Which Patients With Chronic Pain Do The Primary Care Refers to a Tertiary Hospital in a Developing Country? Experience From a University Hospital.

PURPOSE: The study aimed to profile patients with uncontrolled chronic pain referred from primary care to a tertiary hospital in a developing country, and identify factors associated with pain intensity, interference, and its link with mental health. DESIGN: Cross-sectional design. METHODS: Data from 906 adult patients with nonmalignant chronic pain during their first visit to the multidisciplinary pain center at the State University of Rio de Janeiro in 2019 were used. The brief pain inventory and the Hospital Anxiety and Depression Scale questionnaire assessed pain intensity, its impact on daily activity, and symptoms of anxiety and depression. RESULTS: The population was predominantly female (68.8%), over 50 (66.3%), with less than 11 years of education (86.5%), and 75.2% were overweight or obese. Most (81.9%) reported moderate or severe pain, significantly interfering with daily activities (>50%). The lower back was the most commonly affected site. Widespread pain was present in 43.6% of patients. High scores for anxiety (67.4%) and depression (52.2%) were observed. Severe pain was predominantly seen in middle-aged women and individuals with high levels of anxiety and depression. CONCLUSION: Patients with uncontrolled chronic pain referred from primary care to a tertiary hospital were predominantly female, overweight or obese, and exhibited a high prevalence of depression and anxiety. Their pain significantly interfered with daily activities. CLINICAL IMPLICATIONS: The study provides valuable insight into the biopsychosocial characteristics of uncontrolled chronic pain patients in primary care, emphasizing the importance of implementing multidisciplinary approaches to manage chronic pain effectively within primary care settings.

Impact of chronic pelvic pain and painful bladder syndrome on the Pittsburgh Sleep Quality Index on women with deep endometriosis: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: Painful bladder syndrome (PBS) is frequently associated with deep endometriosis (DE), and both conditions cause chronic pelvic pain (CPP), which often impairs sleep quality. This study was aimed at analyzing the impact of CPP plus PBS in women with DE on the global sleep quality index using the Pittsburgh Sleep Quality Index (PSQI) and subsequently examine each sleep dimension. METHODS: One hundred and forty women with DE were included and answered the PSQI and the O'Leary-Sant Interstitial Cystitis Symptoms and Problem Index questionnaires with or without CPP. Women were categorized into good or poor sleepers using the PSQI cutoff; subsequently, a linear regression model was used to analyze the PSQI score and a logistic regression model for each questionnaire's sleep component. RESULTS: Only 13% of women with DE had a good sleep. Approximately 20% of those with DE but no/mild pain were good sleepers; 138 women with DE (88.5%), 94% with PBS, and 90.5% with moderate/severe pain were poor sleepers. For PSQI components, CPP worsened the subjective sleep quality by more than threefold (p = 0.019), increased sleep disturbances by nearly sixfold (p = 0.03), and decreased the sleep duration by practically sevenfold (p = 0.019). Furthermore, PBS increased sleep disturbances by nearly fivefold (p < 0.01). CONCLUSIONS: The addition of PBS to CPP in women with DE is devastating for overall sleep quality, probably because it impacts some sleep dimensions unaffected by CPP and amplifies the problem in those already affected by pain.

Dissociation between macro- and microvascular parameters in the early phase of hemorrhagic shock.

Hemorrhagic shock (HS) therapy is based on macrohemodynamic improvement, but it is not clear if this therapy correlates directly with increases in tissue perfusion. Aiming to clarify this point, we compared norepinephrine (NE, a vasoconstrictor), sodium nitroprusside (NP, a vasodilator) and levosimendan (LEV, an inodilator) treatments on macro and microvascular parameters using the hamster dorsal skinfold chamber preparation. One hour after HS, animals received Ringer's lactate (RL) solution within 10 min, then animals received RL, NP, NE and LEV during 90 min via jugular vein. Macrovascular variables: mean arterial pressure (MAP), heart rate (HR), maximal ventricle pressure (MVP), change in ventricular pressure over time (dP/dt) and microvascular variables: arteriolar and venular diameters, functional capillary density (FCD) and red blood cell velocity (RBCV) were evaluated at baseline, 60 min after HS, 60 and 90 min after treatments. Lactate blood concentrations were evaluated at baseline, 60 min after HS and 90 min after treatments. Hematocrit (Hct), cardiac output (CO), stroke volume (SV) and number of rolling and adhered leukocytes were assessed at 90 min after treatments. Data were considered significant when p < 0.05. NE increased significantly all macrohemodynamic variables compared to baseline (except MAP), and it was the only treatment that increased Hct, CO and SV significantly. NE decreased significantly all microvascular variables in comparison to baseline. NP increased HR, FCD and RBCV and reduced MVP and dP/dt significantly. LEV decreased MVP and dP/dt, arteriolar diameter and FCD and augmented RBCV significantly in comparison to baseline. Blood concentration of lactate increased significantly 60 min after HS. Leukocyte rolling and adhesion were not different between groups. We concluded that, early, during hemorrhagic shock, norepinephrine associated to fluid therapy improved macrohemodynamic parameters but failed to improved microvascular flow. Conversely, sodium nitroprusside association had the opposite effect. Despite its inodilator properties, levosimendan did not improve macro or microhemodynamic parameters when combined to fluid therapy.

