Consensus statement on smoking cessation in patients with pain.

Smoking is closely associated with the development of various cancers and tobacco-related illnesses such as cardiovascular and respiratory disorders. However, data are scarce on the relationship between smoking and both acute and chronic pain. In addition to nicotine, tobacco smoke contains more than 4000 different compounds. Although nicotine is not the sole cause of smoking-induced diseases, it plays a critical role in pain-related pathophysiology. Despite the acute analgesic effects of nicotine, long-term exposure leads to tolerance and increased pain sensitivity due to nicotinic acetylcholine receptor desensitization and neuronal plastic changes. The purpose of smoking cessation interventions in smoking patients with pain is primarily not only to reduce their pain and associated limitations in activities of daily living, but also to improve the outcomes of underlying pain-causing conditions and reduce the risks of tobacco-related disorders. This statement aims to summarize the available evidence on the impact of smoking on pain and to inform medical professionals of the significance of smoking cessation in patients with pain.

Low Skeletal Muscle Mass Is Associated With Perioperative Neurocognitive Disorder Due To Decreased Neurogenesis in Rats.

BACKGROUND: Perioperative neurocognitive disorder (PND) is a postsurgical complication associated with neuroinflammation and impaired hippocampal neurogenesis, in which brain-derived neurotrophic factor (BDNF) plays a key role. Sarcopenia refers to age-related muscle loss that causes cognitive decline, muscle atrophy, and postoperative delirium. Rats with tail suspension (TS) were used to represent a low-activity model, which involves decreased hind limb function by TS. This hind limb unloading by TS can induce sarcopenia in 2 weeks. However, the relationship between PND and muscle atrophy is unclear. In this experiment, we investigated whether preoperative muscle atrophy induced by TS would affect neurogenesis and accelerate PND in rats. METHODS: Sixty 21-week-old rats were assigned to 4 groups: the TS group, the TS with surgery (TS + S) group, the control group, and the control with surgery (control + S) group. After the abdominal manipulation under 3% sevoflurane anesthesia, cognitive function was assessed using the Morris water maze test and a fear-conditioning test. Neurogenesis was evaluated by checking BDNF secretion and immunohistochemical staining in the hippocampus. RESULTS: The TS + S group showed impaired swimming latency (difference of means = 12.4 versus control + S; 95% confidence interval [CI], 2.0-22.7; P = .016) (difference of means = 15.2 versus TS; 95% CI, 0.4-30.1; P = .043) and path length (difference of means = 147.8 versus control + S; 95% CI, 20.7-274.9; P = .020) in the maze test and cued fear memory (difference of means = -26.0 versus TS; 95% CI, -46.4 to -5.6; P = .006) (difference of means = -22.3 versus control + S; 95% CI, -42.7 to -1.9; P = .026) in the fear-conditioning test. The postoperative levels of BDNF in the TS + S and TS groups were reduced compared with the other groups (P = .002). The number of neural precursors in the dentate gyrus was significantly lower in the TS + S group (P < .001). CONCLUSIONS: We observed that preoperative hind limb muscle atrophy, indicated by TS, was associated with an increased occurrence of PND through the reduction in BDNF and neurogenesis after abdominal surgery in young adult rats. Therefore, we concluded that preoperative low skeletal muscle mass can induce PND due to impaired postoperative neurogenesis. Our findings might indicate that low-cost perioperative interventions, such as preoperative exercise, is beneficial to preventing PND.

The Effect of Tranexamic Acid Administration on Perioperative Bleeding in Patients Undergoing Knee or Hip Arthroplasty: A Single-Centre Retrospective Study.

OBJECTIVE: Tranexamic acid (TXA) has been used to reduce perioperative bleeding in various surgeries because of its antifibrinolytic effect. Recently, patients undergoing orthopaedic surgery in our institution received a loading dose of TXA (10 00 mg) before surgery, followed by 100 mg h-1 until the end of surgery. The purpose of the present study was to evaluate the efficacy of TXA administration on the perioperative blood loss in patients undergoing knee arthroplasty or hip arthroplasty. METHODS: A retrospective cross-sectional study was conducted for the records in patients who underwent surgery without TXA administration (control group) and patients who underwent surgery with TXA administration (TXA group). Amount of intraoperative blood loss, intraoperative infusion volume, intraoperative blood transfusion volume, postoperative blood transfusion volume, changes in haemoglobin concentrations (ΔHb) and estimated blood loss were collected. Data were adjusted by propensity score method. RESULTS: A total of 126 (63 in the control group and 63 in the TXA group) patients were included during the study period. Intraoperative infusion, postoperative transfusion, ΔHb and estimated blood loss were significantly reduced in the TXA group, although there were no significant differences in the volumes of intraoperative transfusion and blood loss. CONCLUSION: The administration of TXA (loading dose of 1000 mg and continuous infusion of 100 mg h-1) reduced postoperative transfusion and perioperative blood loss. These results indicated that TXA administration is useful for reducing perioperative blood loss in patients undergoing knee or hip arthroplasty.

