Influence of nociceptive stimulation on analgesia nociception index (ANI) during propofol-remifentanil anaesthesia.

BACKGROUND: Measurement of the balance between nociception and anti-nociception during anaesthesia is challenging and not yet clinically established. The Surgical pleth index (SPI), derived from photoplethysmography, was proposed as a surrogate measure of nociception. Recently, the analgesia nociception index (ANI) derived by heart rate (HR) variability was developed. The aim of the present study was to challenge the ability of ANI compared with SPI to detect standardized noxious stimulation during propofol-remifentanil anaesthesia. METHODS: After Ethics approval and informed consent, 25 patients were anaesthetized with propofol [bispectral index (BIS) 30-60]. A laryngeal mask (LMA) was inserted and remifentanil stepwise increased to effect-site concentrations (Ce(remi)) of 0, 2, and 4 ng ml(-1). At each step, tetanic stimulation (STIM) was applied. ANI, SPI, BIS, HR, and mean arterial pressure (MAP) were obtained before and after LMA insertion and each STIM. Analysis was performed using Wilcoxon rank tests and calculation of prediction probabilities (P(K)). RESULTS: ANI and SPI, but not BIS, HR, or MAP, were significantly (P<0.05) changed at all examined steps. ANI response to STIM was (median [IQR]) -24 [-12-35], -30 [-20 - -40] and -13 [-5 - -27] at 0, 2 and 4 ng ml(-1) Ce(remi). However, prediction of movement to STIM was not better than by chance, as P(K) values were 0.41 (0.08) for ANI and 0.62 (0.08) for SPI. CONCLUSIONS: The two variables, ANI and SPI, enabled consistent reflection of stimulation during propofol-remifentanil anaesthesia. Nevertheless, ANI and SPI may improve detection but not prediction of a possible inadequate nociception-anti-nociception balance. Clinicaltrials.gov Identifier. NCT01522508.

Prediction of fluid responsiveness in infants and neonates undergoing congenital heart surgery.

BACKGROUND: Dynamic variables reliably predict fluid responsiveness (FR) in adults, but no data are available regarding their performance in infants. The aim of this prospective study was to assess whether pulse pressure variation (PPV) and stroke volume variation (SVV), in contrast to central venous pressure (CVP) and global end-diastolic volume (GEDV), are applicable in infants undergoing congenital heart surgery and to assess threshold values that may help to guide fluid administration in these patients. METHODS: Twenty-six anaesthetized infants, mean (sd) weight 9.7 (4.3) kg, were studied during closed-chest conditions and changing loading conditions before and after repair of congenital heart disease. Stroke volume index was measured by transoesophageal echocardiography (SVI(TOE)), CVP was measured via a central venous line, GEDV index (GEDVI) was measured by transpulmonary thermodilution, and PPV and SVV were monitored using the PiCCO monitoring system. RESULTS: Fifteen infants had increased SVI(TOE) with fluid loading ≥15% (responders); 11 infants were defined as non-responders. Analysing the relationship between CVP, GEDVI, SVV, and PPV at baseline with volume-induced percentage change in SVI(TOE), only PPV was significantly correlated with ΔSVI(TOE) both before (r=0.54, P=0.004) and after (r=0.73, P>0.0001). As assessed by receiver-operating characteristic curve analysis, only PPV accurately predicted FR before surgical repair [area under the curve (AUC): 0.79, P=0.01] and after surgical repair (AUC: 0.86, P=0.002). CONCLUSIONS: PPV, in contrast to SVV, CVP, and GEDVI, predicted FR in infants undergoing congenital heart surgery both before and after repair of congenital heart disease.

The effect of short time periods of pre-operative warming in the prevention of peri-operative hypothermia.

The aim of our study was to evaluate the performance of different durations of active pre-operative skin-surface warming (pre-warming) to prevent peri-operative hypothermia and postoperative shivering. We randomly assigned 200 patients, scheduled for surgery of 30-90 min under general anaesthesia, to receive passive insulation or forced-air skin surface warming for 10, 20 or 30 min. Body temperature was measured at the tympanic membrane. Shivering was graded by visual inspection. There were significant differences in changes of core temperature between the non-pre-warmed group and all the pre-warmed groups (p < 0.00001), but none between the three pre-warmed groups (p = 0.54). Without pre-warming, 38/55 (69%) patients became hypothermic (< 36 °C) at the end of anaesthesia, whereas only 7/52 (13%), 3/43 (7%) and 3/50 (6%) patients following 10, 20 or 30 min pre-warming, respectively, became hypothermic (p < 0.001 vs no pre-warming). Shivering was observed in 10 patients without, and in three, three and one patients with pre-warming in the respective groups (p = 0.02). Pre-warming of patients for only 10 or 20 min before general anaesthesia mostly prevents hypothermia and reduces shivering.

