Role of Sigma-1 Receptor/p38 MAPK Inhibition in Acupoint Catgut Embedding-Mediated Analgesic Effects in Complete Freund's Adjuvant-Induced Inflammatory Pain.

BACKGROUND: The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia. METHODS: Rats were prepared with intrathecal catheter implantation. ACE was applied to bilateral "Kunlun" (BL60), "Zusanli" (ST36), and "Sanyinjiao" (SP6) acupoints in the rat model of inflammatory pain (complete Freund's adjuvant [CFA] intraplantar injection). Then, Sig-1R agonist PRE084 or saline was intrathecally given daily. The paw withdrawal thresholds and paw edema were measured before CFA injection and at 1, 3, and 5 day after CFA injection. Western bolt was used to evaluate the protein expression of spinal Sig-1R, p38MAPK, and extracellular signal-regulated kinase (ERK), and immunohistochemistry of Sig-1R was detected at 1, 3, and 5 days after CFA injection. RESULTS: ACE exhibited specific analgesic effects. ACE increased paw withdrawal thresholds and markedly decreased CFA-induced paw edema at 1, 3, and 5 days. ACE downregulated the protein expression of Sig-1R, which was increased significantly at 1, 3, and 5 days after CFA injection. ACE decreased the expression of p38 MAPK and ERK at 1 and 3 days but not at 5 days. However, an injection of Sig-1R agonist PRE084 markedly reversed these alterations, except ERK expression. CONCLUSIONS: The present study demonstrated that ACE exhibited antihyperalgesic effects via the inhibition of the Sig-1R that modulated p38 MAPK, but not ERK, expression in the CFA-induced inflammatory pain model in rats. (C) 2017 International Anesthesia Research Society

http://ift.tt/2swe6fI

Acute Intracardiac Thrombosis and Pulmonary Thromboembolism After Cardiopulmonary Bypass: A Systematic Review of Reported Cases.

Intracardiac thrombosis (ICT) and pulmonary thromboembolism (PE) after cardiopulmonary bypass (CPB) are life-threatening events, but pathological mechanisms are not yet well defined. The aim of this review is to provide an update of case literature of a postbypass hypercoagulable state. Case commonalities among 48 ICT/PE events included congestive heart failure (50%), platelet transfusion (37.5%), CPB duration greater than 3 hours (37.5%), and aortic injury (27.1%). Preexisting thrombophilia was rarely reported, and 16.7% had low activated clotting time,

http://ift.tt/2tP6d8R

Ringer's Lactate Versus Normal Saline in Urgent Cesarean Delivery in a Resource-Limited Setting: A Pragmatic Clinical Trial.

BACKGROUND: Crystalloids are used routinely for perioperative fluid management in cesarean delivery. Few studies have determined the crystalloid of choice in obstetric anesthesia. We compared the effects of Ringer's lactate (RL) versus 0.9% normal saline (NS) on maternal and neonatal blood pH and 24-hour postoperative morbidity in urgent cesarean delivery in a low-resource setting. Our hypothesis was that RL would result in 30% less acidosis than NS. METHODS: This was a pragmatic prospective double-blind randomized controlled trial in the Mulago National Referral Hospital Labor Ward Theater from September 2011 to May 2012. Five hundred parturients were studied; 252 were randomly assigned to NS and 248 to RL groups. Preoperative and postoperative maternal venous blood gases and placental umbilical arterial cord blood gases were analyzed. The primary outcome was incidence of maternal acidosis, as defined by a postoperative drop in venous pH below 7.32 or reduction in base excess below -3 in a previously normal parturient. Maternal 24-hour postoperative morbidity, neonatal pH, and neonatal base excess were the main secondary outcomes. The study was registered in ClinicalTrials.gov as NCT01585740. RESULTS: The overall incidence of maternal acidosis was 38% in NS and 29% in RL (relative risk, 1.29; 95% confidence interval, 1.01-1.66; P = .04). Thirty-two percent of parturients in NS experienced a drop in venous pH below 7.32 postoperatively, compared with 19% in RL (relative risk, 1.65; 95% confidence interval, 1.18-2.31; P = .003). The comparative drop in base excess postoperatively below -3 between the 2 groups was not statistically significant. There were no significant differences in the incidence of maternal 24-hour postoperative morbidity events and neonatal outcomes between the 2 groups. CONCLUSIONS: NS may be a safe choice for intraoperative fluid therapy in urgent cesarean delivery as RL, albeit with an increased incidence of metabolic acidosis. (C) 2017 International Anesthesia Research Society

http://ift.tt/2swbaQ7

The New World Health Organization Recommendations on Perioperative Administration of Oxygen to Prevent Surgical Site Infections: A Dangerous Reductionist Approach?.