The additional oxygen as a carrier gas during long-duration sevoflurane exposure ameliorate the neuronal apoptosis and improve the long-term cognitive function in neonatal rats.

The effects of the oxygen concentration as a carrier gas and long duration anesthesia exposure on neuroapoptosis and cognitive impairments in the developing brain are not fully understood. This study shows that long-duration sevoflurane anesthesia with or without additional oxygen induces neuroapoptosis and long-term cognitive dysfunction in neonatal rats. Seven-day-old rats were exposed to sevoflurane anesthesia for 2, 4, and 6 h with 21% or 30% oxygen. The control group received 21% oxygen alone for 6 h. Post-anesthesia blood gas analysis resulted in hypoxia and hypercapnia. Moreover, PO2 and base excess in the 30% oxygen group were significantly higher than the 21% oxygen group. The numbers of caspase-3-positive cells in both cortical layer 3 and the CA1 region in the hippocampus in the 6 h anesthesia exposure group with 21% oxygen were increased compared with the 6 h anesthesia exposure with 30% oxygen and control groups. Cognitive function was assessed in an additional group of rats, and the brains were stained for NeuN 6 weeks post-anesthesia. Although the Morris water maze task was acquired equally by all rats 3 weeks post-anesthesia, the escape latency was significantly longer in the 6 h sevoflurane with 21% oxygen group than the 6 h with 30% oxygen groups 6 weeks post-exposure. No difference was found with regard to freezing time among the groups in the fear conditioning test. The number of NeuN-positive cells in the CA1 region of the hippocampus in the control group was increased compared with the other groups. These findings indicate that long-duration sevoflurane exposure with 30% oxygen as a carrier gas would ameliorate neuronal apoptosis and improve long-term cognitive function in neonatal rats.

The suppressive effects of landiolol administration on the occurrence of postoperative atrial fibrillation and tachycardia, and plasma IL-6 elevation in patients undergoing esophageal surgery: A randomized controlled clinical trial.

STUDY OBJECTIVE: To determine whether perioperative landiolol administration suppresses postoperative atrial fibrillation (AF) and the plasma cytokines elevation in patients undergoing esophageal cancer surgery. DESIGN: A prospective, randomized controlled trial. SETTING: Akita University Hospital, Akita, Japan, from April 2012 to January 2015. PATIENTS: Forty American Society of Anesthesiologists grade I-II patients undergoing elective esophagectomy. INTERVENTIONS: Patients were randomly divided into two groups, landiolol group (landiolol: 5µg/kg/min) and control group (the same volume of covered saline). Landiolol or saline was infused continuously from the induction of anesthesia until next morning. MEASUREMENTS: We examined the new onset of AF and sinus tachycardia, and measured plasma concentrations of cytokines (IL-1ß, IL-6, IL-8, IL-10, and TNF-α) just before surgery, at the end of surgery, the next day, and 2days after surgery. Data (mean±SD) were analyzed using two-way ANOVA followed by the Bonferroni"s test for post hoc comparison; a P<0.05 was considered statistically significant. MAIN RESULTS: Demographic data were similar between the landiolol and the control groups. The incidence of AF was significantly lower in the landiolol group (1/19=5.3%) compared with the control group (7/20=35%) as well as sinus tachycardia (landiolol group, 0/19=0% vs. control group, 5/20=25%). Plasma IL-6 level at the end of surgery was significantly lower in the landiolol group compared with the control group, but the other plasma cytokines levels were similar between the two groups during the entire study period. CONCLUSIONS: Perioperative landiolol administration suppressed the incidence of new-onset of AF as well as sinus tachycardia, and the plasma IL-6 elevation in patients undergoing esophageal cancer surgery.

Evaluation of postoperative pregabalin for attenuation of postoperative shoulder pain after thoracotomy in patients with lung cancer, a preliminary result.