The shaker potassium channel is no target for xenon anesthesia in short-sleeping Drosophila melanogaster mutants.

BACKGROUND: Xenon seems to be an ideal anesthetic drug. To explore if next to the antagonism at the NMDA-receptor other molecular targets are involved, we tested the xenon requirement in short sleeping Drosophila shaker mutants and in na[har(38)]. METHODS: The Drosophila melanogaster strains wildtype Canton-S, na[har(38)], sh(102) and sh(mns), were raised and sleep was measured. Based on the response of the flies at different xenon concentrations, logEC50 values were calculated. RESULTS: The logEC50-values for WT Canton-S were 1.671 (1.601-1.742 95%-confidence intervall; n = 238; P versus sh(102) > 0,05), for sh(mns) 1.711 (1.650-1.773; n = 242; P versus WT Canton-S > 0,05). The logEC50-value for sh(102) was 1.594 (1.493-1.694; n = 261; P versus sh(mns) > 0.05). The logEC-value of na[har(38)] was 2.076 (1.619-2.532; n = 207; P versus sh(mns) < 0.05, versus sh(102) < 0.05, versus WT Canton-S < 0.05). P values for all shaker mutants were P > 0.05, while na[har(38)] was found to be hyposensitive compared to wildtype (P < 0.05). CONCLUSIONS: The xenon requirement in Drosophila melanogaster is not influenced by a single gene mutation at the shaker locus, whereas a reduced expression of a nonselective cation channel leads to an increased xenon requirement. This supports the thesis that xenon mediates its effects not only via an antagonism at the NMDA-receptor.

[Are deaf patients in Germany informed about their legal rights for a sign language interpreter?]. / Sind gehörlose Patienten in Deutschland über ihren gesetzlichen Dolmetscheranspruch informiert?

Deaf citizens are confronted with barriers in a health-care system shaped by hearing people. Therefore the German legislature provides a supply with sign language interpreters at the expense of the health insurances. The present study initially examines in how far the deaf are informed about this and use said interpreters. Traditional surveys are based on spoken and written language and therefore are unsuitable for the target audience. Because of this, a cross-sectional online study was performed using sign language videos and visually oriented answers to allow a barrier-free participation. With a multivariate analysis, factors increasing deaf people's risks not to be informed of the supply with interpreters were identified: Of 841 deaf participants, 31.4% were not informed of their rights. 41.3% have experience with an interpreter at the doctor's and report a mainly trouble-free reimbursement of costs. Young and modestly educated deaf have a higher risk of not being informed of the interpreter supply. Further information is necessary to provide equality of opportunities to deaf patients utilising medical benefits.

The Landé factors of electrons and holes in lead halide perovskites: universal dependence on the band gap.

The Landé or g-factors of charge carriers are decisive for the spin-dependent phenomena in solids and provide also information about the underlying electronic band structure. We present a comprehensive set of experimental data for values and anisotropies of the electron and hole Landé factors in hybrid organic-inorganic (MAPbI3, MAPb(Br0.5Cl0.5)3, MAPb(Br0.05Cl0.95)3, FAPbBr3, FA0.9Cs0.1PbI2.8Br0.2, MA=methylammonium and FA=formamidinium) and all-inorganic (CsPbBr3) lead halide perovskites, determined by pump-probe Kerr rotation and spin-flip Raman scattering in magnetic fields up to 10 T at cryogenic temperatures. Further, we use first-principles density functional theory (DFT) calculations in combination with tight-binding and k ⋅ p approaches to calculate microscopically the Landé factors. The results demonstrate their universal dependence on the band gap energy across the different perovskite material classes, which can be summarized in a universal semi-phenomenological expression, in good agreement with experiment.

