Editorial: Optimizing opioid prescriptions in the emergency department.

Optimizing opioid prescriptions in the emergency department is essential to address the opioid pandemic while ensuring patient wellbeing. This requires a comprehensive approach that includes exploring alternatives to opioids for pain management, identifying individuals at risk for opioid addiction, implementing evidence-based guidelines, and involving doctors in the management of opioid addiction.

Difficult airway management and low Bispectral Index (BIS) in a patient with left Bochdalek congenital diaphragmatic hernia (CDH).

BACKGROUND: Bochdalek congenital diaphragmatic hernia (CDH) is a developmental defect in the posterolateral diaphragm, allowing herniation of abdominal contents into the thorax causing mechanical compression of the developing lung parenchyma and lung hypoplasia. We describe a case of an adult patient with a Bochdalek hernia who underwent minimally invasive right thoracotomy Perceval bioprosthetic aortic valve replacement (AVR) requiring one-lung ventilation (OLV) on the side of the hernia. This is a complex and challenging case that brings up numerous thought-provoking anesthetic implications. To the best of our knowledge, a Pubmed search did not reveal any publication to date of difficult airway management in an adult patient with CDH. CASE PRESENTATION: The first major problem encountered was patient's crus habitus anatomical condition (exceedingly ventrally displaced trachea) Mallampati Class IV and Cormack-Lehane grade IV extremely difficult endotracheal intubation. Neither glottis nor epiglottis was visible on laryngoscopy; resulting in failed placement of the double-lumen endobronchial tube (DLT) following numerous attempts. The DLT was eventually placed via GlideScope videolaryngoscopy. Whereas the endobroncheal right lung block for left OLV was successfully placed using fiberopticscopy. The crus habitus encroached on OLV tidal volume by the cranially displaced ascending colon and left kidney. Anesthesia was maintained with remifentanil /sevoflurane; adjusted to maintain bispectral index (BIS) at 40-60. Digitally recorded BIS was 38-62 except when BIS precipitously declined to 14-38 (SR, suppression ratio < 10) for 25 min after termination of the cardiopulmonary bypass. CONCLUSIONS: We report a case essentially dealing with an anatomically distorted difficult airway in a patient with left Bochdalek CDH undergoing a complex AVR. We describe anesthetic difficulties and unforeseen issues encountered; such as an extremely difficult DLT placement.

Migraine, interferon ß1a and siponimod immunomodulator therapies.

BACKGROUND: Autoimmunity seems to play a great role in the pathogenesis of migraine headache pain. There is far more evidence that interferon can exacerbate migraines. We report a case where remission of severe comorbid migraine attacks happened with the start of interferon ß1a (Merck, Netherlands) immunomodulation therapy. Therapy for multiple sclerosis was decided according to the severity of the debilitating comorbid migraine headache pain rather than the evolution of multiple sclerosis the far more serious disease. CASE PRESENTATION: A 63-years old patient suffered for 30-years from migraine headache of severe disability assessment scale (MIDAS) Grade-IV = 27. He also suffered for 25-years from optic-sensory relapsing remitting multiple sclerosis (RRMS). Subcutaneous interferon ß1a 44-µg immunomodulation therapy for 4-years resulted in multiple sclerosis complete remission. The start of interferon ß1a therapy for multiple sclerosis seemed to help resolving the comorbid migraine attacks. The visual aura premonitory symptom preceding migraine headache would end up with a feeling of post visual aura clearer field of vision and a feeling of wellbeing. As the patient developed secondary progressive multiple sclerosis (SPMS), oral siponimod 2 mg (Novartis, Ireland), currently the only available therapy for SPMS, replaced his interferon therapy. This was associated with a relapse of migraine severe attacks. Reverting back to interferon therapy was again associated with migraine headache remission. CONCLUSIONS: Interferon ß1a might be an efficic therapy for "autoimmune migraine". With numerous immunomodulators currently available for other systemic autoimmune diseases associated with comorbid migraine; examining the effect of these immunomodulatory therapies on comorbid migraine headache could be beneficial in finding a specific immunomodulator therapy for "autoimmune migraine".

Location matters: Overlooked ethnic-geographic effect in China and Austria on propofol/cisatracurium sex differences among a population pharmacokinetic/pharmacodynamic (PopPK/PD) covariate analysis in men, women, and one transgender subject.

