Timing of blood transfusion in relation to ICU admission-a single centre audit.

There is growing concern that blood transfusion may be associated with adverse outcomes in critically ill patients. Timing of transfusion in relation to intensive care unit (ICU) stay may be important in designing and understanding transfusion studies. The objective of this study was to determine the timing of red blood cell transfusion in relation to admission to an Australian ICU and to describe associations with transfusion requirements. We undertook a retrospective, observational, single-centre cohort study of all patients admitted to the ICU at The Northern Hospital, Melbourne, Australia, between 1 January and 31 December 2008 in order to measure the timing of transfusion in relation to ICU admission and the demographic and outcome data of the cohort. 674 individual hospital admissions were analysed. Overall, 28% (188/674) of patients admitted to ICU received a red cell transfusion during their hospital stay. A total of 55 (28.5%) patients were transfused either before and/or after ICU discharge but never in the ICU. Thirty-five percent (258/741) of red cell units were transfused outside the ICU. The median number of red cell units transfused was three units per patient (interquartile range 1 to 5). There was no difference between transfused and non-transfused groups in either crude mortality or severity-adjusted mortality. In approximately one-third of ICU patients in our study transfusions occurred before admission to, and/or after discharge from, the ICU. This has implications for designing and interpreting transfusion studies in the ICU and requires confirmation in a multi-centre study.

Comparison of intensive care outcome prediction models based on admission scores with those based on 24-hour data.

We compared the performance of six outcome prediction models--three based on 24-hour data and three based on admission-only data--in a metropolitan university-affiliated teaching hospital with a 10-bed intensive care unit. The Acute Physiology and Chronic Health Evaluation models, version II (APACHE II) and version III-J, and the Simplified Acute Physiology Score version II (SAPS II) are based on 24-hour data and were compared with the Mortality Prediction Model version II and the SAPS version III using international and Australian coefficients (SAPS IIIA). Data were collected prospectively according to the standard methodologies for each model. Calibration and discrimination for each model were assessed by the standardised mortality ratio, area under the receiver operating characteristic plot and Hosmer-Lemeshow contingency tables and chi-squared statistics (C10 and H10). Predetermined criteria were area under the receiver operating characteristic plot > 0.8, standardised mortality ratio 95% confidence interval includes 1.0, and C10 and H10 P values >0.05. Between October 1, 2005 and December 31, 2007, 1843 consecutive admissions were screened and after the standard exclusions, 1741 were included in the analysis. The SAPS II and SAPS IIIA models fulfilled and the APACHE II model failed all criteria. The other models satisfied the discrimination criterion but significantly over-predicted mortality risk and require recalibration. Outcome prediction models based on admission-only data compared favourably to those based on 24-hour data.

Acetylcholine-induced vasodilation is mediated by nitric oxide and prostaglandins in human skin.

Acetylcholine (ACh) can effect vasodilation by several mechanisms, including activation of endothelial nitric oxide (NO) synthase and prostaglandin (PG) production. In human skin, exogenous ACh increases both skin blood flow (SkBF) and bioavailable NO levels, but the relative increase is much greater in SkBF than NO. This led us to speculate ACh may dilate cutaneous blood vessels through PGs, as well as NO. To test this hypothesis, we performed a study in 11 healthy people. We measured SkBF by laser-Doppler flowmetry (LDF) at four skin sites instrumented for intradermal microdialysis. One site was treated with ketorolac (Keto), a nonselective cyclooxygenase antagonist. A second site was treated with NG-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase. A third site was treated with a combination of Keto and L-NAME. The fourth site was an untreated control site. After the three treated sites received the different inhibiting agents, ACh was administered to all four sites by intradermal microdialysis. Finally, sodium nitroprusside (SNP) was administered to all four sites. Mean arterial pressure (MAP) was monitored by Finapres, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). For data analysis, CVC values for each site were normalized to their respective maxima as effected by SNP. The results showed that both Keto and L-NAME each attenuated the vasodilation induced by exogenous ACh (ACh control = 79 +/- 4% maximal CVC, Keto = 55 +/- 7% maximal CVC, L-NAME = 46 +/- 6% maximal CVC; P < 0.05, ACh vs. Keto or L-NAME). The combination of the two agents produced an even greater attenuation of ACh-induced vasodilation (31 +/- 5% maximal CVC; P < 0.05 vs. all other sites). We conclude that a portion of the vasodilation effected by exogenous ACh in skin is due to NO; however, a significant portion is also mediated by PGs.

Night-shift discharge from intensive care unit increases the mortality-risk of ICU survivors.

UNLABELLED: Intensive Care (ICU) survivors discharged from ICU to the general ward at night have a higher mortality. We sought to clarify which factors, including night-shift discharge, influence outcome following ICU discharge in a metropolitan hospital, using a cohort study of critically-ill patients between 1/1/1999-30/4/2003. Patients were excluded from analysis if they (a) died in ICU, (b) were transferred to another hospital, (c) had an ICU length of stay <8 hours, or (d) age <16 years. Logistic regression was used to derive a predictive model based on the following variables: patient demographics, severity of illness following ICU admission (APACHE II mortality-risk, p(m)), final diagnosis, discharge timing including premature or delayed (>4 hours) ICU discharge, and "limitation of medical treatment" orders. The outcome measures were patient status at hospital discharge and ICU readmission rate. Of the 1870 ICU survivors, 92 (4.9%) died after discharge from ICU. Patients discharged to the ward during the night-shift (2200-0730 hours) had a higher APACHE II score and crude mortality. The difference in APACHE II p(m) did not reach statistical significance. No significant calendar or seasonal pattern was identified. Logistic regression identified night-shift discharge (RR=1.7; 95% CI 1.03-2.9; P=0.03), limited medical treatment order (RR=5.1; 95% CI 2.2-12) and admission APACHE II p(m) (RR=3.3; 95% CI 1.3-7.6) as independent predictors of patient outcome following ICU transfer to the ward. CONCLUSION: At the time of ICU discharge to the ward three factors are predictive of hospital outcome: timing of ICU discharge, limited medical treatment orders and initial illness severity.

