Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery.

Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein ß (S100ß), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00-1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1ß, and S100ß levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.

Duration of Surgery and Intraoperative Blood Pressure Management Are Modifiable Risk Factors for Postoperative Neurocognitive Disorders After Spine Surgery: Results of the Prospective CONFESS Study.

STUDY DESIGN: Prospective quasi-experimental observational study. OBJECTIVE: The objective of this study was to evaluate whether duration of surgery is a modifiable risk factor for postoperative delirium (POD) after spine surgery and explore further modifiable risk factors. In addition, we sought to investigate the association between POD and postoperative cognitive dysfunction and persistent neurocognitive disorders. SUMMARY OF BACKGROUND DATA: Advances in spine surgery enable technically safe interventions in elderly patients with disabling spine disease. The occurrence of POD and delayed neurocognitive complications ( e.g. postoperative cognitive dysfunction/persistent neurocognitive disorder) remain a concern since these contribute to inferior functional outcomes and long-term care dependency after spine surgery. MATERIALS AND METHODS: This prospective single-center study recruited patients aged 60 years or above and scheduled for elective spine surgery between February 2018 and March 2020. Functional (Barthel Index, BI) and cognitive outcomes [Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery; telephone Montréal Cognitive Assessment] were assessed at baseline, three (V3), and 12 months postoperatively. The primary hypothesis was that the duration of surgery predicts POD. Multivariable predictive models of POD included surgical and anesthesiological parameters. RESULTS: Twenty-two percent of patients developed POD (n=22/99). In a multivariable model, duration of surgery [OR adj =1.61/h (95% CI, 1.20-2.30)], age [OR adj =1.22/yr (95% CI, 1.10-1.36)], and baseline deviations of intraoperative systolic blood pressure [25th percentile: OR adj =0.94/mm Hg (95% CI, 0.89-0.99); 90th percentile: OR adj =1.07/mm Hg (95% CI, 1.01-1.14)] were significantly associated with POD. Postoperative cognitive scores generally improved (V3, ΔCERAD total z -score: 0.22±0.63). However, this positive group effect was counteracted by POD [beta: -0.87 (95% CI, -1.31 to 0.42)], older age [beta: -0.03/yr (95% CI, -0.05 to 0.01)], and lack of functional improvement [ΔBI; beta: -0.04/point (95% CI, -0.06 to 0.02)]. Cognitive scores at twelve months remained inferior in the POD group, adjusted for baseline cognition/age. CONCLUSIONS: This study identified distinct neurocognitive effects after spine surgery, which are influenced by perioperative risk factors. Potential cognitive benefits are counteracted by POD, rendering its prevention critical in an aging population.

Correction: Evaluating Mechanisms of Postoperative Delirium and Cognitive Dysfunction Following Elective Spine Surgery in Elderly Patients (CONFESS): Protocol for a Prospective Observational Trial.

[This corrects the article DOI: 10.2196/15488.].

Evaluating Mechanisms of Postoperative Delirium and Cognitive Dysfunction Following Elective Spine Surgery in Elderly Patients (CONFESS): Protocol for a Prospective Observational Trial.

