Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.

The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (ß=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (ß=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (ß=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the L-serine to D-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.

Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.

Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system (CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underpinnings may elucidate etiological mechanisms. We therefore conducted a genome-wide association study (GWAS) of monoamine metabolite (MM) levels in cerebrospinal fluid (CSF) of 414 human subjects from the general population. In a linear model correcting for covariates, we identified one locus associated with MMs at a genome-wide significant level (standardized ß=0.32, P=4.92 × 10(-8)), located 20 kb from SSTR1, a gene involved with brain signal transduction and glutamate receptor signaling. By subsequent whole-genome expression quantitative trait locus (eQTL) analysis, we provide evidence that this variant controls expression of PDE9A (ß=0.21; P unadjusted=5.6 × 10(-7); P corrected=0.014), a gene previously implicated in monoaminergic transmission, major depressive disorder and antidepressant response. A post hoc analysis of loci significantly associated with psychiatric disorders suggested that genetic variation at CSMD1, a schizophrenia susceptibility locus, plays a role in the ratio between dopamine and serotonin metabolites in CSF. The presented DNA and mRNA analyses yielded genome-wide and suggestive associations in biologically plausible genes, two of which encode proteins involved with glutamate receptor functionality. These findings will hopefully contribute to an exploration of the functional impact of the highlighted genes on monoaminergic transmission and neuropsychiatric phenotypes.

High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery.

BACKGROUND: Postoperative non-cardiac complication rates are as high as 11-28% after high-risk abdominal procedures. Emerging evidence indicates that postoperative cardiac troponin T elevations are associated with adverse outcome in non-cardiac surgery. The aim of this study was to determine the relationship between postoperative high-sensitive cardiac troponin T elevations and non-cardiac complications in patients after major abdominal surgery. METHODS: This prospective observational single-centre cohort study included patients at risk for coronary artery disease undergoing elective major abdominal surgery. Cardiac troponin was measured before surgery and at day 1, 3, and 7. Multivariable logistic regression analysis was performed to examine the adjusted association for different cut-off concentrations of postoperative myocardial injury and non-cardiac outcome. RESULTS: In 203 patients, 690 high-sensitive cardiac troponin T measurements were performed. Fifty-three patients (26%) had a non-cardiac complication within 30 days after surgery. Hospital mortality was 4% (8/203). An increase in cardiac troponin T concentration ≥100% compared with baseline was a superior independent predictor of non-cardiac postoperative clinical complications (adjusted odds ratio 4.3, 95% confidence interval 1.8-10.1, P<0.001) and was associated with increased length of stay (9 days, 95% confidence interval 7-11 vs 7 days, 95% confidence interval 6-8, P=0.004) and increased hospital mortality (12 vs 2%, P=0.028). CONCLUSIONS: A postoperative high-sensitive cardiac troponin T increase ≥100% is a strong predictor of non-cardiac 30 day complications, increased hospital stay and hospital mortality in patients undergoing major abdominal surgery. CLINICALTRIALSGOV IDENTIFIER: NCT02150486.

Remifentanil during cardiac surgery is associated with chronic thoracic pain 1 yr after sternotomy.

BACKGROUND: Chronic thoracic pain after cardiac surgery is a serious condition affecting many patients. The aim of this study was to identify predictors for chronic thoracic pain after sternotomy in cardiac surgery patients by analysing patient and perioperative characteristics. METHODS: A follow-up study was performed in 120 patients who participated in a clinical trial on pain levels in the early postoperative period after cardiac surgery. The presence of chronic thoracic pain was evaluated by a questionnaire 1 yr after surgery. Patients with and without chronic thoracic pain were compared. Associations were studied using multivariable logistic regression analysis. RESULTS: Questionnaires of 90 patients were analysed. Chronic thoracic pain was reported by 18 patients (20%). In the multivariable regression model, remifentanil during cardiac surgery, age below 69 yr, and a body mass index above 28 kg m(-2) were independent predictors for chronic thoracic pain {odds ratios 8.9 [95% confidence interval (CI) 1.6-49.0], 7.0 (95% CI 1.6-31.7), 9.1 (95% CI 2.1-39.1), respectively}. No differences were observed in patient and perioperative characteristics between patients receiving remifentanil (58%, n=52) compared with patients not receiving remifentanil (42%, n=38). The association between remifentanil and chronic thoracic pain appeared dose-dependent, both for total dose and for dose corrected for kilogram lean body mass and duration of surgery (P-value for trend: <0.01 and <0.005, respectively). CONCLUSIONS: In this follow-up study in cardiac surgery patients, intraoperative remifentanil was predictive for chronic thoracic pain in a dose-dependent manner. Randomized studies designed to evaluate the influence of intraoperative remifentanil on chronic thoracic pain are needed to confirm these results.

