Changes in cerebral oxygen saturation following prone positioning for orthopaedic surgery under general anaesthesia: a prospective observational study.

BACKGROUND: Prone positioning is often necessary in orthopaedic surgery. The prone position, however, may result in impaired cerebral venous drainage with a subsequent reduction in cerebral perfusion. As a consequence, cerebral hypoxia may occur with the potential for neurological impairment. OBJECTIVE: We assessed the changes in cerebral oxygen saturation with near-infrared spectroscopy using two different monitors after positioning the patient from supine to prone. DESIGN: Prospective observational study. SETTING: Primary Care University Hospital, from May 2010 to February 2011. PARTICIPANTS: Forty patients undergoing general anaesthetic procedures, of which 35 completed the investigation. Similar measurements were done in 35 volunteers, who were studied while awake. INTERVENTIONS: Near-infrared spectroscopy was measured throughout anaesthesia using INVOS (a trend monitor using two infrared wavelengths) for one hemisphere and FORE-SIGHT (a monitor using four wavelengths of laser light to calculate absolute oxygen saturation) for the other hemisphere in an alternate randomisation pattern. OUTCOME MEASUREMENTS: The primary outcome was a change in cerebral oxygen saturation of more than 5% during prone positioning. A comparison with the changes obtained in awake volunteers following similar positioning was also made. RESULTS: Cerebral oxygen saturation increased during prone positioning with INVOS 0.032% per minute (P < 0.01) and with FORE-SIGHT 0.032% per minute (P < 0.01) in anaesthetised patients. Awake volunteers showed an increase of 0.171% per minute (INVOS) and 0.082% per minute (FORE-SIGHT) during prone positioning. Comparison of INVOS with FORE-SIGHT showed a good association, with a gradient of 0.80% per 1% change (P < 0.01). CONCLUSION: Both monitors detected a small increase in cerebral oxygen saturation of less than 5% in patients undergoing orthopaedic surgery in the prone position and in awake volunteers. This small increase is of limited clinical relevance and prone positioning may be regarded as safe in terms of the maintenance of cerebral oxygen saturation. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01275898.

Robotic assisted prostatic surgery in the Trendelenburg position does not impair cerebral oxygenation measured using two different monitors: A clinical observational study.

BACKGROUND: Robotic assisted prostatic surgery is frequently used because of its reduced side-effects compared with conventional surgery. During surgery, an extreme Trendelenburg position and CO2 pneumoperitoneum are necessary, which may lead to cerebral oedema, can potentially reduce brain perfusion and therefore could impair cerebral oxygenation. Cerebral oxygen saturation can be measured non-invasively using near-infrared spectroscopy (NIRS). OBJECTIVE: The hypothesis of the present study was that steep Trendelenburg positioning during robotic assisted prostatic surgery impairs cerebral oxygen saturation measured using two different NIRS monitors. DESIGN: Clinical observational study. SETTING: Primary care university hospital, study period from March 2012 to February 2013. PATIENTS: A total of 29 patients scheduled for robotic assisted prostatic surgery in a steep Trendelenburg position. INTERVENTIONS: Cerebral oxygen saturation was measured throughout anaesthesia using the INVOS sensor (a trend monitor using two infrared wavelengths) for one hemisphere and the FORE-SIGHT sensor (a monitor using four wavelengths of laser light to calculate absolute oxygen saturation) for the other hemisphere in an alternate randomisation. MAIN OUTCOME MEASURE: Changes in cerebral oxygenation of more than 5% during surgery in the Trendelenburg position. RESULTS: The median duration of Trendelenburg positioning was 190 (interquartile range 130 to 230) min. Cerebral oxygen saturation decreased with INVOS from 74 ± 5% at baseline to a lowest value of 70 ± 4% with a slope of -0.0129 min(-1) (P < 0.01) and with FORE-SIGHT from 72 ± 5% at baseline to a nadir of 70 ± 3% with a slope of -0.008 min(-1) (P < 0.01). Comparing INVOS with FORE-SIGHT, there was a good association, with a slope of 0.86 ± 0.04 (P < 0.01). CONCLUSION: Both monitors showed a clinically irrelevant decrease in cerebral oxygen saturation of less than 5% over 4 h in a steep Trendelenburg position combined with CO2 pneumoperitoneum in patients undergoing robotic assisted prostatic surgery. This extreme positioning seems to be acceptable with regard to cerebral oxygenation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ID NCT01275898.