Outcome of critically ill patients undergoing interhospital transfer.

OBJECTIVE: To quantify the morbidity and mortality associated with acute interhospital transfer of critically ill patients requiring intensive care (ICU) services. DESIGN: Three-year (1 July 1996-30 June 1999) retrospective case-control study based on review of patients' medical records. SETTING: Metropolitan hospitals in Melbourne, Victoria. PARTICIPANTS: 73 (of 75) consecutive, critically ill patients from one metropolitan teaching hospital who were transferred to other hospitals because ICU services were not available. OUTCOME MEASURES: Primary endpoints included inhospital mortality and length of stay in ICU and hospital. Secondary endpoints included time from study entry to ICU admission and the change in predicted mortality risk after resuscitation and transfer to ICU (inter- or intrahospital transfer). RESULTS: The Transfer Group experienced a significant delay in admission to ICU (5.0 [4.0-6.0] v 3.0 [2.0-5.5] hours; P=0.001), and a longer stay in ICU (48 [33-111] v 44 [25-78] hours; P=0.04), and hospital (10 [3-14] v 6 [3-13] days; P=0.02). Hospital mortality in the Transfer Group (24.7%) was not statistically different from that in the Control Group (17.8%; P= 0.41; OR, 1.5; 95% CI, 0.68-3.4). CONCLUSION: Acute interhospital transfer is associated with a delay in ICU admission and a longer stay in ICU and hospital, but no statistically significant difference in mortality. A study of over 300 patient transfers would be required to clarify the morbidity and mortality risk of acute interhospital transfer.

Acute exacerbations of chronic obstructive pulmonary disease and mechanical ventilation: a reevaluation.

OBJECTIVE: To review the intensive care unit (ICU) experience of patients admitted with acute exacerbations of chronic obstructive pulmonary disease. DESIGN: Retrospective case series. SETTING: University teaching hospital. PATIENTS: We reviewed the records of 100 consecutive ICU admissions of patients with acute exacerbations of chronic obstructive pulmonary disease over a period of 4.25 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were characterized using a computerized prospective database and case note review. Multivariate analysis identified variables predicting ICU and hospital length of stay. The Cox proportional hazards model was used to analyze survival after hospital discharge. Seventy-five patients (24 female and 51 male, mean age 68.5 +/- 7 [SD] yrs) with 100 ICU admissions were identified. Premorbid airway obstruction was severe, with forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC) of 0.7 +/- 0.34 L and FEV1/FVC of 39 +/- 16%. Thirty-two percent received home-administered oxygen and 42% were housebound. The pre-ICU admission PaCO2 was 86 +/- 28 torr (11.5 +/- 3.7 kPa), with a pH of 7.24 +/- 0.11 and a PaO2/FIO2 of 190 +/- 66. ICU admission Acute Physiology and Chronic Health Evaluation II score was 18 +/- 5. Forty-three patients were mechanically ventilated for a median of 4 days (range 0.08 to 30). Tracheostomy, in seven patients, was maintained for 21 +/- 7 days. Ventilation time and tracheostomy frequency predicted length of ICU stay (median 3 days; range 1 to 40) and hospital stay (17 days; 4 to 97), respectively. ICU and hospital case-fatality rates were 1% and 11%. Out-of-hospital (24-month) probability of survival was predicted by plasma albumin concentration at the time of ICU admission; this probability of survival was .64 at an albumin concentration of 38 g/L. CONCLUSIONS: ICU admission of severely ill chronic obstructive pulmonary disease patients results in acceptable outcomes. Survival of < or =2 yrs is not affected by mechanical ventilation or tracheostomy requirement.

Design and synthesis of bifunctional isothiocyanate analogs of sulforaphane: correlation between structure and potency as inducers of anticarcinogenic detoxication enzymes.

Thirty-five bifunctional isothiocyanates were synthesized as structural analogs of sulforaphane [(-)-1-isothiocyanato-4(R)-(methylsulfinyl)butane] that was recently isolated from broccoli as the principal and very potent inducer of detoxication (phase 2) enzymes in mouse tissues and murine hepatoma cells (Hepa 1c1c7) in culture (Zhang, Y.; Talalay, P.; Cho, C.-G.; Posner, G.H. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 2399-2403). Determination of the potency of each analog in inducing NAD(P)H:quinone reductase, a phase 2 detoxication enzyme, has allowed generalizations concerning the relation of structure and activity. The most potent analogs were bifunctional derivatives in which the isothiocyanate group was separated from a methylsulfonyl or an acetyl group by three or four carbon atoms, and in some of which these groups were conformationally restricted. Among these analogs, the bicyclic ketoisothiocyanate (+/-)-exo-2-acetyl-6-isothiocyanatonorbornane (30) was a very potent inducer (comparable to sulforaphane) of quinone reductase in hepatoma cells, and it also induced both quinone reductase and glutathione transferases in several mouse organs in vivo. This and related bicyclic ketoisothiocyanates represent potent phase 2 enzyme inducers that are relatively easily synthesized and that may be more stable metabolically than the natural sulfoxide sulforaphane.