Mitochondrial DNA depletion and fatal infantile hepatic failure due to mutations in the mitochondrial polymerase γ (POLG) gene: a combined morphological/enzyme histochemical and immunocytochemical/biochemical and molecular genetic study.

Combined morphological, immunocytochemical, biochemical and molecular genetic studies were performed on skeletal muscle, heart muscle and liver tissue of a 16-months boy with fatal liver failure. The pathological characterization of the tissues revealed a severe depletion of mtDNA (mitochondrial DNA) that was most pronounced in liver, followed by a less severe, but still significant depletion in skeletal muscle and the heart. The primary cause of the disease was linked to compound heterozygous mutations in the polymerase γ (POLG) gene (DNA polymerase γ; A467T, K1191N). We present evidence, that compound heterozygous POLG mutations lead to tissue selective impairment of mtDNA replication and thus to a mosaic defect pattern even in the severely affected liver. A variable defect pattern was found in liver, muscle and heart tissue as revealed by biochemical, cytochemical, immunocytochemical and in situ hybridization analysis. Functionally, a severe deficiency of cytochrome-c-oxidase (cox) activity was seen in the liver. Although mtDNA depletion was detected in heart and skeletal muscle, there was no cox deficiency in these tissues. Depletion of mtDNA and microdissection of cox-positive or negative areas correlated with the histological pattern in the liver. Interestingly, the mosaic pattern detected for cox-activity and mtDNA copy number fully aligned with the immunohistologically revealed defect pattern using Pol γ, mtSSB- and mtTFA-antibodies, thus substantiating the hypothesis that nuclear encoded proteins located within mitochondria become unstable and are degraded when they are not actively bound to mtDNA. Their disappearance could also aggravate the mtDNA depletion and contribute to the non-homogenous defect pattern.

Accuracy of the pleth variability index to predict fluid responsiveness depends on the perfusion index.

BACKGROUND: Respiratory variations in plethysmographic waveform amplitudes derived from pulse oximetry are believed to predict fluid responsiveness. The non-invasive pleth variability index (PVI) is a variable based on the calculation of changes in the perfusion index (PI). The aim of the following study was to examine whether the predictive power of PVI depends on different values of PI. METHODS: Eighty-one patients undergoing elective coronary artery surgery were studied before operation: at baseline after induction of anaesthesia and during passive leg raising (PLR). Each patient was monitored with central venous pressure (CVP), the PiCCO monitor and the non-invasive Masimo monitoring system. Stroke volume index by transpulmonary thermodilution (SVI(TPTD)), pulse pressure variation (PPV), stroke volume variation (SVV) and systemic vascular resistance index (SVRI) were measured using the PiCCO monitoring system. PI and PVI were obtained by pulse oximetry. RESULTS: Responders were defined to increase their SVI(TPTD) >15% after PLR. The highest area under the curve (AUC) was found for PPV (AUC: 0.83, P<0.0001) and SVV (AUC: 0.72, P=0.002), in contrast to PVI (AUC: 0.60, P=0.11) and CVP (AUC: 0.60, P=0.13). The accuracy of PVI to predict fluid responsiveness was improved on analysing patients with higher PI values. PI of about 4% (n=45) achieved statistical significance (AUC: 0.72, P=0.01). CONCLUSION: The PVI was not able to predict fluid responsiveness with sufficient accuracy. In patients with higher perfusion states, the PVI improved its ability to predict haemodynamic changes, strongly suggesting a relevant influence of the PI on the PVI.

Evaluation of the surgical stress index during spinal and general anaesthesia.

