Risk factors for postoperative nausea and vomiting after thoracoscopic pulmonary wedge resection: pitfalls of an increased fentanyl dose.

BACKGROUND: Thoracoscopic pulmonary wedge resection (TPWR) is a surgical procedure that can maintain lung function and is less physically invasive to a patient. However, the risk factors for postoperative nausea and vomiting (PONV) following TPWR remain unknown. We aimed to evaluate multiple risk factors of PONV after TPWR and the impact of PONV on postoperative outcomes. METHODS: We retrospectively reviewed consecutive patients who underwent TPWR for malignant pulmonary tumors at our institution between October 2017 and March 2020. We assessed the differences in the clinical and perioperative parameters between the PONV and non-PONV groups. RESULTS: We reviewed 160 patients, of whom 27 (16.9%) had PONV. Sixteen (59.3%) patients with PONV required postoperative antiemetics. Failed mobilization was associated with PONV requiring postoperative antiemetics (P=0.048). In the multivariate analysis, increased fentanyl dose was an independent risk factor for PONV (P=0.022). Using the receiver operating characteristic curve, the optimal cut-off value for PONV was 3.58 µg/kg/hr (area under the curve =0.665; sensitivity =85.2%; specificity =53.4%; 95% confidence interval: 0.562-0.768; P=0.007). For example, in a case of a 50-kg patient who underwent a 70-min operation (our median operative time), the total dose of fentanyl within 208 µg was the cut-off value for preventing PONV. CONCLUSIONS: An increased dose of fentanyl/kg/h was the strongest risk factor for PONV during TPWR. The optimal cut-off value for PONV was 3.58 µg/kg/hr. It is important to avoid the inadvertent administration of intraoperative fentanyl.

Life-threatening massive bleeding in the pulmonary trunk adjacent to the right ventricular outflow tract during the resection of a large mediastinal germ cell tumor: proposed safety measures in the absence of cardiovascular surgeons: a case report.

This report presents an unusual case of life-threatening massive bleeding in the pulmonary trunk adjacent to the right ventricular outflow tract during resection of a large primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) in the absence of cardiovascular surgeons. The patient was a 21-year-old male whose large mediastinal tumor was diagnosed as an extragonadal PMNSGCT, which was a mixture of a yolk sac tumor and an immature teratoma. Generally, chemotherapy causes extensive peripheral tumor necrosis of PMNSGCTs, thus enabling their complete resection. In this case, surgeons considered the resection as possible by dissecting the peripheral necrotic tissue, and cardiovascular surgeons were thus not consulted. Enlarged modified left hemi-clamshell thoracotomy (HCST) was applied. While dissecting around the pulmonary trunk, the assistant-held forceps accidentally touched the tensed pulmonary trunk, which caused bleeding. We immediately contacted the collaborating cardiac surgery department at another hospital for assistance. Meanwhile, massive bleeding occurred, leading to hemorrhagic shock, and thus direct cardiac massage was required. Our team managed to establish a venoarterial (VA) extracorporeal membrane oxygenation (ECMO). After the arrival of cardiac surgeons, a suction circuit was added, and bleeding was stopped using sutures. Finally, complete resection of the tumor was achieved, and the patient awoke the following day without any brain dysfunction. After discussions with all the members involved in the surgery, we developed an in-hospital consensus on how to perform surgeries for large thoracic tumors safely at our cancer center without the cardiovascular surgery department. We herein present the case and consensus and discuss the relevant issues.

Spinal epidural hematoma during anticoagulant therapy for pulmonary embolism: postoperative complications in a patient with lung cancer.

Spinal epidural hematoma (SEH) is rare but causes neurological disorders. Rapid diagnosis and treatment maximize neurological recovery. We present the case of SEH after lung cancer surgery under epidural and general anesthesia. A 64-year-old man underwent right upper lobectomy. Pulmonary embolism occurred on postoperative day 2. Anticoagulant therapy with fondaparinux and warfarin was started 2 hours after epidural catheter removal and he gradually recovered. On postoperative day 13, the level of prothrombin time-international normalized ratio reached 1.47 and fondaparinux administration was stopped. The next day, he developed back pain and paraplegia, and magnetic resonance imaging revealed a mass between Th4 and Th7 compressing the spinal cord. Emergency decompression laminectomy and hematoma evacuation were performed. After 2.5 months of rehabilitation, he regained almost all motor function and sensation. Late after epidural anesthesia, attention should be paid to possible SEH even though appropriate anticoagulant therapy had been initiated after epidural catheter removal.

