scholarly journals Prognostic Relevance of Altered Lymphocyte Subpopulations in Critical Illness and Sepsis

2019 ◽  
Vol 8 (3) ◽  
pp. 353 ◽  
Author(s):  
Philipp Hohlstein ◽  
Hendrik Gussen ◽  
Matthias Bartneck ◽  
Klaudia Theresa Warzecha ◽  
Christoph Roderburg ◽  
...  

Lymphopenia and functional defects in lymphocytes may impact the prognosis in patients with critical illness or sepsis. Therefore, we prospectively analyzed peripheral blood leukocytes from 63 healthy volunteers, 50 non-critically ill standard care (SC) patients with infections, and 105 intensive care unit (ICU) patients (52 with sepsis, 53 without sepsis) using flow cytometry. Compared to healthy volunteers, SC and ICU patients showed significant leukocytosis, especially in sepsis, while lymphocyte numbers were significantly decreased. All major lymphocyte populations (B, T, and natural killer (NK) cells) decreased in ICU patients. However, we observed a relative reduction of T cells, alongside decreased CD8+ T cells, in critically ill patients, independent of sepsis. High absolute T cell counts (>0.36/nL) at ICU admission were associated with a significantly reduced mortality, independent of patient’s age. Moreover, patients that survived ICU treatment showed dynamic changes within 48 h towards restoration of lymphopenia and T cell depletion, while non-surviving patients failed to restore lymphocyte counts. In conclusion, the flow-cytometric analysis of peripheral blood revealed striking changes in circulating lymphocyte subsets in critically ill patients, independent of sepsis. Lymphopenia and T cell depletion at ICU admission were associated with increased mortality, supporting their relevance as predictive biomarkers and potential therapeutic targets in intensive care medicine.

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 663-679
Author(s):  
L Levitt ◽  
TJ Kipps ◽  
EG Engleman ◽  
PL Greenberg

The efficacy of four separate methods of human bone marrow T lymphocyte depletion was assessed, and the effect of T cells and monocytes on in vitro growth of marrow (CFU-GEMM, BFU-E, and CFU-GM) and peripheral blood (BFU-E) hematopoietic progenitors was determined. Extent of T cell depletion was assessed by multiparameter fluorescent cell sorter (FACS) analysis and by functional studies. Cells staining positively by FACS analysis for one or more of three separate fluorescent pan-T cell monoclonal antibodies (MCAbs) comprised 8.4% to 9.5% of control marrow mononuclear cells (MNCs). T cells constituted 3.2% to 5.1% of marrow following single, sequential, or combination treatment with two different pan-T cell MCAbs (Leu 1 and TM1) plus complement, 1.5% to 2.2% of marrow following solid-phase immunoabsorption (“panning”), 0.2% of marrow after sheep cell rosetting, and only 0.05% of marrow after FACS selective cell sorting and gated separation. T cells made up 59% to 73% of control peripheral blood MNCs and 0.8% to 2.8% of peripheral MNCs following sheep cell rosetting plus treatment with Leu 1 MCAb and complement. Mitogen (PHA, Con A) and allogeneic MLC-induced blastogenic responses (stimulation indices, experimental/control or E/C) revealed a concordant decrement in marrow T cell function after MCAb plus complement (E/C of 3.9 to 9.0), after panning (E/C of 1.6 to 3.5) and after sheep cell rosetting (E/C of 0.7 to 1.3), compared with control marrow (E/C of 5.3 to 15.7). After T cell depletion, marrow BFU-E growth was 95% to 120% of control, CFU-GM growth was 90% to 108% of control, and CFU-GEMM growth was 89% to 111% of control. Marrow T cell and/or monocyte depletion did not alter erythropoietin-dependent BFU-E growth in the absence of Mo-conditioned medium (81% to 95% of control), and the addition of as many as 50 to 100 X 10(3) purified marrow monocytes or T cells to 10(5) autologous nonadherent T cell-depleted marrow target cells had a negligible (P greater than .1) effect on marrow BFU-E growth in vitro. Peripheral blood (PB) BFU-E/10(5) T- depleted target cells were 106% +/- 19% of expected; PB BFU-E growth was significantly diminished after monocyte depletion alone (7% +/- 6% of expected) or after monocyte plus T cell depletion (8% +/- 4% of expected).(ABSTRACT TRUNCATED AT 400 WORDS)