Sevoflurane, Compared With Isoflurane, Minimizes Lung Damage in Pulmonary but Not in Extrapulmonary Acute Respiratory Distress Syndrome in Rats.

BACKGROUND: Volatile anesthetics modulate inflammation in acute respiratory distress syndrome (ARDS). However, it is unclear whether they act differently depending on ARDS etiology. We hypothesized that the in vivo and in vitro effects of sevoflurane and isoflurane on lung damage would not differ in pulmonary (p) and extrapulmonary (exp) ARDS. METHODS: Twenty-four Wistar rats were randomized to undergo general anesthesia (1-2 minutes) with sevoflurane and isoflurane. Animals were then further randomized to receive Escherichia coli lipopolysaccharide (LPS) intratracheally (ARDSp) or intraperitoneally (ARDSexp), and 24 hours after ARDS induction, they were subjected to 60 minutes of sevoflurane or isoflurane anesthesia at 1 minimal alveolar concentration. The primary outcome measure was interleukin (IL)-6 mRNA expression in lung tissue. Secondary outcomes included gas exchange, lung mechanics, histology, and mRNA expression of IL-10, nuclear factor erythroid 2-related factor-2 (Nrf2), surfactant protein (SP)-B, vascular cell adhesion molecule-1, epithelial amiloride-sensitive Na-channel subunits α and γ, and sodium-potassium-adenosine-triphosphatase pump subunits α1 (α1-Na,K-ATPase) and ß1 (ß1-Na,K-ATPase). Additional ARDSp and ARDSexp animals (n = 6 per group) were anesthetized with sodium thiopental but not mechanically ventilated (NV) to serve as controls. Separately, to identify how sevoflurane and isoflurane act on type II epithelial cells, A549 human lung epithelial cells were stimulated with LPS (20 µg/mL) for 24 hours, and SP-B expression was quantified after further exposure to sevoflurane or isoflurane (1 minimal alveolar concentration ) for 60 minutes. RESULTS: In ARDSp, sevoflurane reduced IL-6 expression to a greater degree than isoflurane (P = .04). Static lung elastance (P = .0049) and alveolar collapse (P = .033) were lower in sevoflurane than isoflurane, whereas Nrf2 (P = .036), SP-B (P = .042), and ß1-Na,K-ATPase (P = .038) expressions were higher in sevoflurane. In ARDSexp, no significant differences were observed in lung mechanics, alveolar collapse, or molecular parameters between sevoflurane and isoflurane. In vitro, SP-B expression was higher in sevoflurane than isoflurane (P = .026). CONCLUSIONS: Compared with isoflurane, sevoflurane did not affect lung inflammation in ARDSexp, but it did reduce lung inflammation in ARDSp.

The Effects of Short-Term Propofol and Dexmedetomidine on Lung Mechanics, Histology, and Biological Markers in Experimental Obesity.

