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      Association between lymphocyte expression of the apoptotic receptor Fas and pain in critically ill patients

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          Lymphocyte apoptosis in critical illness is associated with immunosuppression. We explored for the first time the associations between pain ratings and expression of the apoptotic receptor Fas on B and T cells in critically ill patients and the potential mediating effects of adrenocorticotropic hormone (ACTH), cortisol, and substance P (SP).


          This is an exploratory correlational study with repeated measurements (14 days followup) and cross-sectional comparisons.


          This study was conducted in a state hospital in the metropolitan area of Athens, Greece.


          The participants were 36 consecutive critically ill patients and 36 matched controls.

          Outcome measures

          Pain measured by the self-reported numeric rating scale [NRS], the behavioral pain scale, and the pain assessment scale was the primary outcome measure. Flow cytometry (Fas), electrochemiluminescence (ACTH and cortisol) and enzyme-linked immunosorbent assay (SP) were used. Mixed linear models for repeated measurements and bivariable associations at discrete time points were employed.


          Significant pain at rest was noted. Pain ratings associated with Fas expression on cytotoxic T cells ( P=0.041) and B cells ( P=0.005), even after adjustment for a number of clinical treatment factors ( P=0.006 and P=0.052, respectively). On the day that more patients were able to communicate, Fas on B cells ( r=0.897, P=0.029) and cytotoxic T cells ( r=0.832; P=0.037) associated with NRS ratings. Associations between pain ratings and ACTH serum levels were noted ( P<0.05). When stress neuropeptide levels were added to the model, the statistical significance of the associations between pain ratings and Fas expression was attenuated ( P=0.052–0.063), suggesting that stress neuropeptides may partially mediate the association.


          Preliminary evidence for the association between pain and lymphocyte apoptotic susceptibility is provided. The role of pain management in maintaining immunocompetence in critical illness is worth exploring.

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          Most cited references 38

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          Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome.

          To develop an objective scale to measure the severity of the multiple organ dysfunction syndrome as an outcome in critical illness. Systematic literature review; prospective cohort study. Surgical intensive care unit (ICU) of a tertiary-level teaching hospital. All patients (n = 692) admitted for > 24 hrs between May 1988 and March 1990. None. Computerized database review of MEDLINE identified clinical studies of multiple organ failure that were published between 1969 and 1993. Variables from these studies were evaluated for construct and content validity to identify optimal descriptors of organ dysfunction. Clinical and laboratory data were collected daily to evaluate the performance of these variables individually and in aggregate as an organ dysfunction score. Seven systems defined the multiple organ dysfunction syndrome in more than half of the 30 published reports reviewed. Descriptors meeting criteria for construct and content validity could be identified for five of these seven systems: a) the respiratory system (Po2/FIO2 ratio); b) the renal system (serum creatinine concentration); c) the hepatic system (serum bilirubin concentration); d) the hematologic system (platelet count); and e) the central nervous system (Glasgow Coma Scale). In the absence of an adequate descriptor of cardiovascular dysfunction, we developed a new variable, the pressure-adjusted heart rate, which is calculated as the product of the heart rate and the ratio of central venous pressure to mean arterial pressure. These candidate descriptors of organ dysfunction were then evaluated for criterion validity (ICU mortality rate) using the clinical database. From the first half of the database (the development set), intervals for the most abnormal value of each variable were constructed on a scale from 0 to 4 so that a value of 0 represented essentially normal function and was associated with an ICU mortality rate of or = 50%. These intervals were then tested on the second half of the data set (the validation set). Maximal scores for each variable were summed to yield a Multiple Organ Dysfunction Score (maximum of 24). This score correlated in a graded fashion with the ICU mortality rate, both when applied on the first day of ICU admission as a prognostic indicator and when calculated over the ICU stay as an outcome measure. For the latter, ICU mortality was approximately 25% at 9 to 12 points, 50% at 13 to 16 points, 75% at 17 to 20 points, and 100% at levels of > 20 points. The score showed excellent discrimination, as reflected in areas under the receiver operating characteristic curve of 0.936 in the development set and 0.928 in the validation set. The incremental increase in scores over the course of the ICU stay (calculated as the difference between maximal scores and those scores obtained on the first day [i.e., the delta Multiple Organ Dysfunction Score]) also demonstrated a strong correlation with the ICU mortality rate. In a logistic regression model, this incremental increase in scores accounted for more of the explanatory power than admission severity indices. This multiple organ dysfunction score, constructed using simple physiologic measures of dysfunction in six organ systems, mirrors organ dysfunction as the intensivist sees it and correlates strongly with the ultimate risk of ICU mortality and hospital mortality. The variable, delta Multiple Organ Dysfunction Score, reflects organ dysfunction developing during the ICU stay, which therefore is potentially amenable to therapeutic manipulation. (ABSTRACT TRUNCATED)
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            APACHE-acute physiology and chronic health evaluation: a physiologically based classification system.