Author(s):  
Reetu Verma ◽  
Sasmita Panda ◽  
Rajeev Kumar Nishad

Introduction: Patients admitted in the Intensive Care Units (ICUs) experiences various discomforts which may be recognised or unrecognised. These discomforts may arise from the environment, may be related to the ICU care and discomfort related to the health status of the patient and critical care interventions. Aim: To identify the various discomforts in ICU patients, to classify them with respective causes, identify the most common cause among them and whether ICU sedation helps in reducing discomforts. Materials and Methods: This observational study was conducted from 15th July to 15th October 2018 on 120 mixed ICU patients in a Tertiary Care Hospital in India. Patients who were admitted to ICU for more than 24 hours, aged 18 years and above, those who gave written informed consent were observed and enquired for any discomfort. Discomforts have been identified and recorded by a fulltime intensivist by direct observation, by interacting with the patients and asking the family members and others (indirect approach). Through this study discomforts of critically ill patients were broadly classified into four categories 1. Due to existing illness, 2. Due to ICU interventions, 3. Due to improper nursing care and 4. Due to environmental factors. Results: Out of 120 patients studied, 84 patients (70%) reported some kind of discomfort during their ICU stay. Existing illness was the most common cause of discomfort, 80 patients (66.6%) suffered due to it. ICU interventions was the second most common cause, 71 patients (59.1%) had discomfort due to interventions. Thirty five patients (29.1%) suffered due to improper nursing care and 25 patients (20.8%) suffered due to the environmental factors. In this study, it was observed that sedation reduces all kind of discomforts. conclusion: In this study 70% of patients, who were admitted to ICU due to various illness reported some kind of discomfort. The most common cause of ICU discomforts was existing illness followed by ICU interventions. In this study it was observed that sedation reduces all kind of discomforts. Sedated patients tolerate the endotracheal tube better and they had less environmental and procedure related discomforts. With the present study observation it can be suggested that ICU charts of nurses and doctors can carry a separate column for mentioning discomforts in different duty shifts. However, with the use of appropriate analgesia and sedation discomfort can be reduced.


Author(s):  
Priya S. Dhawan ◽  
Jennifer A. Tracy

Acquired weakness in critically ill patients is common, affecting between one-third to one-half of patients in the intensive care unit (ICU). Exposure to simultaneous stressors such as metabolic derangements, fluid and electrolyte shifts, infection, catabolic stress, and medications put patients in the ICU at risk for damage to both nerve and skeletal muscle with substantial and often lasting morbidity. Critical illness polyneuropathy is a length-dependent, axonal peripheral neuropathy occurring in patients in the ICU and unrelated to the primary illness. Critical illness myopathy is an ICU-associated muscle disorder occurring independently of denervation and uniquely identified by electrophysiologic and histologic characteristics.


2000 ◽  
Vol 9 (3) ◽  
pp. 192-198 ◽  
Author(s):  
JE Hupcey ◽  
HE Zimmerman

BACKGROUND: Critically ill patients vary in their memories of their experience in the intensive care unit. Some have little recall and need to learn about their critical illness. Others have more vivid memories of their experiences, some of which were extremely unpleasant. Patients' not knowing what was happening may have exacerbated the unpleasant experiences. OBJECTIVES: To elicit the experience of knowing for critically ill patients and to explore the differences in perceptions between patients who were intubated and those who were not intubated during the illness. METHODS: Grounded theory was used to explore the meaning of knowing and not knowing and the process by which knowing occurs. Unstructured interviews were done with 14 patients. RESULTS: Knowing had 2 phases: the need to know (1) during and (2) after the critical illness. The first phase had 3 facets: needing information, needing to be oriented, and having confusing perceptions. The second phase had 2 facets: needing information about what had happened and piecing together events. Many experiences with knowing during and after a critical illness were similar for both intubated and nonintubated patients. The main difference was the intensity of the experience in some categories. CONCLUSIONS: Critically ill patients have a strong need to know throughout and after their time in the intensive care unit. Nurses must address this need for constant reorientation to the past and present in these patients. In addition, adequate nursing staff must be available for these patients.


BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e023961
Author(s):  
Elizabeth D E Papathanassoglou ◽  
Yoanna Skrobik ◽  
Kathleen Hegadoren ◽  
Patrica Thompson ◽  
Henry Thomas Stelfox ◽  
...  

