Effects of methylprednisolone on blood-brain barrier and cerebral inflammation in cardiac surgery-a randomized trial.

BACKGROUND: Cognitive dysfunction is a frequent complication to open-heart surgery. Cerebral inflammation caused by blood-brain barrier (BBB) dysfunction due to a systemic inflammatory response is considered a possible etiology. The effects of the glucocorticoid, methylprednisolone, on cerebrospinal fluid (CSF) markers of BBB function, neuroinflammation, and brain injury in patients undergoing cardiac surgery with cardiopulmonary bypass were studied. METHODS: In this prospective, randomized, blinded study, 30 patients scheduled for elective surgical aortic valve replacement were randomized to methylprednisolone 15 mg/kg (n = 15) or placebo (n = 15) as a bolus dose administered after induction of anesthesia. CSF and blood samples were obtained the day before and 24 h after surgery for assessment of systemic and brain inflammation (interleukin-6, interleukin-8, tumor necrosis factor-alpha), axonal injury (total-tau, neurofilament light chain protein), neuronal injury (neuron-specific enolase), astroglial injury (S-100B, glial fibrillary acidic protein), and the BBB integrity (CSF/serum albumin ratio). RESULTS: In the control group, there was a 54-fold and 17-fold increase in serum interleukin-6 and interleukin-8, respectively. This systemic activation of the inflammatory cytokines was clearly attenuated by methylprednisolone (p < 0.001). The increase of the CSF levels of the astroglial markers was not affected. A postoperative BBB dysfunction was seen in both groups as the CSF/serum albumin ratio increased from 6.4 ± 8.0 to 8.0 in the placebo group (p < 0.01) and from 5.6 ± 2.3 to 7.2 in the methylprednisolone group (p < 0.01) with no difference between groups (p = 0.98). In the CSF, methylprednisolone attenuated the interleukin-6 release (p < 0.001), which could be explained by the fall in systemic interleukin-6, and the serum to CSF gradient of IL-6 seen both at baseline and after surgery. In the CSF, methylprednisolone enhanced the interleukin-8 release (p < 0.001) but did not affect postoperative changes in CSF levels of tumor necrosis factor alpha. Serum levels of S-100B and neuron-specific enolase increased in both groups with no difference between groups. CSF levels of total tau, neurofilament light chain protein, and neuron-specific enolase were not affected in any of the groups. CONCLUSIONS: Preventive treatment with high-dose methylprednisolone attenuated the systemic inflammatory response to open-heart surgery with cardiopulmonary bypass, but did not prevent or attenuate the increase in BBB permeability or the neuroinflammatory response. TRIAL REGISTRATION: Clinical Trials, Identifier: NCT01755338 , registered 24 December 2012.

Epoprostenol for the treatment of increasing oxygenator pressure drop during cardiopulmonary bypass. A case report.

A change of oxygenator during cardiopulmonary bypass is a technically high-risk procedure with potential for a serious adverse event for the patient. This case report describes a case of increased pressure drop and pre-oxygenator blood pressure during cardiopulmonary bypass successfully treated with pre-oxygenator-administered epoprostenol.

Hypotension During Endovascular Treatment of Ischemic Stroke Is a Risk Factor for Poor Neurological Outcome.

BACKGROUND AND PURPOSE: In retrospective studies, patients receiving general anesthesia for endovascular treatment for acute ischemic stroke have worse neurological outcome compared with patients receiving conscious sedation. It has been suggested that this is caused by general anesthesia-associated hypotension. We investigated the effect of intraprocedural hypotension on neurological outcome. METHODS: One hundred eight patients with acute ischemic stroke, who underwent endovascular treatment in general anesthesia between 2007 and 2012, were included. Analyzed predictors of neurological outcome were age, sex, comorbidities, baseline National Institutes of Health Stroke Scale, intraprocedural relative changes in mean arterial blood pressure from baseline, blood glucose, modified Thrombolysis in Cerebral Infarction score, and elapsed time from stroke to computed tomography, groin puncture, and recanalization/end of procedure. RESULTS: A fall in mean arterial blood pressure of >40% was an independent predictor for poor neurological outcome (P=0.032), as were higher admission National Institutes of Health Stroke Scale score (P=0.008) and lack of recanalization (P=0.003). CONCLUSIONS: Profound intraprocedural hypotension is an independent predictor for poor neurological outcome in patients with acute ischemic stroke undergoing endovascular therapy in general anesthesia.

Can baroreflex sensitivity and heart rate variability predict late neurological outcome in patients with traumatic brain injury?

