Successful management of rocuronium-induced anaphylaxis with sugammadex: A case report.

Although anaphylaxis during anaesthesia is a rare event, neuromuscular blocking drugs are responsible for 62% of anaesthesia-related anaphylaxis. However, sugammadex, a modified gamma-cyclodextrin, can encapsulate rocuronium molecules and cause the rapid reversal of the neuromuscular blockade. A 68-year-old man who presented for a radical prostatectomy was induced with IV fentanyl/propofol/rocuronium. He had not received rocuronium previously but had received cisatracurium. Shortly after anaesthesia, the patient's heart rate abruptly increased, and systolic blood pressure (SBP) dropped to 40 mm Hg. Despite cardiopulmonary resuscitation and intensive management, his haemodynamic stability did not improve until he received IV sugammadex, 200 mg. Intradermal skin tests showed he was positive for cisatracurium, rocuronium and succinylcholine. The patient was suspected to have cross-reactivity of rocuronium with cisatracurium. This case highlights the potential benefit of sugammadex as an adjunct to conventional measures during rocuronium-induced anaphylaxis.

Correction to: 4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia-reperfusion through attenuating endoplasmic reticulum stress.

Unfortunately, Fig. 5 was incorrectly published in the original publication. The complete corrected Fig. 5 is given below.

4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia-reperfusion through attenuating endoplasmic reticulum stress.

Vasculitic peripheral neuropathy (VPN) is characterized by acute-to-subacute onset of painful sensory and motor disturbances that result from inflammatory obliteration of nerve blood vessels and subsequent ischaemic injury. Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of various peripheral neuropathies, and 4-phenylbutyric acid (4-PBA) is a chemical chaperone that inhibits ER stress signaling. We investigated the effects of 4-PBA on neuropathic pain associated with VPN induced by ischaemia-reperfusion (IR) and its underlying mechanisms. Male Sprague-Dawley rats were allocated to one of the following groups: sham, sham + 4-PBA, IR, and IR + 4-PBA. IR was achieved by occluding the femoral artery for 4 h followed by reperfusion. The behavioral parameters were assessed, and the expression of ER stress markers and nuclear factor (NF)-κB in sciatic nerves was measured. The behavioral data confirmed that VPN induced by IR leads to hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength, indicating the development of neuropathic pain and debilitating symptoms of VPN. The molecular data revealed that VPN induced by IR activated ER stress sensors and effector molecules as well as NF-κB in the sciatic nerves, indicating the involvement of ER stress and NF-κB-mediated neuroinflammation. Notably, 4-PBA significantly reduced the expression of all these markers and improved all behavioral changes induced by IR. This study demonstrated that ER stress and NF-κB-mediated neuroinflammation contribute to VPN induced by IR and that 4-PBA has protective potential against neuropathic pain associated with VPN.

Platonin preserves blood-brain barrier integrity in septic rats.

OBJECTIVES: Platonin possesses potent anti-inflammatory and antioxidative capacities. Because systemic inflammation and oxidative stress are crucial in mediating sepsis-induced blood-brain barrier (BBB) integrity loss, this study elucidated the effects of platonin on preserving BBB integrity in septic rats. METHODS: A total of 72 adult male rats (200-250 g) were randomized to receive cecal ligation and puncture (CLP), CLP plus platonin, sham operation, or sham operation plus platonin (n = 18 in each group). Systemic inflammation and oxidation levels and BBB integrity in the surviving rats were determined after 24-hour monitoring. RESULTS: Plasma levels of interleukin-6 (IL-6) and malondialdehyde (MDA)-markers of systemic inflammation and oxidation-and the grading of Evans blue staining of the brains, BBB permeability to Evans blue dye, and brain edema levels-markers of BBB integrity-in rats that received CLP were significantly higher than rats that received sham operation (all p < 0.001). By contrast, the plasma levels of IL-6 (p < 0.001) and MDA (p < 0.001), and the grading of Evans blue staining (p = 0.015), BBB permeability to Evans blue dye (p = 0.043), and brain edema levels (p = 0.034) in rats that received CLP plus platonin were significantly lower than rats that received CLP. Experimental data further revealed that the concentration of tight junction protein claudin-5, a major structural component of BBB, in rats that received CLP was significantly lower than rats that received CLP plus platonin (p = 0.023). CONCLUSION: Platonin could attenuate sepsis-induced BBB integrity loss in rats.