BACKGROUND: Elderly people are at particular high risk for postoperative delirium (POD) following spine surgery, which is associated with longer hospital stays, higher costs, risk for delayed complications, long-term care dependency, and cognitive dysfunction (POCD). It is insufficiently understood which mechanisms and risk factors contribute to the development of POD and POCD following these major but plannable surgeries. OBJECTIVE: This study aims to identify modifiable risk factors in spine surgery. A better understanding thereof would help adapt medical management and surgical strategies to individual risk profiles. METHODS: This is a single-center observational study jointly conducted by the departments of neurosurgery, neurology, and anesthesiology at a tertiary care hospital in Germany. All patients aged 60 years and older presenting to the neurosurgery outpatient clinic or ward for elective spine surgery are screened for eligibility. Exclusion criteria include presence of neurodegenerative or history of psychiatric disease and medication with significant central nervous system activity (eg, antidepressants, antipsychotics, sedatives). Surgical and anesthetic procedures including duration of surgery as primary end point of this study are thoroughly documented. All patients are furthermore evaluated for their preoperative cognitive abilities by a number of tests, including the Consortium to Establish a Registry for Alzheimer's Disease Plus test battery. Physical, mental, and social health and well-being are assessed using the Patient-Reported Outcome Measurement Information System Profile 29 and Hospital Anxiety and Depression Scale. Patients additionally receive preoperative cerebrovascular ultrasound and structural and functional brain imaging. The immediate postoperative period includes screening for POD using the Nursing Delirium Screening Scale and validation through Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria. We furthermore investigate markers of (neuro)inflammation (eg, interleukins, C-reactive protein, tumor necrosis factor alpha). Preoperative examinations are repeated 3 months postoperatively to investigate the presence of POCD and its mechanisms. Statistical analyses will compare delirious and nondelirious patients for predictors of immediate (POD) and delayed (POCD) cognitive dysfunction. RESULTS: This is the first study to prospectively evaluate risk factors for POD and POCD in spine surgery. Recruitment is ongoing, and data collection is estimated to be finished with the inclusion of 200 patients by mid-2020. CONCLUSIONS: The identification of mechanisms, possibly common, underlying POD and POCD would be a major step toward defining effective interventional strategies early in or even before the postoperative period, including the adaptation of surgical strategies to individual risk profiles. TRIAL REGISTRATION: ClinicalTrials.gov NCT03486288; https://clinicaltrials.gov/ct2/show/NCT03486288. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15488.

Computerized 4-choice reaction time test for the measurement of psychomotor recovery after general anesthesia.

The recovery of patients after general anesthesia is usually estimated by using clinical scores. Since there is a lack of objective methods for assessing psychomotor recovery, the aim of this study was to evaluate three psychological tests for this purpose. Patients, scheduled for ambulatory gynecological surgery, underwent 3 standard psychological tests before (T1), 15 min after the surgery (T2) and on discharge from the recovery room (T3). The tests used were Wechsler memory scale (test 1, working memory capacity), d2-test (test 2, concentration endurance) and computer-based 4-choice-reaction time (4CRT, test 3, reaction time) as well as Postanesthesia Discharge Scoring System (PADSS). The same test battery was used in healthy female volunteers, all test results were compared at the different time points. In 109 patients, working memory capacity and concentration (tests 1 and 2) decreased, the reaction time (test 3) was prolonged at T2 in comparison with T1 and T3 (P < 0.01). PADSS increased from 8 (T2) to 10 (T3) (medians, P < 0.001). Fifty-seven healthy volunteers demonstrated a practice effect in all 3 tests through the course of the study (P <0.01). 4CRT test had shortest duration and enabled computerized data processing. All three tests objectively assess the recovery of psychomotor function in patients after general anesthesia, the computer-based 4CRT seems to be the most convenient for the clinical routine.

Auricular acupuncture for treatment of preoperative anxiety in patients scheduled for ambulatory gynaecological surgery: a prospective controlled investigation with a non-randomised arm.

OBJECTIVE: Auricular acupuncture (AA) is a promising alternative treatment for situational anxiety. The aim of this pilot investigation was to test the acceptability and feasibility of AA as a treatment for preoperative anxiety (PA) in preparation for a subsequent randomised controlled trial. METHODS: AA was offered for treatment of PA to female patients who were scheduled for ambulatory gynaecological surgery. In patients who agreed, indwelling fixed needles were applied bilaterally at the points MA-IC1, MA-TF1, MA-SC, MA-AH7 and MA-T the day before surgery. Patients who declined AA but agreed to be examined constituted the control group (no intervention). State anxiety (primary outcome) was measured using the State-Trait-Anxiety Inventory (STAI) before AA (time I), the evening before surgery (time II) and immediately before surgery (time III). Anxiety was measured with a 100 mm visual analogue scale (VAS-100); heart rate, blood pressure and serum cortisol were also quantified. RESULTS: Data from 62 patients (32 with AA and 30 with no intervention) were analysed. Whereas preoperative anxiety was reduced after AA the evening before surgery (P<0.01), anxiety levels in the control group increased from the first to the last measurement (P<0.001). Secondary outcomes were comparable between the patients from both groups. CONCLUSIONS: AA was acceptable and feasible as a treatment for preoperative anxiety. The results were used for the sample size calculation of a subsequent randomised controlled clinical trial. TRIAL REGISTRATION NUMBER: NCT02656966; Results.

