Stress Ulcer Prophylaxis Barletta, Jeffrey F; Bruno, Jeffrey J; Buckley, Mitchell S ...
Critical care medicine
44, Issue:
7
Journal Article
Peer reviewed
Stress ulcer prophylaxis is commonly administered to critically ill patients for the prevention of clinically important stress-related mucosal bleeding from the upper gastrointestinal tract. Despite ...widespread incorporation of stress ulcer prophylaxis into practice around the world, questions are emerging about its indications and impact. This clinically focused article will review current controversies related to stress ulcer prophylaxis for critically ill adult patients, including bleeding frequency, risk factors, comparative efficacy, adverse effect profile, and overall cost-effectiveness of the available stress ulcer prophylaxis regimens.
A MEDLINE search was conducted from inception through August 2015.
Selected publications describing stress ulcer prophylaxis in adult patients were retrieved (original research, systematic reviews, and practice guidelines); their bibliographies were also reviewed to identify additional pertinent publications.
Data from relevant publications were abstracted and summarized.
The existing evidence is organized to describe the patients most likely to benefit from stress ulcer prophylaxis, review the comparative efficacy of proton pump inhibitors and histamine 2 receptor antagonists, the adverse effects of stress ulcer prophylaxis, and overall cost-effectiveness.
Many stress ulcer prophylaxis recommendations are based on older studies at risk of bias, which may not be applicable to modern practice. Stress ulcer prophylaxis should be limited to patients considered to be at high risk for clinically important bleeding. When evaluating only the trials at low risk for bias, the evidence does not clearly support lower bleeding rates with proton pump inhibitors over histamine 2 receptor antagonists; however, proton pump inhibitors appear to be the dominant drug class used worldwide today. The current rate of upper gastrointestinal bleeding and the relative adverse effects of acid suppression on infectious risk may drive not only the effectiveness, but also the cost-effectiveness of stress ulcer prophylaxis today. Research is currently underway to better address these issues.
A novel assay for endotoxin, based on the ability of antigen-antibody complexes to prime neutrophils for an augmented respiratory burst response, was studied in a cohort study of 857 patients ...admitted to an intensivecare unit (ICU). On the day of ICU admission, 57.2% of patients had either intermediate (⩾0.40 endotoxin activity EA units) or high (⩾0.60 units) EA levels. Gram-negative infection was present in 1.4% of patients with low EA levels, 4.9% with intermediate levels, and 6.9% with high levels; EA had a sensitivity of 85.3% and a specificity of 44.0% for the diagnosis of gram-negative infection. Rates of severe sepsis were 4.9%, 9.2%, and 13.2%, and ICU mortality was 10.9%, 13.2%, and 16.8% for patients with low, intermediate, and high EA levels, respectively. Stepwise logistic regression analysis showed that elevated Acute Physiology and Chronic Health Evaluation II score, gram-negative infection, and emergency admission status were independent predictors of EA.
Objective To review the literature on the use of inhaled nitric oxide to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and to summarise the effects of nitric oxide, compared ...with placebo or usual care without nitric oxide, in adults and children with ALI or ARDS.Design Systematic review and meta-analysis.Data sources Medline, CINAHL, Embase, and CENTRAL (to October 2006), proceedings from four conferences, and additional information from authors of 10 trials.Review methods Two reviewers independently selected parallel group randomised controlled trials comparing nitric oxide with control and extracted data related to study methods, clinical and physiological outcomes, and adverse events.Main outcome measures Mortality, duration of ventilation, oxygenation, pulmonary arterial pressure, adverse events. Results 12 trials randomly assigning 1237 patients met inclusion criteria. Overall methodological quality was good. Using random effects models, we found no significant effect of nitric oxide on hospital mortality (risk ratio 1.10, 95% confidence interval 0.94 to 1.30), duration of ventilation, or ventilator-free days. On day one of treatment, nitric oxide increased the ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) (13%, 4% to 23%) and decreased the oxygenation index (14%, 2% to 25%). Some evidence suggested that improvements in oxygenation persisted until day four. There was no effect on mean pulmonary arterial pressure. Patients receiving nitric oxide had an increased risk of developing renal dysfunction (1.50, 1.11 to 2.02).Conclusions Nitric oxide is associated with limited improvement in oxygenation in patients with ALI or ARDS but confers no mortality benefit and may cause harm. We do not recommend its routine use in these severely ill patients.
Diverse perspectives improve the quality of scholarly initiatives. The demographic and professional diversity of scientists who contribute to critical care research and publications has not been ...described for the Canadian Critical Care Trials Group. Our objective was to describe the diversity of authors of publications from the Canadian Critical Care Trials Group.
We conducted a quantitative content analysis of peer-reviewed articles published on behalf of the Canadian Critical Care Trials Group.
