Effectiveness of Implementing Modified Early Warning System and Rapid Response Team for General Ward Inpatients.

This retrospective study assessed the effectiveness and impact of implementing a Modified Early Warning System (MEWS) and Rapid Response Team (RRT) for inpatients admitted to the general ward (GW) of a medical center. This study included all inpatients who stayed in GWs from Jan. 2017 to Feb. 2022. We divided inpatients into GWnon-MEWS and GWMEWS groups according to MEWS and RRT implementation in Aug. 2019. The primary outcome, unexpected deterioration, was defined by unplanned admission to intensive care units. We defined the detection performance and effectiveness of MEWS according to if a warning occurred within 24 h before the unplanned ICU admission. There were 129,039 inpatients included in this study, comprising 58,106 GWnon-MEWS and 71,023 GWMEWS. The numbers of inpatients who underwent an unplanned ICU admission in GWnon-MEWS and GWMEWS were 488 (.84%) and 468 (.66%), respectively, indicating that the implementation significantly reduced unexpected deterioration (p < .0001). Besides, 1,551,525 times MEWS assessments were executed for the GWMEWS. The sensitivity, specificity, positive predicted value, and negative predicted value of the MEWS were 29.9%, 98.7%, 7.09%, and 99.76%, respectively. A total of 1,568 warning signs accurately occurred within the 24 h before an unplanned ICU admission. Among them, 428 (27.3%) met the criteria for automatically calling RRT, and 1,140 signs necessitated the nursing staff to decide if they needed to call RRT. Implementing MEWS and RRT increases nursing staff's monitoring and interventions and reduces unplanned ICU admissions.

Olmesartan Ameliorates Organ Injury and Mortality in Rats With Peritonitis-Induced Sepsis.

INTRODUCTION: Sepsis and related complications lead to high morbidity and mortality in humans and animals. Olmesartan medoxomil (OLM), a nonpeptide angiotensin II type 1 receptor blocker, has antiinflammatory and antioxidative effects in various experimental animal models. The present study aimed to investigate whether OLM protects against sepsis in a clinically relevant model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). METHODS: Sepsis was induced by CLP in anesthetized rats. OLM was administered intraperitoneally 3 h after CLP onset. Hemodynamic, biochemical, and inflammatory parameters were analyzed. RESULTS: The administration of OLM in CLP rats significantly improved their survival rate. Moreover, OLM mitigated CLP-induced hypotension and organ injury (indicated by biochemical parameters), but not tachycardia. OLM significantly reduced the plasma levels of interleukin-6 and nitric oxide. CONCLUSIONS: OLM markedly attenuated CLP-induced hypotension and organ injury, and hence improved survival by inhibiting the inflammatory response and nitrosative stress in this clinically relevant model of sepsis.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice.

Xenon, an inert anesthetic gas, is increasingly recognized to possess desirable properties including cytoprotective and anti-inflammatory effects. Here we evaluated the effects of xenon on the progression of lupus nephritis (LN) in a mouse model. A two hour exposure of either 70% xenon or 70% nitrogen balanced with oxygen was administered daily for five weeks to female NZB/W F1 mice that had been induced to develop accelerated and severe LN. Xenon treatment improved kidney function and renal histology, and decreased the renal expression of neutrophil chemoattractants, thereby attenuating glomerular neutrophil infiltration. The effects of xenon were mediated primarily by deceasing serum levels of anti-double stranded DNA autoantibody, inhibiting reactive oxygen species production, NF-κB/NLRP3 inflammasome activation, ICAM-1 expression, glomerular deposition of IgG and C3 and apoptosis, in the kidney; and enhancing renal hypoxia inducible factor 1-α expression. Proteomic analysis revealed that the treatment with xenon downregulated renal NLRP3 inflammasome-mediated cellular signaling. Similarly, xenon was effective in improving renal pathology and function in a spontaneous LN model in female NZB/W F1 mice. Thus, xenon may have a therapeutic role in treating LN but further studies are warranted to determine applicability to patients.