Auricular Acupoints with Reduced Skin Resistance: Detection in Patients Scheduled for Hip Arthroplasty.

Objective: The detection of auricular acupuncture (AA) points by measuring electrical skin resistance (ESR) is often used in diagnostics and therapy; however, systematic investigations of ESR in AA points are rare. The aim of this study was to examine the frequency of detection of AA points with reduced ESR in patients scheduled for unilateral hip arthroplasty. Materials and Methods: Data were obtained from 2 prospective clinical trials, which studied the perioperative analgesic effects of AA in patients with unilateral degenerative hip osteoarthritis. Three AA points (MA-TF1, MA-AH4, and MA-IC1) were examined in these patients before arthroplasty surgery using a SVESA (Neuralstift SVESA 1070, SVESA, Muenchen, Germany) neural pen. The frequency of AA points detection on the ipsi- and contralateral sides of the affected hip joint was registered and analyzed with a χ2 test. Results: The data of 114 patients (60 females) were available for analysis. AA points with lower ESR were detected more frequently on the side ipsilateral to the affected joint rather than on the contralateral side: 81% versus 37% of patients (P < 0.0001). None of the AA points could be identified at all in 13% of patients with diabetes mellitus versus 3% of patients without diabetes mellitus (P = 0.07). Conclusions: AA points with low ESR were detected more frequently on the side ipsilateral to the underlying pathology. This finding is in agreement with neurophysiologic data. The therapeutic value of this finding should be clarified in future studies.

The Impact of Integrated Multidisciplinary Palliative Care Program on Symptoms in Patients at the Palliative Care Ward-An Audit and a Protocol of Prospective Controlled Investigation.

An integrated multidisciplinary palliative care (IMPC) program is a promising tool to improve symptom control in patients at the end of life. The aim was to study the feasibility of the IMPC program in patients at the palliative care (PC) ward. A retrospective audit, using the extended Edmonton Symptom Assessment Scale (ESAS), was conducted on the PC ward of the university hospital. Consecutive patients who were admitted for the IMPC program during 1 year were considered. One hundred forty-eight cases (93% with underlying cancer) were analyzed. The intensity of pain levels, nausea, vomiting, shortness of breath, and sleep disorders decreased at least by 50% ( P < .0001) during the 13 (median) days of IMPC. Integrated multidisciplinary PC program was associated with symptom improvements in patients at the PC ward. The information generated supports sample size calculation for a prospective controlled trial.

Feasibility and safety of dilatational tracheotomy using the rigid endoscope: a multicenter study.

BACKGROUND: Fiberoptic tracheo-bronchoscopy is the most commonly used procedure for percutaneous dilational tracheotomy (PDT). However, PDT can be associated with major complications, including death. Furthermore it is unclear, whether the tracheal ring fractures may contribute to the development of tracheal stenosis after PDT nor whether tracheal ring fractures can be prevented by using a rigid endoscope for this procedure. The purpose of this study was to evaluate the feasibility of and the incidence of complications for PDT using the rigid tracheotomy endoscope (TED). METHODS: In a prospective multicenter observational study from 2006 to 2010, 180 adult patients in intensive care and those scheduled for ear, nose and throat surgery underwent PDT using TED. Data collection was performed using a structured protocol. The patients were observed according to PDT phase (phase 1: puncture, phase 2: dilatation and phase 3: cannula insertion). The descriptive data are given as the number (percent) of cases and the mean ± standard deviation (SD) where appropriate. The relationships between dichotomous and categorical parameters were analyzed using the chi-square test. P values ≤ 0.05 were considered significant. RESULTS: PDT was performed in 179 patients. The procedure time was 14.8 ± 6.2 (mean ± SD) minutes. Pneumothorax or procedure-related lethal complications did not occur. Other adverse events included tracheal ring fractures (17.1%), desaturations (6.8%), special incidents (6.2%), bleeding (5.5%), anesthesia complications (4.5%) and posterior tracheal wall injuries (1.1%). CONCLUSION: The use of TED in PDT is feasible, and the incidence of complications and adverse events was comparable with that of PDT using the flexible endoscope. Tracheal ring fractures in PDT cannot be avoided by the use of a rigid endoscope. With TED, the airway always remains open thus the use of jet ventilation via the TED during PDT is possible.

