Management of postoperative atrial fibrillation

The impact of postoperative atrial fibrillation (PAF) on patient outcomes has prompted intense investigation into the optimal methods for prevention and treatment of this complication. In the prevention of PAF, β-blockers and amiodarone are particularly effective and are recommended by guidelines. However, their use requires caution due to the possibility of drug-related adverse effects. Aside from these risks, perioperative prophylactic treatment with statins seems to be effective for preventing PAF and is associated with a low incidence of adverse effects. PAF can be treated by rhythm control, heart-rate control, and antithrombotic therapy. For the purpose of heart rate control, β-blockers, calcium-channel antagonists, and amiodarone are used. In patients with unstable hemodynamics, cardioversion may be performed for rhythm control. Antithrombotic therapy is used in addition to heart-rate maintenance therapy in cases of PAF >48-h duration or in cases with a history of cerebrovascular thromboembolism. Anticoagulation is the first choice for antithrombotic therapy, and anticoagulation management should focus on maintaining international normalized ratio (INRs) in the 2.0–3.0 range in patients <75 years of age, whereas prothrombin-time INR should be controlled to the 1.6–2.6 range in patients ≥75 years of age. In the future, dabigatran could be used for perioperative management of PAF, because it does not require regular monitoring and has a quick onset of action with short serum half-life. Preventing PAF is an important goal and requires specific perioperative management as well as other approaches. PAF is also associated with lifestyle-related diseases, which emphasizes the ongoing need for appropriate lifestyle management in individual patients

Evaluation of Pharyngeal Airway in Acromegaly

Objectives: Perioperative airway management may be particularly challenging in patients with acromegaly undergoing trans‐sphenoidal pituitary surgery (TSS). Management for airway obstruction is required prior to pituitary surgery to minimize perioperative hypoxia. The purpose of this retrospective study was to evaluate airway obstruction by simulation of computational fluid dynamics (CFD) using computed tomography (CT) images in patients who had undergone TSS. Methods: CT images of the nasopharyngeal airways of patients with acromegaly (n = 5) or nonfunctional pituitary adenoma (n = 6) undergoing TSS from April 2012 to January 2017 were used to construct these airways in three dimensions. Estimated airflow pressure and velocity in the retropalatal airway (RA), oropharyngeal airway (OA), and hypopharyngeal airway (HA) were simulated using CFD. Results: Estimated pharyngeal airflow pressure in the HA, OA, and RA was significantly greater in patients with acromegaly than in those with nonfunctional pituitary adenomas whereas the estimated pharyngeal airflow velocity was significantly impaired only in the RA of patients with acromegaly. Minimum postoperative SpO2 both within 3 hours and from 3 to 12 hours after the end of anesthesia was significantly lower in the patients with acromegaly. Additionally, estimated volume of tongue and pharyngeal airflow pressure in the HA, OA, and RA correlated with minimum postoperative SpO2. Conclusion: Pharyngeal airflow pressure estimated from CT images is high in patients with acromegaly, and these values correlate with postoperative minimum values for SpO2. Preoperative evaluation of CT images by CFD can predict difficulty in airway management and perioperative hypoxia

Orexin Receptor Blockade-Induced Sleep Preserves the Ability to Wake in the Presence of Threat in Mice

Retention of the ability to wake from sleep in response to dangerous situations is an ideal characteristic of safe hypnotics. We studied the effects of a dual orexin receptor antagonist-22 (DORA-22) and the GABA-A receptor modulator, triazolam, on the ability to wake in response to aversive stimuli. We examined four modalities of sensory inputs, namely, auditory (ultrasonic sound), vestibular (trembling), olfactory (predator odor), and autonomic (hypoxia) stimuli. When the mice fell asleep, one of the four stimuli was applied for 30 s. In the case of auditory stimulation, latency to arousal following vehicle, DORA-22, and triazolam administration was 3.0 (2.0–3.8), 3.5 (2.0–6.5), and 161 (117–267) s (median and 25–75 percentile in the parentheses, n = 8), respectively. Latency to return to sleep after arousal was 148 (95–183), 70 (43–98), and 60 (52–69) s, respectively. Similar results were obtained for vestibular and olfactory stimulation. During the hypoxic stimulation, latencies for arousal and returning to sleep were not significantly different among the groups. The findings of this study are consistent with the distinct mechanisms of these sleep promoting therapies; GABA-A receptor activation by triazolam is thought to induce widespread central nervous system (CNS) suppression while DORA-22 more specifically targets sleep/wake pathways through orexin receptor antagonism. These data support the notion that DORA-22 preserves the ability to wake in response to aversive and consciousness-inducing sensory stimuli, regardless of modality, while remaining effective in the absence of threat. This study provides a unique and important safety evaluation of the potential for certain hypnotics