Maintenance of anesthesia in morbidly obese patients using propofol with continuous BIS-monitoring: a comparison of propofol-remifentanil and propofol-epidural anesthesia.

PURPOSE: Aim of this study was to evaluate maintenance of anesthesia using propofol with continuous Bispectral Index (BIS)-monitoring in morbidly obese patients receiving propofol-remifentanil and propofol-epidural anesthesia. METHODS: In the first group in ten morbidly obese patients receiving remifentanil analgesia, a propofol infusion was started at 10 mg/kg/hr and modified by aiming at BIS values between 40-60 together with predefined hemodynamic parameters. In the second group, the propofol dose resulting from the first group was prospectively evaluated in a matched cohort of six morbidly obese patients receiving propofol-epidural analgesia aiming for the same BIS and hemodynamic parameters. In both groups, propofol concentration and infusion rates, BIS and hemodynamic values were collected. RESULTS: In the propofol-remifentanil group (Body Mass Index (BMI) 39-60 kg/m2), the mean propofol infusion rate that corresponded to the predefined BIS and hemodynamic parameters was 4.8 mg/kg/hr (SD 1.5). On this basis, a maintenance dose of 5 mg/kg/hr was started in the propofol-epidural group (BMI 38-58 kg/m2). In this second group, the mean propofol infusion rate that corresponded to predefined BIS and hemodynamic parameters was 5.0 mg/kg/hr (SD 0.6). Between the two groups, there was no difference in the propofol concentration-BIS relation. CONCLUSION: Using both BIS and hemodynamic parameters as an endpoint, a maintenance dose of propofol of 4-6 mg/kg/hr is proposed for maintenance of anesthesia in morbidly obese patients undergoing bariatric surgery either in combination with remifentanil or epidural analgesia. There was no difference in propofol concentration-BIS relation in morbidly obese patients receiving propofol-remifentanil or propofol-epidural anesthesia.

Anti Xa activity after high dose LMWH thrombosis prophylaxis in covid 19 patients at the intensive care unit.

INTRODUCTION: Coagulopathy in Coronavirus disease 2019 (covid-19) has been demonstrated by an increase in D-dimer, prothrombin time (PT), fibrinogen and factor VIII. Venous thromboembolic events are a common abnormality in patients with covid-19. We evaluate the results of intensive care unit (ICU) thrombosis prophylaxis of 5700 international unit (IU) nadroparin low molecular weight heparin (LMWH) twice daily. METHODS: After introduction of this high-dose pharmacological thrombosis prophylaxis twice weekly anti-factor Xa (anti Xa) concentrations and results from routine laboratory and viscoelastic hemostatic tests in 16 ICU covid-19 patients were evaluated. RESULTS: During one week, median peak anti Xa activities were 0.38 [0.16-0.45] and 0.38 [0.20-0.58] at time point 1 and 2 respectively. Laboratory coagulation tests showed PT, AT and platelet count (PltC) values within normal range and markedly increased D-dimer and fibrinogen levels. Viscoelastic tests showed a maximum clot strength just above normal reference value, while fibrin clot strength was strongly increased. The overall contribution of fibrin to clot strength was high with 71 [56-85]%. CONCLUSION: Anti Xa activity was within the target range of pharmacodynamic endpoint for covid-19 patients but viscoelastic tests still demonstrated a procoagulant pattern.

Anesthesia Geriatric Evaluation (AGE): A Care-Ethical Perspective of a Multi-Disciplinary Approach for Tailored Preoperative Interventions.

Background: Frailty is considered to be an important risk factor for mortality in hospitalized patients. This study evaluates a preoperative frailty-screening tool called Anesthesia Geriatric Evaluation (AGE). Research into the concept of frailty, with a focus on multidisciplinary team meetings, may provide further insight for health care professionals in the understanding of frailty in everyday care situations. Methods: The research method chosen for this research is QUAGOL: Qualitative Analysis Guide of Leuven, which aims to reconstruct the story of the participants on a theoretical level and analyze the concepts found. Results: The following themes illustrate the analyzed concepts found: competence, resilience, sharing responsibility, broad frame of reference, obligation, and significance. Conclusion: AGE seems to create more awareness among health care professionals about frailty and tries to involve patients in their care process by making them aware of their abilities, motivation, and involving them in decisions to be made. This study shows that a shared decision-making process for surgical patients is often difficult to accomplish since AGE is still a paternalistic process of a multidisciplinary team with a medical perspective.