Vagal sensory evoked potentials disappear under the neuromuscular block - an experimental study.

BACKGROUND: Transcutaneous vagal nerve stimulation is a promising treatment modality in patients suffering mood disorders and chronic pain, however, the mechanisms are still to be elucidated. A recently developed technique of EEG responses to electrical stimulation of the inner side of the tragus suggests that these responses are far field potentials, generated in the vagal system - Vagal Sensory Evoked Potentials (VSEP). OBJECTIVE: To reproduce the VSEP technique free from myogenic artifacts. METHODS: Fourteen ASA I-II patients scheduled for elective surgery in standardized Total Intravenous Anesthesia (TIVA) were enrolled. Transcutaneous electrical stimulation was applied to the inner side of the right tragus. Averaged EEG responses were recorded from the electrode positions C4-F4 and T4-O2 before and after induction of TIVA, during the maximal effect of the non-depolarizing muscle relaxing agent, cis-atracurium (C-AR) and after recovery from C-AR under TIVA. RESULTS: Typical response curves with P1, N1 and P2 peaks could be reproduced in all patients before and after anesthesia induction. The response curves disappeared during the C-AR action and re-appeared after recovery from C-AR under TIVA. CONCLUSION: The disappearance of the scalp responses to electrical tragus stimulation under the neuromuscular block suggests a muscular origin of these potentials.

The effect of auricular acupuncture on fentanyl requirement during hip arthroplasty: a randomized controlled trial.

OBJECTIVES: Although auricular acupuncture (AA) is suggested to be effective in treatment of pain, it has not yet been used for intraoperative analgesia. Therefore, we studied whether the AA reduces intraoperative analgesic requirement during total hip arthroplasty (THA). METHODS: One hundred and twenty patients scheduled for THA were enrolled in this patient-anesthesiologist-blinded study. The patients were randomly assigned to receive needling of specific AA points or a sham procedure (needling of 3 nonacupoints on the ear helix) ipsilateral to the surgery site. Fixed indwelling AA needles were placed in the evening before THA and withdrawn on the day after surgery. The patients received general anesthesia with desflurane, which end-tidal concentration was kept within 3.5 volume % to 5.5 volume % to maintain the Bispectral Index within 40% to 55%. The anesthesiologists were asked to titrate fentanyl to keep the heart rate and blood pressure within 20% of baseline values. The primary outcome was fentanyl amount given during surgery. The secondary outcome measures were incidence of nausea and vomiting and time to first request of analgesics in the recovery room. The success of patients' and anesthesiologist blinding was also documented. RESULTS: The data of fentanyl requirement of 116 patients were available for the final analysis. Patients from AA group required 15% less fentanyl during surgery than the controls (4.6±1.1 µg/kg vs. 5.2±1.3 µg/kg; mean±SD; P=0.008). Demographic data and secondary outcome measures were comparable in both groups. DISCUSSION: Regarding the modest clinical effect, AA should be further investigated for its clinical usefulness for complementary analgesia during the surgery.

Acute high-dose sodium selenite administration improves intestinal microcirculation without affecting cytokine release in experimental endotoxemia.

We evaluated the effects of acute high-dose sodium selenite (SEL) administration on the intestinal microcirculation and the release of the cytokines TNF-alpha, IL-1beta, IL-6 and IL-10 in experimental endotoxemia (induced by lipopolysaccharide-LPS). Three groups of animals (n=30) were studied: control group, endotoxemic group (15 mg kg(-1) i.v. LPS from E. coli) and SEL-treated LPS group (100 microg kg(-1) SEL i.v.). SEL treatment resulted in a significant reduced number of firmly adhering leukocytes in intestinal submucosal venules and reduced significantly the impairment of the intestinal functional capillary density. Despite of the improvement of microcirculatory parameters, we did not detect any changes in the pattern of cytokine release. In conclusion, administration of high-dose sodium SEL attenuates leukocyte adhesion and improves capillary perfusion within the intestinal microcirculation without affecting release of the cytokines TNF-alpha, IL-1beta, IL-6 and IL-10 in experimental endotoxemia.

