Anaesthetic efficacy and postinduction hypotension with remimazolam compared with propofol: a multicentre randomised controlled trial.

Remimazolam, a short-acting benzodiazepine, may be used for induction and maintenance of total intravenous anaesthesia, but its role in the management of patients with multiple comorbidities remains unclear. In this phase 3 randomised controlled trial, we compared the anaesthetic efficacy and the incidence of postinduction hypotension during total intravenous anaesthesia with remimazolam vs. propofol. A total of 365 patients (ASA physical status 3 or 4) scheduled for elective surgery were assigned randomly to receive total intravenous anaesthesia with remimazolam (n = 270) or propofol (n = 95). Primary outcome was anaesthetic effect, quantified as the percentage of time with Narcotrend® Index values ≤ 60, during surgery (skin incision to last skin suture), with a non-inferiority margin of -10%. Secondary outcome was the incidence of postinduction hypotensive events. Mean (SD) percentage of time with Narcotrend Index values ≤ 60 during surgery across all patients receiving remimazolam (93% (20.7)) was non-inferior to propofol (99% (4.2)), mean difference (97.5%CI) -6.28% (-8.89-infinite); p = 0.003. Mean (SD) number of postinduction hypotension events was 62 (38.1) and 71 (41.1) for patients allocated to the remimazolam and propofol groups, respectively; p = 0.015. Noradrenaline administration events (requirement for a bolus and/or infusion) were also lower in patients allocated to remimazolam compared with propofol (14 (13.5) vs. 20 (14.6), respectively; p < 0.001). In conclusion, in patients who were ASA physical status 3 or 4, the anaesthetic effect of remimazolam was non-inferior to propofol.

Prehospital management of patients with suspected acute coronary syndrome : Real world experience reflecting current guidelines.

BACKGROUND: In case of suspected acute coronary syndrome (ACS), international guidelines recommend to obtain a 12-lead ECG as soon as possible after first medical contact, to administrate platelet aggregation inhibitors and antithrombins, and to transfer the patient as quickly as possible to an emergency department. METHODS: A German emergency care service database was retrospectively analysed from 2014 to 2016. Data were tested for normal distribution and the Mann-Whitney test was used for statistical analysis. Results are presented as medians (IQR). RESULTS: A total of 1424 patients with suspected ACS were included in the present analysis. A 12-lead ECG was documented in 96% of patients (n = 1369). The prehospital incidence of ST-segment elevation myocardial infarction (STEMI) was 18% (n = 250). In 981 patients (69%), acetylsalicylic acid (ASA), unfractionated heparin (UFH), or ASA and UFH was given. Time in prehospital care differed significantly between non-STEMI (NSTEMI) ACS (37 [IQR 30, 44] min) and STEMI patients (33 [IQR 26, 40] min, n = 1395, p < 0.0001). Most of NSTEMI ACS and STEMI patients were brought to the emergency care unit, while 30% of STEMI patients were directly handed over to a cardiac catheterization laboratory. CONCLUSIONS: Prehospital ECG helps to identify patients with STEMI, which occurs in 18% of suspected ACS. Patients without ST-elevations suffered from longer prehospital care times. Thus, it is tempting to speculate that ST-elevations in patients prompt prehospital medical teams to act more efficiently while the absence of ST-elevations even in patients with suspected ACS might cause unintended delays. Moreover, this analysis suggests the need for further efforts to make the cardiac catheterization laboratory the standard hand-over location for all STEMI patients.

[Is deep anesthesia dangerous?]. / Ist tiefe Narkose gefährlich?

Regarding the question of an adequate depth of anesthesia, over the past decade anesthesiologists have focused on the prevention of intraoperative consciousness in combination with explicit memory. Recent studies approached the topic from a different way postulating that deep anesthesia, quantified as time with a bispectral index (BIS)< 45, is associated with increased postoperative mortality and four out of the five published studies revealed such a correlation. However, the finding is limited by a suboptimal study design, e.g. none of the studies presented randomized data. Furthermore, it is ambiguous whether the correlation is causal as the administration of deep anesthesia determines higher postoperative mortality or the study results reveal an epiphenomenon. An epiphenomenon implies e.g. that patients with cancer respond to general anesthesia with deeper cortical depression. In summary, as long as there is a lack of adequately performed randomized trials, there is no reason why anesthesiologists should change the current practice.