Influence of beach chair position on cerebral oxygen saturation: a comparison of INVOS and FORE-SIGHT cerebral oximeter.

BACKGROUND: Although beach chair position (BCP) is frequently used for shoulder surgery, a potentially detrimental influence on cerebral oxygenation is discussed. Therefore, the present study investigated changes in regional cerebral oxygen saturation (rSO2/StO2) during BCP comparing 2 different devices for near-infrared spectroscopy measurement. METHODS: Data were collected in 35 patients undergoing shoulder surgery in BCP and compared with a control group of 35 awake volunteers. The rSO2/StO2 was assessed using INVOS and FORE-SIGHT monitors. Mean arterial blood pressure (MAP), peripheral oxygen saturation (SpO2), PeCO2, FiO2, end-tidal sevoflurane concentration, and rSO2/StO2 were measured before positioning, during BCP, and in supine position after surgery. RESULTS: A decrease in rSO2/StO2 could be observed after BCP (INVOS: 76.1% supine vs. 66.7% BCP, P<0.001; FORE-SIGHT: 78.6% supine, 66.1% BCP, P<0.001), which was reversible in supine position. This decrease correlated with MAP during BCP, while in supine position no correlation was detected. In control group BCP did not influence rSO2/StO2. Changes detected with INVOS or FORE-SIGHT cerebral oximeter did not differ. CONCLUSION: BCP is associated with a decrease in rSO2/StO2 of 10% in anesthetized patients, which is reversible after repositioning. No changes occurred in supine position under general anesthesia as well as in awake subjects in BCP. This underlines the assumption that vasodilation by anesthetics in combination with BCP evoke a drop in rSO2/StO2. A strict hemodynamic management may be necessary to prevent desaturation events. Despite different technology used by the devices, the results of INVOS and FORE-SIGHT cerebral oximeters are comparable.

Cerebrovascular autoregulation in critically ill patients during continuous hemodialysis.

PURPOSE: In chronic renal failure, intermittent hemodialysis decreases cerebral blood flow velocity (CBFV); however, in critically ill patients with acute renal failure, the effect of continuous venovenous hemodialysis (CVVHD) on CBFV and cerebrovascular autoregulation (AR) is unknown. Therefore, a study was undertaken to investigate the potential effect of CVVHD on CBFV and AR in patients with acute renal failure. METHODS: This cohort study investigated 20 patients with acute renal failure who required CVVHD. In these patients, the CBFV and index of AR (Mx) were measured using transcranial Doppler before and during CVVHD. RESULTS: The median Mx values at baseline were 0.33 [interquartile range (IQR): 0.02-0.55], and during CVVHD, they were 0.20 [0.07-0.40]. The differences in Mx (CVVHD--baseline) was (median [IQR]) -0.015 [-0.19-0.05], 95% confidence interval (CI) -0.16 to 0.05. The Mx was > 0.3 in 11/20 patients at baseline measurement. Six of these patients recovered to Mx < 0.3 during CVVHD. The CBFV was (median [IQR]) 47 [36-59] cm · sec(-1) at baseline and 49 [36-66] cm · sec(-1) during CVVHD. The difference of CBFV was 0.0 [-4 - 2.7], 95% CI -2.5 to 4.2. CONCLUSION: Compared with patients with intermittent hemodialysis, CVVHD did not influence CBFV and AR in critically ill patients with acute renal failure, possibly due to lower extracorporeal blood flow, slower change of plasma osmolarity, and a lower fluid extraction rate. In a subgroup of patients with sepsis, the AR was impaired at baseline in more than half of the patients, and this was reversed during CVVHD. The trial was registered at ClinicalTrials.gov ID: NCT01376531.