Effects of activated protein C on the mesenteric microcirculation and cytokine release during experimental endotoxemia.

PURPOSE: Activated protein C (APC) is the first anti-inflammatory drug to be approved for the treatment of severe sepsis. However, the underlying mechanisms are not completely elucidated. Therefore, the aim of our study was to evaluate the effects of APC on the microcirculation (mesenteric leukocyte-endothelial interaction, plasma extravasation) using intravital microscopy (IVM) and on cytokine release during experimental endotoxemia in rats. METHODS: We divided forty, male, Lewis rats into four groups (n = 10 per group): Controls, LPS (15 mg x kg(-1) lipopolysaccharide iv), APC (2 mg x kg(-1) APC iv), and LPS+APC. We determined mesenteric leukocyte-endothelial interactions and plasma extravasation at zero, one and two hours following administration of LPS and APC by IVM. Plasma levels of tumour necrosis factor-alpha, IL-1beta, interleukin (IL)-6, and IL-10 were measured at zero and at two hours. RESULTS: Leukocyte adherence (-74%) and plasma extravasation (-28%) during endotoxemia were diminished significantly following APC treatment, compared to untreated LPS animals (P = 0.0001 and P = 0.0004, respectively). Interleukin-1ss release was also significantly reduced by APC treatment (2567.4 +/- 320.9 pg x mL(-1) in the LPS group vs 1626.1 +/- 427.2 pg x mL(-1) in the LPS+APC group; P = 0.001). CONCLUSION: These rodent experiments showed that APC treatment significantly attenuated deterioration of the mesenteric microcirculation and systemic IL-1ss release caused by endotoxin challenge. Because of the crucial role of the microcirculation in ongoing sepsis pathogenesis and multiple organ dysfunction syndrome, these effects may be of clinical importance.

s-Carboxymethylcysteine inhibits carbachol-induced constriction of epithelium-denuded rat and human airway preparations.

1. The effects of s-carboxymethyl-L-cysteine (S-CMC), either administered orally to rats or incubated with tissue preparations from rats and humans, on isometric contractions of tracheal smooth muscle were investigated in the present study using an improved in vitro model of tracheal tube or ring preparations. The involvement of the tracheal epithelium in the observed effects was also investigated. 2. The experimental model permitted selective perfusion of the airway tube, luminal-IN or serosal-OUT, and measurement of airway smooth muscle contraction or relaxation in preparations with (+) or without (-) epithelium (Ep), excluding direct effects of airway mucus. 3. We found that oral pretreatment of rats with S-CMC (mixed with water; 200 mg/kg per day for 2 weeks), but not short pre-incubation of preparations in vitro (10(-3) mol/L S-CMC for 1 h), diminished the sensitivity of -Ep preparations to carbachol compared with controls (EC(50) (-log(10) mol/L) values: 5.5 +/- 0.1 vs 5.8 +/- 0.1, respectively, for IN perfusion (P < 0.005); 5.6 +/- 0.1 vs 5.9 +/- 0.1, respectively, for OUT perfusion (P < 0.005)), whereas the sensitivity of preparations to aminophylline was not affected. Normal sensitivity to carbachol stimulation was re-established if preparations were pre-incubated with capsaicin. 4. It was also found that longer pre-incubation (4 h) of ring-preparations of human bronchus with S-CMC (10(-5) mol/L) in vitro resulted in a diminished response to carbachol stimulation. 5. In conclusion, S-CMC had small inhibitory effects on the sensitivity of rat and human airway smooth muscle to carbachol, particularly in endothelium-denuded preparations. Whether the epithelium was responding to S-CMC by producing some contracting factor(s) requires further investigation.

Millimetre wave therapy for pain relief after total knee arthroplasty: a randomised controlled trial.