P2X7 is involved in the anti-inflammation effects of levobupivacaine.

BACKGROUND: We sough to elucidate whether purinergic P2X7 receptor is actively involved in the effects of levobupivacaine on inhibiting microglia activation. MATERIALS AND METHODS: Microglia were treated with lipopolysaccharide (LPS, 50 ng/mL), LPS plus levobupivacaine (50 µM), or LPS plus levobupivacaine plus the P2X7 receptor agonist Bz-ATP (100 µM) and denoted as the LPS, LPS + Levo, and LPS + Levo + Bz-ATP group, respectively. Microglia activation was measured by assaying inflammatory molecules expression. Microglia activation was also measured by assaying neuronal cell viability using coculture of microglia and neurons, as activated microglia may cause neuron injury. We also measured the levels of P2X7 receptor activation in microglia using ethidium uptake assay. RESULTS: Our data confirmed the effects of levobupivacaine on inhibiting inflammatory molecules upregulation in activated microglia, as the concentrations of interleukin (IL)-1ß, tumor necrosis factor α, IL-6, and macrophage inflammatory protein 2, of the LPS + Levo group were significantly lower than those of the LPS group (all P < 0.05). Moreover, Bz-ATP significantly abrogated the inhibitory effects of levobupivacaine, as concentrations of IL-1ß, tumor necrosis factor α, IL-6, and macrophage inflammatory protein 2 of the LPS + Levo + Bz-ATP group were significantly higher than those of the LPS + Levo group (all P < 0.05). In contrast, neuronal cell viability of the LPS + Levo group was significantly higher than those of the LPS and LPS + Levo + Bz-ATP groups (P = 0.012 and 0.002). Moreover, levels of P2X7 receptor activation of the LPS and LPS + Levo + Bz-ATP groups were significantly higher than that of the LPS + Levo group (P = 0.003 and 0.006). CONCLUSIONS: P2X7 receptor is involved in the effects of levobupivacaine on inhibiting microglial activation.

Levosimendan attenuates multiple organ injury and improves survival in peritonitis-induced septic shock: studies in a rat model.

INTRODUCTION: The aim of this study was to investigate the effects of levosimendan on rodent septic shock induced by cecal ligation and puncture (CLP). METHODS: Three hours after peritonitis-induced sepsis, male Wistar rats were randomly assigned to receive an intravenous infusion of levosimendan (1.2 µg/kg/min for 10 min and then 0.3 µg/kg/min for 6 h) or an equivalent volume of saline and vehicle (5% dextrose) solution. RESULTS: The levosimendan-treated CLP animals had significantly higher arterial pressure and lower biochemical indices of liver and kidney dysfunction compared to the CLP animals (P < 0.05). Plasma interleukin-1ß, nitric oxide and organ superoxide levels in the levosimendan-treated CLP group were less than those in CLP rats treated with vehicle (P < 0.05). In addition, the inducible nitric oxide synthase (iNOS) in lung and caspase-3 expressions in spleen were significantly lower in the levosimendan-treated CLP group (P < 0.05). The administration of CLP rats with levosimendan was associated with significantly higher survival (61.9% vs. 40% at 18 h after CLP, P < 0.05). At postmortem examination, the histological changes and neutrophil filtration index in liver and lung were significantly attenuated in the levosimendan-treated CLP group (vs. CLP group, P < 0.05). CONCLUSIONS: In this clinically relevant model of septic shock induced by fecal peritonitis, the administration of levosimendan had beneficial effects on haemodynamic variables, liver and kidney dysfunction, and metabolic acidosis. (1) Lower levels of interleukin-1ß, nitric oxide and superoxide, (2) attenuation of iNOS and caspase-3 expressions, and (3) decreases of neutrophil infiltration by levosimendan in peritonitis-induced sepsis animals suggest that anti-inflammation and anti-apoptosis effects of levosimendan contribute to prolonged survival.

Hyperoncotic albumin attenuates lung and intestine injuries caused by peritonitis-induced sepsis in rats.