BACKGROUND: Administering anesthetics to the obese population requires caution because of a variety of reasons including possible interactions with the inflammatory process observed in obese patients. Propofol and dexmedetomidine have protective effects on pulmonary function and are widely used in short- and long-term sedation, particularly in intensive care unit settings in lean and obese subjects. However, the functional and biological effects of these drugs in obesity require further elucidation. In a model of diet-induced obesity, we compared the short-term effects of dexmedetomidine versus propofol on lung mechanics and histology, as well as biological markers of inflammation and oxidative stress modulation in obesity. METHODS: Wistar rats (n = 56) were randomly fed a standard diet (lean) or experimental diet (obese) for 12 weeks. After this period, obese animals received sodium thiopental intraperitoneally and were randomly allocated into 4 subgroups: (1) nonventilated (n = 4) for molecular biology analysis only (control); (2) sodium thiopental (n = 8); (3) propofol (n = 8); and (4) dexmedetomidine (n = 8), which received continuous IV administration of the corresponding agents and were mechanically ventilated (tidal volume = 6 mL/kg body weight, fraction of inspired oxygen = 0.4, positive end-expiratory pressure = 3 cm H2O) for 1 hour. RESULTS: Compared with lean animals, obese rats did not present increased body weight but had higher total body and trunk fat percentages, airway resistance, and interleukin-6 levels in the lung tissue (P = 0.02, P = 0.0027, and P = 0.01, respectively). In obese rats, propofol, but not dexmedetomidine, yielded increased airway resistance, bronchoconstriction index (P = 0.016, P = 0.02, respectively), tumor necrosis factor-α, and interleukin-6 levels, as well as lower levels of nuclear factor-erythroid 2-related factor-2 and glutathione peroxidase (P = 0.001, Bonferroni-corrected t test). CONCLUSIONS: In this model of diet-induced obesity, a 1-hour propofol infusion yielded increased airway resistance, atelectasis, and lung inflammation, with depletion of antioxidative enzymes. However, unlike sodium thiopental and propofol, short-term infusion of dexmedetomidine had no impact on lung morphofunctional and biological variables.

Fluid resuscitation therapy in endotoxemic hamsters improves survival and attenuates capillary perfusion deficits and inflammatory responses by a mechanism related to nitric oxide.

BACKGROUND: Relative hypovolemia is frequently found in early stages of severe sepsis and septic shock and prompt and aggressive fluid therapy has become standard of care improving tissue perfusion and patient outcome. This paper investigates the role of the nitric oxide pathway on beneficial microcirculatory effects of fluid resuscitation. METHODS: After skinfold chamber implantation procedures and endotoxemia induction by intravenous Escherichia coli lipopolysaccharide administration (2 mg x kg(-1)), male golden Syrian hamsters were fluid resuscitated and then sequentially treated with L-Nω-Nitroarginine and L-Arginine hydrochloride (LPS/FR/LNNA group). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables including venular leukocyte rolling and adhesion. Macro-hemodynamic, biochemical and hematological parameters as well as survival rate were also evaluated. Endotoxemic hamsters treated with fluid therapy alone (LPS/FR group) and non-treated animals (LPS group) served as controls. RESULTS: Fluid resuscitation was effective in reducing lipopolysaccharide-induced microcirculatory changes. After 3 hours of lipopolysaccharide administration, non-fluid resuscitated animals (LPS group) had the lowest functional capillary density (1% from baseline for LPS group vs. 19% for LPS/FR one; p <0.05). At the same time point, arteriolar mean internal diameter was significantly wider in LPS/FR group than in LPS one (100% vs. 50% from baseline). Fluid resuscitation also reduced leukocyte-endothelium interactions and sequestration (p <0.05 for LPS vs. LPS/FR group) and increased survival (median survival time: 2 and 5.5 days for LPS and LPS/FR groups, respectively; p <0.05). Nitric oxide synthase inhibition prevented these protective effects, while L-Arginine administration markedly restored many of them. CONCLUSION: Our results suggest that the underlying mechanism of fluid therapy is the restoration of nitric oxide bioavailability, because inhibition of NOS prevented many of its beneficial effects. Nevertheless, further investigations are required in experimental models closer to conditions of human sepsis to confirm these results.

Nonobese Young Females with Polycystic Ovary Syndrome have Nutritive Microvascular Dysfunction: A Pilot Study.

OBJECTIVE: To investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables. METHODS: Fourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/m2) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCVmax), and time taken to reach RBCVmax (TRBCVmax). RESULTS: Subjects with PCOS had lower RBCV and higher TRBCVmax compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, P<.01) and (5 [5-6] vs. 4 [3-5] s, P<.05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCVmax (ρ = -0.49, P<.05) and to TRBCVmax (ρ = 0.41, P<.05). SHBG correlated with RBCVmax (ρ = 0.52, P<.01) while estradiol (E2) levels correlated with RBCV (ρ = 0.80, P<.001) and RBCVmax (ρ = 0.46, P<.05). CONCLUSION: Microvascular dysfunction characterized by reduced RBCVmax and prolonged TRBCVmax was present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction.