Polaprezinc Protects Mice against Endotoxin Shock.

Polaprezinc (PZ), a chelate compound consisting of zinc and l-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-alpha levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after LPS injection. PZ inhibited the increases in plasma NO as well as TNF-alpha after LPS. Compatibly, PZ suppressed LPS-induced inducible NO synthase mRNA transcription in the mouse lungs. PZ also improved LPS-induced lung injury. However, PZ did not enhance the induction of heat shock protein (HSP) 70 in the mouse lungs after LPS. Pretreatment of RAW264 cells with PZ suppressed the production of NO and TNF-alpha after LPS addition. This inhibition likely resulted from the inhibitory effect of PZ on LPS-mediated nuclear factor-kappaB (NF-kappaB) activation. Zinc sulfate, but not Car, suppressed NO production after LPS. These results indicate that PZ, in particular its zinc subcomponent, inhibits LPS-induced endotoxin shock via the inhibition of NF-kappaB activation and subsequent induction of proinflammatory products such as NO and TNF-alpha, but not HSP induction.

Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70.

Polaprezinc, a chelate compound consisting of zinc and l-carnosine, is clinically used as a medicine for gastric ulcers. It has been shown that induction of heat shock protein (HSP) is involved in protective effects of polaprezinc against gastric mucosal injury. In the present study, we investigated whether polaprezinc and its components could induce HSP70 and prevent acetaminophen (APAP) toxicity in mouse primary cultured hepatocytes. Hepatocytes were treated with polaprezinc, zinc sulfate or l-carnosine at the concentration of 100 microM for 9 h, and then exposed to 10 mM APAP. Polaprezinc or zinc sulfate increased cellular HSP70 expression. However, l-carnosine had no influence on it. Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment. In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP. Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP. These results suggested that polaprezinc, in particular its zinc component, induces HSP70 expression in mouse primary cultured hepatocytes, and inhibits lipid peroxidation after APAP treatment, resulting in protection against APAP toxicity.

Priming with rocuronium or vecuronium prevents remifentanil-mediated muscle rigidity and difficult ventilation.

PURPOSE: The aim of this study was to test our hypothesis that priming with rocuronium would prevent muscle rigidity and difficult ventilation due to remifentanil administration. METHODS: One hundred patients, American Society of Anesthesiologists (ASA) status I or II, were recruited into the study, and randomly allocated to one of four protocols (n = 25 each). Remifentanil was administered at 0.2 microg.kg(-1).min(-1) in group A and at 0.7 microg.kg(-1).min(-1) in groups B, C, and D. Priming with vecuronium (0.02 mg.kg(-1)) or rocuronium (0.06 mg.kg(-1)) was performed at the same time as the infusion of remifentanil in groups C and D, respectively. Anesthesia was induced with 1 mg.kg(-1)propofol 2 min after the start of remifentanil infusion. After the patient had lost consciousness, the anesthesiologist performed mask ventilation, and watched for the presence of muscle rigidity. Ventilation and rigidity were evaluated using a scoring system. RESULTS: Of the 100 patients, 9 were excluded; the number of patients in group A was 24, while groups B and D had 22 patients each, and group C had 23 patients. A lower dose of remifentanil (group A) or priming with vecuronium or rocuronium (groups C, D) significantly reduced the incidence of some difficulty with ventilation (P = 0.0010, P = 0.0053, and P = 0.021, respectively, vs group B). Of the patients in group B, 10 (45.5%) developed some difficulty with ventilation, and ventilation was impossible in 2 of them. On the other hand, 1 (4.1%) of the patients in group A, 2 (8.7%) in group C, and 3 (13.6%) in group D developed some difficulty with ventilation. CONCLUSION: The present study showed that priming with rocuronium or vecuronium reduced the incidence of difficult ventilation by avoiding the muscle rigidity caused by remifentanil.