Sensitive cardiac troponin in the diagnosis and risk stratification of acute heart failure.

BACKGROUND: The aim of our study was to investigate the diagnostic and prognostic value of a sensitive cardiac troponin I (s-cTnI) assay in patients with acute heart failure (AHF). METHODS: Sensitive cardiac troponin I was measured in 667 consecutive patients at presentation to the emergency department with acute dyspnoea. Three s-cTnI strata were predefined: below the limit of detection (<0.01 µg L(-1) , undetectable), detectable but still within the normal range (0.01-0.027 µg L(-1) ) and increased (≥0.028 µg L(-1) , ≥99th percentile). The final diagnosis was adjudicated by two independent cardiologists blinded to the s-cTnI levels. Median follow-up in patients with AHF was 371 days. RESULTS: Levels of s-cTnI were higher in patients with AHF (n = 377, 57%) compared to patients with noncardiac causes of acute dyspnoea (median 0.02 vs. <0.01 µg L(-1) , P < 0.001). In patients with AHF, in-hospital mortality increased with increasing s-cTnI in the three strata (2%, 5% and 14%, P < 0.001). One-year mortality also increased with increasing s-cTnI (21%, 33% and 47%, P < 0.001). s-cTnI remained an independent predictor of 1-year mortality [adjusted odds ratio 1.03 for each increase of 0.1 µg L(-1) , 95% confidence interval (CI) 1.02-1.05, P < 0.001] after adjustment for other risk factors including B-type natriuretic peptide. The net reclassification improvement was 68% (P < 0.001), and absolute integrated discrimination improvement was 0.18 (P < 0.001). The diagnostic accuracy of s-cTnI for the diagnosis of AHF as quantified by the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.75-0.82). CONCLUSIONS: Sensitive cardiac troponin I is a strong predictor of short- and long-term prognosis in AHF that helps to reclassify patients in terms of mortality risk. Detectable levels of s-cTnI, even within the normal range, are independently associated with mortality.

Organotypic cultures as tools for testing neuroactive drugs - link between in-vitro and in-vivo experiments.

The development of neuroactive drugs is a time consuming procedure. Candidate drugs must be run through a battery of tests, including receptor studies and behavioural tests on animals. As a rule, numerous substances with promising properties as assessed in receptor studies must be eliminated from the development pipeline in advanced test phases because of unforeseen problems like intolerable side-effects or unsatisfactory performance in the whole organism. Clearly, test systems of intermediate complexity would alleviate this inefficiency. In this review, we propose cultured organotypic brain slices as model systems that could bridge the 'interpolation gap' between receptors and the brain, with a focus on the development of new general anaesthetics with lesser side effects. General anaesthesia is based on the modulation of neurotransmitter receptors and other conductances located on neurons in diverse brain regions, including cerebral cortex and spinal cord. It is well known that different components of general anaesthesia, e.g. hypnosis and immobility, are produced by the depression of neuronal activity in distinct brain regions. The ventral horn of the spinal cord is an important structure for the induction of immobility. Thus, the potentially immobilizing effects of a newly designed drug can be estimated from its depressant effect on neuronal network activity in cultured spinal slices. A drug's sedative and hypnotic potential can be examined in cortical cultures. Combined with genetically engineered mice, this approach can point to receptor subtypes most relevant to the drug's intended net effect and in return can help in the design of more selective drugs. In conclusion, the use of organotypic cultures permits predictions of neuroactive properties of newly designed drugs on an intermediate level, and should therefore open up avenues for a more creative and economic drug development process.

Inhibitory ligand-gated ion channels as substrates for general anesthetic actions.

General anesthetics have been in clinical use for more than 160 years. Nevertheless, their mechanism of action is still only poorly understood. In this review, we describe studies suggesting that inhibitory ligand-gated ion channels are potential targets for general anesthetics in vitro and describe how the involvement of y-aminobutyric acid (GABA)(A) receptor subtypes in anesthetic actions could be demonstrated by genetic studies in vivo.

[The GABA(A) receptor family: possibilities for the development of better anesthetics]. / Die GABA(A)-Rezeptor-Familie: Möglichkeiten für die Entwicklung besserer Anästhetika.