Millimetre wave therapy (MWT) is a promising complementary method for pain relief, however rigorous investigations of its effectiveness are needed. The purpose of this study was to examine if MWT can reduce opioid requirement compared to sham procedure applied for relief of acute pain in patients after total knee arthroplasty (TKA). Eighty patients undergoing TKA were randomly assigned to receive MWT or sham procedure. Patients and evaluators were blinded to the group allocation. MWT consisted of six sessions, each session of 30 min duration. During each session the knee wound was exposed to electromagnetic waves with frequency 50-75 GHz and power density 4.2 mW/cm(2). Postoperative analgesia with piritramide, a weak opioid with 0.7 potency of morphine delivered via patient-controlled analgesia pump, was directed to achieve pain intensity of less than 40 on a 100 mm visual analogue scale (VAS). The primary outcome measure was postoperative piritramide requirement for three days after surgery. Secondary outcome measures were: total ibuprofen requirement from the fourth postoperative day to discharge; success of patients' blinding; patients' satisfaction with pain relief; incidence of analgesia-related side effects; heart rate and blood pressure. Piritramide requirement was similar in both groups whereby all patients reported adequate pain relief measured on a VAS. Secondary outcome measures were also comparable in both groups. The majority of patients in both groups believed they had received true MWT and wanted to repeat it in future. Millimetre waves applied to surfaces of surgical wounds did not reduce opioid requirement compared to the sham procedure after TKA.

Auricular acupuncture for pain relief after ambulatory knee surgery: a randomized trial.

BACKGROUND: Auricular acupuncture is a promising method for postoperative pain relief. However, there is no evidence for its use after ambulatory surgery. Our aim was to test whether auricular acupuncture is better than invasive needle control for complementary analgesia after ambulatory knee surgery. METHODS: One hundred and twenty patients undergoing ambulatory arthroscopic knee surgery under standardized general anesthesia were randomly assigned to receive auricular acupuncture or a control procedure. Fixed indwelling acupuncture needles were inserted before surgery and retained in situ until the following morning. Postoperative rescue analgesia was directed to achieve pain intensity less than 40 mm on a 100-mm visual analogue scale. The primary outcome measure was the postoperative requirement for ibuprofen between surgery and examination the following morning. RESULTS: Intention-to-treat analysis showed that patients from the control group (n = 59) required more ibuprofen than patients from the auricular acupuncture group (n = 61): median (interquartile range) 600 (200-800) v. 200 (0-600) mg (p = 0.012). Pain intensity on a visual analogue scale was similar in both groups at all time points registered. The majority of patients in both groups believed that they had received true acupuncture and wanted to repeat it in future. INTERPRETATION: Auricular acupuncture reduced the requirement for ibuprofen after ambulatory knee surgery relative to an invasive needle control procedure.

Activated protein C improves intestinal microcirculation in experimental endotoxaemia in the rat.

INTRODUCTION: Successful treatment of severe sepsis and septic shock remains a major challenge in critical care medicine. The recently introduced recombinant human activated protein C (APC) remarkably improved the outcome of septic patients. The influence of APC on intestinal circulation is still poorly understood. Therefore, the present study aimed to investigate the effects of APC on intestinal microcirculation during experimental endotoxaemia in rats by using intravital microscopy. METHODS: A total of 44 male Lewis rats were randomly assigned to receive intravenous injections of 15 mg/kg lipopolysaccharide alone (LPS) (n = 11) or LPS followed by subsequent injection of 2 mg/kg recombinant human APC (LPS + APC) (n = 11), whereas control animals received either APC (n = 11) or saline (n = 11). Animals underwent observations of functional capillary density and leucocyte adherence on venular endothelium in the microcirculation of the intestinal wall by means of intravital fluorescence microscopy. Indicators of macrocirculation as well as plasma levels of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-10 were measured. RESULTS: Although APC administration of both LPS-treated and control rats did not change macrocirculation or release of inflammatory cytokines, it increased mucosal and muscular functional capillary density (p < 0.001 and p < 0.05, respectively) and reduced the number of firmly adhering leucocytes in intestinal submucosal V1 and V3 venules (p < 0.01) in LPS + APC-treated compared with LPS-treated animals, which did not receive APC. No remarkable differences that could be attributed to APC treatment were observed between the two control groups. CONCLUSION: APC administration during experimental endotoxaemia improved intestinal microcirculation by protecting functional capillary density as a measure of microvascular perfusion and exerted anti-inflammatory effects by reducing leucocyte adherence to the endothelium in submucosal venules. Therefore, beneficial effects of APC in septic patients might be due, in part, to improved intestinal microcirculation.