Sealing of a tracheoesophageal fistula using a Sengstaken-Blakemore tube for mechanical ventilation during general anesthesia.

A 78-yr-old man was admitted to our hospital because of repeated episodes of pneumonia. Both fiberoptic bronchoscopy and esophagoscopy revealed a large tracheoesophageal fistula and protrusion of the metal stent from the esophagus into the trachea. Placement of a Dumon stent was planned for sealing this fistula under general anesthesia. Anesthetic management is difficult because of the care needed to prevent aspiration of esophageal contents and diversion of oxygen through the fistula into the stomach from the trachea when patients are under mechanical ventilation. Our method of sealing a large tracheoesophageal fistula with a Sengstaken-Blakemore tube was performed successfully.

Geranylgeranylacetone ameliorates inflammatory response to lipopolysaccharide (LPS) in murine macrophages: inhibition of LPS binding to the cell surface.

We investigated whether pretreatment with geranylgeranylacetone (GGA), a potent heat shock protein (HSP) inducer, could inhibit proinflammatory cytokine liberation and nitric oxide (NO) production in lipopolysaccharide (LPS)-treated murine macrophages. The levels of NO and tumor necrosis factor-alpha (TNF-alpha) released from murine macrophage RAW 264 cells were increased dose- and time-dependently following treatment with LPS (1 microg/ml). GGA (80 microM) treatment 2 h before LPS addition significantly suppressed TNF-alpha and NO productions at 12 h and 24 h after LPS, respectively, indicating that GGA inhibits activation of macrophages. However, replacement by fresh culture medium before LPS treatment abolished the inhibitory effect of GGA on NO production in LPS-treated cells. Furthermore, GGA inhibited both HSP70 and inducible NO synthase expressions induced by LPS treatment despite an HSP inducer. When it was examined whether GGA interacts with LPS and/or affects expression of Toll-like receptor 4 (TLR4) and CD14 on the cell surface, GGA inhibited the binding of LPS to the cell surface, while GGA did not affect TLR4 and CD14 expressions. These results indicate that GGA suppresses the binding of LPS to the cell surface of macrophages, resulting in inhibiting signal transduction downstream of TLR4.

Mechanisms of protection by melatonin against acetaminophen-induced liver injury in mice.

The present study was performed to determine whether melatonin protects mouse liver against severe damage induced by acetaminophen (APAP) administration and where melatonin primarily functions in the metabolic pathway of APAP to protect mouse liver against APAP-induced injury. Treatment of mice with melatonin (50 or 100 mg/kg, p.o.) 8 or 4 hr before APAP administration (750 mg/kg, p.o.) suppressed the increase in plasma alanine aminotransferase and aspartate aminotransferase activities in a dose- and a time-dependent manner. Melatonin treatment (100 mg/kg, p.o.) 4 hr before APAP administration remarkably inhibited centrilobular hepatic necrosis with inflammatory cell infiltration and increases in hepatic lipid peroxidation and myeloperoxidase activity, an index of tissue neutrophil infiltration, as well as release of nitric oxide and interleukin-6 into blood circulation at 9 hr after APAP administration. However, melatonin neither affected hepatic reduced glutathione (GSH) content nor spared hepatic GSH consumption by APAP treatment. Moreover, pretreatment with melatonin 4 hr before APAP administration did not influence the induction of hepatic heat shock protein 70 (HSP70) by APAP and melatonin alone did not induce HSP70 in mouse liver. These results indicate that exogenously administered melatonin exhibits a potent hepatoprotective effect against APAP-induced hepatic damage probably downstream of the activity of cytochrome P450 2E1, which works upstream of GSH conjugation in the pathway of APAP metabolism, via its anti-nitrosative and anti-inflammatory activities in addition to its antioxidant activity.

Geranylgeranylacetone protects against acetaminophen-induced hepatotoxicity by inducing heat shock protein 70.