BACKGROUND: Although in modern anaesthesia, monitoring depth of anaesthesia and quality of neuromuscular block are routine, monitoring of analgesia still remains challenging. Recently, the surgical stress index (SSI), derived from finger photoplethysmographic signal, was introduced as a surrogate variable reflecting the nociception-antinociception balance. This study aimed at evaluating the SSI in patients undergoing regional anaesthesia either alone or combined with sedation compared with patients undergoing general anaesthesia (GA). METHODS: Seventy-one patients undergoing general (n=24) or spinal anaesthesia with (n=24) or without sedation (n=23) were included. SSI was measured the day before surgery and at defined time points during anaesthesia and surgery and also in the recovery room. SSI was compared with haemodynamic variables like heart rate and systolic arterial pressure. RESULTS: The SSI was higher in patients undergoing spinal anaesthesia [mean 65, CI (59.3-70.5)] compared with GA [48 (39.9-56.4), P<0.01], and baseline [41 (37.3-44.2), P<0.001]. During spinal anaesthesia with sedation [44 (36.2-50.9)], it was comparable with the baseline level (P>0.05). In comparison with baseline, SSI in the recovery room was higher in patients after GA [59 (48.4-67.9), P<0.025] but not after spinal anaesthesia [53 (47.6-60.1), P>0.05] or after spinal anaesthesia with sedation [54 (45.8-65.1), P>0.05]. Changes of the SSI were not reflected by changes of haemodynamic variables. CONCLUSIONS: In fully awake patients under spinal anaesthesia, the SSI does not reflect the nociception-antinociception balance. This may be due to the influence of mental stress on the sympathetic nervous system. Even light sedation attenuates these influences.

Surgical stress index in response to pacemaker stimulation or atropine.

BACKGROUND: The surgical stress index (SSI) is a new monitoring tool for the assessment of nociception during general anaesthesia. It is calculated based on the heart beat interval and the pulse wave amplitude. Correlation of SSI with nociceptive stimuli and opioid effect-site concentrations has been demonstrated, but the influence of isolated modulation of heart rate (HR) on SSI is still unclear. The aim of this study was to evaluate the effect on SSI of atropine administration and cardiac pacing. METHODS: In 18 anaesthetized ASA III ICU patients, either repetitive cardiac pacemaker stimulation or administration of atropine (10 microg kg(-1)) was performed, and the effect on SSI, arterial pressure, spectral entropy, and bispectral index was analysed. RESULTS: Cardiac pacing at 100 beats min(-1) was followed by an increase in SSI from 26 [17-35 (10-41)] to 59 [53-72 (48-78)] {median [inter-quartile range (range)]} (P=0.0006), whereas other variables remained unaffected. Also, atropine administration increased SSI from 27 [20-34 (16-39)] to 58 [48-70 (41-81)] (P=0.007) without significant effect on other variables except HR. A recalibration of SSI during cardiac pacing leads to a significant decrease in SSI to 49 [40-52 (36-57)] (P=0.03), whereas recalibration after atropine administration had no effect. CONCLUSIONS: SSI values measured in patients receiving atropine or in patients with pacemakers should be interpreted cautiously.

Correlation and agreement between the bispectral index vs. state entropy during hypothermic cardio-pulmonary bypass.

BACKGROUND: The bispectral index (BIS) and spectral entropy enable monitoring the depth of anaesthesia. Mild hypothermia has been shown to affect the ability of electroencephalography monitors to reflect the anaesthetic drug effect. The purpose of this study was to investigate the effect of hypothermia during a cardio-pulmonary bypass on the correlation and agreement between the BIS and entropy variables compared with normothermic conditions. METHODS: This prospective clinical study included coronary artery bypass grafting patients (n=25) evaluating correlation and agreement (Bland-Altman analysis) between the BIS and both spectral and response entropy during a hypothermic cardio-pulmonary bypass (31-34 degrees C) compared with nomothermic conditions (34-37.5 degrees C). Anaesthesia was maintained with propofol and sufentanil and adjusted clinically, while the anaesthetist was blinded to the monitors. RESULTS: The BIS and entropy values decreased during cooling (P<0.05), but the decrease was more pronounced for entropy variables compared with BIS (P<0.05). The correlation coefficients (bias+/-SD; percentage error) between the BIS vs. spectral state entropy and response entropy were r(2)=0.56 (1+/-11; 42%) and r(2)=0.58 (-2+/-11; 43%) under normothermic conditions, and r(2)=0.17 (10+/-12; 77%) and r(2)=0.18 (9+/-11; 68%) under hypothermic conditions, respectively. Bias was significantly increased under hypothermic conditions (P<0.001 vs. normothermia). CONCLUSION: Acceptable agreement was observed between the BIS and entropy variables under normothermic but not under hypothermic conditions. The BIS and entropy variables may therefore not be interchangeable during a hypothermic cardio-pulmonary bypass.

Differences between bispectral index and spectral entropy during xenon anaesthesia: a comparison with propofol anaesthesia.