All peer-reviewed articles that were published on behalf of the Canadian Critical Care Trials Group between 1994 and October 2020.
For each publication, we recorded the study design, the number of authors, and national or international collaboration. For the lead author, the senior author, and each coauthor, we recorded the following facets of diversity: gender, professional role, medical discipline, geographic location, academic stage, and visible minority status.
None.
We identified 354 eligible publications; 74% (263/354) reported observational cohort studies, randomized trials, and surveys. Of 4,246 authors, 1,205 were unique individuals. The mean (sd) number of authors per publication was 12 (7.1). Of all 4,246 authors, 37% were women, and 13.7% were members of a visible minority group. Of all lead or senior authors, 40% and 34% respectively were women; 15% of lead and 10% of senior authors were members of a visible minority group. Three-quarters (73%) of publications listed authors from more than one profession, and more than half (54%) listed authors from more than one medical discipline. Nearly half of publications (45%) listed authors who were early career faculty, 33% listed authors who were trainees, and 67% listed authors who were from visible minority groups. Authors from different provinces and from different countries were listed in 67% and 40% of publications, respectively.
Authors of Canadian Critical Care Trials Group publications are diverse with regard to demographic and professional characteristics.
To determine the utility of angiopoietin-1 and angiopoietin-2 as potentially novel biomarkers of morbidity and mortality in patients with severe sepsis.
Multicenter longitudinal cohort study.
Three ...tertiary hospital intensive care units in Hamilton, Ontario, Canada.
A total of 70 patients with severe sepsis were enrolled within 24 hrs of meeting the inclusion criteria for severe sepsis and followed until day 28, hospital discharge, or death.
Clinical data and plasma samples were obtained at intensive care unit admission for all 70 patients and then daily for 1 wk and weekly thereafter for a subset of 43 patients. Levels of angiopoietin-1 and angiopoietin-2 in stored plasma samples were measured and compared with clinical characteristics, including the primary outcomes of 28-day mortality and morbidity measured by the Multiple Organ Dysfunction score.
Lower angiopoietin-1 plasma levels (≤ 5.5 ng/mL) at admission were associated with increased likelihood of death (relative risk 0.49 95% confidence interval of 0.25-0.98, p = .046). Lower angiopoietin-1 levels remained a significant predictor of 28-day mortality in a multiple logistic regression model (adjusted odds ratio of 0.282 95% confidence interval of 0.086-0.93, p = .037). Analysis of serial data using linear mixed models confirmed that sepsis survivors had higher levels of angiopoietin-1 (p = .012) and lower daily levels of angiopoietin-2 (p = .022) than nonsurvivors. Furthermore, survivors had higher peak angiopoietin-1 levels (median 13 vs. 10 ng/mL, p = .019) and lower nadir angiopoietin-2 levels (median 2.8 vs. 6.2 ng/mL, p = .013) than nonsurvivors. A score incorporating angiopoietin-1 and angiopoietin-2 and three other markers of endothelial activation discriminated with high accuracy between fatal and nonfatal cases (c-index of 0.80 95% confidence interval of 0.69-0.90, p < .001). Plasma levels of angiopoietin-2 correlated with clinical markers of organ dysfunction and molecular markers of endothelial cell activation.
Angiopoietin-1 levels at admission and both angiopoietin-1 and angiopoietin-2 levels measured serially correlated with 28-day mortality in severe sepsis. Angiopoietin-2 levels also correlated with organ dysfunction/injury and a validated clinical sepsis score. These results suggest the use of angiopoietins as clinically informative biomarkers of disease severity and patient outcome in severe sepsis.