Geranylgeranylacetone (GGA), an anti-ulcer drug, has been reported to induce heat shock protein (HSP) 70 in several animal organs. The present study was performed to determine whether GGA protects mouse liver against acetaminophen (APAP)-induced injury and whether it has potential as a therapeutic agent for APAP overdose. Hepatic damage was induced by single oral administration of APAP (500 mg/kg). GGA at 400 mg/kg was given orally 4 or 8h before, or 0.5h after APAP administration. Treatment of mice with GGA 4h before or 0.5h after APAP administration suppressed increases in transaminase activities and ammonia content in blood as well as hepatic necrosis. Such GGA treatment significantly increased hepatic HSP70 accumulation after APAP administration. Furthermore, GGA inhibited increases in hepatic lipid peroxide content and hepatic myeloperoxidase activity after APAP administration. In contrast, GGA neither inhibited hepatic cytochrome P450 2E1 activity nor suppressed hepatic glutathione depletion after APAP administration. The protective effect of GGA treatment 4h before APAP on hepatotoxicity induced by APAP was completely inhibited with quercetin, known as an HSP inhibitor. In conclusion, GGA has been identified as a new antidote to APAP injury, acting by induction of HSP70. The potential of GGA as a therapeutic tool is strongly supported by its ability to inhibit hepatic injury even when administered after ingestion of APAP.

Oral administration of geranylgeranylacetone improves survival rate in a rat endotoxin shock model: administration timing and heat shock protein 70 induction.

The present study was performed to determine whether oral pretreatment with geranylgeranylacetone (GGA) inhibits proinflammatory cytokine liberation and nitric oxide (NO) production in lipopolysaccharide (LPS)-treated rats and protects rats against death from LPS-induced endotoxin shock, and whether such protection by GGA is related to heat shock protein (HSP) 70 induction in multiple organs of rats. GGA (200 mg/kg) was given orally to rats. LPS (20 mg/kg) was administered intraperitoneally 4, 8, 16, or 24 h after GGA administration. The survival of rats was monitored over 24 h after LPS administration. GGA treatment at 8 or 16 h before LPS dramatically improved the survival rate of LPS-treated rats. Plasma levels of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) and NO 6 h after LPS administration in these GGA-pretreated rats were less than one-half of those in rats treated with LPS alone. A GGA challenge 8 or 16 h before LPS administration enhanced HSP70 expression in rat organs after LPS. Treatment with GGA 8 h before LPS minimized hepatic and renal damage. Furthermore, the protective effect of GGA on mortality in LPS-treated rats was inhibited with quercetin, known as an HSP70 inhibitor. These results suggest that oral administration of GGA at an optimal time before LPS injection induces and enhances HSP70 expression in several organs, inhibits proinflammatory cytokine and NO production, and prevents organ damage, resulting in an improved survival rate.

The presence of oxidized phosphatidylserine on Fas-mediated apoptotic cell surface.

A growing body of evidence suggests that phosphatidylserine (PS) oxidation is linked with its transmembrane migration from the inner to the outer leaflet of the plasma membrane during apoptosis. However, there is no direct evidence for the presence of oxidized PS (PSox) on the surface of cells undergoing apoptosis. The present study was performed to detect PSox externalized to the cell surface after Fas engagement in Jurkat cells. Treatment of Jurkat cells with anti-Fas antibody induced caspase-3 activation, chromatin condensation, PS externalization, generation of reactive oxygen species, intracellular glutathione depletion, disruption of mitochondrial transmembrane potential and release of cytochrome c from mitochondria. To determine externalized PS and phosphatidylethanolamine (PE), Jurkat cells were treated with anti-Fas antibody and then labeled with membrane-impermeable fluorescamine, a probe for visualizing lipids that contain primary amino groups. Their total lipids were extracted and subjected to two-dimensional high-performance thin-layer chromatography (HPTLC). The HPTLC plate was sprayed with N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride to detect phospholipid hydroperoxides. PSox was present in small amounts within but not on the surface of normal cells. Treatment with anti-Fas antibody increased PSox within the cells and caused PSox to appear on the cell surface. In contrast, PE on the surface of Fas-ligated cells was not oxidized. Thus, the present study demonstrates for the first time the presence of PSox both within and on the surface of apoptotic cells.