Relationship between norepinephrine dose, tachycardia and outcome in septic shock: A multicentre evaluation.

PURPOSE: Septic shock is associated with massive release of endogenous catecholamines. Adrenergic agents may exacerbate catecholamine toxicity and contribute to poor outcomes. We sought to determine whether an association existed between tachycardia and mortality in septic shock patients requiring norepinephrine for more than 6 h despite adequate volume resuscitation. MATERIALS AND METHODS: Multicentre retrospective observational study on 730 adult patients in septic shock consecutively admitted to eight European ICUs between 2011 and 2013. Three timepoints were selected: T1 (first hour of infusion of norepinephrine), Tpeak (time of highest dose during the first 24 h of treatment), and T24 (24-h post-T1). Binary logistic regression models were constructed for the three time-points. RESULTS: Overall ICU mortality was 38.4%. Mortality was higher in those requiring high-dose (≥0.3 mcg/kg/min) versus low-dose (<0.3 mcg/kg/min) norepinephrine at T1 (53.4% vs 30.6%; p < 0.001) and T24 (61.4% vs 20.4%; p < 0.0001). Patients requiring high-dose with concurrent tachycardia had higher mortality at T1; in the low-dose group tachycardia was not associated with mortality. Resolving tachycardia (from T1 to T24) was associated with lower mortality compared to patients where tachycardia persisted (27.8% vs 46.4%; p = 0.001). CONCLUSIONS: Use of high-dose norepinephrine and concurrent tachycardia are associated with poor outcomes in septic shock.

A low observed-to-expected postoperative mortality ratio in a Swiss high-standard peri-operative care environment - an observational study.

QUESTIONS UNDER STUDY/PRINCIPLES: The objective was to assess observed-to-expected in-hospital postoperative 30-day mortality and to identify associated risks. METHODS: A single centre, retrospective study was performed in Geneva University Hospitals, Switzerland. Hospitalised adult surgical patients who received anaesthesia and stayed in the Post Anaesthesia Care Unit - Intermediate Care Unit (PACU-IMC) between July 2008 and June 2011 were included. Outcome measure was in-hospital 30-day mortality. Expected probabilities of in-hospital death were estimated with the surgical mortality probability model (S-MPM). Descriptive statistics were calculated. Univariate and multivariate logistic regressions (odds ratio [OR] with 95% confidence interval [95% CI]) were used to identify risk factors of mortality. RESULTS: Overall in-hospital mortality was 0.8% (176/24 160 patients). Observed 30-day in-hospital mortality was 0.7%; expected mortality from the S-MPM was 1.2%. Independent risk factors were age (OR 1.05, 95% CI 1.03-1.06), American Society of Anesthesiologists Physical Status score (ASA PS 3-5 vs ASA PS 1-2: OR 5.48, 95% CI 3.12-9.63), nonelective surgery (vs elective surgery) (OR 3.15, 95% CI 2.04-4.86), head surgery (OR 2.83, 95% CI 1.41-5.67) and duration of PACU-IMC stay (OR 1.00, 95% CI 1.00-1.00). A protective factor was a high body mass index (OR 0.92, 95% CI 0.89-0.96). The procedural risk, type and time of anaesthesia and day of intervention were not independent risk factors of mortality. CONCLUSION: The postoperative observed-to-expected mortality ratio was favourable. Independent postoperative risk factors for mortality were well-established factors such as age, ASA PS, non elective surgery but also duration of PACU-IMC stay which was considered as a surrogate of postoperative complications.

Continuous assessment of labour pain using handgrip force.

BACKGROUND: Assessment of dynamic changes in painful experiences, such as labour, using conventional rating scales (eg, numerical rating scale [NRS]) has limitations. An alternative for continuous pain evaluation could be a signal generated by voluntary action of the parturient. Remifentanil administration for obstetric analgesia could be improved by these dynamic measures of labour pain. In the present study, handgrip force was measured by a dynamometer to signal labour pain. OBJECTIVES: To evaluate: whether continuous monitoring of labour pain using handgrip force allows for determination of pain measurement during contractions; and the correlation between handgrip force and pain intensity on NRS. METHODS: The present observational, single-centre study included 43 parturients. After calibration of the dynamometer for individual hand muscle strength, pain was recorded during early and late labour using a dynamometer and an NRS. The primary end point was the correlation coefficient between NRS ratings and peak intensity recorded by the dynamometer. RESULTS: All dynamometer-registered readings were also registered by the external tocogram. All contractions recorded by external tocogram were also registered by the dynamometer. Handgrip force was moderately correlated with pain scores on the NRS. Mean handgrip force during contractions had the highest correlation coefficient (Pearson's r=0.67) compared with peak handgrip force (r=0.56) and area under the curve of handgrip force (r=0.55). CONCLUSIONS: Pain intensity and duration can be assessed continuously using handgrip force measured via a dynamometer. The feedback of intensity and duration of pain could optimize patient-controlled remifentantil application for obstetric analgesia and other situations of highly variable pain intensity.

Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions: a statement from the ESA-ESICM joint taskforce on perioperative outcome measures.

There is a need for large trials that test the clinical effectiveness of interventions in the field of perioperative medicine. Clinical outcome measures used in such trials must be robust, clearly defined and patient-relevant. Our objective was to develop standards for the use of clinical outcome measures to strengthen the methodological quality of perioperative medicine research. A literature search was conducted using PubMed and opinion leaders worldwide were invited to nominate papers that they believed the group should consider. The full texts of relevant articles were reviewed by the taskforce members and then discussed to reach a consensus on the required standards. The report was then circulated to opinion leaders for comment and review. This report describes definitions for 22 individual adverse events with a system of severity grading for each. In addition, four composite outcome measures were identified, which were designed to evaluate postoperative outcomes. The group also agreed on standards for four outcome measures for the evaluation of healthcare resource use and quality of life. Guidance for use of these outcome measures is provided, with particular emphasis on appropriate duration of follow-up. This report provides clearly defined and patient-relevant outcome measures for large clinical trials in perioperative medicine. These outcome measures may also be of use in clinical audit. This report is intended to complement and not replace other related work to improve assessment of clinical outcomes following specific surgical procedures.

Human stem cell-based three-dimensional microtissues for advanced cardiac cell therapies.

Cardiac stem cell therapy has been proposed as a therapy option to treat the diseased myocardium. However, the low retention rate of transplanted single-cell suspensions remains a major issue of current therapy strategies. Therefore, the concept of scaffold-free cellular self-assembly into three-dimensional microtissues (3D-MTs) prior to transplantation may be beneficial to enhance retention and survival. We compared clinically relevant, human stem cell sources for their ability to generate 3D-MTs with particular regards to formation characteristics, proliferation-activity, viability and extracellular-matrix production. Single-cell suspensions of human bone marrow- and adipose tissue-derived mesenchymal stem cells (hBMMSCs and hATMSCs), Isl1(+) cardiac progenitors derived from human embryonic stem cells (hESC-Isl1(+) cells), and undifferentiated human induced pluripotent cells (hiPSCs) were characterized before to generate 3D-MTs using a hanging-drop culture. Besides the principal feasibility of cell-specific 3D-MT formation, a detailed head-to-head comparison between cell sources was performed using histology, immunocyto- and histo-chemistry as well as flow cytometry. Round-oval shaped and uniform 3D-MTs could be successfully generated from all cell types starting with a loose formation within the first 24 h that fully stabilized after 3 days and resulting in a mean 3D-MT diameter of 194.56 ± 18.01 µm (hBMMSCs), 194.56 ± 16.30 µm (hATMSCs), 159.73 ± 19.20 µm (hESC-Isl1(+) cells) and 120.95 ± 7.97 µm (hiPSCs). While all 3D-MTs showed a homogenous cell distribution, hiPSC-derived 3D-MTs displayed a compact cell formation primarily located at the outer margin. hESC-Isl1(+) and hiPSC-derived 3D-MTs maintained their proliferation-activity which was rather limited in the MSC-based 3D-MTs. All four 3D-MT types revealed a comparable viability in excess of 70% and showed a cell-specific expression profile being comparable to their single-cell counterparts. Extracellular matrix (ECM) production during 3D-MT formation was observed for all cell-specific 3D-MTs, with hiPSC-derived 3D-MTs being the fastest one. Interestingly, ECM distribution was homogenous for hATMSC- and hiPSC-based 3D-MTs, while it appeared to be primarily concentrated within in the center of hESC-Isl1(+) and hBMMSC-based 3D-MTs. The results of this head-to-head comparative study indicated that 3D-MTs can be successfully generated from hESC-derived Isl1(+) cells, hiPSCs and MSC lines upon hanging drop culture. Cell-specific 3D-MTs displayed sufficient viability and instant ECM formation. The concept of 3D-MT in vitro generation prior to cell transplantation may represent a promising delivery format for future strategies to enhance cellular engraftment and survival.

Effectiveness of the surgical safety checklist in a high standard care environment.