Akrinor-induced relaxation of pig coronary artery in vitro is transformed into alpha1-adrenoreceptor-mediated contraction by pretreatment with propranolol.

Akrinor (AKR), a mixture of theodrenaline (TDR) and cafedrine (CDR), is a sympathomimetic agent used to counter transitory hypotension. Although some cases of vascular complications associated with AKR have been reported there are no experimental data about its direct effects on coronary arteries. The effects of AKR, TDR, CDR, and ephedrine (EDR) were studied on the isometric contraction of the ring preparations of pig coronary arteries precontracted with KCl. The influence of endothelium removal and preincubation with nonselective beta-adrenoreceptor antagonist propranolol (PROP), alpha(1)-adrenoreceptor antagonist prazosin, dopamine receptor antagonist SCH 23390, and adenosine receptor antagonist CGS 15943 were also tested. AKR, TDR, and CDR produced relaxation of the preparations. Preparations without endothelium were more sensitive to AKR relaxing effects. EDR produced an increase of vascular ring tonus. AKR, TDR, and EDR produced contraction in preparations pretreated with PROP. Higher concentrations of AKR relaxed PROP-pretreated preparations. AKR-induced contraction could be prevented by pretreatment with prazosin. Dopamine and adenosine receptor antagonists did not influence relaxing effects of AKR. In conclusion, AKR and its constituents induce the relaxation of pig coronary artery preparations precontracted with KCl. The observed contraction in the preparations pretreated with PROP was probably due to stimulation of unmasked alpha(1)-adrenoreceptors.

Auricular acupuncture reduces intraoperative fentanyl requirement during hip arthroplasty--a randomized double-blinded study.

We studied whether auricular acupuncture reduces analgesic requirement during total hip arthroplasty. Sixty-four patients were enrolled in this patient/anesthesiologist-blinded study according to inclusion criteria. They were randomly assigned to receive acupuncture with indwelling fixed needles (points lung, shenmen, forehead and hip) or sham procedure (4 non-acupuncture points on the helix). Surgery was performed under standardized general anesthesia with volatile anesthetic isoflurane and opioid analgesic fentanyl, whereby isoflurane concentration was kept constant. Demographics, fentanyl requirement, duration of general anesthesia and success of patients' blinding were registered. Patients from the acupuncture group required 21% less fentanyl during surgery than those who received sham procedure. Other outcome measures were similar in both groups. Auricular acupuncture reduced fentanyl requirement compared to sham procedure during hip arthroplasty.

Thermostatic tissue platform for intravital microscopy: 'the hanging drop' model.

Intravital microscopy imposes the particular problem of the combined control of the body temperature of the animal and the local temperature of the observed organ or tissues. We constructed and tested, in the rat ileum microcirculation preparation, a new organ-support platform. The platform consisted of an organ bath filled with physiological solution, and contained a suction tube, a superfusion tube, an intestine-support hand that was attached to a micromanipulator and a thermometer probe. To cover the intestine we used a cover glass plate with a plastic ring glued on its upper surface. After a routine procedure (anaesthesia, monitoring and surgery), the intestine segment (2-3 cm long) was gently exteriorized and placed on the 'hand' of the organ support. A small part of the intestine formed a small 'island' in the bath that was filled with physiological salt solution. The cover glass was secured in place. The physiological salt solution from the superfusion tube, which was pointed to the lower surface of the cover glass, formed a 'hanging drop'. The objective of the microscope was then immersed into distilled water that was formed by the cover glass plastic ring. The 'hanging drop' technique prevented any tissue quenching, ensured undisturbed microcirculation, provided for stable temperature and humidity, and permitted a clear visual field.