In October 2016, the World Health Organization (WHO) published recommendations for preventing surgical site infections (SSIs). Among those measures is a recommendation to administer oxygen at an inspired fraction of 80% intra- and postoperatively for up to 6 hours. SSIs have been identified as a global health problem, and the WHO should be commended for their efforts. However, this recommendation focuses only on the patient's "wound," ignores other organ systems potentially affected by hyperoxia, and may ultimately worsen patient outcomes. The WHO advances a "strong recommendation" for the use of a high inspired oxygen fraction even though the quality of evidence is only moderate. However, achieving this goal by disregarding other potentially lethal complications seems inappropriate, particularly in light of the weak evidence underpinning the use of high fractions of oxygen to prevent SSI. Use of such a strategy thus should be intensely discussed by anesthesiologists and perioperative physicians. Normovolemia, normotension, normoglycemia, normothermia, and normoventilation can clearly be safely applied to most patients in most clinical scenarios. But the liberal application of hyperoxemia intraoperatively and up to 6 hours postoperatively, as suggested by the WHO, is questionable from the viewpoint of anesthesia and perioperative medicine, and its effects will be discussed in this article. (C) 2017 International Anesthesia Research Society

http://ift.tt/2swbO07

Defining the Primary Outcomes and Justifying Secondary Outcomes of a Study: Usually, the Fewer, the Better.

One of the first steps in designing and conducting a research study is identifying the primary and any secondary study outcomes. In an experimental, quasi-experimental, or analytic observational research study, the primary study outcomes arise from and align directly with the primary study aim or objective. Likewise, any secondary study outcomes arise from and directly align with any secondary study aim or objective. One designated primary study outcome then forms the basis for and is incorporated literally into the stated hypothesis. In a Methods section, authors clearly state and define each primary and any secondary study outcome variable. In the same Methods section, authors clearly describe how all primary and any secondary study outcome variables were measured. Enough detail is provided so that a clinician, statistician, or informatician can know exactly what is being measured and that other investigators could duplicate the measurements in their research venue. The authors provide published substantiation (preferably) or other documented evidence of the validity and reliability of any applied measurement instrument, tool, or scale. A common pitfall-and often fatal study design flaw-is the application of a newly created ("home-grown") or ad hoc modification of an existing measurement instrument, tool, or scale-without any supporting evidence of its validity and reliability. An optimal primary outcome is the one for which there is the most existing or plausible evidence of being associated with the exposure of interest or intervention. Including too many primary outcomes can (a) lead to an unfocused research question and study and (b) present problems with interpretation if the treatment effect differed across the outcomes. Inclusion of secondary variables in the study design and the resulting manuscript needs to be justified. Secondary outcomes are particularly helpful if they lend supporting evidence for the primary endpoint. A composite endpoint is an endpoint consisting of several outcome variables that are typically correlated with each. In designing a study, researchers limit components of a composite endpoint to variables on which the intervention of interest would most plausibly have an effect, and optimally with preliminary evidence of an effect. Ideally, components of a strong composite endpoint have similar treatment effect, frequency, and severity-with the most important being similar severity. (C) 2017 International Anesthesia Research Society

http://ift.tt/2swqM62

Skeletal Muscle Metabolic Dysfunction in Patients With Malignant Hyperthermia Susceptibility.

BACKGROUND: Malignant hyperthermia (MH), a pharmacogenetic disorder of skeletal muscle, presents with a potentially lethal hypermetabolic reaction to certain anesthetics. However, some MH-susceptible patients experience muscle weakness, fatigue, and exercise intolerance in the absence of anesthetic triggers. The objective of this exploratory study was to elucidate the pathophysiology of exercise intolerance in patients tested positive for MH with the caffeine-halothane contracture test. To this end, we used phosphorus magnetic resonance spectroscopy, blood oxygen level-dependent functional magnetic resonance imaging (MRI), and traditional exercise testing to compare skeletal muscle metabolism in MH-positive patients and healthy controls. METHODS: Skeletal muscle metabolism was assessed using phosphorus magnetic resonance spectroscopy and blood oxygen level-dependent functional MRI in 29 MH-positive patients and 20 healthy controls. Traditional measures of physical capacity were employed to measure aerobic capacity, anaerobic capacity, and muscle strength. RESULTS: During 30- and 60-second exercise, MH-positive patients had significantly lower ATP production via the oxidative pathway compared to healthy controls. MH-positive patients also had a longer recovery time with blood oxygen level-dependent functional MRI compared to healthy controls. Exercise testing revealed lower aerobic and anaerobic capacity in MH-positive patients compared to healthy controls. CONCLUSIONS: Results of this exploratory study suggest that MH-positive patients have impaired aerobic metabolism compared to healthy individuals. This could explain the exercise intolerance exhibited in MH-susceptible patient population. (C) 2017 International Anesthesia Research Society

http://ift.tt/2tP6g4u

Essays on the financing of new firms: new evidence on stability and country effects

http://ift.tt/2uQXYpN