            Investigations describing the utilization pattern and documenting the value of intensive care are limited by the lack of a reliable and valid classification system. In this paper, the authors describe the development and initial validation of acute physiology and chronic health evaluation (APACHE), a physiologically based classification system for measuring severity of illness in groups of critically ill patients. APACHE uses information available in the medical record. In studies on 582 admissions to a university hospital ICU and 223 admissions to a community hospital ICU, APACHE was reliable in classifying ICU admissions. In validation studies involving these 805 admissions, the acute physiology score of APACHE demonstrated consistent agreement with subsequent therapeutic effort and mortality. This was true for a broad range of patient groups using a variety of sensitivity analyses. After successful completion of multi-institutional validation studies, the APACHE classification system could be used to control for case mix, compare outcomes, evaluate new therapies, and study the utilization of ICUs.
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              Assessing pain in critically ill sedated patients by using a behavioral pain scale.

              To establish the validity and reliability of a new behavioral pain scale (BPS) for critically ill sedated adult patients. Prospective evaluation. Ten-bed trauma and surgical intensive care unit in a university teaching hospital. Thirty mechanically ventilated patients who were receiving analgesia and sedation. Assessments with the BPS were completed consecutively at standardized times (morning, afternoon, night) by pairs of evaluators (nurse and nurse's aide). They collected physiologic parameters and BPS results before and during care procedures: non-nociceptive (group 1, compression stockings application and central venous catheter dressing change), nociceptive (group 2, endotracheal suctioning and mobilization), and retested nociceptive (group 3). The BPS score was the sum of three items that had a range score of 1-4: facial expression, movements of upper limbs, and compliance with mechanical ventilation. Two hundred and sixty nine assessments were completed, including 104, 134, and 31 measurements in groups 1, 2 and 3, respectively. There was no difference in Ramsay scale scores between the three groups (Ramsay 4-6). Nociceptive stimulations (group 2) resulted in significantly higher BPS values than non-nociceptive ones (group 1, 4.9 vs. 3.5, p <.01), whereas the two groups had comparable BPS values before stimulation (3.1 vs. 3.0). A trend was found in group 2 between the dosage of sedation/analgesia and BPS: the higher the dosage, the lower BPS values and BPS changes to nociceptive stimulation. Group 3 had BPS values similar to group 2 at rest (3.2 vs. 3.2) and during the procedure (4.4 vs. 4.5), with good interrater correlations (r(2) =.71 and.50, respectively). These results indicate that the expression of pain can be scored validly and reliably by using the BPS in sedated, mechanically ventilated patients. Further studies are warranted regarding the utility of the BPS in making clinical decisions about the use of analgesic drugs in the intensive care unit.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                13 January 2017
                : 10
                : 175-181
                [1 ]Faculty of Nursing, University of Alberta, Edmonton, AB, Canada
                [2 ]Department of Nursing, Cyprus University of Technology, Limassol, Cyprus
                [3 ]Department of Nursing, School of Health Sciences, National and Kapodistrian University of Athens
                [4 ]Surgical Care Unit, The Onassis Cardiac Surgery Center, Kallithea
                [5 ]School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
                Author notes
                Correspondence: Elizabeth DE Papathanassoglou, Faculty of Nursing, University of Alberta, Edmonton Clinic Health Academy, 11405-87th Avenue, Edmonton, AB T6G 1C9, Canada, Tel +1 780 492 5674, Email papathan@ 123456ualberta.ca

                These authors contributed equally to this work

                © 2017 Papathanassoglou et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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