BACKGROUND: Hyperoncotic albumin may be a therapeutic option to improve tissue perfusion and organ injury in sepsis. To clarify the hypothesis and its mechanism, hyperoncotic albumin was administered to the rats in a polymicrobial sepsis-peritonitis model. MATERIALS AND METHODS: Peritonitis was induced by a surgery of cecal ligation and puncture (CLP) in 27 male Wistar rats. For control purposes, sham operations without ligating and puncturing the cecum were performed in 20 rats. Three hours later, rats were randomized to receive intravenously 3 mL/kg of 5% albumin, 25% albumin, or normal saline. All the hemodynamic and biochemical parameters were measured during the 18-h observation. RESULTS: In septic rats, 25% albumin attenuated hypotension, vascular hyporeactivity to norepinephrine, and the elevated serum levels of lactate dehydrogenase and blood urea nitrogen. However, these improvements were not noted in CLP rats after 5% albumin treatment. In addition, 25% albumin decreased metabolic acidosis and improved the CLP-induced hypoperfusion in the intestine and kidney. Superoxide levels in the aorta and lung and the protein expression of inducible nitric oxide synthase in the lung were also attenuated by 25% albumin in CLP rats. Microscopic findings confirmed that 25% albumin attenuated the substantial swelling and cell infiltration in the intestine and lung caused by CLP. CONCLUSIONS: In this sepsis rat model, 25% albumin reduced macro- and microhemodynamic changes and attenuated intestine and lung injuries in peritonitis-induced sepsis.

Suppressive effects of levobupivacaine on endotoxin-induced microglial activation.

BACKGROUND: We sought to elucidate the effects of levobupivacaine on modulating endotoxin-induced upregulation of inflammatory mediators and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways in activated microglia. MATERIALS AND METHODS: Confluent murine microglia (BV-2) were treated with endotoxin (lipopolysaccharide, 50 ng/mL) or endotoxin plus levobupivacaine (5, 25, or 50 µM) and denoted as the LPS, LPS + L(5), LPS + L(25), and LPS + L(50) groups, respectively. Levobupivacaine was administered immediately after endotoxin. Control groups were run simultaneously. RESULTS: The concentrations of inflammatory mediators, including macrophage inflammatory protein-2 (P = 0.023 and 0.016), tumor necrosis factor-α (P = 0.025 and 0.020), interleukin (IL)-1ß (P = 0.018 and 0.014), IL-6 (P = 0.029 and 0.023), nitric oxide (P = 0.025 and 0.026), and prostaglandin E2 (P = 0.028 and 0.016) of the LPS + L(25) and LPS + L(50) groups were significantly lower than those of the LPS group. The concentrations of macrophage inflammatory protein-2 (P = 0.035), IL-1ß (P = 0.024), nitric oxide (P = 0.031), and prostaglandin E2 (P = 0.036) but not tumor necrosis factor-α and interleukin-6 of the LPS + L(5) group were also significantly lower than those of the LPS group. These data revealed that effects of endotoxin on upregulating inflammatory mediators were inhibited by levobupivacaine. Moreover, effects of endotoxin on activating NF-κB, including inhibitor-κB degradation, NF-κB nuclear translocation, and NF-κB-DNA binding, were also inhibited by levobupivacaine. Similarly, effects of endotoxin on activating MAPKs, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAPK, were also significantly inhibited by levobupivacaine. CONCLUSIONS: Levobupivacaine significantly inhibited endotoxin-induced upregulation of inflammatory mediators and activation of NF-κB and MAPKs signaling pathways in activated microglia.

The effects of collateral meridian therapy for knee osteoarthritis pain management: a pilot study.