We enrolled 114 patients, aged 65-83 years, undergoing elective surgery (duration > 2h) into a randomised, controlled study to evaluate the performance of bispectral index and spectral entropy for monitoring depth of xenon versus propofol anaesthesia. In the propofol group, bispectral index and state entropy values were comparable. In the xenon group, bispectral index values resembled those in the propofol group, but spectral entropy levels were significantly lower. Mean arterial blood pressure was higher and heart rate was lower in the xenon group than in the propofol group. Bispectral index and spectral entropy considerably diverged during xenon but not during propofol anaesthesia. We therefore conclude that these measures are not interchangeable for the assessment of depth of hypnosis and that bispectral index is likely to reflect actual depth of anaesthesia more precisely compared with spectral entropy.

Influence of different remifentanil concentrations on the performance of the surgical stress index to detect a standardized painful stimulus during sevoflurane anaesthesia.

BACKGROUND: Although measurement of cerebral hypnotic drug effect and muscle relaxation is common clinical routine during anaesthesia, a reliable measurement of the neurophysiological effects evoked by a painful stimulus is still missing. Recently, the surgical stress index (SSI) has been introduced as a surrogate measure of 'nociception'. The present study aimed to examine the influence of increasing remifentanil concentrations on the ability of SSI to detect a standardized painful stimulus during sevoflurane anaesthesia. METHODS: Twenty-four patients received incremental or decremental doses of 0, 2, and 4 ng ml(-1) remifentanil effect-site concentration (Ce(remi)) during 0.7 MAC sevoflurane. Painful tetanic stimulation was applied at least 5 min after changing Ce(remi). SSI, heart rate (HR), response entropy (RE), state entropy (SE), RE-SE difference, and bispectral index (BIS) were obtained in each patient before and after stimulation. Further prediction of an author-defined response to painful stimulus was analysed. RESULTS: SSI and BIS, but not HR, SE, RE, or RE-SE difference were significantly altered after stimulation. Change in SSI (Delta SSI) was significantly dependent on Ce(remi), as Delta SSI was [median (inter-quartile range)] 20 (15-31), 10 (1-19), and 3 (1-10) at 0, 2, and 4 ng ml(-1) Ce(remi). In 10 out of 63 cases, SSI detected response to stimulation, not detected by another variable. SSI was unable to predict movement after stimulation as P(K) value is 0.59 (0.09). CONCLUSIONS: The SSI response to tetanic stimulation was dependent on the remifentanil concentration.

[Cholesterol ester storage disease: a rare disease or a rare diagnosis?]. / Cholesterinesterspeicherkrankheit: Eine seltene, weil zu selten diagnostizierte Krankheit?

We report the case of a 13-year-old boy with a longstanding history of unspecific hepatomegaly. The morphological investigations were diagnostic of a cholesterol ester storage disease (CESD), a rare autosomal recessive inherited disease with deficient activity of lysosomal acid lipase (LAL). The combination of hepatomegaly with accumulation of macrophages and ultrastructural evidence of lysosomal lipid storage are groundbreaking for the diagnosis. The probability of a underdiagnosis or false disease classification, for example as nonalcoholic steatohepatitis (NASH), is high, particularly with regard to genetic data which indicate a higher incidence of the disease.

Overexpression of cyclin D1, D3, and p21 in an infantile renal carcinoma with Xp11.2 TFE3-gene fusion.

Renal carcinomas harboring the TFE-3 translocation are rare and occur predominately in children and adolescents. Here, we report a case of infantile renal carcinoma with TFE3 translocation and show that the cell cycle is deregulated in this type of carcinoma. It is characterized by nuclear accumulation of cyclin D1 and D3 in combination with high levels of cyclin-dependent kinase inhibitor p21Cip1/Waf1 but without accumulation of p53, p16INK4a, or mdm2. The combined overexpression of p21, cyclin D1, and cyclin D3 was found exclusively in this type but not in other, more common types of renal carcinoma/oncocytoma (n=27). These results further underscore that renal carcinomas with Xp11. 2 translocations/TFE3-gene fusion represent a special type of renal neoplasm showing deregulation of specific cell cycle components. The analysis of further cases has to prove whether the derangement of the cell cycle is uniform and correlates with the specific type of molecular genetic derangement.

[Prevention of perioperative hypothermia : Implementation of the S3 guideline]. / Vermeidung perioperativer Hypothermie : Umsetzung der S3-Leitlinie.