Minocycline ameliorates lung and liver dysfunction in a rodent model of hemorrhagic shock/resuscitation plus abdominal compartment syndrome.

BACKGROUND: We sought to elucidate whether minocycline, a broad-spectrum tetracycline antibiotic with potent anti-inflammation capacity, could mitigate inflammatory response and organ dysfunction in the lungs and liver induced by hemorrhagic shock/resuscitation (HS) plus abdominal compartment syndrome (ACS). MATERIALS AND METHODS: Adult male rats were randomized to receive HS plus ACS or HS plus ACS plus minocycline (denoted as the HS/A and HS/A-M group, respectively; n = 12). Sham-instrumentation groups were employed to serve as the controls. Hemorrhagic shock/resuscitation was induced by blood drawing (mean arterial pressure: 40-45 mm Hg for 60 min) followed by shed blood/saline mixture reinfusion. Subsequently, intra-abdominal pressure (IAP) was increased to 25 mm Hg by injecting air into the preplaced intraperitoneal latex balloon to induce ACS. Minocycline (20 mg/kg) was intravenously administered immediately after resuscitation. IAP was maintained at 25 mm Hg for 6 h. Then, all rats were euthanized. RESULTS: The levels of polymorphonuclear leukocyte infiltration, the wet/dry weight ratio, and the concentrations of inflammatory molecules (e.g., chemokine, cytokine, and prostaglandin E2) in lung and liver tissues of the HS/A group were significantly higher than those of the HS/A-M groups (all P < 0.05). Moreover, the levels of lung dysfunction (assayed by arterial blood gas) and liver dysfunction (assayed by plasma concentrations of bilirubin, aspartate aminotransferase, and alaninine aminotransferase) of the HS/A group were significantly higher than those of the HS/A-M group (all P < 0.05). CONCLUSIONS: Minocycline ameliorates inflammatory response and organ dysfunction in the lungs and liver induced by hemorrhagic shock/resuscitation plus abdominal compartment syndrome.

Adverse effects of bilateral lower limb ischemia-reperfusion on inducing kidney injuries in rats could be ameliorated by platonin.

OBJECTIVES: Bilateral lower limb ischemia-reperfusion (I/R) could cause significant oxidative stress, elicit inflammatory response, and subsequently induce kidney injury in animals. We tested the effects of platonin, a potent antioxidant, on mitigating the kidney injury induced by lower limb I/R in rats. METHODS: Adult male rats were allocated to receive I/R or I/R plus platonin (100 µg/kg intravenous injection immediately after reperfusion), and denoted as the I/R or the I/R-P group, respectively (n = 10 in each group). Sham groups were run simultaneously. Bilateral lower limb I/R was achieved by applying rubber-band tourniquets high around each thigh for 3 hours, followed by reperfusion for 6 hours. After sacrifice, the level of kidney injury was assayed. RESULTS: I/R significantly increased the plasma concentrations of blood urea nitrogen (BUN) and creatinine (Cr). However, this effect could be mitigated by platonin, as the plasma concentrations of BUN and Cr of the I/R-P group were significantly lower than those of the I/R group. Moreover, histological findings revealed moderate injury in kidney tissues of the I/R group and mild injury in those of the I/R-P group. In addition, the leukocyte infiltration and myeloperoxidase activity in kidney tissues as well as the renal concentrations of inflammatory molecules (i.e., cyclooxygenase-2/prostaglandin E(2), interleukin-6, and macrophage inflammatory protein-2) and malondialdehyde (i.e., the index of lipid peroxidation) of the I/R group were significantly higher than those of the I/R-P group. CONCLUSION: Platonin attenuates kidney injury induced by bilateral lower limb I/R in rats.

Limb ischemic preconditioning mitigates lung injury induced by haemorrhagic shock/resuscitation in rats.