IntroductionDelirium is a common complication of critical illness, associated with negative patient outcomes. Preventive or therapeutic interventions are mostly ineffective. Although relaxation-inducing approaches may benefit critically ill patients, no well-designed studies target delirium prevention as a primary outcome. The objective of this study is to assess feasibility and treatment effect estimates of a multimodal integrative intervention incorporating relaxation, guided imagery and moderate pressure touch massage for prevention of critical illness delirium and for related outcomes.Methods and analysisRandomised, controlled, single-blinded trial with two parallel groups (1:1 allocation: intervention and standard care) and stratified randomisation (age (18–64 years and ≥65 years) and presence of trauma) with blocking, involving 104 patients with Intensive Care Delirium Screening Checklist (ICDSC): 0–3 recruited from two academic intensive care units (ICUs). Intervention group participants receive the intervention in addition to standard care for up to five consecutive days (or until transfer/discharge); control group participants receive standard care and a sham intervention. We will assess predefined feasibility outcomes, that is, recruitment rates and protocol adherence. The primary clinical outcome is incidence of delirium (ICDSC ≥4). Secondary outcomes include pain scores, inflammatory biomarkers, heart rate variability, stress and quality of life (6 weeks and 4 months) post-ICU discharge. Feasibility measures will be analysed descriptively, and outcomes will be analysed longitudinally. Estimates of effects will be calculated.Ethics and disseminationThe study has received approval from the Human Research Ethics Board, University of Alberta. Results will inform the design of a future multicentre trial.Trial registration numberNCT02905812; Pre-results.


Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Jonathan Grip ◽  
Tobias Falkenström ◽  
Panuwat Promsin ◽  
Jan Wernerman ◽  
Åke Norberg ◽  
...  

Abstract Background Plasma lactate concentrations and their trends over time are used for clinical prognosis, and to guide treatment, in critically ill patients. Although heavily relied upon for clinical decision-making, lactate kinetics of these patients is sparsely studied. Aim To establish and validate a feasible method to study lactate kinetics in critically ill patients. Methods Healthy volunteers (n = 6) received a bolus dose of 13C-labeled lactate (20 μmol/kg body weight), and 43 blood samples were drawn over 2 h to determine the decay in labeled lactate. Data was analyzed using non-compartmental modeling calculating rates of appearance (Ra) and clearance of lactate. The area under the curve (AUC) was calculated using a linear-up log-down trapezoidal approach with extrapolation beyond 120 min using the terminal slope to obtain the whole AUC. After evaluation, the same protocol was used in an unselected group of critically ill patients (n = 10). Results Ra for healthy volunteers and ICU patients were 12.8 ± 3.9 vs 22.7 ± 11.1 μmol/kg/min and metabolic clearance 1.56 ± 0.39 vs 1.12 ± 0.43 L/min, respectively. ICU patients with normal lactate concentrations showed kinetics very similar to healthy volunteers. Simulations showed that reducing the number of samples from 43 to 14 gave the same results. Our protocol yielded results on lactate kinetics very similar to previously published data using other techniques. Conclusion This simple and user-friendly protocol using an isotopically labeled bolus dose of lactate was accurate and feasible for studying lactate kinetics in critically ill ICU patients. Trial registration ANZCTR, ACTRN12617000626369, registered 8 March 2017. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372507&isReview=true


2006 ◽  
Vol 91 (11) ◽  
pp. 4381-4386 ◽  
Author(s):  
Stefan Jochberger ◽  
Nils G. Morgenthaler ◽  
Viktoria D. Mayr ◽  
Günter Luckner ◽  
Volker Wenzel ◽  
...  

Abstract Context: Determination of arginine vasopressin (AVP) concentrations may be helpful to guide therapy in critically ill patients. A new assay analyzing copeptin, a stable peptide derived from the AVP precursor, has been introduced. Objective: Our objective was to determine plasma copeptin concentrations. Design: We conducted a post hoc analysis of plasma samples and data from a prospective study. Setting: The setting was a 12-bed general and surgical intensive care unit (ICU) in a tertiary university teaching hospital. Patients: Our subjects were 70 healthy volunteers and 157 ICU patients with sepsis, with systemic inflammatory response syndrome (SIRS), and after cardiac surgery. Interventions: There were no interventions. Main Outcome Measures: Copeptin plasma concentrations, demographic data, AVP plasma concentrations, and a multiple organ dysfunction syndrome score were documented 24 h after ICU admission. Results: AVP (P < 0.001) and copeptin (P < 0.001) concentrations were significantly higher in ICU patients than in controls. Patients after cardiac surgery had higher AVP (P = 0.003) and copeptin (P = 0.003) concentrations than patients with sepsis or SIRS. Independent of critical illness, copeptin and AVP correlated highly significantly with each other. Critically ill patients with sepsis and SIRS exhibited a significantly higher ratio of copeptin/AVP plasma concentrations than patients after cardiac surgery (P = 0.012). The American Society of Anesthesiologists’ classification (P = 0.046) and C-reactive protein concentrations (P = 0.006) were significantly correlated with the copeptin/AVP ratio. Conclusions: Plasma concentrations of copeptin and AVP in healthy volunteers and critically ill patients correlate significantly with each other. The ratio of copeptin/AVP plasma concentrations is increased in patients with sepsis and SIRS, suggesting that copeptin may overestimate AVP plasma concentrations in these patients.