To improve perioperative quality and patient safety, the German S3 guideline should be consistently implemented to avoid perioperative hypothermia. Perioperative normothermia is a quality indicator and should be achieved by anesthesiologists and surgeons. To detect hypothermia early during the perioperative process, measuring body temperature should be started 1-2 h preoperatively. Patients should be actively warmed for 20-30 min before starting anesthesia. Prewarming is most effective and should be included in the preoperative process. Patients should be informed about the risks of perioperative hypothermia and members of the perioperative team should be educated. A standard operating procedure (SOP) to avoid hypothermia should be introduced in every operative unit. The incidence of postoperative hypothermia should be evaluated in operative patients every 3-6 months. The goals should be to measure body temperature in >80% of patients undergoing surgery and for >70% to exhibit a core temperature >36 °C at the end of surgery.

Nanoscale analysis of the oxidation state and surface termination of praseodymium oxide ultrathin films on ruthenium(0001).

The complex structure and morphology of ultrathin praseodymia films deposited on a ruthenium(0001) single crystal substrate by reactive molecular beam epitaxy is analyzed by intensity-voltage low-energy electron microscopy in combination with theoretical calculations within an ab initio scattering theory. A rich coexistence of various nanoscale crystalline surface structures is identified for the as-grown samples, notably comprising two distinct oxygen-terminated hexagonal Pr2O3(0001) surface phases as well as a cubic Pr2O3(111) and a fluorite PrO2(111) surface component. Furthermore, scattering theory reveals a striking similarity between the electron reflectivity spectra of praseodymia and ceria due to very efficient screening of the nuclear charge by the extra 4f electron in the former case.

Aggressive scapular chondroblastoma with secondary metastasis--a case report and review of literature.

Chondroblastoma is a benign bone tumor, accounting for approximately one percent of all benign bone tumors. It mostly occurs in typical locations such as long bones. Malignant transformation including metastasis has been described in only a few cases. Therefore, we report a unique case of chondroblastoma with tumor manifestation in the 7th decade of life, location of the tumor in the scapula and occurrence of metastasis in the soft tissue of the mandible branch. Due to aggravation of the clinical course, a scapula en bloc resection was performed. The differential diagnosis is discussed and the current literature concerning malignant transformation of chondroblastoma is reviewed.

Benign symmetric lipomatosis with axonal neuropathy and abnormalities in specific mitochondrial tRNA regions.

Benign symmetric lipomatosis, also called Madelung's disease, is characterized by lipomata and fatty infiltrations. Involvement of the nervous system has occasionally been described, mitochondrial dysfunctions have been suggested. We report a 55 year old male suffering from benign symmetric lipomatosis with associated axonal neuropathy and hyperlipoproteinemia. He showed a remarkable phenotype of neuropathy i.e. no sensory disturbance, ubiquitous fasciculations and muscle cramps, furthermore reduced COX activity and abnormalities in specific mitochondrial tRNA regions.

Expression of multiple endocrine neoplasia 2B RET in neuroblastoma cells alters cell adhesion in vitro, enhances metastatic behavior in vivo, and activates Jun kinase.

Point mutations, deletions, and recombinations of the RET proto-oncogene are associated with several inherited human diseases of neural crest-derived cells: Hirschsprung's disease, familial medullary thyroid carcinoma, and the multiple endocrine neoplasia (MEN) syndromes, types 2A and 2B. RET expression is restricted to normal and malignant cells of neural crest origin, such as human neuroblastoma cells. To better understand the role of the activated RET oncogene in neural crest cells, we transfected two adherent human neuroblastoma tumor cell lines with oncogenic MEN2 mutant RET cDNAs. Transfectant clones from both cell lines overexpressing MEN2B RET demonstrated a marked increase in the cell fraction growing in suspension. Both control and MEN2B cells formed tumors at the site of injection in all cases. However, mice injected with MEN2B cells developed lung metastases at a much higher frequency than control mice. Only RET protein derived from MEN2A transfectant cells had increased autokinase activity, whereas MEN2B transfectant cells demonstrated selective activation of the mitogen-activated protein kinase, Jun kinase-1 (Jnk1). These results indicate a biochemical signaling pathway that may link oncogenic RET with the metastatic process.