AIM OF THE STUDY: Haemorrhagic shock and subsequent resuscitation induce acute lung injury. We elucidated whether bilateral lower limb ischemic pre-conditioning (IP) could mitigate lung injury in haemorrhagic shock/resuscitation rats. The role of heme oxygenase-1 (HO-1) was also elucidated. METHOD: Adult male rats were randomized to receive haemorrhagic shock/resuscitation (HS), HS plus IP, or HS plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Sham groups were employed simultaneously. For pre-conditioning, 3 cycles of limb IP (10 min ischemia followed by 10 min reperfusion) were performed immediately before haemorrhagic shock. Haemorrhagic shock (mean arterial pressure: 40-45 mmHg) was induced by blood drawing and maintained for 120 min. SnPP was injected 5 min before resuscitation. Shed blood/saline mixtures were re-infused to achieve resuscitation. After monitoring for another 8h, rats were sacrificed. Arterial blood gas and alveolar-arterial oxygen difference (lung function index), histology, polymorphonuclear leukocytes/alveoli ratio (leukocyte infiltration index), wet/dry weight ratio (water content index), inflammatory molecules (e.g., chemokine, cytokine, prostaglandin E(2)), and malondialdehyde (lipid peroxidation index) assays were preformed. RESULTS: Haemorrhagic shock/resuscitation induced significant lung function alterations and significant increases in leukocyte infiltration, water content, inflammation, and lipid peroxidation in lungs. Histological analysis confirmed that haemorrhagic shock/resuscitation caused marked lung injury. Limb IP significantly mitigated the adverse effects of haemorrhagic shock/resuscitation. Moreover, the protective effects of limb IP were reversed by SnPP. CONCLUSIONS: Limb IP mitigates lung injury in haemorrhagic shock/resuscitation rats. The mechanisms may involve HO-1.

Protective effects of dexmedetomidine-ketamine combination against ventilator-induced lung injury in endotoxemia rats.

BACKGROUND: Pulmonary inflammatory response is crucial in mediating the development of ventilator-induced lung injury (VILI) in animals experiencing endotoxemia. Dexmedetomidine and ketamine are two sedative agents with potent anti-inflammatory capacity. We sought to elucidate the anti-inflammatory effects of dexmedetomidine-ketamine combination against VILI in endotoxemia rats. MATERIALS AND METHODS: Eighty-four adult male rats were allocated to receive normal saline, VILI, VILI plus dexmedetomidine-ketamine combination (D+K), lipopolysaccharide (LPS), LPS plus D+K, LPS plus VILI, or LPS plus VILI plus D+K (designated as the NS, V, V-D+K, LPS, LPS-D+K, LPS/V, and LPS/V-D+K group, respectively; n = 12 in each group). VILI was induced by high-tidal volume ventilation (tidal volume 20 mL/kg; respiratory rate 50 breath/min; FiO(2) 21%). After being mechanically ventilated for 4 h, rats were sacrificed and the levels of pulmonary inflammatory response were evaluated. RESULTS: Histologic findings revealed severe, moderate, and mild inflammation in lung tissues of the LPS/V, LPS, and V groups, respectively, whereas those of the LPS/V-D+K, LPS-D+K, and V-D+K groups revealed moderate, mild, and normal to minimal inflammation, respectively. Moreover, the total cell number and the concentrations of macrophage inflammatory protein-2 and interleukin-1ß in bronchoalveolar lavage fluid as well as the lung water content, leukocyte infiltration, myeloperoxidase activity, and the concentrations of inducible nitric oxide synthase/nitric oxide, and cyclooxygenase 2/prostaglandin E(2) in lung tissues of the LPS/V, LPS, and V groups were significantly higher than those of the LPS/V-D+K, LPS-D+K, and V-D+K groups, respectively. CONCLUSIONS: Dexmedetomidine-ketamine combination could mitigate pulmonary inflammatory response induced by VILI in endotoxemia rats.

L-type calcium channels and µ-opioid receptors are involved in mediating the anti-inflammatory effects of naloxone.