A quick literature search using "sex/gender" vs. the commonly used hypnotic propofol or neuromuscular-blocking agent cisatracurium will reveal numerous contradictory sex difference publications depending on the ethnic-geographic location of where these studies were conducted. We induced anesthesia with cisatracurium besylate (GlaxoSmithKline) 100 µg kg-1 administered exactly 1 minute following propofol (AstraZeneca) 2 mg kg-1 . In 20 male and 20 female ethnic Han-Chinese test set patients (Xi'an China), and in similar ethnic white Austrian validation set patients (Graz Austria), we quantified propofol/cisatracurium pharmacodynamic parameters namely propofol onset time, lag time, plasma concentrations (Cp ) at loss-of-behavioral response (LOBR) using bispectral index (BIS); cisatracurium onset time, lag time, and Cp at T1 % (first twitch of train-of-four) complete twitch suppression using mechanomyography (MMG). Serial arterial blood samples were collected for population pharmacokinetic (PopPK) analysis of all demographic and biological covariates (region, sex, age, weight, and height) versus volumes of distribution and clearances pharmacokinetic parameters. In Chinese women (but not in white women), propofol Cp at LOBR was 33.60% lower than men and cisatracurium Cp at T1 % complete twitch suppression was 21.49% lower than men, a clear pharmacodynamic assertion. Region and weight were significant PopPK covariates. We demonstrated that sex differences are influenced by ethnic-geographic location as only in Chinese women (but not in white women) propofol Cp at LOBR and cisatracurium Cp at T1 % complete twitch suppression were lower than in men. When defining sex differences, ethnic-geographic location should be taken into consideration as a predictive factor for optimizing propofol/cisatracurium initial loading recommended dosages.

Propofol-Bispectral Index (BIS) Electroencephalography (EEG) Pharmacokinetic-Pharmacodynamic Model in Patients With Post-Cerebral Hemorrhage Hydrocephalus.

Background. Titrating hypnotic agents for patients who suffer from a cerebral insult is a challenging task. To date there is no real gold standard to precisely quantify electroencephalography (EEG) response in a fashion that could be utilized for patients with post-cerebral hemorrhage hydrocephaly. While we must administer "as per usual" analgesics for noxious stimuli, we have to administer the hypnotic agents more "sparingly" due to lack of objective monitoring. Methods. We compared 15 adult post-cerebral hemorrhage hydrocephalus patients undergoing ventriculo-peritoneal shunt placement with 15 controls matched for gender and approximate age. We set propofol target controlled infusion estimated plasma concentrations (Cp) to gradually reach 4 µg/mL over 4 minutes. To precisely quantify post-cerebral hemorrhage mental dysfunction, we used electronically retrieved bispectral index (BIS) and propofol Cp data points to create individual inhibitory monophasic mathematical model for each patient that incorporates an independent hysteresis "lag" function. Results. In post-cerebral hemorrhage patients Cp-BIS curve, C50 (propofol concentration associated with inhibitory 50% BIS response) cutoff point was significantly shifted to the left by 39%. Whereas before infusion and at stable propofol 4 µg/mL aneurismal surgical sides ipsilateral (75 ± 13, 25 ± 9) and contralateral (73 ± 15, 27 ± 9) mean ± SD BIS values were significantly lower than ipsilateral (95 ± 3, 46 ± 12) and contralateral (94 ± 3, 46 ± 12) matched controls. Conclusions. Using BIS as surrogate marker of propofol hypnotic effect, BIS monitoring in patients with post-cerebral hemorrhage hydrocephaly showed a pattern of change and trend that was similar albeit 39% significantly lower than subjects without.

Age progression from vicenarians (20-29 year) to nonagenarians (90-99 year) among a population pharmacokinetic/pharmacodynamic (PopPk-PD) covariate analysis of propofol-bispectral index (BIS) electroencephalography.