Challenges in measuring sleep quality among women with endometriosis: A comparison of two questionnaires.

OBJECTIVE: This study aimed to underscore the issues associated with the dichotomization of categories in sleep questionnaires among women diagnosed with endometriosis and sleep disturbances, as well as their potential impact on the validity of the research findings. BACKGROUND: A range of questionnaires is employed across settings from primary care to research to classify sleep disturbances. Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI) are two frequently utilized instruments for evaluating sleep. Nonetheless, these tools may produce divergent outcomes when applied to the same population. METHODS: To evaluate the sleep quality of patients with deep endometriosis (DE), two self-administered questionnaires were utilized: ISI and PSQI. Patients rated their average pelvic pain over the preceding four weeks on a numeric rating scale (NRS) ranging from 0 to 10. Patients with an ISI score >14 or PSQI >5 were classified as poor sleepers, while the others as good sleepers. RESULTS: Among the 161 patients who completed both sleep questionnaires, 129 (80 %) rated their subjective sleep quality as good. However, when the scores from the sleep questionnaires were analyzed, only 17 (11 %) patients were classified as good sleepers by the PSQI, whereas the ISI classified 83 (52 %) patients as good sleepers. When comparing the standardized scores, moderate to good reliability was found (intraclass correlation coefficient, 0.76; 95 % confidence interval, 0.69-0.82). CONCLUSION: Both questionnaires yield consistent scores that seem comparable in women with DE; however, the cutoff values seem inadequate for this population. Therefore, we can probably rely on both questionnaire scores, yet their recommended cutoff values should be approached with caution.

Brain stimulation for treatment-resistant depression.

Depression is one of the main public health problems in the world, having a high prevalence and being considered the main cause of disability. An important portion of patients does not respond to treatment with the initial trial of conventional antidepressants in the current depressive episode of moderate to severe intensity, which characterizes treatment-resistant depression. In this context, non-invasive neuromodulation procedures use an electric current or magnetic field to modulate the central nervous system, and they represent a new option for patients with treatment-resistant depression.

Case report: Injected corticosteroids for treating leprosy isolated neuritis.

One of the main manifestations of leprosy is peripheral nerve impairment. Early diagnosis and treatment are important to reduce the impact of neurological impairment, which can cause deformities and physical disabilities. Leprosy neuropathy can be acute or chronic, and neural involvement can occur before, during, or after multidrug therapy, and especially during reactional episodes when neuritis occurs. Neuritis causes loss of function in the nerves and can be irreversible if left untreated. The recommended treatment is corticosteroids, usually through an oral regimen at an immunosuppressive dose. However, patients with clinical conditions that restrict corticosteroid use or that have focal neural involvement may benefit from the use of ultrasound-guided perineural injectable corticosteroids. In this study, we report two cases that demonstrate how the treatment and follow-up of patients with neuritis secondary to leprosy, using new techniques, can be provided in a more individualized way. Nerve conduction studies in association with neuromuscular ultrasound were used to monitor the response to treatment with injected steroids, focusing on neural inflammation. This study provides new perspectives and options for this profile of patients.

Prevalence of chronic pain in Brazil: A systematic review and meta-analysis.

OBJECTIVE: This review synthesized existing studies on the prevalence of chronic pain in Brazil and its associated factors to produce a recent estimation to guide public health politics. METHODS: A search was carried out in the Ovid Medline, Embase, Web of Science, and BVS Regional/Lilacs databases to identify population-based cross-sectional studies from 2005 to 2020, which reported the prevalence of benign chronic pain in Brazil (more than three months). The risk of bias was assessed using design, sample size determination, and random selection as essential issues. Pooled prevalence estimates were calculated for chronic pain in the general and elderly populations. The protocol was registered on Prospero (CRD42021249678). RESULTS: Of the 682 identified, 15 macheted the authors' inclusion criteria. Chronic pain prevalence in the general adult population ranged from 23.02% to 41.4% (pooled estimate 35.70%, 95% Cis 30.42 to 41.17) and was described as moderate to intense. It was associated with female sex, old age, lower education, intense professional activity, excessive alcohol consumption, smoking, central obesity, mood disorder, and sedentarism. The Southeastern and Southern regions presented a higher prevalence. The prevalence in the elderly population ranged from 29.3% to 76.2% (pooled estimate 47.32%, 95% Cis 33.73 to 61.11). In addition, this population visited doctors more frequently, had more sleep disorders, and was more dependent on daily living activities. Almost fifty percent of both populations with chronic pain reported pain-induced disability. CONCLUSION: Chronic Pain is highly prevalent in Brazil and associated with significant distress, disability, and poorly controlled.

