Early suppression of peripheral mononuclear blood cells in sepsis in response to stimulation with cytomegalovirus, OKT3, and pokeweed mitogen.

Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early sepsis compared with postoperative patients. IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [days 1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients with sepsis (n = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, n = 10). In a second cohort, HLA-DRA expression was assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV (P = 0.01), OKT3 (P = 0.02), and PWM (P = 0.02 on day 5), whereas unstimulated IFNγ secretion did not differ. HLA-DRA expression was also significantly decreased in patients with sepsis at all time points (P = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as HLA-DRA expression was already decreased upon ICU admission in patients with sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with sepsis.NEW & NOTEWORTHY We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients with early sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with sepsis.

Screening for delirium after surgery: validation of the 4 A's test (4AT) in the post-anaesthesia care unit.

Postoperative delirium is common and has multiple adverse consequences. Guidelines recommend routine screening for postoperative delirium beginning in the post-anaesthesia care unit. The 4 A's test (4AT) is a widely used assessment tool for delirium but there are no studies evaluating its use in the post-anaesthesia care unit. We evaluated the performance of the 4AT in the post-anaesthesia care unit in a tertiary German medical centre. Adults who were able to provide informed consent, were not scheduled for postoperative intensive care, and who did not have dementia or severe neuropsychiatric disorders underwent screening by trained research staff with the Nurse Delirium Screening Scale and a new German translation of the 4AT in a random order at the point of discharge from the post-anaesthesia care unit. Reference standard assessment of delirium was psychiatric evaluation by experienced clinicians. Five hundred and forty-three patients (mean age (SD) 52 (18) years) were analysed; 22 (4.1%) patients developed delirium. The sensitivity and specificity of the 4AT were 95.5% (95%CI 77.2-99.9) and 99.2% (95%CI 98.1-99.8), respectively. The area under the receiver operator characteristic curve was 0.998 (95%CI 0.995-1.000). The Nursing Delirium Screening Scale had a sensitivity of 27.3% (95%CI 10.7-50.2) and specificity of 99.4% (95%CI 98.3-99.9), with an area under the curve of 0.761 (95%CI 0.629-0.894). These findings suggest that the 4AT is an effective and robust instrument for delirium detection in the post-anaesthesia care unit.

Misleading symptoms and successful noninvasive rewarming of a patient with severe hypothermia (23.1 °C).

Accidental severe hypothermia is a medical emergency in which symptoms may include coma, apnea, pulmonary edema, ventricular dysrhythmia or asystole. Despite optimal treatment, mortality remains high. This article reports a case of severe hypothermia in a geriatric hypothyroid patient, where despite a body core temperature of 23.1 °C the patient presented conscious and with stable vital signs, pronounced motor response, and a Glasgow Coma Scale score of 9. Blood gas analysis (alpha stat at 37 °C) indicated sufficient pulmonary function. A noninvasive rewarming approach proved successful and resulted in discharge without sequelae. This case highlights that symptoms considered pathognomonic for specific stages of hypothermia should be interpreted with great care in clinical practice. Hypothyroidism may have contributed to this uncommon clinical presentation. Body temperature needs to be taken into account when interpreting blood gas analyses. Even at the stage of severe hypothermia, noninvasive forced-air warming enabled rewarming without complications.

[Epigenetics : Important aspects for anesthesiologists, pain and intensive care physicians]. / Epigenetik : Wichtiges für Anästhesisten, Schmerz- und Intensivmediziner.

Epigenetics, i.e. an altered reading of the genome without altering the genes themselves is a growing scientific field. A distinction is made between changes in the DNA by modification of the histones and non-coding RNA that alter the messenger (m)RNAs. Epigenetic modifications can be triggered by personal circumstances or other external factors and therefore influence the occurrence of diseases. Epigenetics are therefore of particular interest to anesthesiologists, pain specialists and intensive care physicians, as anesthetic drugs may have a long-term influence on protein transcription leading for example to alterations in neurocognition after anesthesia, chronification of postoperative pain and immune response in sepsis. Non-coding microRNAs known to be altered in a variety of perioperatively relevant diseases e. g. heart infarct, might serve as prognostic factors of perioperative outcome. Moreover, there are ways to influence epigenetic changes through life style and certain medications. In this review article, examples of anesthesia, intensive care and pain medicine-relevant diseases and the influence of epigenetics on them are presented.

The (pro)renin receptor / ATP6ap2 is expressed in the murine hippocampus by adult and newly generated neurons.