Linalool Odor-Induced Anxiolytic Effects in Mice

In folk medicine, it has long been believed that odorous compounds derived from plant extracts can have anxiolytic effects. Among them, linalool, one of the terpene alcohols in lavender extracts, has been reported to have the anxiolytic effects. However, the anxiolytic nature of the linalool odor itself as well as its potential action through the olfactory system has not been thoroughly examined. In this study, we examined the anxiolytic effects of linalool odor with light/dark box test and with elevated plus maze (EPM), and found that linalool odor has an anxiolytic effect without motor impairment in mice. The effect was not observed in anosmic mice, indicating that it was triggered by olfactory input evoked by linalool odor. Furthermore, the effect was antagonized by flumazenil, indicating that the linalool odor-induced anxiolytic effect was mediated by γ-aminobutyric acid (GABA)ergic transmission via benzodiazepine (BDZ)-responsive GABAA receptors. These results provide information about the potential central neuronal mechanisms underlying the odor-induced anxiolytic effects and the foundation for exploring clinical application of linalool odor in anxiety treatments

Peripheral Administration of Morphine Attenuates Postincisional Pain by Regulating Macrophage Polarization through COX-2-Dependent Pathway

BACKGROUND: Macrophage infiltration to inflammatory sites promotes wound repair and may be involved in pain hypersensitivity after surgical incision. We recently reported that the development of hyperalgesia during chronic inflammation is regulated by macrophage polarity, often referred to as proinflammatory (M1) or anti-inflammatory (M2) macrophages. Although opioids such as morphine are known to alter the inflammatory milieu of incisional wounds through interactions with immunocytes, the macrophage-mediated effects of morphine on the development of postincisional pain have not been well investigated. In this study, we examined how morphine alters pain hypersensitivity through phenotypic shifts in local macrophages during the course of incision-induced inflammation. RESULTS: Local administration of morphine in the early phase, but not in the late phase alleviated mechanical hyperalgesia, and this effect was reversed by clodronate-induced peripheral depletion of local macrophages. At the morphine-injected incisional sites, the number of pro-inflammatory F4/80(+)iNOS(+)M1 macrophages was decreased during the course of pain development whereas increased infiltration of wound healing F4/80(+)CD206(+)M2 macrophages was observed during the early phase. Morphine increased the gene expression of endogenous opioid, proenkephalin, and decreased the pronociceptive cytokine, interleukin-1β. Heme oxygenase (HO)-1 promotes the differentiation of macrophages to the M2 phenotype. An inhibitor of HO-1, tin protoporphyrin reversed morphine-induced analgesic effects and the changes in macrophage phenotype. However, local expression levels of HO-1 were not altered by morphine. Conversely, cyclooxygenase (COX)-2, primarily produced from peripheral macrophages in acute inflammation states, was up-regulated in the early phase at morphine-injected sites. In addition, the analgesic effects and a phenotype switching of infiltrated macrophages by morphine was reversed by local administration of a COX inhibitor, indomethacin. CONCLUSIONS: Local administration of morphine alleviated the development of postincisional pain, possibly by altering macrophage polarity at the incisional sites. A morphine-induced shift in macrophage phenotype may be mediated by a COX-2-dependent mechanism. Therefore, μ-opioid receptor signaling in macrophages may be a potential therapeutic target during the early phase of postincisional pain development

Pituitary adenylate cyclase-activating polypeptide type 1 receptor signaling evokes long-lasting nociceptive behaviors through the activation of spinal astrocytes in mice