OBJECTIVE: The purpose of this preliminary study was to examine whether collateral meridian (CM) therapy was feasible in treating knee osteoarthritis (OA) pain. METHODS: Twenty-eight patients with knee OA and knee pain were randomly allocated to 2 groups. The CM group patients received CM therapy, whereas the control patients received placebo treatment for knee pain relief. Patients in the CM group received 2 CM treatments weekly for 3 weeks. The outcome measures were pain intensity on a visual analog scale, and knee function was determined using the Western Ontario and McMaster Universities Osteoarthritis Index. RESULTS: In the CM group, the posttreatment visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were lower than those of the control group; a significant reduction in pain intensity (P = .02, P = .01, respectively) and improvement in knee function (P = .04, P = .03, respectively) were shown in the CM group at the second and third week. CONCLUSION: Collateral meridian therapy may be feasible and effective for knee OA pain relief and knee function recovery. Therefore, additional randomized control trials are warranted.

Analgesic Effectiveness of Dinalbuphine Sebacate in Video-Assisted Thoracoscopic Wedge Resection and Its Effect on Reducing Postoperative Pulmonary Complications: A Retrospective Cohort Study.

BACKGROUND: Inadequate postoperative analgesia may cause postoperative complications, such as pulmonary complications. This study evaluated the analgesic effectiveness of a single preoperative injection of dinalbuphine sebacate (DS) in patients undergoing video-assisted thoracoscopic wedge resection and assessed whether it can reduce the incidence of postoperative pulmonary complications (PPCs). METHODS: In this study, the data of 757 patients who underwent VATS wedge resection at a medical center were retrospectively reviewed. The patients were divided into the DS group and the conventional analgesia (CA) group. The following parameters were analyzed: analgesic consumption during hospitalization, the incidence of PPCs, and the postoperative use of oxygen therapy. RESULTS: Compared with the CA group, the DS group had lower nalbuphine, tramadol, parecoxib, acetaminophen, diclofenac, and utraphen consumption during the postoperative period; higher morphine and ketorolac consumption; and comparable fentanyl consumption. Nonetheless, the frequency of requesting pain relief was significantly lower in the DS group. No significant between-group differences were noted in the incidence of PPCs. However, the DS group had fewer requirements for oxygen therapy in the ward, early removal of chest tubes, and shorter length of hospital stay. CONCLUSION: A single preoperative injection of DS reduced the frequency of salvage analgesic administration and total consumption of certain postoperative analgesics, suggesting the effective pain relief of DS, and it did not increase the incidence of PPCs. Additionally, it reduced the need for postoperative oxygen therapy, which may suggest a better prognosis and smoother postoperative pulmonary recovery for patients.

Transcutaneous electrical nerve stimulation on ST36 and SP6 acupoints prevents hyperglycaemic response during anaesthesia: a randomised controlled trial.

BACKGROUND AND OBJECTIVE: Hyperglycaemia is a common result of stress signals caused by pain and surgical procedure. Volatile anaesthetics also directly manipulate glucose homeostasis by affecting pancreatic insulin release and induce hyperglycaemia without surgical stress. We determined the preoperative application of transcutaneous electrical nerve stimulation (TENS) to the Chinese acupoints ST36 (Zusanli) and SP6 (Sanyinjiao) as a complementary therapy for controlling plasma glucose and improving insulin resistance during anaesthesia. METHODS: We designed a single-blind, randomised controlled clinical study of female patients, scheduled for elective hysterectomy. The 52 patients consented to enrolment and were assigned to receive either TENS (n = 26) on bilateral ST36 and SP6 acupoints with continuous mode at a frequency of 15 Hz and the intensity of 10 mA synchronously for 30 min or non-stimulation (placebo group, n = 26) preoperatively. Haemodynamics, blood glucose and plasma insulin were measured during general anaesthesia. RESULTS: At baseline, there was no significant difference between the TENS group and the placebo group in plasma glucose and insulin levels as well as homeostasis model assessment (HOMA) index. In the placebo group, plasma glucose, insulin and HOMA index increased during induction of general anaesthesia, surgical incision, and throughout the operation. Plasma glucose and insulin levels as well as HOMA index were significantly lower in the TENS group as compared to the placebo group at different time points after discontinuation of TENS application. These results indicate the positive effect of prevention of hyperglycaemia and the increased sensitivity of plasma insulin in the TENS group. CONCLUSION: We found TENS at bilateral ST36 and SP6 acupoints to be an alternative means of managing the plasma glucose level and improving insulin resistance perioperatively.