PURPOSE: The (pro)renin receptor ((P)RR) is receptor that has been shown to be involved in developmental processes. Adult neurogenesis shares many similarities with fetal and embryonic neuronal development, but is restricted to some brain areas, including the hippocampus. We therefore investigated the expression of the (P)RR within the adult hippocampal formation and investigated whether (P)PR is expressed by adult and newly generated neurons in the dentate gyrus. METHODS: (P)PR protein expressing cells in the hippocampus were analyzed using immunohistochemistry. Double-labeling with markers for adult neurogenesis was used to investigate whether newly formed cells also express (P)PR. RESULTS: (P)PR is expressed by neuronal cells with the hippocampus. (P)RR protein is expressed during different stages of adult neurogenesis within the dentate gyrus (DG). (P)RR is not expressed by Sox2 positive neuronal stem cells, but by doublecortin positive cells located both in the subgranular zone and the granular layer of the DG. CONCLUSIONS: The results indicate that (P)PR is mainly expressed by adult neurons in the hippocampus as well as in late stages of adult neurogenesis within the hippocampus. However, to clarify the involvement of this receptor in adult hippocampal neurogenesis and neuronal cell differentiation in detail, functional analyses needed to be performed.

Venous air embolism during semi-sitting craniotomy evokes thrombocytopenia.

Venous air embolism activates platelets in vitro and can evoke platelet dysfunction in swine. We tested the hypothesis that venous air embolism during semi-sitting craniotomy induces thrombocytopenia in humans. We analysed the charts of 799 patients who had an elective craniotomy in the semi-sitting position between 1990 and June 2009. Venous air embolism occurred in 52 patients (6.5%) and was associated with a decrease in mean (SD) in platelet count from 270 (75) × 109 l⁻¹ to 194 (62) × 109 l⁻¹ (p < 0.001). In age-matched controls without venous air embolism mean (SD) platelet count did not change (254 (82) × 109 l⁻¹ vs. 250 (97) × 109 l⁻¹ (NS). While mean (SD) haematocrit fell slightly in both groups (venous air embolism: 0.40 (0.05) to 0.32 (0.04), p <0.001; no venous air embolism: 0.41 (0.04) to 0.35 (0.05), p < 0.001), normalising platelet count to haematocrit did not alter the results.

Cardiac air transit following venous air embolism and right ventricular air aspiration.

Using intra-cardiac echocardiography in anaesthetised swine we tested the hypotheses that embolised air (i) passes immediately through the right atrium into the ventricle; (ii) persists in the right ventricle for a long time; (iii) is detectable for longer within the right ventricle or main pulmonary artery than the right atrium, and (iv) right ventricular aspiration recovers more air than right atrial aspiration. Following intravenous injection of different air volumes the air appeared in the right atrium in a mean (95% CI) of 3 s (2.5-3.5 s) and almost simultaneously in the right ventricle after 5 s (3.9-6.0 s), but air persisted for longer in the right ventricle (420 s; (367-473 s)) and pulmonary artery (541 s; (475-606 s)) than in the right atrium (404 s (353-457 s)), particularly with larger air volumes and in the semi-upright position. More air was recovered via a right ventricular catheter than an atrial catheter (52% vs 25%, p < 0.01).

Venous air embolism induces both platelet dysfunction and thrombocytopenia.

BACKGROUND: In vitro, air bubbles can induce platelet activation and platelet to air bubble binding. We therefore tested in vivo the hypothesis that venous air embolism (VAE) induces (1) platelet dysfunction and (2) thrombocytopenia. METHODS: Adult swine (60.8+/-3.9 kg; n=8) were anaesthetized, mechanically ventilated, and placed in a semi-upright position. Air boli (0.5-80 ml) were injected randomly via an ear vein, and arterial blood was sampled after cumulative air dosages of 0, 80, 160, and 240 ml. Coagulation was assessed by impedance aggregometry, rotational thrombelastometry, whole blood count, plasmatic coagulation variables, and fibrinogen, d-dimer, protein C, and antithrombin plasma concentrations, respectively. RESULTS: VAE induced a 47% decrease in platelet count (303 vs. 160 nl(-1); P<0.001) over the dose range assessed, with haematocrit being unaltered. Furthermore, VAE-impaired platelet aggregation induced by adenosine diphosphate, arachidonic acid, collagen, and the thromboxan analogue U46619 over the dose range assessed independent of thrombocytopenia. (P<0.05 vs. baseline). In contrast, rotational thrombelastometry alone was quite insensitive in detecting VAE-induced coagulation changes, showing only at near lethal air dosages a prolonged clot formation time following activation with tissue factor, contact activator, and during spontaneous coagulation (P<0.05 vs. baseline). CONCLUSIONS: VAE induces both a dose-dependent decrease in platelet count and a marked decrease in platelet aggregation, independent of thrombocytopenia (P<0.05 vs. baseline).