Influence of PEEP on cerebral blood flow and cerebrovascular autoregulation in patients with acute respiratory distress syndrome.

BACKGROUND: High levels of positive end-expiratory pressure (PEEP), as part of the treatment in patients with acute respiratory distress syndrome (ARDS), may prevent alveolar collapse and maintain oxygenation. PEEP potentially reduces cerebral venous return, increases intracranial blood volume, and may, therefore, affect cerebral blood flow (CBF) and cerebrovascular autoregulation (AR). This study investigates the effect of PEEP on CBF and AR in patients with respiratory failure. METHODS: CBF velocity was measured using transcranial doppler and correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx>0.3 indicates impaired AR). Mx was measured at lower PEEP levels and after increasing PEEP. Only an increase of Mx of >0.2 was considered to be clinically relevant. Two 1-sided Wilcoxon tests. RESULTS: Twenty mechanically ventilated patients with ARDS were included. Elevation of PEEP from 9.2±1 to 14.3±1 cm H2O did not influence CBF velocity but increased Mx from 0.317±0.35 to 0.414±0.32 (difference ≤0.2). Mx was >0.3 in 11/20 patients during baseline measurements, indicating impaired AR. CONCLUSIONS: Surprisingly, AR was impaired in 55% of the patients with ARDS. This should be taken into account when managing cerebral perfusion pressure to avoid cerebral hyperperfusion or hypoperfusion. Increasing PEEP from 9.2 to 14.3 cm H2O had no further clinically relevant effect on AR, independent of preexisting AR impairment.

Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium.

INTRODUCTION: Sepsis-associated delirium (SAD) increases morbidity in septic patients and, therefore, factors contributing to SAD should be further characterized. One possible mechanism might be the impairment of cerebrovascular autoregulation (AR) by sepsis, leading to cerebral hypo- or hyperperfusion in these haemodynamically unstable patients. Therefore, the present study investigates the relationship between the incidence of SAD and the status of AR during sepsis. METHODS: Cerebral blood flow velocity was measured using transcranial Doppler sonography and was correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx>0.3 indicates impaired AR). Mx was measured daily during the first 4 days of sepsis. Diagnosis of a SAD was performed using the confusion assessment method for ICU (CAM-ICU) and, furthermore the predominant brain electrical activity in electroencephalogram (EEG) both at day 4 after reduction of sedation to RASS >-2. RESULTS: 30 critically ill adult patients with severe sepsis or septic shock (APACHE II 32 ± 6) were included. AR was impaired at day 1 in 60%, day 2 in 59%, day 3 in 41% and day 4 in 46% of patients; SAD detected by CAM-ICU was present in 76 % of patients. Impaired AR at day 1 was associated with the incidence of SAD at day 4 (p = 0.035). CONCLUSIONS: AR is impaired in the great majority of patients with severe sepsis during the first two days. Impaired AR is associated with SAD, suggesting that dysfunction of AR is one of the trigger mechanisms contributing to the development of SAD. TRIAL REGISTRATION: clinicalTrials.gov ID NCT01029080.

Perfusion index and plethysmographic variability index in patients with interscalene nerve catheters.