Angiotensin-(1-7) treatment blocks lipopolysaccharide-induced organ damage, platelet dysfunction, and IL-6 and nitric oxide production in rats.

Sepsis can lead to shock, multiple organ failure, and even death. Platelets play an active role in the pathogenesis of sepsis-induced multiple organ failure. Angiotensin (Ang)-(1-7), a biologically active peptide, counteracts various effects of Ang II and attenuates inflammatory responses, reactive oxygen species production, and apoptosis. We evaluated the effects of Ang-(1-7) on organ injury and platelet dysfunction in rats with endotoxaemia. We treated male Wistar rats with saline or lipopolysaccharide (LPS, 10 mg, intravenously) then Ang-(1-7) (1 mg/kg, intravenous infusion for 3 h beginning 30 min after LPS administration). We analysed several haemodynamic, biochemical, and inflammatory parameters, as well as platelet counts and aggregation. Ang-(1-7) improved hypotension and organ dysfunction, and attenuated plasma interleukin-6, chemokines and nitric oxide production in rats after LPS administration. The LPS-induced reduction in platelet aggregation, but not the decreased platelet count, was restored after Ang-(1-7) treatment. The protein expression of iNOS and IκB, but not phosphorylated ERK1/2 and p38, was diminished in Ang-(1-7)-treated LPS rats. The histological changes in liver and lung were significantly attenuated in Ang-(1-7)-treated LPS rats. Our results suggest that Ang-(1-7) ameliorates endotoxaemic-induced organ injury and platelet dysfunction, likely through the inhibition of the inflammatory response and nitric oxide production.

Hypertonic saline, mannitol and hydroxyethyl starch preconditioning of platelets obtained from septic patients attenuates CD40 ligand expression in vitro.

BACKGROUND: Because platelet CD40 ligand (CD40L) expression plays an important role in inflammatory conditions, reduction of CD40L expression may be beneficial for patients with sepsis. Although hypertonic saline, mannitol, and hydroxyethyl starch (HES) solutions have been shown to modulate inflammatory responses, their effects on platelet CD40L expression are unclear. We assessed the effects of hypertonic saline, mannitol, and HES solutions on platelet CD40L expression. METHODS: Platelet-rich plasma samples were obtained from septic patients and diluted to 1%, 2.5%, 5%, or 7.5% (vol/vol) with 7.5% saline, 3% saline, 0.9% saline, 20% mannitol, 10% HES (200/0.5), or Ringer's solution. Twenty-five samples were used per dilution. To determine platelet CD40L expression, platelet samples were stimulated with thrombin (0.1 U/mL), incubated with fluorochrome-conjugated platelet antibodies, and analyzed using flow cytometry. RESULTS: Preconditioning of platelet-rich plasma with hypertonic saline, mannitol, and HES attenuated CD40L expression at dilution ratios of 5%, 1%, and 1%, respectively. The decreases were concentration dependent. The effects of mannitol and HES on CD40L expression were almost identical and were superior to those of 3% saline. In contrast, 0.9% saline and Ringer's solution had no effect on CD40L expression. CONCLUSIONS: Our data show that resuscitation fluids, such as hypertonic saline, mannitol, and HES, inhibit agonist-induced CD40L expression on platelets. These resuscitation fluids may have an anti-inflammatory action when administered to septic patients.

Effect of epidural neuraxial blockade-dependent sedation on the Ramsay Sedation Scale and the composite auditory evoked potentials index in surgical intensive care patients.