BACKGROUND: Pharmacokinetic/pharmacodynamic (PK/PD) modeling has made an enormous contribution to intravenous anesthesia. Because of their altered physiological, pharmacological and pathological aspects, titrating general anesthesia in the elderly is a challenging task. METHODS: Eighty patients were consecutively enrolled divided by decades from vicenarians (20-29 year) to nonagenarians (90-99 year) into eight groups. Using target controlled infusion (TCI) and electroencephalographic (EEG)-derived bispectral index (BIS) we set propofol plasma concentration (Cp) to gradually reach 3.5 µg mL-1 over 3.5-min. In each patient, we constructed a PK/PD model and conducted a population PK/PD (PopPK-PD) covariate analysis. RESULTS: Age was significant covariate for baseline BIS effect (E0), inhibitory propofol concentration at 50% BIS decline (IC50) and maximum BIS decline (Emax). First-order rate constant Ke0 of 0.47 min-1 in vicenarians (20-29 year) gradually increased with age-progression to 1.85 min-1 in nonagenarians (90-99 year). Simulation modelling showed that clinically recommended Cp of 3.5 µg mL-1 for 20-29 year BIS 50 should be reduced to 3.0 for 30-49 year, 2.5 for 50-69 year and 2.0 for 80-89 year. CONCLUSION: We quantified and graded EEG-BIS age-progression among different age groups divided by decades. We demonstrated deeper BIS values with decades' age progression. Our data has important implications for propofol dosing. The practical information for physicians in their daily clinical practice is using propofol Cp of 3.5 µg mL-1 might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of Cp 3.5 µg mL-1 for 20-29 year should be gradually decreased to 2.0 µg mL-1 for 80-89 year. CLINICAL TRIAL REGISTRY NUMBERS: European Community Clinical Trials Database EudraCT (http://eudract.emea.eu) initial trial registration number: 2011-002847-81, and subsequently registered at www.clinicaltrials.gov; trial registration number: NCT02585284. Xijing Hospital of Fourth Military Medical University ethics committee approval number 20110707-4.

Correction to: Mindray 3-directional NMT Module (a new generation "Tri-axial" neuromuscular monitor) versus the Relaxometer mechanomyograph and versus the TOF-Watch SX acceleromyograph.

In the original publication of the article, the article note "Ashraf A. Dahaba and Zhao Yang Xiao equally contributed to the study and are both first authors." was published incorrectly. The correct statement should read as "Ashraf A. Dahaba and Zhao Yang Xiao equally contributed to the study and are both first authors and are both co-corresponding authors."

Benefits and boundaries of processed electroencephalography (pEEG) monitors when they do not concur with standard anesthetic clinical monitoring: lights and shadows.

Numerous clinical conditions that have a direct effect on electroencephalography (EEG) cerebral function could also directly influence brain function monitors (BFM) indices. There is no conventional comparator technology for BFM assessment. The conventional comparator technology used as a benchmark for assessing BFMs technologies chosen by the UK National Institute for Health and Care Excellence (NICE) to reflect the currently used standards in the National Health Service (NHS), was demarcated as "standard anesthetic clinical monitoring" and precisely defined as "the combination of routine clinical observation and electronic monitoring used in clinical practice to assess the adequacy of anesthesia." Because BFMs are EEG-derived parameters, all conditions that can "alter" the raw EEG signal would subsequently change BFM indices to reflect other unrelated EEG events of patient-dependent pathophysiologic perturbations. In many instances we are often confronted with disparate BFM values that do not concur with "standard anesthetic clinical monitoring". Changes in BFM indices during acute cerebral pathology would be highly beneficial to trained informed clinicians as it alerts to something they would not otherwise be aware was happening. This fact-based, citation-supported, narrative review article provides better understanding of BFMs' limitations through examining various published reports of all values that did not coincide with a "standard anesthetic clinical monitoring" whether arising from an underlying alteration of patients' own EEG or those due to shortcomings in the BFM design or performance. The notion of just "riding the numbers" seems to be not a good anesthesia practice; rather we should interpret these BFM indices within context and limitations.

Mindray 3-directional NMT Module (a new generation "Tri-axial" neuromuscular monitor) versus the Relaxometer mechanomyograph and versus the TOF-Watch SX acceleromyograph.

