Influence of the postoperative inflammatory response on cognitive decline in elderly patients undergoing on-pump cardiac surgery: a controlled, prospective observational study

BACKGROUND: The role of non-infective inflammatory response (IR) in the aetiology of postoperative cognitive dysfunction (POCD) is still controversial. The aim of this controlled, prospective observational study was to assess the possible relationship between the grade of IR, defined by procalcitonin (PCT) changes, and development of POCD related to cardiac surgery. METHODS: Forty-two patients, who were >/= 60 years of age and scheduled for elective cardiac surgery, were separated into the low inflammatory (LIR) and high inflammatory (HIR) response groups based on their PCT levels measured on the first postoperative day. A matched normative control group of 32 subjects was recruited from primary care practice. The PCT and C-reactive protein (CRP) levels were monitored daily during the first five postoperative days. The cognitive function and mood state were preoperatively tested with a set of five neurocognitive tests and two mood inventories and at the seventh postoperative day. The Reliable Change Index modified for practice (RCIp) using data from normative controls was applied to determine the significant decline in test performance. RESULTS: The LIR (n = 20) and HIR (n = 22) groups differed significantly in the PCT (p 0.05). Additionally, there was no difference in the mood states, anxiety levels and perioperative parameters known to influence the development of POCD. CONCLUSIONS: In this study, the magnitude of the non-infective inflammatory response generated by on-pump cardiac surgery did not influence the development of POCD in the early postoperative period in elderly patients

Open-heart surgery increases cerebrospinal fluid levels of Alzheimer-associated amyloid β

BACKGROUND: Neurocognitive dysfunction occurs frequently after open-heart surgery. It has been suggested that cognitive decline after cardiac surgery with cardiopulmonary bypass (CPB) could be a functional consequence of Alzheimer's disease (AD)-like neuropathological changes. The aim of the present study was to evaluate the cerebrospinal fluid (CSF) levels of amyloid β peptide (Aβ(1-42) ) and soluble fragments of amyloid precursor protein (sAPP) as well as the cerebral inflammatory response to open-heart surgery. METHODS: Ten patients undergoing aortic valve replacement with CPB were included. CSF was obtained the day before and 24h after surgery for assessment of CSF levels of Aβ(1-42) α-cleaved sAPP and β-cleaved sAPP (sAPP-β). Furthermore, CSF and serum levels of the inflammatory cytokines: tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) were also assessed. RESULTS: Cardiac surgery with CPB increased CSF levels of Aβ(1-42) from 447±92 to 641±83ng/l (P=0.011), while CSF levels of sAPP-β decreased from 276±35 to 192±21ng/ml (P=0.031). CSF levels of TNF-α increased from ≤0.60 to 0.79±0.26ng/l (P=0.043), IL-6 from 1.89±0.53 to 22.8±6.9ng/l (P=0.003) and IL-8 from 39.8±7.8 to 139±18.3ng/l (P<0.001). CONCLUSIONS: Cardiac surgery with CPB causes a profound cerebral inflammatory response, which was accompanied by increased post-operative CSF levels of the AD biomarker Aβ(1-42) . We hypothesize that these changes may be relevant to Alzheimer-associated amyloid build-up in the brain and cognitive dysfunction after cardiac surgery with CPB

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

Detection of cerebral ischemia in neurovascular surgery using quantitative frequency-domain near-infrared spectroscopy.

ObjectThere is great value in monitoring for signs of ischemia during neurovascular procedures. Current intraoperative monitoring techniques provide real-time feedback with limited accuracy. Quantitative frequency-domain near-infrared spectroscopy (Q-NIRS) allows measurement of tissue oxyhemoglobin (HbO2), deoxyhemoglobin (HHb), and total hemoglobin (tHb) concentrations and brain tissue oxygen saturation (SO2), which could be useful when monitoring for evidence of intraoperative ischemia.MethodsUsing Q-NIRS, the authors monitored 25 neurovascular procedures including aneurysm clip placement, arteriovenous malformation resection, carotid endarterectomy, superficial temporal artery-middle cerebral artery (MCA) bypass surgery, external carotid artery-MCA bypass surgery, encephaloduromyosynangiosis, and balloon occlusion testing. The Q-NIRS technology provides measurable cerebral oxygenation values independent from those of the scalp tissue. Thus, alterations in the variables measured with Q-NIRS quantitatively reflect cerebral tissue perfusion. Bilateral monitoring was performed in all cases. Five of the patients exhibited evidence of clinical ischemic events during the procedures. One patient suffered blood loss with systemic hypotension and developed diffuse brain edema intraoperatively, one patient suffered an ischemic event intraoperatively and developed an occipital stroke postoperatively, and one patient showed slowing on electroencephalography intraoperatively during carotid clamping; in two patients balloon occlusion testing failed. In all cases of ischemic events occurring during the procedure, Q-NIRS monitoring showed a decrease in HbO2, tHb, and SO2, and an increase in HHb.Conclusions. Quantitative frequency-domain near-infrared spectroscopy provides quantifiable and continuous real-time information about brain oxygenation and hemodynamics in a noninvasive manner. This continuous intraoperative oxygenation monitoring is a promising method for detecting ischemic events during neurovascular procedures