BACKGROUND/PURPOSE: Peripheral deafferentation induced by neuraxial anesthesia reduces the degree of cortical arousal. This study investigated whether epidural analgesia blockade decreased sedation, as measured by the rapidly extracted auditory evoked potentials index, A-line autoregressive index (AAI) and Ramsay Sedation Scale (RSS) in sedated surgical intensive care patients, and looked at whether this was a concentration-dependent effect of lidocaine. METHODS: Forty patients underwent major lower abdominal surgery and received epidural analgesia in the surgical intensive care unit. Patients were continuously sedated with propofol to achieve an RSS value of 3, randomly divided into two groups, and received epidural analgesia with 10 mL of 0.5% or 1% lidocaine. Sedation was evaluated using the RSS and AAI, and analgesia was evaluated using a visual analog scale (VAS). RSS, AAI, electromyography (EMG) activity of AAI and VAS values were recorded at 5 minutes before and 30, 60 and 90 minutes after epidural lidocaine administration. RESULTS: Epidural 0.5% lidocaine produced a reduction of AAI, EMG and VAS at 30, 60 and 90 minutes after administration. For 1% epidural lidocaine administration, AAI, EMG and VAS were also reduced at 30, 60 and 90 minutes after epidural lidocaine administration. However, there was no difference in the AAI between the two concentrations; moreover, no significant change was observed in the RSS. CONCLUSION: Epidural lidocaine analgesia could potentiate sedation in patients evaluated by the AAI, but had no effect on the RSS. The present study suggests that the AAI could provide an objective and more precise index than the RSS in evaluation of sedation level in patients who are undergoing epidural pain management in the intensive care unit.

[The current situation and trends in the clinical treatment of shock].

Shock is defined as hypoperfusion of tissues and/or organs. The initial focus of resuscitation following shock is on establishing an open airway and ensuring adequate ventilation and circulation. Causes of shock can be recognized quickly via clinical manifestations. A professional physical examination and observation of response to therapy can result in early diagnosis of the causes of unstable vital signs. Identification of shock symptoms in order to administer appropriate treatment quickly is key to saving patient lives, because "time is tissue". In all shock cases, treatments begin with an evaluation, resuscitation and immediate treatment of life-threatening symptoms. Patients may experience more than one kind of shock simultaneously, which further complicates their assessment and treatment. The critical care of shock should be done thoroughly and systematically in order to assess and manage patients so as to avoid dysfunctions in one organ damaging others. During emergency and critical management of shock patients, once a certain stage of assessment is completed, further evaluation is necessary to assess condition improvement. If improvement is confirmed, maintenance therapy may be considered. If improvement is not confirmed, it should be considered whether treatment is inadequate or misfocused, or whether the patient's response is atypically poor. In addition to timely resuscitation and ICU care, there are specific effective treatments for each type of shock. Such must be administered in accordance with guidelines, standard protocols and goal-oriented approaches. Trends in shock management currently focus on integrating guidelines, standard protocols and goal-oriented approaches into a "treatment bundle", which facilitates the implementation of clinical medical care and completes specific goals within a specified time limit to reduce the risk of multiple organ failure and death due to shock.

Distinct expression of synaptic NR2A and NR2B in the central nervous system and impaired morphine tolerance and physical dependence in mice deficient in postsynaptic density-93 protein.

Postsynaptic density (PSD)-93, a neuronal scaffolding protein, binds to and clusters N-methyl-D-aspartate receptor (NMDAR) subunits NR2A and NR2B at cellular membranes in vitro. However, the roles of PSD-93 in synaptic NR2A and NR2B targeting in the central nervous system and NMDAR-dependent physiologic and pathologic processes are still unclear. We report here that PSD-93 deficiency significantly decreased the amount of NR2A and NR2B in the synaptosomal membrane fractions derived from spinal cord dorsal horn and forebrain cortex but did not change their levels in the total soluble fraction from either region. However, PSD-93 deficiency did not markedly change the amounts of NR2A and NR2B in either synaptosomal or total soluble fractions from cerebellum. In mice deficient in PSD-93, morphine dose-dependent curve failed to shift significantly rightward as it did in wild type (WT) mice after acute and chronic morphine challenge. Unlike WT mice, PSD-93 knockout mice also showed marked losses of NMDAR-dependent morphine analgesic tolerance and associated abnormal sensitivity in response to mechanical, noxious thermal, and formalin-induced inflammatory stimuli after repeated morphine injection. In addition, PSD-93 knockout mice displayed dramatic loss of jumping activity, a typical NMDAR-mediated morphine withdrawal abstinence behavior. These findings indicate that impaired NMDAR-dependent neuronal plasticity following repeated morphine injection in PSD-93 knockout mice is attributed to PSD-93 deletion-induced alterations of synaptic NR2A and NR2B expression in dorsal horn and forebrain cortex neurons. The selective effect of PSD-93 deletion on synaptic NMDAR expression in these two major pain-related regions might provide the better strategies for the prevention and treatment of opioid tolerance and physical dependence.