BACKGROUND: Interscalene nerve blocks provide adequate analgesia, but there are no objective criteria for early assessment of correct catheter placement. In the present study, pulse oximetry technology was used to evaluate changes in the perfusion index (PI) in both blocked and unblocked arms, and changes in the plethysmographic variability index (PVI) were evaluated once mechanical ventilation was instituted. METHODS: The PI and PVI values were assessed using a Radical-7™ finger pulse oximetry device (Masimo Corp., Irvine, CA, USA) in both arms of 30 orthopedic patients who received an interscalene catheter at least 25 min before induction of general anesthesia. Data were evaluated at baseline, on application of local anesthetics; five, ten, and 15 min after onset of interscalene nerve blocks; after induction of general anesthesia; before and after a 500 mL colloid fluid challenge; and five minutes thereafter. RESULTS: In the 25 patients with successful blocks, the difference between the PI values in the blocked arm and the PI values in the contralateral arm increased within five minutes of the application of the local anesthetics (P < 0.05) and increased progressively until 15 min. After induction of general anesthesia, the PI increased in the unblocked arm while it remained relatively constant in the blocked arm, thus reducing the difference in the PI. A fluid challenge resulted in a decrease in PVI values in both arms. CONCLUSION: The perfusion index increases after successful interscalene nerve blockade and may be used as an indicator for successful block placement in awake patients. The PVI values before and after a fluid challenge can be useful to detect changes in preload, and this can be performed in both blocked and unblocked arms.

CRP-induced levels of oxidative stress are higher in brain than aortic endothelial cells.

C-reactive protein (CRP) has been demonstrated to induce blood-brain barrier disruption (BBB) involving NAD(P)H-oxidase dependent oxidative stress. It is unclear why CRP affects the BBB and not other vascular beds following stroke. Therefore we examined CRP receptor and NAD(P)H-oxidase expression levels in bovine brain- (BEC) and aortic endothelial cells. Dichlorodihydrofluorescein measurements revealed significantly higher CRP-induced reactive oxygen species (ROS) levels in BEC. Protein expression of the CRP-receptors CD16, CD32 and of the NAD(P)H-oxidase subunit p22phox were also significantly higher in BEC. In conclusion BEC show a higher vulnerability to CRP due to increased levels of CRP receptors and the NAD(P)H-oxidase.

Cellular mechanisms of IL-17-induced blood-brain barrier disruption.

Recently T-helper 17 (Th17) cells were demonstrated to disrupt the blood-brain barrier (BBB) by the action of IL-17A. The aim of the present study was to examine the mechanisms that underlie IL-17A-induced BBB breakdown. Barrier integrity was analyzed in the murine brain endothelial cell line bEnd.3 by measuring the electrical resistance values using electrical call impedance sensing technology. Furthermore, in-cell Western blots, fluorescence imaging, and monocyte adhesion and transendothelial migration assays were performed. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice. IL-17A induced NADPH oxidase- or xanthine oxidase-dependent reactive oxygen species (ROS) production. The resulting oxidative stress activated the endothelial contractile machinery, which was accompanied by a down-regulation of the tight junction molecule occludin. Blocking either ROS formation or myosin light chain phosphorylation or applying IL-17A-neutralizing antibodies prevented IL-17A-induced BBB disruption. Treatment of mice with EAE using ML-7, an inhibitor of the myosin light chain kinase, resulted in less BBB disruption at the spinal cord and less infiltration of lymphocytes via the BBB and subsequently reduced the clinical characteristics of EAE. These observations indicate that IL-17A accounts for a crucial step in the development of EAE by impairing the integrity of the BBB, involving augmented production of ROS.-Huppert, J., Closhen, D., Croxford, A., White, R., Kulig, P., Pietrowski, E., Bechmann, I., Becher, B., Luhmann, H. J., Waisman, A., Kuhlmann, C. R. W. Cellular mechanisms of IL-17-induced blood-brain barrier disruption.

Mechanisms of C-reactive protein-induced blood-brain barrier disruption.

BACKGROUND AND PURPOSE: Increased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood-brain barrier stability and to analyze the underlying signaling pathways. METHODS: We used a cell coculture model of the blood-brain barrier and the guinea pig isolated whole brain preparation. RESULTS: We could show that CRP at clinically relevant concentrations (10 to 20 microg/mL) causes a disruption of the blood-brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fcgamma receptors CD16/32 followed by p38-mitogen-activated protein kinase-dependent reactive oxygen species formation by the NAD(P)H-oxidase. The resulting oxidative stress increased myosin light chain kinase activity leading to an activation of the contractile machinery. Blocking myosin light chain phosphorylation prevented the CRP-induced blood-brain barrier breakdown and the disruption of tight junctions. CONCLUSIONS: Our data identify a previously unrecognized mechanism linking CRP and brain edema formation and present a signaling pathway that offers new sites of therapeutic intervention.