Peripheral blood gene expression profiles linked to monoamine metabolite levels in cerebrospinal fluid.

The blood-brain barrier separates circulating blood from the central nervous system (CNS). The scope of this barrier is not fully understood which limits our ability to relate biological measurements from peripheral to central phenotypes. For example, it is unknown to what extent gene expression levels in peripheral blood are reflective of CNS metabolism. In this study, we examine links between central monoamine metabolite levels and whole-blood gene expression to better understand the connection between peripheral systems and the CNS. To that end, we correlated the prime monoamine metabolites in cerebrospinal fluid (CSF) with whole-genome gene expression microarray data from blood (N=240 human subjects). We additionally applied gene-enrichment analysis and weighted gene co-expression network analyses (WGCNA) to identify modules of co-expressed genes in blood that may be involved with monoamine metabolite levels in CSF. Transcript levels of two genes were significantly associated with CSF serotonin metabolite levels after Bonferroni correction for multiple testing: THAP7 (P=2.8 × 10-8, ß=0.08) and DDX6 (P=2.9 × 10-7, ß=0.07). Differentially expressed genes were significantly enriched for genes expressed in the brain tissue (P=6.0 × 10-52). WGCNA revealed significant correlations between serotonin metabolism and hub genes with known functions in serotonin metabolism, for example, HTR2A and COMT. We conclude that gene expression levels in whole blood are associated with monoamine metabolite levels in the human CSF. Our results, including the strong enrichment of brain-expressed genes, illustrate that gene expression profiles in peripheral blood can be relevant for quantitative metabolic phenotypes in the CNS.

Impact of left heart bypass on the results of thoracoabdominal aortic aneurysm repair.

BACKGROUND: This study evaluated the role of left heart bypass on the results of thoracoabdominal aortic aneurysm (TAAA) operations. METHODS: Two hundred fifty-eight patients had surgical repair of a thoracoabdominal aortic aneurysm between 1981 and 1998 using the inlay technique. Simple cross-clamping was used in 47.7% and left heart bypass (atriodistal) in 52.3%. Further surgical technique was identical: liberal intercostal or lumbar artery reimplantation, cerebrospinal fluid drainage (since 1989), administration of a renal cooling solution, permissive mild hypothermia, and no pharmacologic protection. Both univariate and multivariate analysis were used. RESULTS: The hospital mortality rate was 10.1% overall: 14.6% in the cross-clamp group, and 5.9% in the bypass group (p = 0.02). The risk of hospital death increased with aneurysm rupture (odds ratio 5.6) and when the patient needed postoperative dialysis (odds ratio 7.5). The use of left heart bypass had a mild protective effect on hospital death (odds ratio 0.56). The incidence of postoperative renal failure requiring dialysis was 8.3% overall: 10.9% in the cross-clamp group, and 5.9% in the bypass group (p = 0.16). After multivariate analysis, a longer operative procedure (odds ratio 1.01 per minute) and a longer reappearance time of blue dye in the urine (odds ratio 1.05 per minute) increased the risk of dialysis, whereas the use of atriodistal bypass reduced that risk (odds ratio 0.08). Paraplegia or paraparesis occurred in 10.9% of patients overall: 13.2% in the cross-clamp group, and 8.8% in the bypass group (p = 0.27). After logistic regression, rupture increased the risk of paraplegia or paraparesis (odds ratio 3.2) and dissection reduced it (odds ratio 0.23). CONCLUSIONS: The use of atriodistal bypass is beneficial in patients who had thoracoabdominal aortic aneurysm repair. Hospital mortality rates, postoperative dialysis, and paraplegia/paraparesis were reduced.

Within patient variability of lower extremity muscle responses to transcranial electrical stimulation with pulse trains in aortic surgery.