Therapeutic effects of hypertonic saline on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats.

OBJECTIVE: Significant mortality in patients with sepsis results from the development of multiple organ dysfunction syndrome. Small-volume resuscitation with 7.5% NaCl hypertonic saline has been proposed to restore physiologic hemodynamics in hemorrhagic shock. Therefore, we hypothesized that hypertonic saline resuscitation could alleviate the development of multiple organ dysfunction syndrome in sepsis induced by cecal ligation and puncture. DESIGN: Randomized, prospective animal experiment. SETTING: Academic research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: The animals were randomly allocated to one of four groups: 1) sham operation (0.9% NaCl, 4 mL/kg intravenously, at 3 hrs after laparotomy); 2) sham operation plus hypertonic saline (7.5% NaCl, 4 mL/kg intravenously, at 3 hrs after laparotomy); 3) cecal ligation and puncture (0.9% NaCl, 4 mL/kg intravenously, at 3 hrs after cecal ligation and puncture); and 4) cecal ligation and puncture plus hypertonic saline (7.5% NaCl, 4 mL/kg intravenously, at 3 hrs after cecal ligation and puncture). MEASUREMENTS AND MAIN RESULTS: Cecal ligation and puncture for 18 hrs was associated with circulatory failure (i.e., hypotension and vascular hyporeactivity to norepinephrine), multiple organ dysfunction syndrome (examined by biochemical variables and histologic studies), and 18-hr mortality. Hypertonic saline not only ameliorated the deterioration of hemodynamic changes but also attenuated neutrophil infiltration in the lung and the liver of septic animals. Hypertonic saline increased the survival rate at 9 and 18 hrs compared with the cecal ligation and puncture group. Moreover, hypertonic saline reduced plasma nitric oxide and interleukin-1beta and organ O2-* levels in rats that underwent cecal ligation and puncture. CONCLUSIONS: Hypertonic saline prevented circulatory failure, alleviated multiple organ dysfunction syndrome, and decreased the mortality rate in animals receiving cecal ligation and puncture. These beneficial effects of hypertonic saline may be attributed to reducing the plasma concentration of nitric oxide and interleukin-1beta as well as the organ O2-* level and decreasing lung neutrophil infiltration and liver necrosis. Our study suggests that hypertonic saline could be a potential and inexpensive therapeutic agent in the early sepsis of animals or patients.

Combined effects of propofol and dexamethasone on rats with endotoxemia.

