Adult patients, tight glucose control is not associated with significantlyReduced hospital mortality but is associated with an increased risk of
Hypoglycemia.
Antithrombin III for critically ill patients.
Cochrane Database Syst Rev. 2008 Jul 16;(3):CD005370.
BACKGROUND: Critical illness is associated with uncontrolled inflammation and
vascular damage which can result in multiple organ failure and death.
Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties
but the efficacy and any harmful effects of AT III supplementation in critically
ill patients are unknown. OBJECTIVES: To assess the benefits and harms of AT III
in critically ill patients. SEARCH STRATEGY: We searched the Cochrane Central
Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE; EMBASE;
Science Citation Index Expanded; International Web of Science; CINAHL; LILACS;
and the Chinese Biomedical Literature Database (up to November 2006). We
contacted authors and manufacturers in the field. SELECTION CRITERIA: We included
all randomized clinical trials, irrespective of blinding or language, that
compared AT III with no intervention or placebo in critically ill patients. DATA
COLLECTION AND ANALYSIS: Our primary outcome measure was mortality. We each
independently abstracted data and resolved any disagreements by discussion. We
presented pooled estimates of the intervention effects on dichotomous outcomes as
relative risks (RR) with 95% confidence intervals (CI). We performed subgroup
analyses to assess risk of bias, the effect of AT III in different populations
(sepsis, trauma, obstetric, and paediatric patients), and the effect of AT III in
patients with or without the use of concomitant heparin. We assessed the adequacy
of the available number of participants and performed a trial sequential analysis
to establish the implications for further research. MAIN RESULTS: We included 20
randomized trials with a total of 3458 participants; 13 of these trials had high
risk of bias. When we combined all trials, AT III did not statistically
significantly reduce overall mortality compared with the control group (RR 0.96,
95% CI 0.89 to 1.03; no heterogeneity between trials). A total of 32 subgroup and
sensitivity analyses were carried out. Analyses based on risk of bias, different
populations, and the role of adjuvant heparin gave insignificant differences. AT
III reduced the multiorgan failure score among survivors in an analysis involving
very few patients. AT III increased bleeding events (RR 1.52, 95% CI 1.30 to
1.78). AUTHORS' CONCLUSIONS: AT III cannot be recommended for critically ill
patients based on the available evidence. A randomized controlled trial of AT
III, without adjuvant heparin, with prespecified inclusion criteria and good bias
protection is needed.
Empirical fluconazole versus placebo for intensive care unit patients: a
Randomized trial.
Ann Intern Med. 2008 Jul 15;149(2):83-90.
Schuster MG, Edwards JE Jr, Sobel JD, Darouiche RO, Karchmer AW, Hadley S,
Slotman G, Panzer H, Biswas P, Rex JH.
BACKGROUND: Invasive infection with Candida species is an important cause of
morbidity and mortality in intensive care unit (ICU) patients. Optimal preventive
strategies have not been clearly defined. OBJECTIVE: To see whether empirical
fluconazole improves clinical outcomes more than placebo in adult ICU patients at
high risk for invasive candidiasis. DESIGN: Double-blind, placebo-controlled,
randomized trial conducted from 1995 to 2000. SETTING: 26 ICUs in the United
States. PATIENTS: 270 adult ICU patients with fever despite administration of
broad-spectrum antibiotics. All had central venous catheters and an Acute
Physiology and Chronic Health Evaluation II score greater than 16. INTERVENTION:
Patients were randomly assigned to either intravenous fluconazole, 800 mg daily,
or placebo for 2 weeks and were followed for 4 weeks thereafter. Two hundred
forty-nine participants were available for outcome assessment. MEASUREMENTS: A
composite primary outcome that defined success as all 4 of the following:
resolution of fever; absence of invasive fungal infection; no discontinuation
because of toxicity; and no need for a nonstudy, systemic antifungal medication
(as assessed by a blinded oversight committee). RESULTS: Only 44 of 122 (36%)
fluconazole recipients and 48 of 127 (38%) placebo recipients had a successful
outcome (relative risk, 0.95 [95% CI, 0.69 to 1.32; P = 0.78]). The main reason
for failure was lack of resolution of fever (51% for fluconazole and 57% for
placebo). Documented invasive candidiasis occurred in 5% of fluconazole
recipients and 9% of placebo recipients (relative risk, 0.57 [CI, 0.22 to 1.49]).
Seven (5%) fluconazole recipients and 10 (7%) placebo recipients had adverse
events resulting in discontinuation of the study drug. Discontinuation because of
abnormal liver test results occurred in 3 (2%) fluconazole recipients and 5 (4%)
placebo recipients. Limitations: Twenty-one randomly assigned patients were not
included in the analysis because they either did not meet entry criteria or did
not have postbaseline assessments. Fewer fungal infections than anticipated
occurred in the control group. Confidence bounds were wide and did not exclude
potentially important differences in outcomes between groups. CONCLUSION: In
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