Recently introduced Mindray "3-directional" neuromuscular transmission transducer (NMT, Shenzhen, China) acceleromyograph) claim to monitor thumb movement in 3 different directions. We compared NMT with the gold standard Relaxometer® mechanomyograph (MMG, Groningen University, Netherlands) in Study-1 and with TOF-Watch SX™ (WTCH) acceleromyograph from which it was developed in Study-2. We used first twitch (T1%) and train-of-four (TOF) ratio rocuronium 0.6 mg kg-1 neuromuscular block to evaluate NMT diagnostic accuracy in indicating 3 clinically relevant time points namely; MMG T1 5% (95% twitch depression) for tracheal intubation, MMG T1 25% for repeat neuromuscular blocking agents (NMBAs) administration, and MMG 0.9 TOF ratio full neuromuscular block recovery. We compared onset time (time from beginning of rocuronium administration until maximal depression), Dur25 (time until T1 25% recovery) and Dur0.9 (time until 0.9 TOF ratio recovery). In Study-1, NMT showed low sensitivity in indicating MMG time for tracheal intubation, repeat NMBAs administration and full neuromuscular block recovery (6.25%, 38.9% and 38.9% respectively). NMT onset time, Dur25 and Dur0.9 (2:51 ± 00:57, 36:50 ± 24:25, 70:08 ± 25:27 min:s) were significantly longer than MMG (1:56 ± 00:46, 30:26 ± 20:24, 62:03 ± 20:01). In Study-2, NMT onset time, Dur25 and Dur0.9 (02:37 ± 00:53, 35:38 ± 11:54, 53:40 ± 13:49) were not significantly different than WTCH (02:23 ± 00:45, 33:27 ± 12:51, 53:57 ± 12:47). NMT could not efficaciously detect MMG time for tracheal intubation; NMBAs repeat dose administration or full neuromuscular block recovery. Data from NMT cannot be used interchangeably with MMG. Our study revealed that NMT Tri-axial acceleromyography seems to offer no advantage over the MMG gold standard or the classic Mono-axial TOF-Watch SX monitor.

Thinking outside the box. Off-label use of Bispectral Index within context and limitations for conditions other than depth of anesthesia.

Numerous articles appeared in literature using brain function monitors (BFM), such as Bispectral Index (BIS) to assess cerebral cognitive conditions not related to depth of anesthesia. BIS cannot be considered a "true" reflection of the electroencephalography (EEG) signal nor an independent measure of brain function. BIS algorithm was retrospectively derived from EEG changes with incremental doses of γ-amino butyric acid (GABA)ergic anesthetic agents while measuring 3 descriptors. In many instances we are confronted with BIS values that do not concur with clinically judged anesthetic state arising from an underlying alteration of the patients' own EEG. Because BIS is an EEG derived parameter; conditions that can "alter" the raw EEG signal would subsequently change BIS to reflect other unrelated EEG events of patient-dependent pathophysiologic perturbations. Could we use BIS monitor outside the scope of the operating room to "grade" other EEG conditions? Actually the answer to that seems to be a "very cautious" yes. Because BIS is a rather appealing scale from 100 to 0, it is tempting to find numerical cut-off values for conditions that are already clinically graded like West Haven hepatic encephalopathy. Having said that I strongly argue against going as far as using BIS in Critical Care Unit (CCU) setting, there are too much heterogeneity and many disease states in the CCU patients, other than sedatives /hypnotics, that would strongly influence BIS values, in effect rendering BIS not only useless most of the time but can also be misleading.

Correction to: Advances in anesthesia technology are improving patient care, but many challenges remain.

Unfortunately, after publication of this article [1], it was noticed that the name of Ashraf A. Dahaba is incorrectly displayed as Ashraf Dahaba. The full, corrected author list can be seen here.

Advances in anesthesia technology are improving patient care, but many challenges remain.

Although significant advances in clinical monitoring technology and clinical practice development have taken place in the last several decades, in this editorial we argue that much more still needs to be done. We begin by identifying many of the improvements in perioperative technology that have become available in recent years; these include electroencephalographic depth of anesthesia monitoring, bedside ultrasonography, advanced neuromuscular transmission monitoring systems, and other developments. We then discuss some of the perioperative technical challenges that remain to be satisfactorily addressed, such as products that incorporate poor software design or offer a confusing user interface. Finally we suggest that the journal support initiatives to help remedy this problem by publishing reports on the evaluation of medical equipment as a means to restore the link between clinical research and clinical end-users.

The "Plateau" Phenomenon of Stepwise Extracorporeal Albumin Dialysis Bispectral Index Hepatic Encephalopathy Recovery.

The Bispectral Index™ monitor, an electroencephalographic-derived parameter, can quantify hepatic encephalopathy cerebral function recovery and differentiate between West Haven grades 1 to 4. I report a very peculiar "plateau" phenomenon of 3 clear distinct plateaus of stepwise albumin dialysis Bispectral Index hepatic encephalopathy recovery during an 8-hour Molecular Adsorbent Recirculating System™ (MARS™) liver-assist extracorporeal detoxification, manifesting in conjunction with 3 West Haven grade recoveries. In the patients, I observed recovery of cerebral function after hepatic encephalopathy as a series of plateaus with abrupt transitions between the plateaus, rather than the gradual recovery I anticipated.