OBJECTIVE: Thirty-one to 97% of patients who undergo thoracotomy for lung cancer experience ipsilateral shoulder pain, marring the otherwise excellent relief provided by thoracic epidural analgesia. The aim of this study was to test whether the addition of pregabalin to the treatment for shoulder pain would provide a significant benefit. METHODS: Twenty patients undergoing thoracic surgery for lung cancer were enrolled in the control group between May 2012 and December 2012, and 20 patients were enrolled in the pregabalin group between January 2013 and July 2013, consecutively. All patients had standard pre- and intraoperative care. Patients received pregabalin 150 mg po POD 1 and then non-steroidal anti-inflammatory drugs (NSAIDs) po 2 h later (pregabalin group), or they received only NSAIDs po at exactly the same times (control group). Pain severity was then measured using a 100-mm visual analog scale (VAS) scoring system. RESULTS: The VAS scores indicated that patients in the pregabalin group had significantly less shoulder pain on postoperative day (POD) 2 than those in the control group (control: 27.9 ± 28.1 vs. pregabalin: 11.8 ± 14.4; p = 0.030). No differences in pain were observed between the two groups on other POD. There were significant differences on only POD 2 in the patients with shoulder pain immediately after surgery. Three of the pregabalin-treated patients showed mild somnolence. CONCLUSIONS: Postoperative administration of pregabalin provided significant relief of postoperative shoulder pain during earlier POD after thoracic surgery for lung cancer when received multimodal analgesia in combination with NSAIDs.

Combination of oral clonidine and intravenous low-dose ketamine reduces the consumption of postoperative patient-controlled analgesia morphine after spine surgery.

OBJECTIVE: Because ketamine, clonidine, and morphine modulate nociceptive pain, coadministration of these drugs would augment the activity of postoperative analgesic drugs. The purpose of this study was to evaluate the effects of coadministration of ketamine and clonidine on postoperative morphine consumption in patients after spine surgery. METHODS: The patients undergoing spine surgery were allocated randomly to one of the four study groups, which are as follows: group M (n = 12), intravenously (IV) administered patient-controlled analgesia (PCA) morphine alone; group MK (n = 12), IV-PCA morphine plus intra- and postoperative ketamine; group MC (n = 13), IV-PCA morphine plus oral clonidine premedication; group MCK (n = 12), IV-PCA morphine plus intra- and postoperative ketamine and clonidine premedication. The patients in the MC and MCK groups received 4 µg/kg clonidine orally, whereas those in the MK and MCK groups received IV bolus of ketamine (10 mg) at a rate of 2 mg/kg/hour during anesthesia. Patients were arranged to use IV-PCA mode for administration of drugs, which was programmed to deliver a bolus dose of 2-mg morphine (groups M and MC), or boluses of 2-mg morphine and 2-mg ketamine (groups MK and MCK). Scores of visual analog scale (VAS) for pain, morphine requirement, vital signs, nausea, sedation, and other side effects were followed up to 60 hours after surgery. RESULTS: Although there were significant differences in VAS pain scores at rest 24-48 hours after the surgery, the VAS pain score at movement was similar among the groups. The number of PCA request and cumulative morphine requirement were significantly lower in the MCK group than in the M group. CONCLUSION: This study results show that the administration of perioperative low-dose ketamine combined with clonidine premedication could reduce the consumption of postoperative PCA morphine following spine surgery.

[Comparison of levobupivacaine and ropivacaine for postoperative epidural analgesia].

BACKGROUND: Levobupivacaine is a long acting local anesthetic with less cardiovascular toxicity. Recently we can use levobupivacaine for postoperative analgesia. We retrospectively compared levobupivacaine with ropivacaine for the postoperative epidural analgesia in patients undergoing gynecological abdominal surgery. METHODS: The patients who had received epidural and general anesthesia from October 2008 to April 2009 were allocated into two groups. Analgesia intensity, the time to receive the first analgesic, and the number of times to use the additional analgesics were observed for three postoperative days. RESULTS: There was no difference in demographic data between the levobupivacaine and ropivacaine groups. In the levobupivacaine group (n=23) the patient received epidural 0.24% levobupivacaine and fentanyl, while the patients in the ropivacaine group (n=43) epidural 0.19% ropivacaine and fentanyl, at the rate of 3.5 ml x hr(-1). The volume of epidural fentanyl was similar between the groups. The time from the end of surgery to receive the first analgesic was longer in the levobupivacaine group than in the ropivacaine group. The number of the patients who did not require additional analgesia was greater in the levobupivacaine group than in the ropivacaine group. The patients who received metocropramide to treat nausea were fewer in the levobupivacaine group, compared with the ropivacaine group. CONCLUSIONS: These results suggest that the use of epidural 0.24% levobupivacaine in the patients undergoing the gynecological surgery is superior to the use of 0.19% ropivacaine.

Esmolol and landiolol, selective beta1-adrenoreceptor antagonists, provide neuroprotection against spinal cord ischemia and reperfusion in rats.