Clinically used anesthetics show amnestic, sedative, hypnotic and immobilizing properties. On a molecular level these drugs affect several receptors in the cell membrane of neurons. By using genetically engineered mice a linkage can now be made between actions on certain receptors and clinically desired and undesired effects. Experiments show that a certain GABA(A) receptor subtype mediates hypnosis and immobility, whereas another subtype is involved in side-effects like sedation and hypothermia. These findings form the basis for the development of new drugs, acting highly specific and with fewer side-effects.

Chorionicity inaccurately predicted by early ultrasound: a case report.

Ultrasound has been found to be extremely accurate in diagnosing the chorionicity of multiple gestations. Prenatal counselling and/or planning for selective termination is most often based on the sonographic prediction of chorionicity. We present a case of triplet pregnancy in which early sonographic prediction of chorionicity did not match the pathological diagnosis at delivery.

External cephalic version with ruptured membranes and adequate amniotic fluid volume.

The use of external cephalic version in the patient with ruptured membranes is examined and the first successful reported case is described. No difficulties or complications were encountered. We conclude that use of this procedure in the presence of ruptured membranes has been unjustly slighted and that external version may offer an important alternative to the patient with ruptured membranes, adequate amniotic fluid, and malpresentation. We caution that this should only be attempted under continuous monitoring, in patients with adequate amniotic fluid, and in facilities where immediate cesarean section is available. We believe that a larger trial is warranted, and we encourage that this be done.

A comparison of early and delayed induction of labor with spontaneous rupture of membranes at term.

The management of women with spontaneous rupture of membranes at term in the absence of labor and with a cervix unfavorable for induction of labor is controversial. In this randomized study of 182 patients, we report the effects of delayed versus early induction of labor on maternal and neonatal outcome. Qualifying patients not in labor at 6 hours after spontaneous rupture of membranes were randomized to either immediate oxytocin induction (86 women) or expectant management with oxytocin induction at 24 hours if labor had not occurred spontaneously (96 women). The cesarean section rate did not differ between the two groups. Women in the delayed group had significantly longer hospitalization (P less than .003), and their infants were significantly more likely to receive antibiotics (P = .006). Infectious morbidity (positive cultures or x-ray-documented pneumonia) occurred in five of the neonates in the delayed group, all of whose mothers had an initial digital cervical examination, but in none of the neonates in the early group, a difference that did not reach statistical significance (P = .061). Five (28%) of 18 infants from the delayed group whose mothers had received an initial digital cervical examination became infected, compared with none of the 78 infants from the delayed group whose mothers did not have digital examinations (P less than .001). We conclude that there is no advantage to delaying induction of labor when women present at term with spontaneous rupture of membranes.

Diaphanography in the diagnosis of breast cancer.

In diaphanography, a light source is applied to the breast to visualize lesions through a television camera sensitive to infrared light. Diaphanography and mammography were performed on 1,476 patients in a screening population. Twenty-six cancers in 24 patients were confirmed by biopsy; detection rates were 96% for mammography, 58% for diaphanography, and 62% for physical examination. Mammography was significantly more sensitive than either diaphanography or physical examination (p less than 0.005). Mammography detected 10 cancers that were missed at physical examination, whereas diaphanography detected five such lesions. It is concluded that diaphanography does not satisfy the criteria of a screening procedure, but because the examination is completely innocuous, it may serve as an adjunct to physical examination. In addition, the authors developed a breast model for diaphanography that appears to correlate with the human breast and demonstrates some of the physics and limitations of diaphanography.

Evolution of chick type I procollagen genes.

Although the major types of vertebrate collagen have a number of structural properties in common, significant DNA sequence homologies have not been detected between different portions of the helical coding domains within the same gene or between different genes. However, under non-stringen hybridization conditions we found considerable cross-homology within and between alpha 1(I) and alpha 2(I) chick cDNAs in the coding regions for helical sequences. Detailed analyses at the DNA sequence level have led us to propose that the gene for chick pro alpha 2(I) collagen arose from a 9-bp primordial sequence. A consensus sequence for the 9-bp repeat was derived: GGTCCTCCT, which codes for a Gly-Pro-Pro triplet. The primordial ancestor of this 9-bp unit, GGTCCTXCT, apparently underwent duplication and divergence. Each resulting 9-bp sequence was triplicated to form a 27-bp domain, and a condensation event produced a 54-bp domain. This genetic unit then underwent multiple rounds of amplification to form the ancestral gene for the full-length helical section of alpha 2(I). A different 9-bp consensus sequence (GGTCCCCCC) seems to have been the basis of the chick pro alpha 1(I) gene.