Intraoperative recording of myogenic motor responses evoked by transcranial electrical stimulation is a method of controlling the integrity of the motor pathways during clamping of the aorta. It is important to know the within patient variability of the transcranial motor evoked potential (tcMEP), before changes within the variability range are interpreted as abnormal during the period of aortic cross clamping. Lower limb muscle responses were obtained in 11 patients, following transcranial electrical stimulation with pulse trains, of 4, 6 and 8 pulses. Under the conditions of partial neuromuscular blockade and a stable low dose propofol/fentanyl/nitrous oxide anaesthetic state, this study shows that multipulse transcranial electrical stimulation reliably produces muscle responses of the lower limb in all patients tested with a coefficient of variation (CV) of around 20%. Eight pulses in the stimulation train produce neurophysiological facilitation that exceeds a 4 pulse train in terms of area under the curve (AUC) and response duration. The use of multipulse stimulation rather than double or single pulse stimulation is recommended in order to increase the clinical efficacy of tcMEP monitoring in aortic surgery.

An integrated population pharmacokinetic meta-analysis of propofol in morbidly obese and nonobese adults, adolescents, and children.

This study describes a population pharmacokinetic meta-analysis of propofol to characterize the influence of body size measures and age in morbidly obese and nonobese adults, adolescents, and children. Sixty morbidly obese and nonobese adult patients (55-167 kg; 21-79 years) and 34 morbidly obese and nonobese adolescents and children (37-184 kg; 9-20 years) were included. The results show that clearance increased with total body weight in an allometric function while age was found to influence clearance in a bilinear fashion with two distinct slopes, reflecting an initial increase and subsequent decrease as a result of aging. Using these two functions, the influence of both (over)weight and age on propofol clearance was well characterized, which may provide a basis for dosing across this diverse group of patients.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e73; doi:10.1038/psp.2013.47; advance online publication 11 September 2013.

Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR.

Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10(-7)) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.

Efficacy of an intravenous bolus of morphine 2.5 versus morphine 7.5 mg for procedural pain relief in postoperative cardiothoracic patients in the intensive care unit: a randomised double-blind controlled trial.

As pain in the intensive care unit (ICU) is still common despite important progress in pain management, we studied the efficacy of an intravenous bolus of morphine 2.5 vs 7.5 mg for procedural pain relief in patients after cardiothoracic surgery in the ICU. In a prospective double-blind randomised study, 117 ICU patients after cardiothoracic surgery were included. All patients were treated according a pain titration protocol for pain at rest, consisting of continuous morphine infusions and paracetamol, applied during the entire ICU stay. On the first postoperative day, patients were randomised to intravenous morphine 2.5 (n=59) or 7.5 mg (n=58) 30 minutes before a painful intervention (turning of patient and/or chest drain removal). Pain scores using the numeric rating scale (Numeric Rating Scale, range 0 to 10) were rated at rest (baseline) and around the painful procedure. At rest (baseline), overall incidence of unacceptable pain (Numeric Rating Scale ≥4) was low (Numeric Rating Scale >4; 14 vs 17%, P=0.81) for patients allocated to morphine 2.5 and 7.5 mg respectively. For procedure-related pain, there was no difference in incidence of unacceptable pain (28 vs 22%, P=0.53) mean pain scores (2.6 [95% confidence interval 2.0 to 3.2] vs 2.7 [95% confidence interval 2.0 to 3.4]) between patients receiving morphine 2.5 and 7.5 mg respectively. In intensive care patients after cardiothoracic surgery with low pain levels for pain at rest, there was no difference in efficacy between intravenous morphine 2.5 mg or morphine 7.5 mg for pain relief during a painful intervention.

Aminotransferase levels in relation to short-term use of acetaminophen four grams daily in postoperative cardiothoracic patients in the intensive care unit.