Skeletal fluorosis (SF) is endemic primarily in regions with fluoride (F)-contaminated well water, but can reflect other types of chronic F exposure. Calcium (Ca) and vitamin D (D) deficiency can ...exacerbate SF. A 51-year-old man with years of musculoskeletal pain and opiate use was hypocalcemic with secondary hyperparathyroidism upon manifesting recurrent long bone fractures. He smoked cigarettes, drank large amounts of cola beverage, and consumed little dietary Ca. Then, after 5 months of Ca and D3 supplementation, serum 25(OH)D was 21 ng/mL (Nl, 30–100), corrected serum Ca had normalized from 7.8 to 9.4 mg/dL (Nl, 8.5–10.1), alkaline phosphatase (ALP) had decreased from 1080 to 539 U/L (Nl, 46–116), yet parathyroid hormone (PTH) had increased from 133 to 327 pg/mL (Nl, 8.7–77.1). Radiographs revealed generalized osteosclerosis and a cystic lesion in a proximal femur. DXA BMD Z-scores were +7.4 and +0.4 at the lumbar spine and “1/3” radius, respectively. Bone scintigraphy showed increased uptake in two ribs, periarticular areas, and proximal left femur at the site of a subsequent atraumatic fracture. Elevated serum collagen type I C-telopeptide 2513 pg/mL (Nl, 87–345) and osteocalcin >300 ng/mL (Nl, 9–38) indicated rapid bone turnover. Negative studies included hepatitis C Ab, prostate-specific antigen, serum and urine electrophoresis, and Ion Torrent mutation analysis for dense or high-turnover skeletal diseases. After discovering markedly elevated F concentrations in his plasma 4.84 mg/L (Nl, 0.02–0.08) and spot urine 42.6 mg/L (Nl, 0.2–3.2), a two-year history emerged of “huffing” computer cleaner containing difluoroethane. Non-decalcified histology of a subsequent right femur fracture showed increased osteoblasts and osteoclasts and excessive osteoid. A 24-hour urine collection contained 27 mg/L F (Nl, 0.2–3.2) and <2 mg/dL Ca. Then, 19 months after “huffing” cessation and improved Ca and D3 intake, yet with persisting bone pain, serum PTH was normal (52 pg/mL) and serum ALP and urine F had decreased to 248 U/L and 3.3 mg/L, respectively. Our experience combined with 15 publications in PubMed concerning unusual causes of non-endemic SF where the F source became known (19 cases in all) revealed: 11 instances from high consumption of black tea and/or F-containing toothpaste, 1 due to geophagia of F-rich soil, and 7 due to “recreational” inhalation of F-containing vapors. Circulating PTH measured in 14 was substantially elevated in 2 (including ours) and mildly increased in 2. The severity of SF in the cases reviewed seemed to reflect cumulative F exposure, renal function, and Ca and D status. Several factors appeared to influence our patient's skeletal disease: i) direct anabolic effects of toxic amounts of F on his skeleton, ii) secondary hyperparathyroidism from degradation-resistant fluorapatite bone crystals and low dietary Ca, and iii) impaired mineralization of excessive osteoid due to hypocalcemia.
•Fluorocarbon “huffing” is an under-appreciated cause of skeletal fluorosis (SF).•We present a SF case with hyperparathyroidism, osteosclerosis, and osteomalacia.•SF may go undetected due to variation in symptoms, radiology, and biochemistry.•Dietary calcium, prior bone health, and skeletal F exposure influence SF features.•SF is common in endemic areas. We review unusual, non-endemic causes of SF.
Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of ...severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU).
We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation - Survival Using Glucose Algorithm Regulation) study.
We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval CI 0.83-1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5-8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44-0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78-1.28; mixed ICU: RR 0.99, 95% CI 0.86-1.12). The different targets of intensive insulin therapy (glucose level < or = 6.1 mmol/L v. < or = 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia.
Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.
Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear.
To examine ...the effect of different resuscitative fluids on mortality in patients with sepsis.
MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014.
Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied.
Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed.
14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence).
These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect.
Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality.
The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.
Purpose
Systematic review and network meta-analysis to investigate the efficacy of noninvasive respiratory strategies, including noninvasive positive pressure ventilation (NIPPV) and high-flow nasal ...cannula (HFNC), in reducing extubation failure among critically ill adults.
Methods
We searched databases from inception through October 2021 for randomized controlled trials (RCTs) evaluating noninvasive respiratory support therapies (NIPPV, HFNC, conventional oxygen therapy, or a combination of these) following extubation in critically ill adults. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was reintubation. We used GRADE to rate the certainty of our findings.
Results
We included 36 RCTs (6806 patients). Compared to conventional oxygen therapy, NIPPV (OR 0.65 95% CI 0.52–0.82) and HFNC (OR 0.63 95% CI 0.45–0.87) reduced reintubation (both moderate certainty). Sensitivity analyses showed that the magnitude of the effect was highest in patients with increased baseline risk of reintubation. As compared to HFNC, no difference in incidence of reintubation was seen with NIPPV (OR 1.04 95% CI 0.78–1.38, low certainty). Compared to conventional oxygen therapy, neither NIPPV (OR 0.8 95% CI 0.61–1.04, moderate certainty) or HFNC (OR 0.9 95% CI 0.66–1.24, low certainty) reduced short-term mortality. Consistent findings were demonstrated across multiple subgroups, including high- and low-risk patients. These results were replicated when evaluating noninvasive strategies for prevention (prophylaxis), but not in rescue (application only after evidence of deterioration) situations.
Conclusions
Our findings suggest that both NIPPV and HFNC reduced reintubation in critically ill adults, compared to conventional oxygen therapy. NIPPV did not reduce incidence of reintubation when compared to HFNC. These findings support the preventative application of noninvasive respiratory support strategies to mitigate extubation failure in critically ill adults, but not in rescue conditions.
Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural ...anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis.
We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model.
Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n = 128) and the mean age of children ranged from 0.9 to 18 years (n = 66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma.
Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.
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