BACKGROUND: We sought to elucidate the effects of naloxone on regulating the up-regulation of inflammatory molecules and activation of the transcription factor nuclear factor-kappaB (NF-κB) induced by endotoxin. Possible roles of the µ-opioid receptors and L-type calcium channels in mediating the effects of naloxone in this regard were also investigated. MATERIALS AND METHODS: RAW264.7 cells were treated with phosphate buffered saline, naloxone, lipopolysaccharide (LPS), LPS plus naloxone, LPS plus naloxone plus morphine (i.e., the nonselective opioid receptors agonist), LPS plus naloxone plus fentanyl (i.e., the µ-opioid receptors agonist), or LPS plus naloxone plus BAY-K8644 (i.e., the L-type calcium channel activator). After harvesting, production of inflammatory molecules and expression NF-κB were evaluated. RESULTS: The effects of LPS on inducing the up-regulation of macrophage inflammatory protein-2, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E(2)/cyclooxygenase 2 were inhibited by naloxone. Naloxone also inhibited the effects of LPS on inducing NF-κB activation, including inhibitor-κB (I-κB) degradation, NF-κB nuclear translocation, and NF-κB-DNA binding. The effects of naloxone on inhibiting IL-1ß up-regulation and NF-κB activation were enhanced by morphine. In contrast, the effects of naloxone on inhibiting IL-1ß up-regulation and I-κB degradation were counteracted by fentanyl. Moreover, except for TNF-α, the effects of naloxone on inhibiting inflammatory molecules up-regulation and NF-κB activation were significantly counteracted by BAY-K8644. CONCLUSIONS: Naloxone significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-κB activation. The mechanisms may involve antagonizing the L-type calcium channels and, to a lesser extent, the µ-opioid receptors.

Functional study of the effect of phosphatase inhibitors on KCNQ4 channels expressed in Xenopus oocytes.

AIM: KCNQ4 channels play an important part in adjusting the function of cochlear outer hair cells. The aim of this study was to investigate the effects of ser/thr phosphatase inhibitors on human KCNQ4 channels expressed in Xenopuslaevis oocytes. METHODS: Synthetic cRNA encoding human KCNQ4 channels was injected into Xenopus oocytes. We used a two-electrode voltage clamp to measure the ion currents in the oocytes. RESULTS: Wild-type KCNQ4 expressed in Xenopus oocytes showed the typical properties of slow activation kinetics and low threshold activation. The outward K(+) current was almost completely blocked by a KCNQ4 blocker, linopirdine (0.25 mmol/L). BIMI (a PKC inhibitor) prevented the effects of PMA (a PKC activator) on the KCNQ4 current, indicating that PKC may be involved in the regulation of KCNQ4 expressed in the Xenopus oocyte system. Treatment with the ser/thr phosphatase inhibitors, cyclosporine (2 micromol/L), calyculin A (2 micromol/L) or okadaic acid (1 micromol/L), caused a significant positive shift in V(1/2) and a decrease in the conductance of KCNQ4 channels. The V(1/2) was shifted from -14.6+/-0.5 to -6.4+/-0.4 mV by cyclosporine, -18.8+/-0.5 to -9.2+/-0.4 mV by calyculin A, and -14.1+/-0.5 to -0.7+/-0.6 mV by okadaic acid. Moreover, the effects of these phosphatase inhibitors (okadaic acid or calyculin A) on the induction of a positive shift of V(1/2) were augmented by further addition of PMA. CONCLUSION: These results indicate that ser/thr phosphatase inhibitors can induce a shift to more positive potentials of the activation curve of the KCNQ4 current. It is highly likely that the phosphatase functions to balance the phosphorylated state of substrate protein and thus has an important role in the regulation of human KCNQ4 channels expressed in Xenopus oocytes.

Sudden hearing loss after general anesthesia--a case report.

Hearing impairment following many types of neuraxial anesthetic techniques has alreadly been reported previously. However, postoperative sudden hearing loss after general anesthesia (excluding cardiopulmonary bypass cases) for nonotologic surgery is rarely reported. We present a 42-year-old female patient, who underwent ophthalmologic surgery under general anesthesia because of diabetic retinopathy and developed postoperative hearing loss of the left ear. Sensorineural hearing loss was diagnosed and it has persisted without improvement for 2 years following surgery.

Folding of the epiglottis - an unusual complication to be recognized after laryngoscopic endotracheal intubation.

We report a case of folding of the epiglottis during endotracheal intubation, an unusual complication of intubation. A 36-year-old female patient underwent laryngeal microsurgery for a vocal polyp. Following anesthesia induction, an endotracheal tube (ID = 6.0 mm, cuffed) was advanced through an intubating laryngoscope via the oropharyngeal route. At the beginning of the surgery, the otolaryngologist noted that the patient's epiglottis was folded under the view of the surgical laryngoscopy. The endotracheal tube was adjusted immediately by withdrawing it 0.5 cm with the cuff deflated. Slight edema of the upper ridge of the epiglottis was noted. There were no sequelae such as laryngeal spasm or vocal cord palsy after the surgery. The "peardrop" phenomenon is suggested as a possible cause of this event. Potential adverse outcomes of this unusual occurrence are reviewed.