BACKGROUND: Previous studies have suggested that depressed heart rate variability (HRV) and baroreflex sensitivity (BRS) are associated with early mortality and morbidity in patients with acute brain injuries of various etiologies. The aim of the present study was to assess changes in HRV and BRS in isolated traumatic brain injury (TBI), with the hypothesis that measurement of autonomic nervous system dysfunction can provide prognostic information on late neurological outcome. MATERIALS AND METHODS: Nineteen patients with TBI, requiring mechanical ventilation, sedation and analgesia, and with arterial and intracranial pressure monitoring for at least 1 week, were included. Physiological and treatment variables were collected and power spectral analyses of HRV and BRS analyses in time domain were performed daily. HRV in the high-frequency (HF) and low-frequency (LF) domains, as well as LF/HF ratio and total power, were investigated. The power of these variables to predict poor (Glasgow Outcome Scale Extended [GOSE] score <5), late (1 y) neurological outcome was assessed. RESULTS: Total power, LF, HF, and BRS were all significantly depressed in patients with GOSE score <5. This difference could not be explained by a more severe brain injury at admission or more extensive use of sedative or analgesic drugs. The autonomic variables predicted the late neurological outcome with areas under the receiver-operating curves between 0.78 and 0.83 (sensitivity: 0.63 to 0.88 and specificity: 0.73 to 0.82). CONCLUSIONS: HRV and BRS measures in TBI patients during intensive care treatment, including sedative, analgesic, and vasoactive drugs, may identify patients with poor late neurological outcome.

Cerebrospinal fluid markers of brain injury, inflammation, and blood-brain barrier dysfunction in cardiac surgery.

BACKGROUND: Neurocognitive dysfunction occurs frequently after open-heart surgery. Cerebral microembolization, inflammation, blood-brain barrier (BBB) dysfunction, and impaired cerebral oxygenation are considered among possible etiologies. The relationships between intraoperative microembolic signals and the release of cerebrospinal fluid (CSF) markers of inflammation, neuronal and glial cell injuries, and BBB function were evaluated after cardiac surgery with cardiopulmonary bypass. METHODS: Ten patients undergoing aortic valve replacement were included. The CSF was obtained the day before and 24 hours after surgery for assessment of neuronal damage (neuron-specific enolase, total tau, and neurofilament light chain protein), glial cell injury (S-100B, glial fibrillary acidic protein), BBB integrity (CSF to serum albumin ratio) and cytokines (interleukin-6, interleukin-8). Intraoperative extent of microemboli and their occurrence were described using the transcranial Doppler technique. RESULTS: Intraoperatively, 354±79 microemboli were detected; 81% after release of the aortic cross clamp. The S-100B and glial fibrillary acidic protein increased by 35% (p<0.01) and 25% (p=0.055), respectively. Neuron-specific enolase, total tau, and neurofilament light chain protein, were not significantly affected by the surgery. The CSF albumin increased by 13% (p<0.05) while serum albumin decreased by 27% (p<0.0001). Thus, CSF to serum albumin ratio increased by 61% (p=0.011). There was a 3.5- and 12-fold increase in interleukin-6 (p<0.001) and interleukin-8 (p<0.05), respectively. Microembolic signals did not correlate to changes in CSF glial injury markers, the CSF to serum albumin ratio, or CSF cytokines. CONCLUSIONS: Cardiac surgery with cardiopulmonary bypass causes cerebral inflammation, glial cell injury, and BBB dysfunction without biochemical signs of neuronal damage. These changes are not associated with intraoperative microembolization.

The effects of isoflurane-induced electroencephalographic burst suppression on cerebral blood flow velocity and cerebral oxygen extraction during cardiopulmonary bypass.

UNLABELLED: We investigated the effects of isoflurane-induced burst suppression, monitored with electroencephalography (EEG), on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE), and autoregulation in 16 patients undergoing cardiac surgery. The experimental procedure was performed during nonpulsatile cardiopulmonary bypass (CPB) with mild hypothermia (32 degrees C) in fentanyl-anesthestized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular vein bulb oxygen saturation, and jugular venous pressure (JVP) were continuously measured. Autoregulation was tested during changes in mean arterial blood pressure (MAP) within a range of 40-80 mm Hg, induced by sodium nitroprusside and phenylephrine before (control) and during additional isoflurane administration to an EEG burst-suppression level of 6-9/min. Isoflurane induced a 27% decrease in CBFV (P < 0.05) and a 13% decrease in COE (P < 0.05) compared with control. The slope of the positive relationship between CBFV and cerebral perfusion pressure (CPP = MAP - JVP) was steeper with isoflurane (P < 0.05) compared with control, as was the slope of the negative relationship between CPP and COE (P < 0.05). We conclude that burst-suppression doses of isoflurane decrease CBFV and impair autoregulation of cerebral blood flow during mildly hypothermic CPB. Furthermore, during isoflurane administration, blood flow was in excess relative to oxygen demand, indicating a loss of metabolic autoregulation of flow. IMPLICATIONS: The effects of isoflurane on cerebral blood flow velocity (CBFV) and oxygen extraction (COE) as a function of perfusion pressure were studied. When added to fentanyl anesthesia, isoflurane induced a 27% and 13% decrease in CBFV and COE, respectively. CBFV became more pressure-dependent with isoflurane indicating an impaired autoregulation.