MK801 blocks hypoxic blood-brain-barrier disruption and leukocyte adhesion.

The aim of the present study was to examine the signaling pathways of hypoxia followed by reoxygenation (H/R)-induced disruption of the blood-brain-barrier (BBB) in a co-culture of astrocytes and brain endothelial cells (BEC) in vitro. We analyzed the possible stabilizing effect of MK801, a highly selective N-methyl-d-aspartate receptor (NMDAR) antagonist, on BBB integrity. Levels of reactive oxygen species (ROS), glutamate (Glut) release and monocyte adhesion were measured under normoxia and H/R. BBB integrity was monitored measuring the trans-endothelial electrical resistance (TEER). TEER values dropped under H/R conditions which was abolished by MK801. Glut release from astrocytes, but not from endothelial cells was significantly increased under H/R, as were ROS levels and monocyte adhesion. The oxidative stress was blocked by MK801 and the NAD(P)H-oxidase inhibitor apocynin. We observed that calcium (Ca(2+)) signaling plays a crucial role during ROS generation and monocyte adhesion under H/R. ROS levels were decreased by applying ryanodine, a blocker of Ca(2+) release from the endoplasmic reticulum (ER) and by lowering the extracellular Ca(2+) concentration. Xestospongin C, which blocks IP(3) mediated Ca(2+) release from the ER did not alter ROS production under H/R conditions. These findings indicate that both extracellular Ca(2+) influx and ryanodine-mediated intracellular Ca(2+) release from the ER during H/R contribute to ROS formation at the BBB. Blocking ROS or Ca(2+) signaling prevented H/R-induced monocyte adhesion to BEC. We conclude, that the activation of NMDAR under H/R by Glut increases intracellular Ca(2+) levels, contributes to BBB disruption, ROS generation and monocyte adhesion.

Fluvastatin prevents glutamate-induced blood-brain-barrier disruption in vitro.

Glutamate is an important excitatory amino acid in the central nervous system. Under pathological conditions glutamate levels dramatically increase. Aim of the present study was to examine whether the HMG-CoA inhibitor fluvastatin prevents glutamate-induced blood-brain-barrier (BBB) disruption. Measurements of transendothelial electrical resistance (TEER) were performed to analyze BBB integrity in an in vitro co-culture model of brain endothelial and glial cells. Myosin light chain (MLC) phosphorylation was detected by immunohistochemistry, or using the in-cell western technique. Intracellular Ca2+ and reactive oxygen species (ROS) levels were analyzed using the fluorescence dyes Ca-green or DCF. Glutamate induced a time- (1-3 h) and concentration- (0.25-1 mmol/l) dependent decrease of TEER values that was blocked by the NMDA-receptor antagonist MK801, the Ca2+ chelator BAPTA, the NAD(P)H-oxidase inhibitor apocynin and the MLC-kinase inhibitor ML-7. Furthermore we observed a concentration-dependent increase of intracellular Ca2+ and ROS after glutamate application. Glutamate caused an increase of MLC phosphorylation that was antagonized by apocynin, or BAPTA, indicating that Ca2+ and ROS signaling is involved in the activation of the contractile machinery. Fluvastatin (10-25 micromol/l) completely abolished the glutamate-induced barrier disruption and oxidative stress. The BBB-protecting effect of fluvastatin was completely lost if the cells were treated with the nitric oxide (NO) synthase inhibitor L-NMMA (300 micromol/l). In the present study we demonstrated that glutamate-induced BBB disruption involves Ca2+ signalling via NMDA receptors, which is followed by an increased ROS generation by the NAD(P)H-oxidase. This oxidative stress then activates the MLC kinase. Fluvastatin preserves barrier function in a NO-dependent way and reduces glutamate-induced oxidative stress.