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

Summary: Trendelenburg positioning in combination with pneumoperitoneum during robotic‐assisted prostatic surgery possibly impairs cerebrovascular autoregulation. If cerebrovascular autoregulation is disturbed, arterial hypertension might induce cerebral hyperaemia and brain oedema, while low arterial blood pressure can induce cerebral ischaemia. The time course of cerebrovascular autoregulation was investigated during use of the Trendelenburg position and a pneumoperitoneum for robotic‐assisted prostatic surgery using transcranial Doppler ultrasound. Cerebral blood flow velocity was correlated with arterial blood pressure and the autoregulation index (Mx) was calculated. In 23 male patients, Mx was assessed at baseline, after induction of general anaesthesia, during the Trendelenburg position (40–45°), and after repositioning. During the Trendelenburg position, Mx increased over time, indicating an impairment of cerebrovascular autoregulation. After repositioning, Mx recovered to baseline levels. It can be concluded that with longer durations of Trendelenburg position and pneumoperitoneum, cerebrovascular autoregulation deteriorates, and, therefore, blood pressure management should be adapted to avoid cerebral oedema and the duration of Trendelenburg position should be as short as possible.

Propofol reduces cerebral blood flow (CBF) secondary to cerebral metabolic depression. However, in vitro and in vivo studies demonstrate that propofol directly dilates the vascular smooth muscle. This study investigates the effects of propofol-induced changes in bispectral index (BIS) on cerebral microcirculation and oxygenation during craniotomies. In 21 craniotomy patients undergoing routine craniotomy, anaesthesia was maintained with propofol 4-10 mg kg⁻¹ h⁻¹ and remifentanil 0.1-0.4 µg kg⁻¹ min⁻¹. Propofol concentration was adjusted to achieve higher BIS (target 40) or lower BIS (target 20). Regional measurements of capillary venous blood flow (rvCBF), oxygen saturation (srvO₂), and haemoglobin amount (rvHb) at 2 mm (grey matter) and 8 mm (white matter) cerebral depth were randomly performed at higher and lower BIS by combined laser-Doppler flowmetry and spectroscopy. Calculations: approximated arteriovenous difference in oxygen content (avDO₂) and cerebral metabolic rate of oxygen (aCMRO₂). mean values (sd). Mann-Whitney test (*P<0.05). Results Human cerebral microcirculation and oxygen saturation were assessed at propofol dosages 5.1 (2.3) mg kg⁻¹ h⁻¹ [BIS 40 (9)] and 7.8 (2.1) mg kg⁻¹ h⁻¹ [BIS 21 (7)]. Propofol-induced reduction in BIS resulted in increased srvO₂ (P=0.018), and decreased avDO₂ (P=0.025) and aCMRO(2) (P=0.022), in 2 mm cerebral depth, while rvCBF and rvHb remained unchanged. In 8 mm cerebral depth, srvO₂, rvCBF, rvHb, and also calculated parameters avDO₂ and aCMRO₂ remained unaltered. Findings suggest alteration of the CBF/CMRO₂ ratio by propofol in cortical brain regions; therefore, it might be possible that propofol affects coupling of flow and metabolism in the cerebral microcirculation.

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). 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. Clinical observational study. Primary care university hospital, study period from March 2012 to February 2013. A total of 29 patients scheduled for robotic assisted prostatic surgery in a steep Trendelenburg position. 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. Changes in cerebral oxygenation of more than 5% during surgery in the Trendelenburg position. 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). 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. clinicaltrials.gov Identifier: ID NCT01275898.

The present study assesses the utility of a novel invasive device (O2C-, oxygen-to-see-device) for intraoperative measurement of the cerebral microcirculation. CO2 vasoreactivity during 2 different propofol concentrations was used to investigate changes of capillary venous cerebral blood flow (rvCBF), oxygen saturation (srvO2), and hemoglobin concentration (rvHb) during craniotomy. Thirty-four patients were randomly assigned to a low propofol (4 mg/kg/h) versus a high propofol (6 mg/kg/h) group. A fiberoptic probe was applied on the cortex next to the surgical site. Measurements were performed during lower (35 mm Hg) and higher (45 mm Hg) levels of partial pressure of carbon dioxide (paCO2). Arterio-venous difference in oxygen concentration (avDO2) and approximated cerebral metabolic rate of oxygen (aCMRO2) were calculated for each paCO2 state. Linear models were fitted to test changes of end points in response to paCO2 and propofol concentration. In comparison to the lower levels of paCO2, higher levels of paCO2 increased rvCBF (P<0.001), and srvO2 (P=0.002). RvHb remained unchanged during measurements (P=0.325). Calculated avDO2 decreased with increasing paCO2 (P<0.001), whereas aCMRO2 did not change during the study (P=0.999). Propofol concentration had no effect on measured or calculated end points. Increase of rvCBF by paCO2 indicates a preserved CO2 reactivity independent of propofol anesthesia. The consecutive rise in srvO2 implies enhanced oxygen availability due to vasodilatation. Unchanged rvHb represents constant venous hemoglobin concentration. As expected, calculated avDO2 decreases with increased paCO2, whereas aCMRO2 remains unchanged. Despite the promising technical approach, the technology needs validation and further investigation for usage during neurosurgery.