A volunteer study suggested that taking paracetamol 4 g daily could result in elevated alanine aminotransferase plasma levels in a substantial proportion of healthy volunteers. The safety of this dose of paracetamol for acute postoperative pain remains controversial. This study aimed to examine the incidence of alanine aminotransferase elevations after short-term use of paracetamol 4 g daily, as part of the standard pain management protocol, for 93 consecutive patients after cardiothoracic surgery. Alanine aminotransferase levels and other liver function tests were measured preoperatively as baseline and once daily after surgery during the intensive care unit stay. Preoperative alanine aminotransferase levels of more than one time the upper limit of normal (ULN >40 U/l) was observed in 11% (n=10) of the patients but none of these baseline alanine aminotransferase levels exceeded three times the ULN (>3 x ULN). The average daily dose of paracetamol administered was 50 mg/kg (SD=16) after surgery. Postoperative alanine aminotransferase levels of >1 x ULN was observed in 17% (n=16), and 4% (n=4) exceeded >3 x ULN The other liver function tests of the latter four patients, including aspartate aminotransferase (range 173 to 5590 U/l), gamma-glutamyltransferase (range 56 to 103 U/l), lactate dehydrogenase (range 376 to 3518 U/l) and the International Normalised Ratio (range 2.0 to 6.6), were all abnormal. These four patients all had right ventricular failure or cardiogenic shock during the postoperative period which could explain the significant rises in alanine aminotransferase after surgery. In conclusion, the incidence of significant alanine aminotransferase elevations after using daily paracetamol as an analgesic agent for cardiac surgery, at a dose of 4 g per day, was low and mostly due to complications after surgery. Our results, albeit still very limited, provided some reassurance about the safety of paracetamol 4 g daily, as a supplementary analgesic agent for adult patients undergoing cardiac surgery.

Inhibition of cortical laser-evoked potentials by transcutaneous electrical nerve stimulation.

Objectives. This study attempts to confirm the hypothesis that transcutaneous electrical stimulation (TENS) of peripheral Aß fibers inhibits nociceptive processing, by quantifying the change of laser-evoked potential (LEP) components, using a 980-nm diode laser. Materials and Methods. Cutaneous heat stimuli were delivered to the dorsum of the right hand in 13 volunteers. LEPs and pain intensity ratings were recorded before, during, and after the use of TENS (110 Hz) at the dorsolateral forearm. Area under the curve (AUC), LEP amplitudes (N2P2), and peak latencies (N2, P2) were calculated. The paired samples t-test was used for statistical analysis. Results. A significant reduction of LEP amplitudes and AUC was found during and after the use of TENS (p < 0.05). After 10 min of TENS this was associated with a clinically relevant decrease of pain intensity. Conclusions. Our data suggest that TENS inhibits nociceptive processing. Ten minutes of TENS exerts a clinically relevant pain reduction.

Measurements of cerebrospinal fluid concentrations of S100beta protein during and after thoracic endovascular stent grafting.

OBJECTIVES: Thoracic endovascular aortic repair is associated with postoperative spinal cord ischemia in approximately 1 to 12.5% of all cases. S100beta is a protein that is released during acute damage of the central nervous system. This study was performed to determine the concentration of S100beta in cerebrospinal fluid during and after stenting of the thoracic aorta in patients at high risk for spinal cord ischemia. DESIGN: Prospective clinical study. MATERIALS AND METHODS: Eight patients who underwent elective thoracic aortic stent grafting underwent lumbar spinal fluid drainage. These patients were at high risk to develop spinal cord ischemia. METHODS: CSF samples for analysis of S100beta protein were drawn after induction of anesthesia, during stenting, once every hour the following six hours and 20 hours after repair. RESULTS: No significant increase in S100beta protein could be detected in CSF and no neurological deficits were detected postoperatively. CONCLUSIONS: The results of this study show us that there is no significant release of S100beta protein in CSF during stenting of the thoracic aorta in this subgroup of patients at high risk for spinal cord ischemia, consistent with clinical exam that there was no significant damage to the central nervous system.

Clinical prospective study of biochemical markers and evoked potentials for identifying adverse neurological outcome after thoracic and thoracoabdominal aortic aneurysm surgery.

BACKGROUND: Neurological deficit after repair of a thoracic or thoracoabdominal aortic aneurysm (TAA/TAAA) remains a devastating complication. The aim of our study was to investigate the clinical value of biochemical markers [S-100B, neurone-specific enolase (NSE) and lactate dehydrogenase (LD)], evoked potentials and their combinations for identifying adverse neurological outcome after TAA/TAAA surgery. METHODS: From 69 patients, cerebrospinal fluid and blood samples for biochemical analysis were drawn after the induction of anaesthesia, during the cross-clamp period, 5 min, 2, 4, 6, 8, and 19 h, respectively, after reperfusion. In addition, continuous perioperative recording of motor-evoked potentials after transcranial electrical stimulation (tcMEP) and somatosensory-evoked potentials was carried out. Furthermore, neurological examinations were performed. RESULTS: In patients with a defined decrease in lower extremity tcMEP during the cross-clamp period, we found that combinations of the serum concentrations of S-100B and tcMEP ratios at 4, 6, and 8 h after reperfusion had a positive and negative predictive value of 100% in predicting adverse neurological outcome after TAA/TAAA surgery. Furthermore, combinations of the serum concentrations of S-100B and NSE or LD at 19 h after reperfusion had both a positive and negative predictive value of 100% in identifying patients with adverse outcome after TAA/TAAA repair. CONCLUSIONS: TcMEP monitoring during TAA/TAAA surgery seems to be an effective but not completely sufficient guide in our protective multi-modality strategy. Combinations of the serum concentrations of S-100B and tcMEP ratios during the early reperfusion period might be associated with adverse neurological complications. Furthermore, biochemical markers could detect central nervous system injury on the first postoperative day and may have prognostic value.