2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Kim C. M. van der Elst ◽  
Anette Veringa ◽  
Jan G. Zijlstra ◽  
Albertus Beishuizen ◽  
Rob Klont ◽  
...  

ABSTRACT In critically ill patients, drug exposure may be influenced by altered drug distribution and clearance. Earlier studies showed that the variability in caspofungin exposure was high in intensive care unit (ICU) patients. The primary objective of this study was to determine if the standard dose of caspofungin resulted in adequate exposure in critically ill patients. A multicenter prospective study in ICU patients with (suspected) invasive candidiasis was conducted in the Netherlands from November 2013 to October 2015. Patients received standard caspofungin treatment, and the exposure was determined on day 3 of treatment. An area under the concentration-time curve from 0 to 24 h (AUC0–24) of 98 mg · h/liter was considered adequate exposure. In case of low exposure (i.e., <79 mg · h/liter, a ≥20% lower AUC0–24), the caspofungin dose was increased and the exposure reevaluated. Twenty patients were included in the study, of whom 5 had a positive blood culture. The median caspofungin AUC0–24 at day 3 was 78 mg · h/liter (interquartile range [IQR], 69 to 97 mg · h/liter). A low AUC0–24 (<79 mg · h/liter) was seen in 10 patients. The AUC0–24 was significantly and positively correlated with the caspofungin dose in mg/kg/day (P = 0.011). The median AUC0–24 with a caspofungin dose of 1 mg/kg was estimated using a pharmacokinetic model and was 114.9 mg · h/liter (IQR, 103.2 to 143.5 mg · h/liter). In conclusion, the caspofungin exposure in ICU patients in this study was low compared with that in healthy volunteers and other (non)critically ill patients, most likely due to a larger volume of distribution. A weight-based dose regimen is probably more suitable for patients with substantially altered drug distribution. (This study has been registered at ClinicalTrials.gov under registration no. NCT01994096.)


2019 ◽  
Vol 55 (1) ◽  
pp. 1901044 ◽  
Author(s):  
Shuo Liu ◽  
Chunxue Wang ◽  
Gary Green ◽  
Hanjing Zhuo ◽  
Kathleen D. Liu ◽  
...  

Shorter peripheral blood leukocyte (PBL) telomere length (TL) has been associated with poor outcomes in various chronic lung diseases. Whether PBL-TL is associated with survival from critical illness was tested in this study.We analysed data from a prospective observational cohort study of 937 critically ill patients at Vanderbilt University Medical Center (VUMC). PBL-TL was measured using quantitative PCR of DNA isolated from PBLs. Findings were validated in an independent cohort of 394 critically ill patients with sepsis admitted to the University of California San Francisco (UCSF).In the VUMC cohort, shorter PBL-TL was associated with worse 90-day survival (adjusted hazard ratio (aHR) 1.3, 95% CI 1.1–1.6 per 1 kb TL decrease; p=0.004); in subgroup analyses, shorter PBL-TL was associated with worse 90-day survival for patients with sepsis (aHR 1.5, 95% CI 1.2–2.0 per 1 kb TL decrease; p=0.001), but not trauma. Although not associated with development of acute respiratory distress syndrome (ARDS), among ARDS subjects, shorter PBL-TL was associated with more severe ARDS (OR 1.7, 95% CI 1.2–2.5 per 1 kb TL decrease; p=0.006). The associations of PBL-TL with survival (adjusted HR 1.6, 95% CI 1.2–2.1 per 1 kb TL decrease; p=0.003) and risk for developing severe ARDS (OR 2.5, 95% CI 1.1–6.3 per 1 kb TL decrease; p=0.044) were validated in the UCSF cohort.Short PBL-TL is strongly associated with worse survival and more severe ARDS in critically ill patients, especially patients with sepsis. These findings suggest that telomere dysfunction may contribute to outcomes from critical illness.


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