OBJECTIVE: To clarify the effect of combined treatment with propofol and dexamethasone on hemodynamics, organ injury, and survival rate in rats with endotoxemia. DESIGN: Randomized, prospective animal experiment. SETTING: Academic research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats were divided into five groups: a control group, a group of conscious rats infused with Escherichia coli lipopolysaccharide, two groups of lipopolysaccharide rats treated with either propofol or dexamethasone, and a group of lipopolysaccharide rats with combined treatment of propofol and dexamethasone. MEASUREMENTS AND MAIN RESULTS: All hemodynamic and biochemical variables were measured during the 6-hr observation. Propofol plus dexamethasone attenuated hypotension and delayed hypoglycemia and metabolic acidosis caused by coadministration of E. coli lipopolysaccharide. In addition, propofol plus dexamethasone attenuated the lipopolysaccharide-induced multiple organ dysfunctions, such as lung, liver, and kidney. The increases in serum tumor necrosis factor-alpha, tissue nitric oxide, and superoxide anion levels were attenuated by propofol plus dexamethasone in lipopolysaccharide rats. Microscopic findings confirmed that propofol plus dexamethasone attenuated the substantial swelling and cell infiltration in lung and kidney caused by endotoxin. The 22-hr survival rate after endotoxin injection was markedly increased in lipopolysaccharide rats with combined treatment compared with the lipopolysaccharide rats (80% vs. 0%). CONCLUSIONS: The combined treatment with propofol plus dexamethasone reduced mortality rate and attenuated organ injury in conscious rats treated with lipopolysaccharide. These protective effects may be associated with their anti-inflammatory capacity and antioxidant activity.

Composite auditory evoked potential index versus bispectral index to estimate the level of sedation in paralyzed critically ill patients: a prospective observational study.

BACKGROUND: Electromyographic activity (EMG) has been reported to elevate the Bispectral Index (BIS) in patients not receiving neuromuscular blockade while under sedation in the intensive care unit (ICU). We investigated the change of the composite A-line autoregressive index (AAI) and BIS after administration of muscle relaxants in sedated surgical ICU patients. METHODS: We prospectively investigated 38 patients who required administration of a muscle relaxant while continuously sedated with midazolam hydrochloride and fentanyl citrate to achieve a Ramsay Sedation Scale value equal to 5. BIS, EMG activity of BIS (EMG-BIS), signal quality index of BIS, AAI, EMG activity of AAI (EMG-AAI), and acceleromyography at the adductor pollicis muscle were recorded simultaneously every 5 min for 30 min before and after neuromuscular blockade. Student's t-test, the Wilcoxon's signed ranks test, and the Spearman test were calculated using the standard statistics software SPSS 10.0 (SPSS Inc., Chicago, IL). RESULTS: After administration of a muscle relaxant, BIS (58.61+/-7.45 vs 44.68+/-6.65, P<0.001), EMG-BIS (37.33+/-7.15 vs 27.24+/-1.51, P<0.001), AAI (34.11+/-10.96 vs 15.97+/-6.69, P<0.001), and EMG-AAI (59.58+/-9.57 vs 1.00+/-0.00, P<0.001) decreased significantly. Significant correlations between BIS and EMG-BIS (rs=0.75, P<0.001) and AAI and EMG-AAI (rs=0.87, P<0.001) were also found during the baseline period. CONCLUSIONS: This study demonstrated that, in sedated ICU patients, BIS and AAI markedly decreased after administration of myorelaxant, and the decreased BIS and AAI values after neuromuscular blockade were correlated to those usually seen in the state of surgical anesthesia, respectively.

A patient with postpolio syndrome developed cauda equina syndrome after neuraxial anesthesia: A case report.

Combined spinal anesthesia and postoperative epidural analgesia is widely used in orthopedic surgery. Uncommon but serious neurologic complications of neuraxial anesthesia (NA) include direct trauma during needle or catheter insertion, central nervous system infections, and neurotoxicity of local anesthetics. Cauda equina syndrome (CES) is a rare complication after NA but can result in severe neurologic deterioration that may require surgical intervention. We present a case of a 69-year-old woman with postpolio syndrome who developed CES after combined spinal anesthesia and postoperative epidural analgesia. Perioperative observations and follow-up examinations, including magnetic resonance imaging, revealed no evidence of direct needle- or catheter-induced trauma, spinal hematoma, spinal ischemia, intraneural anesthetic injection, or infection. We speculate that CES symptoms were observed because of enhanced sensitivity to a combination of regional anesthetic technique-related microtrauma and neurotoxicity of bupivacaine and ropivacaine. Thus, practitioners should be aware that patients with preexisting neurologic diseases may be at increased risk for CES after NA.