BACKGROUND: Paraplegia is a devastating and unpredictable complication occasionally resulting from surgery of the thoracic and thoracoabdominal aorta. Because ultrashort-acting selective beta(1)-adrenoreceptor antagonists provide neuroprotective effects after brain ischemia, we hypothesized that they would also ameliorate spinal cord injury after transient ischemia and reperfusion in rats. METHODS: Male Sprague-Dawley rats were randomly assigned to one of the following 4 groups: saline (received IV infusion of 0.9% saline at a rate of 0.5 mL/h, n = 8), esmolol (esmolol 200 microg/kg/min, n = 8), landiolol (landiolol 50 microg/kg/min), or sham surgical (n = 6). Infusion of saline or drugs was initiated 30 minutes before spinal cord ischemia and continued for the subsequent 24-hour reperfusion. Spinal cord ischemia was induced by intraaortic balloon occlusion combined with proximal arterial hypotension for 10 minutes. The spinal cord was then reperfused for 24 hours. Ischemic injury was assessed in terms of the motor deficit index score of the hindlimb and the number of viable motor nerve cells in the anterior spinal cord at 24 hours after reperfusion. RESULTS: The motor deficit index scores were significantly lower in the esmolol and landiolol groups compared with the saline group (P < 0.05). Histopathologic evaluation of the spinal cord showed less damage in the esmolol and landiolol groups than in the saline group (P < 0.05). CONCLUSIONS: These data show that ultrashort-acting selective beta(1)-adrenoreceptor antagonists can reduce neurological injury in a rat model of spinal cord ischemia-reperfusion.

Epoxyeicosanoid signaling in CNS function and disease.

Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites of cytochrome P450 epoxygenase enzymes recognized as key players in vascular function and disease, primarily attributed to their potent vasodilator, anti-inflammatory and pro-angiogenic effects. Although EETs' actions in the central nervous system (CNS) appear to parallel those in peripheral tissue, accumulating evidence suggests that epoxyeicosanoid signaling plays different roles in neural tissue compared to peripheral tissue; roles that reflect distinct CNS functions, cellular makeup and intercellular relationships. This is exhibited at many levels including the expression of EETs-synthetic and -metabolic enzymes in central neurons and glial cells, EETs' role in neuro-glio-vascular coupling during cortical functional activation, the capacity for interaction between epoxyeicosanoid and neuroactive endocannabinoid signaling pathways, and the regulation of neurohormone and neuropeptide release by endogenous EETs. The ability of several CNS cell types to produce and respond to EETs suggests that epoxyeicosanoid signaling is a key integrator of cell-cell communication in the CNS, coordinating cellular responses across different cell types. Under pathophysiological conditions, such as cerebral ischemia, EETs protect neurons, astroglia and vascular endothelium, thus preserving the integrity of cellular networks unique to and essential for proper CNS function. Recognition of EETs' intimate involvement in CNS function in addition to their multi-cellular protective profile has inspired the development of therapeutic strategies against CNS diseases such as cerebral ischemia, tumors, and neural pain and inflammation that are based on targeting the cellular actions of EETs or their biosynthetic and metabolizing enzymes. Based upon the emerging importance of epoxyeicosanoids in cellular function and disease unique to neural systems, we propose that the actions of "neuroactive EETs" are best considered separately, and not in aggregate with all other peripheral EETs functions.

[Emergent percutaneous coronary intervention therapy after renal transplantation].

A 54-year-old man was scheduled for renal transplantation. There was no cardiac event except ST-segment depression during surgery. One hour after surgery, the patient complained of a chest pain, and received immediate percutaneous coronary intervention therapy, which was successfully performed. We need close monitoring after surgery even if the patients have no cardiac complication before surgery.

Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack.

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) is a risk factor for stroke. However, TIA may also serve as a preconditioning stimulus, reducing damage from subsequent stroke. We tested the hypothesis that experimental TIA induces expression of P450 2C11, an arachidonic acid epoxygenase that produces vasodilator epoxyeicosatrienoic acids, leading to increased tissue perfusion and reduced stroke damage. METHODS: Wistar rats underwent three 10-minute middle cerebral artery occlusions (TIA) or sham surgery. Three days later, animals were subjected to 2-hour middle cerebral artery occlusion and 24 hours of reperfusion. Brains were stained with 2,3,5-triphenyltetrazolium chloride for infarct size measurement or processed for quantification of P450 2C11 mRNA and protein with the use of RNase protection assay and Western blotting. Regional cerebral blood flow (CBF) at the end of 2-hour ischemia was measured in separate groups of rats with iodoantipyrine autoradiography. RESULTS: Cerebral infarct was reduced by >50% in TIA- versus sham-preconditioned animals. 2C11 mRNA and protein were increased in ipsilateral hemisphere by 3 days after TIA but not sham surgery. Induction of 2C11 by TIA was also evident in ipsilateral hemisphere at 24 hours after 2-hour middle cerebral artery occlusion and 24 hours of reperfusion. End-ischemic regional CBF was not different between TIA- and sham-pretreated groups. CONCLUSIONS: We conclude that experimental TIA induces ischemic tolerance by a mechanism temporally linked to upregulation of P450 2C11. Enzyme induction does not attenuate ischemic severity by amplifying end-ischemic CBF.