BACKGROUND: Use of surgical safety checklists has been associated with significant reduction in postoperative surgical site infection (SSI), morbidity, and mortality. OBJECTIVE: To evaluate the effectiveness of an intraoperative checklist in high-risk surgical patients in a high standard care environment with long-standing regular perioperative safety control programs. RESEARCH DESIGN: Quasi-experiment pre-post checklist implementation. SUBJECTS: Surgical patients above 16 years with an American Society of Anesthesiologists (ASA) score 3-5 operated upon at a large tertiary hospital. MEASURES: Unplanned return to operating room for any reason, reoperation for SSI, unplanned admission to intensive care unit, and in-hospital death within 30 days. RESULTS: A total of 609 patients (53% elective, 85% ASA 3, mean age 70 y) were included before and 1818 after implementation (52% elective, 87% ASA 3, mean age 69 y), the latter with 552, 558, and 708 in period I, II, and III, respectively. Comparing preimplementation to postimplementation periods: unplanned return to operating room occurred in 45/609 (7.4%) versus 109/1818 (6.0%) interventions [adjusted risk ratios (RR) 0.82; 95% confidence interval (CI), 0.59-1.14]; reoperation for SSI in 18/609 (3.0%) versus 109/1818 (1.7%) interventions (adjusted RR 0.56; 95% CI, 0.32-1.00); unplanned admission to intensive care unit in 17 (2.8%) versus 48 (2.6%) interventions (adjusted RR 0.90; 95% CI, 0.52-1.55); and in-hospital death occurred in 26 (4.3%) versus 108 (5.9%) patients (adjusted RR 1.44; 95% CI, 0.97-2.14). Checklist use during 77 interventions prevented 1 reoperation for SSI. CONCLUSIONS: A trend toward reduced reoperation rates for SSI was observed after checklist implementation in this high standard care environment; no influence on other outcome measures was observed.

A survey of standardised drug syringe label use in European anaesthesiology departments.

CONTEXT: Standardised drug syringe labelling may reduce drug errors, but data on drug syringe labelling use in European anaesthesiology departments are lacking. OBJECTIVES: Survey investigating if standardised drug syringe labelling is used, and if there are geographical, demographic and professional differences in hospitals with and without use of drug syringe labelling. DESIGN: Structured, web-based anonymised questionnaire. SETTING: European anaesthesia departments. PARTICIPANTS: Members of the European Society of Anaesthesiology. INTERVENTION: Online survey from 2 February to 12 April 2011. MAIN OUTCOME MEASURE: Standardised drug syringe labelling use and, if yes, drug syringe labelling for insulin and norepinephrine. METHODS: Descriptive and comparative analyses of users and nonusers of standardised drug syringe labelling. RESULTS: One thousand and sixty-four of 4163 members (25.6%) from 72 countries participated, among whom 660 (62.0%) used standardised drug syringe labelling; in Northern and Western Europe, there were 428 users of drug syringe labelling and 112 nonusers, and in Southern and Eastern Europe, there were 184 users and 255 nonusers (P < 0.001). Three hundred and ninety-four (37%) respondents used standardised drug syringe labelling hospital-wide; 202 (30.1%) used International Organisation of Standardisation-based standardised drug syringe labelling, 101 (15.1%) used similar systems, 278 (41.5%) used other systems and 89 (13.3%) used labels supplied by drug manufacturers. The label colour for insulin was reported as white or 'none' in 519 (76.7%) answers and another colour in 158 (23.3%). The label colour for norepinephrine was reported as violet in 206 (30.4%) answers, white or 'none' in 226 (33.3%), red in 114 (16.8%) and another colour in 132 (19.5%). A standardised drug syringe labelling system supplied by the pharmaceutical industry was supported by 819 (76.9%) respondents, and not supported by 227 (21.3%). CONCLUSION: A majority of European anaesthesiology departments used standardised drug syringe labelling, with regional differences and mostly without following an international standard. Thus, there are options for quality improvement in drug syringe labelling.

Standardised drug labelling in intensive care: results of an international survey among ESICM members.

PURPOSE: Standardised coloured drug labels may increase patient safety in the intensive care unit (ICU). The rates of adherence to standardised drug syringe labelling (DSL) in European and non-European ICUs, and the standards applied are not known. The aim of this survey among ESICM members was to assess if and what standardised drug syringe labelling is used, if the standards for drug syringe labelling are similar internationally and if intensivists expect that standardised DSL should be delivered by the pharmaceutical industry. METHODS: A structured, web-based, anonymised survey on standardised DSL, performed among ESICM members (March-May 2011; Clinicaltrials.gov NCT01232088). Descriptive data analysis was performed and Fisher's exact test was applied where applicable. RESULTS: Four hundred eighty-two submissions were analysed (20 % non-European). Thirty-five percent of the respondents reported that standardised drug labelling was used hospital-wide, and 39 % reported that standardised DSL was used in their ICU (Europe: Northern 53 %, Western 52 %, Eastern 17 %, Southern 22 %). The International Organization of Standardization (ISO) 26825 norm in its original form was used by 30 %, an adapted version by 19 % and local versions by 45 %; 6 % used labels that were included in the drug's packaging. Eighty percent wished that the pharmaceutical industry supplied ISO 26825 norm labelling together with the drugs. CONCLUSIONS: Standardised DSL is not widely applied in European and non-European ICUs and mostly does not adhere strictly to the ISO norm. The frequency and quality of DSL differs to a great extent among European regions. This leaves much room for improvement.