A prospective study of agitation in a medical-surgical ICU: incidence, risk factors, and outcomes

STUDY OBJECTIVES: Although agitation is thought to be common in the ICU, it has been poorly studied. We evaluated the incidence, risks factors, and outcomes of agitation in ICU. DESIGN: Prospective observational study. INTERVENTIONS: None. METHOD: All consecutive ICU admissions over an 8-month period were analyzed. MEASUREMENTS AND RESULTS: Two hundred eleven patients were admitted a total of 216 times during the period of the study. Twenty-nine patients were excluded from the study because their pathology findings did not allow an evaluation of their level of consciousness; 182 patients were actually enrolled. Agitation developed in 95 of 182 patients (52%). Agitation began 4.4 +/- 5.6 days (+/- SD) after admission to the ICU and lasted 3.9 +/- 4.1 days. Patients with agitation had a higher Simplified Acute Physiology Score II on ICU admission than those who did not have agitation (40 +/- 16 vs 33 +/- 13, p < 0.01). By stepwise logistic regression, the independent risks factors for development of agitation included psychoactive drug use at the time of ICU admission (odds ratio, 5.63; 95% confidence interval [CI], 1.32 to 23.70), history of alcohol abuse (odds ratio, 3.32; 95% CI, 1.12 to 10.00), dysnatremia (odds ratio, 4.95; 95% CI, 1.95 to 12.54), fever (odds ratio, 4.52; 95% CI, 1.80 to 11.49), use of sedatives in the ICU (odds ratio, 4.03; 95% CI, 1.62 to 10.40), and sepsis (odds ratio, 2.61; 95% CI, 1.03 to 6.58). Agitation was associated with a prolonged ICU stay (16 +/- 19 days vs 6 +/- 6 days, p = 0.0001), nosocomial infections (34% vs 7%, p < 0.0001), unplanned extubations (17% vs 2%, p = 0.003), and unplanned central venous catheter removal (16% vs 1%, p = 0.001), but not with mortality (12% in the agitation group vs 8% in patients without agitation). CONCLUSIONS: Agitation is a common event in a mixed medical-surgical ICU. It is associated with adverse outcomes including prolonged stay, nosocomial infections, and unplanned extubations. A better knowledge of incidence and risk factors should facilitate identification of patients at risk and decrease the incidence of agitation.     

Impact of stent deployment procedural factors on long-term effectiveness and safety of sirolimus-eluting stents (final results of the multicenter prospective STLLR trial)

Drug-eluting stent failures were associated with various clinical factors. However, the clinical impact of stent deployment technique was unknown. This study was designed to evaluate the frequency and impact of suboptimal percutaneous coronary intervention on long-term outcomes of 1,557 patients treated with sirolimus-eluting stents (SESs) in 41 US hospitals. All steps of the interventional procedure were scrutinized by an independent core laboratory to determine the occurrence of geographic miss (GM). GM included longitudinal (LGM; injured or diseased segment not covered by SES) or axial GM (balloon-artery size ratio <0.9 or >1.3) mismatches. Patients with and without GM were stratified (GM vs no-GM group). Patients, investigators, and the independent clinical event adjudication committee were blind to study group assignments. The primary end point was 1-year target-vessel revascularization (TVR) rate. Incidences and predictors of GM and safety outcomes were secondary end points. GM occurred in 943 patients (66.5%): 47.6% had LGM, 35.2% had axial GM, and 16.5% had both. One-year TVR rates were 5.1% in the GM group versus 2.5% in the no-GM group (p=0.025). TVR was 6.1% in the LGM versus 2.6% in the no-LGM subgroups (p=0.001). The association of GM with 1-year TVR was independent of clinical or anatomic factors (hazard ratio 2.0, 95% confidence interval 1.0 to 4.02, p=0.05). There was a 3-fold increase in myocardial infarction rates associated with GM (2.4% vs 0.8%; p=0.04). In conclusion, GM occurred frequently during SES implantation and was associated with increased risk of TVR and myocardial infarction at 1 year. These results emphasized the need for improvement in contemporary percutaneous coronary intervention practices and technologies.     

Delivery and Biodistribution of Traceable Polymeric Micellar Diclofenac in the Rat

The nonsteroidal anti-inflammatory drugs elevate cardiovascular risk, perhaps, due to their accumulation in the heart and kidneys. We designed nanodelivery systems for cardiotoxic diclofenac to reduce its presence in these organs. Diclofenac ethyl ester (DFEE) was encapsulated in traceable micelles based on poly(ethylene oxide)-b-poly(ε-caprolactone) (DFEE-PCL-TM) or poly(ethylene oxide)-b-poly(α-benzyl carboxylate-ε-caprolactone) (DFEE-PBCL-TM). Diclofenac pharmacokinetics and tissue distribution were studied after intravenous (iv) and intraperitoneal administration of the nanoformulations and compared with those after iv doses of free diclofenac (n = 3-6/group). The average diameters for DFEE-PBCL-TM and DFEE-PCL-TM were 37.2 ± 0.06 and 45.1 ± 0.06 nm, respectively. Drug concentration dropped below the assay sensitivity after free drug administration in 6 h, but persisted for 24 h following DFEE-PBCL-TM (2.3 ± 1.4 μg/mL) and DFEE-PCL-TM (1.9 ± 0.6 μg/mL) iv administration. The diclofenac heart:blood and kidney:blood ratios were 5- to 12-fold lower with the nanoformulations than with free diclofenac. Near-infrared fluorescence measurements in tissues suggested exposure patterns to nanocarriers parallel with those achieved for delivered diclofenac by nanoformulations. Administration of DFEE-PCL-TM by iv or intraperitoneal injection, resulted in comparable pharmacokinetics and 6 h postdose near-infrared fluorescence in the heart, kidneys, liver, and spleen. When compared to each other, DFEE-PBCL-TM showed significantly lower diclofenac levels in the heart compared to DFEE-PCL-TM (0.3 ± 0.03 vs. 0.5 ± 0.1 μg/g). Developed nanoformulations of diclofenac prolonged diclofenac circulation and reduced its presence in the heart and kidneys, strongly suggesting cardiac-safe delivery vehicles for diclofenac.