AbstractIntrathecal (i.t.) administration of pituitary adenylate cyclase-activating polypeptide (PACAP) induces long-lasting nociceptive behaviors for more than 60 min in mice, while the involvement of PACAP type1 receptor (PAC1-R) has not been clarified yet. The present study investigated signaling mechanisms of the PACAP-induced prolonged nociceptive behaviors. Single i.t. injection of a selective PAC1-R agonist, maxadilan (Max), mimicked nociceptive behaviors in a dose-dependent manner similar to PACAP. Pre- or post-treatment of a selective PAC1-R antagonist, max.d.4, significantly inhibited the nociceptive behaviors by PACAP or Max. Coadministration of a protein kinase A inhibitor, Rp-8-Br-cAMPS, a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase inhibitor, PD98059 or a c-Jun N-terminal kinase (JNK) inhibitor, SP600125, significantly inhibited the nociceptive behaviors by Max. Immunohistochemistry and immunoblotting analysis revealed that spinal administration of Max-induced ERK phosphorylation and JNK phosphorylation, and also augmented an astrocyte marker, glial fibrillary acidic protein in mouse spinal cord. Furthermore, an astroglial toxin, l-α-aminoadipate, significantly attenuated the development of the nociceptive behaviors and ERK phosphorylation by Max. These results suggest that the activation of spinal PAC1-R induces long-lasting nociception through the interaction of neurons and astrocytes

Odour-induced analgesia mediated by hypothalamic orexin neurons in mice

Various folk remedies employ certain odorous compounds with analgesic effects. In fact, linalool, a monoterpene alcohol found in lavender extracts, has been found to attenuate pain responses via subcutaneous, intraperitoneal, intrathecal, and oral administration. However, the analgesic effects of odorous compounds mediated by olfaction have not been thoroughly examined. We performed behavioural pain tests under odourant vapour exposure in mice. Among six odourant molecules examined, linalool significantly increased the pain threshold and attenuated pain behaviours. Olfactory bulb or epithelium lesion removed these effects, indicating that olfactory sensory input triggered the effects. Furthermore, immunohistochemical analysis revealed that linalool activated hypothalamic orexin neurons, one of the key mediators for pain processing. Formalin tests in orexin neuron-ablated and orexin peptide-deficient mice showed orexinergic transmission was essential for linalool odour-induced analgesia. Together, these findings reveal central analgesic circuits triggered by olfactory input in the mammalian brain and support a potential therapeutic approach for treating pain with linalool odour stimulation

Comparison of the MultiViewScope Stylet Scope and the direct laryngoscope with the Miller blade for the intubation in normal and difficult pediatric airways: A randomized, crossover, manikin study.

BACKGROUND:Managing difficult pediatric airway is challenging. The MultiViewScope (MVS) Stylet Scope is reported to be useful in difficult pediatric airway. In this randomized crossover study, we compared the effectiveness of the MVS Stylet Scope to a standard direct laryngoscope with Miller #1 blade in simulated normal and difficult airways. METHODS:Fifteen expert anesthesiologists and Fifteen anesthesiology residents participated in the study. Participants were asked to perform intubation with the Airsim Baby manikin first, and then with the Airsim Pierre Robin manikin. Participants in each group used the intubation devices in a randomized order. The primary outcome was the time of successful intubation. The secondary outcomes were the force exerted on the incisors during intubation, Cormack-Lehane scale, the difficulty of intubation. RESULTS:There were no differences between MVS Stylet Scope and Direct laryngoscope in the time of successful intubation by the expert anesthesiologists or the anesthesiology residents in a normal or difficult pediatric airway. MVS Stylet Scope significantly improved the force exerted on the incisors during intubation in the expert anesthesiologists or the anesthesiology residents in a normal or difficult pediatric airway. MVS Stylet Scope significantly improved Cormack-Lehane scale, and the difficulty of intubation with difficult pediatric airway situation in both expert anesthesiologists and anesthesiology residents. CONCLUSIONS:Although less forces on the incisors and improved view of glottis were observed with the MVS Stylet Scope, MVS Stylet Scope did not shorten the time of intubation. The results of this study mean that the MVS Stylet Scope may be a less invasive airway devise than the direct laryngoscope with the Miller blade in the pediatric airway management. For the next step, we need to evaluate the MVS Stylet Scope in the real patients as an observational study