CI: 0.07 to 4.13) and diarrhea (OR = 0.99, 95% CI: 0.58 to 1.70). CONCLUSIONS No evidence confirms that returning residual gastric aspirates provides more benefits than discarding them without increasing potential complications. Rigorously designed, multi-center, large-sample randomized controlled trials must be further conducted to validate the role of discarding or returning residual gastric aspirates.
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Mannitol in Critical Care and Surgery Over 50+ Years: A Systematic Review of Randomized Controlled Trials and Complications With Meta-Analysis.
Zhang, W, Neal, J, Lin, L, Dai, F, Hersey, DP, McDonagh, DL, Su, F, Meng, L
Journal of neurosurgical anesthesiology. 2019;(3):273-284
Abstract
OBJECTIVE Despite clinical use spanning 50+ years, questions remain concerning the optimal use of mannitol. The published reviews with meta-analysis frequently focused on mannitol's effects on a specific physiological aspect such as intracranial pressure (ICP) in sometimes heterogeneous patient populations. A comprehensive review of mannitol's effects, as well as side effects, is needed. METHODS The databases Medline (OvidSP), Embase (OvidSP), and NLM PubMed were systematically searched for randomized controlled trials (RCTs) comparing mannitol to a control therapy in either the critical care or perioperative setting. Meta-analysis was performed when feasible to examine mannitol's effects on outcomes, including ICP, cerebral perfusion pressure, mean arterial pressure (MAP), brain relaxation, fluid intake, urine output, and serum sodium. Systematic literature search was also performed to understand mannitol-related complications. RESULTS In total 55 RCTs were identified and 7 meta-analyses were performed. In traumatic brain injury, mannitol did not lead to significantly different MAP (SMD [95% confidence interval (CI)] =-3.3 [-7.9, 1.3] mm Hg; P=0.16) but caused significantly different serum sodium concentrations (SMD [95% CI]=-8.0 [-11.0, -4.9] mmol/L; P<0.00001) compared with hypertonic saline. In elective craniotomy, mannitol was less likely to lead to satisfactory brain relaxation (RR [95% CI]=0.89 [0.81, 0.98]; P=0.02), but was associated with increased fluid intake (SMD [95% CI]=0.67 [0.21, 1.13] L; P=0.004), increased urine output (SMD [95% CI]=485 [211, 759] mL; P=0.0005), decreased serum sodium concentration (SMD [95% CI]=-6.2 [-9.6, -2.9] mmol/L; P=0.0002), and a slightly higher MAP (SMD [95% CI]=3.3 [0.08, 6.5] mm Hg; P=0.04) compared with hypertonic saline. Mannitol could lead to complications in different organ systems, most often including hyponatremia, hyperkalemia, and acute kidney injury. These complications appeared dose dependent and had no long-term consequences. CONCLUSIONS Mannitol is effective in accomplishing short-term clinical goals, although hypertonic saline is associated with improved brain relaxation during craniotomy. Mannitol has a favorable safety profile although it can cause electrolyte abnormality and renal impairment. More research is needed to determine its impacts on long-term outcomes.