Kohei Godai

Three cases of suspected sugammadex-induced hypersensitivity reactions.

Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.

Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone attenuates postincisional pain by regulating macrophage polarization.

Acute inflammation triggered by macrophage infiltration to injured tissue promotes wound repair and may induce pain hypersensitivity. Peroxisome proliferator-activated receptor γ (PPAR)γ signaling is known to regulate heterogeneity of macrophages, which are often referred to as classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages have considerable antimicrobial activity and produce a wide variety of proinflammatory cytokines. In contrast, M2 macrophages are involved in anti-inflammatory and homeostatic functions linked to wound healing and tissue repair. Although it has been suggested that PPARγ agonists attenuate pain hypersensitivity, the molecular mechanism of macrophage-mediated effects of PPARγ signaling on pain development has not been explored. In this study, we investigated the link between the phenotype switching of macrophage polarization induced by PPARγ signaling and the development of acute pain hypersensitivity. Local administration of rosiglitazone significantly ameliorated hypersensitivity to heat and mechanical stimuli, and paw swelling. Consistent with the down-regulation of nuclear factor κB (NFκB) phosphorylation by rosiglitazone at the incisional sites, the number of F4/80(+)iNOS(+) M1 macrophages was decreased whereas numbers of F4/80(+)CD206(+) M2 macrophages were increased in rosiglitazone-treated incisional sites 24 h after the procedure. In addition, gene induction of anti-inflammatory M2-macrophage-associated markers such as arginase1, FIZZ1 and interleukin (IL)-10 were significantly increased, whereas M1-macrophage-related molecules such as integrin αX, IL-1β, MIP2α and leptin were decreased at rosiglitazone-treated incisional sites. Moreover, transplantation of rosiglitazone-treated peritoneal macrophages into the incisional sites significantly attenuated hyperalgesia. We speculate that local administration of rosiglitazone significantly alleviated the development of postincisional pain, possibly through regulating macrophage polarity at the inflamed site. PPARγ signaling in macrophages may be a potential therapeutic target for the treatment of acute pain development.

Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone attenuates inflammatory pain through the induction of heme oxygenase-1 in macrophages

&NA; Activation of PPAR&ggr; signaling in macrophages promotes differentiation of macrophages to M2 phenotype. PPAR&ggr; agonist rosiglitazone attenuated CFA‐induced inflammatory pain by a PPAR&ggr;/HO‐1‐dependent pathway in macrophages. &NA; Macrophage infiltration to inflammatory sites promotes tissue repair and may be involved in pain hypersensitivity. Peroxisome proliferator‐activated receptor (PPAR)&ggr; signaling is known to regulate polarity of macrophages, which are often referred to as proinflammatory (M1) and antiinflammatory (M2) macrophages. We recently showed that the PPAR&ggr; agonist rosiglitazone ameliorated the development of postincisional hyperalgesia by increasing the influx of M2 macrophages to inflamed sites. It has been suggested that heme oxygenase (HO)‐1, upregulated by PPAR&ggr; signaling, promotes differentiation of macrophages to M2 phenotype. In this study, we investigated how rosiglitazone alters pain hypersensitivity by a PPAR&ggr;HO‐1‐dependent mechanism during the course of inflammation induced by complete Freund’s adjuvant. Local administration of rosiglitazone alleviated mechanical hyperalgesia, with increased gene induction of HO‐1. Phenotype switching of infiltrated macrophages to M2 by rosiglitazone was reversed by an HO‐1 inhibitor, tin protoporphyrin, at the inflamed sites. Direct stimulation of peritoneal macrophages with rosiglitazone also increased HO‐1 induction in the presence of lipopolysaccharide/interferon‐&ggr;. Moreover, rosiglitazone increased gene induction of endogenous opioid proenkephalin, both at inflamed sites and in isolated macrophages. Administration of naloxone blocked the analgesic effects of rosiglitazone. We speculate that rosiglitazone alleviated the development of inflammatory pain, possibly through regulating the M1/M2 balance at the inflamed site by a PPAR&ggr;/HO‐1‐dependent mechanism. PPAR&ggr; signaling in macrophages may be a potential therapeutic target for the treatment of acute pain development.

Peripheral administration of morphine attenuates postincisional pain by regulating macrophage polarization through COX-2-dependent pathway

BackgroundMacrophage 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.ResultsLocal 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.ConclusionsLocal 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.

Perfusion index as a possible predictor for postanesthetic shivering

BackgroundPostanesthetic shivering can be triggered by surgical stress and several aspects of anesthetic management and is frequently preceded by a decrease in peripheral blood flow due to thermoregulatory vasoconstriction. As perfusion index correlates with peripheral blood flow, we examined whether perioperative perfusion index, measured using pulse oximetry, might be correlated with postanesthetic shivering.MethodsTwenty-eight patients presenting for elective abdominal surgery were enrolled. Core (esophagus) and peripheral (finger) temperatures and perfusion index were recorded in the perioperative periods. Correlations between perfusion index and peripheral temperature and core-to-peripheral temperature gradient were then explored. Plasma levels of epinephrine and norepinephrine were also measured. The extent of shivering was graded after emergence from anesthesia.ResultsPerfusion index declined before emergence from anesthesia in patients who then developed postanesthetic shivering. This coincided with the time at which the difference between core and peripheral temperature became dissociated and peripheral temperature declined. Perioperative perfusion index was correlated with peripheral temperature and peripheral-core temperature gradient. Perfusion index at closure of the peritoneum predicted postanesthetic shivering and was significantly correlated with the extent of shivering. Plasma levels of both epinephrine and norepinephrine were significantly elevated after shivering events.ConclusionsPerfusion index was significantly lower in patients with postanesthetic shivering before emergence from anesthesia, indicating that measurement of perfusion index during and before the end of anesthesia might be a useful means of predicting postanesthetic shivering.