Effect of nitrous oxide on myogenic motor potentials evoked by a six pulse train of transcranial electrical stimuli: a possible monitor for aortic surgery.

Intraoperative recording of myogenic motor potentials evoked by transcranial electrical stimulation (tcMEP) is a method of monitoring the integrity of the vulnerable motor pathways during thoracoabdominal aortic aneurysm (TAAA) surgery. Deflation of the left lung during TAAA surgery may result in impairment of arterial oxygenation. Ventilation with nitrous oxide may cause further desaturation. We studied the effects of 20%, 40% and 60% nitrous oxide in oxygen on within-patient variability and magnitude of tcMEP in response to six pulse transcranial electrical stimulation during fentanyl-low-dose propofol anaesthesia with partial neuromuscular block. Ten patients (two females; aged 63-74 yr) were studied. After achieving a stable anaesthetic state and before surgery, 10 tcMEP were recorded from the right tibialis anterior muscle during addition of 20%, 40% and 60% nitrous oxide in oxygen in random order. When ventilation with 40% or 60% nitrous oxide in oxygen was performed, there was 50-70% depression of tcMEP amplitude (P < 0.05) and 40-60% reduction in tcMEP area under the curve (P < 0.05) compared with 20% nitrous oxide in oxygen. There was no significant difference in the coefficients of variation for tcMEP between the three nitrous oxide anaesthetic regimens. Our results suggest that increasing doses of nitrous oxide reduce the MEP waveform to six pulse transcranial electrical stimulation, but even with 60% nitrous oxide in oxygen, the tcMEP were recordable and as reproducible as with 20% and 40% nitrous oxide regimens. The method is sufficiently robust for use in aortic surgery.

Within-patient variability of myogenic motor-evoked potentials to multipulse transcranial electrical stimulation during two levels of partial neuromuscular blockade in aortic surgery.

UNLABELLED: Intraoperative recording of myogenic motor responses evoked by transcranial electrical stimulation (tcMEPs) is a method of assessing the integrity of the motor pathways during aortic surgery. To identify conditions for optimal spinal cord monitoring, we investigated the effects of manipulating the level of neuromuscular blockade (T1 response of the train-of-four (TOF) stimulation 5%-15% versus T1 response 45%-55% of baseline), as well as the number of transcranial pulses (two versus six stimuli) on the within-patient variability and amplitude of tcMEPs. Ten patients (30-76 yr) scheduled to undergo surgery on the thoracic and thoracoabdominal aorta were studied. After achieving a stable anesthetic state and before surgery, 10 tcMEPs were recorded from the right extensor digitorum communis muscle and the right tibialis anterior muscle in response to two-pulse and six-pulse transcranial electrical stimulation with an interstimulus interval of 2 ms during two levels of neuromuscular blockade. The right thenar eminence was used for recording the level of relaxation. The tcMEP amplitude using the six-pulse paradigm was larger (P < 0.01; leg and arm) compared with the amplitude evoked by two-pulse stimulation during both levels of relaxation. The within-patient variability, expressed as median coefficient of variation, was less when six-pulse stimulation was used. At a T1 response of 45%-55% of baseline, larger, less variable tcMEPs were recorded than at a T1 response of 5%-15%. Our results suggest that the best quality of tcMEP signals (tibialis anterior muscle) is obtained when the six-pulse paradigm is used with a stable level of muscle relaxation (the first twitch of the TOF-thenar eminence-at 45%-55% of baseline). IMPLICATIONS: This study shows that six-pulse (rather than two-pulse) transcranial electrical stimulation during a stable anesthetic state and a stable neuromuscular blockade aimed at 45%-55% (rather than 5%-15%) of baseline provides reliable and recordable muscle responses sufficiently robust for spinal cord monitoring in aortic surgery.