Successful airway management using a MultiViewScope handle with a stylet scope in a patient with Schwartz–Jampel syndrome

Schwartz–Jampel syndrome (SJS) is a rare disorder characterized by micrognathia, kyphoscoliosis, and myotonia. The greatest challenge in the anesthetic management of patients with SJS is performing tracheal intubation. The MultiViewScope (MVS) is a video laryngoscope system in which the video monitor handle can be attached to a stylet scope, laryngoscope blade, or fiberscope. We report a 21-month-old boy with SJS who required general anesthesia. Direct laryngoscopy was impossible because of his limited mouth opening; however, his trachea was easily intubated using an MVS handle with a stylet scope. The MVS is useful for managing difficult airways associated with SJS.

Phenylephrine does not improve oxygenation during one-lung ventilation: A randomized, double-blind, cross-over study

Background Phenylephrine is an α1 adrenergic receptor agonist that causes pulmonary vasoconstriction, and so may effectively enhance hypoxic pulmonary vasoconstriction (HPV). However, there is little evidence that phenylephrine augments HPV in clinical situations. This study aimed to evaluate the clinical effects of phenylephrine infusion on oxygenation during one-lung ventilation (OLV) in patients undergoing thoracic surgery. Methods This was a prospective, randomized, double-blind, cross-over study. Included patients were those undergoing elective thoracic surgery in the lateral decubitus position with OLV. Patients were randomly allocated to two groups. The N-P group initially had OLV with normal saline infusion for 30 minutes; after a 10 minute interval, OLV was then maintained with phenylephrine infusion for 30 minutes. The P-N group had the drug-infusion in the reverse order. The primary outcome was arterial partial pressure of oxygen. Secondary outcomes were mean arterial pressure, heart rate, pulse pressure variation, perfusion index, and difference between bladder and skin temperature. Statistical analysis was performed using the student t-test, Fishers exact test, and ANOVA for Cross-over design. P < 0.05 was considered statistically significant. Results Twenty-nine patients were analyzed. Although phenylephrine infusion significantly increased mean arterial pressure (P < 0.001), arterial partial pressure of oxygen did not differ between the two timepoints (P = 0.19). There was no carryover effect in arterial partial pressure of oxygen (P = 0.14). Phenylephrine infusion significantly decreased heart rate (P = 0.02) and pulse pressure variation (P < 0.001). Conclusions Phenylephrine infusion did not improve oxygenation during OLV. The present results indicate that phenylephrine does not have clinically meaningful effects on HPV. Trial registration University Hospital Medical Information Network 000024317

Difficult airway associated with bifid glottis and coexistent subglottic stenosis in a patient with Pallister–Hall syndrome: a case report

BackgroundPallister–Hall syndrome is a rare disorder characterized by hypothalamic hamartoma, hypopituitarism, bifid epiglottis, and micrognathia.Case presentationWe describe the airway management under general anesthesia of a 15-year-old female with Pallister–Hall syndrome whose airway was compromised with bifid epiglottis and acquired subglottic stenosis. The three options considered for airway management were tracheal intubation, a supraglottic device, and surgical tracheotomy. Tracheal intubation provides a secured airway, but extubation can be difficult. A supraglottic device minimizes airway injury, but it does not completely protect the airway from aspiration.ConclusionsThe patient’s airway was successfully managed using a supraglottic device with aspiration prophylaxis. Airway management devices should be selected according to each patients’ individual circumstances.

Schwartz–Jampel syndrome is not related to malignant hyperthermia

Schwartz–Jampel syndrome (SJS) is a rare syndrome that is clinically characterized by myotonia and skeletal abnormalities. Most reports regarding SJS have stated that patients with SJS are susceptible to malignant hyperthermia (MH). The statement is incorrect. There is no report showing that SJS is related to MH. Scientific evidence also shows that patients with myotonias are not susceptible to MH except for that with hypokalemic periodic paralysis. Medical practitioners must recognize that SJS is not related to MH.

Management of general anesthesia in a child with Miller–Dieker syndrome: a case report

Miller–Dieker syndrome (MDS) is a rare disorder characterized by type I lissencephaly and a distinctive facial appearance that may include prominent forehead, bitemporal hollowing, and micrognathia. MDS is associated with epilepsy. We here report an 18-month-old girl with MDS who required general anesthesia. The child had an extremely low Bispectral Index (BIS) value prior to undergoing general anesthesia. Her perioperative course was uneventful. This case highlights some of the important anesthetic concerns in patients with MDS, which include potentially difficult airways and extremely low BIS values.