Evaluation of Pain Prevalence in Children Who Experienced Perinatal Hypoxia-Ischemia Events: Characteristics and Associations With Sociodemographic Factors.

INTRODUCTION: Pain in children who suffer from hypoxia-ischemia (HI) events is still not widely studied. Hypoxia-ischemia is characterized by the momentary or permanent cessation of blood flow and, consequently, of oxygen supply, becoming the main cause of encephalopathy in children. Hyperalgesia was identified in animals undergoing prenatal hypoxia-ischemia by researchers from the Universidade do Estado do Rio de Janeiro (UERJ). Premature and asphyxiated newborns have been admitted to the neonatal intensive care unit (NICU) of Pedro Ernesto University Hospital (HUPE) in Brazil and are monitored by the Outpatient Follow-up of High-Risk Newborns Project (SARAR), but no pain assessment was performed. OBJECTIVE: To assess pain in children born in high-risk situations, such as prematurity and perinatal asphyxia, with higher chances of perinatal HI, discharged from the NICU/HUPE, and followed by SARAR. METHODOLOGY: The study was approved by the HUPE Research Ethics Committee. The epidemiological, descriptive, cross-sectional study started in 2021 and finished in 2023, with the application of the pain assessment tool or instrument adapted from the Lübeck Pain-Screening Questionnaire to the caregivers and with the collection of growth and development data. The population consisted of asphyxiated infants born with a gestational age greater than 35 weeks and submitted to the Therapeutic Hypothermia protocol and premature infants discharged from the NICU between two (gestational age 1 (GA1)) and 12 years old. For most of them, pain prevalence was assessed according to its frequency and intensity, as were sociodemographic variables of the child and mother, neural alterations, and the Children's Developmental Scale (DENVER II). The percentage differences between the evaluated factors and the presence of pain were performed using Fisher's exact test and medians using the non-parametric Wilcoxon rank-sum test, both appropriate for the small sample of children. Significance levels of 10% were considered for trends and 5% for statistically significant differences. RESULTS: Of the 86 children included in our search, 26 (30%) were born with a gestational age greater than 35 weeks and diagnosed with perinatal asphyxia (hereinafter referred to as the asphyxiation group), and 60 (70%) were premature. Pain was reported by 22 (25%) children, of whom 54.4% reported moderate or severe pain. The head and abdomen were the most reported sites (36%). Differences were observed in the percentage distribution of pain between asphyxiates and premature infants (11% vs. 32%; p-value 0.061 on the Fisher test) and between females and males (34% vs. 17%; p-value 0.085 on the Fisher test). Black and Brown children had higher median pain scale values than White children (p-value < 0.027, Wilcoxon rank sum test). CONCLUSION: There is a higher prevalence of pain in girls, in the head, in premature infants, and greater intensity among Black and Brown children. Therefore, knowing the pain profile can help improve their quality of life by offering treatments.

High fat diet induces central obesity, insulin resistance and microvascular dysfunction in hamsters.

Microvascular dysfunction is an early finding in obesity possibly related to co-morbidities like diabetes and hypertension. Therefore we have investigated changes on microvascular function, body composition, glucose and insulin tolerance tests (GTT and ITT) on male hamsters fed either with high fat (HFD, n=20) or standard (Control, n=21) diet during 16 weeks. Total body fat and protein content were determined by carcass analysis, aorta eNOS and iNOS expression by immunoblotting assay and mean blood pressure (MAP) and heart rate (HR) by an arterial catheter. Microvascular reactivity in response to acetylcholine and sodium nitroprusside, functional capillary density (FCD), capillary recruitment induced by a hyperinsulinemic status and macromolecular permeability after 30 min ischemia was assessed on either cheek pouch or cremaster muscle preparations. Compared to Control, HFD animals have shown increased visceral fat (6.0 ± 0.8 vs. 13.8 ± 0.6g/100g BW), impaired endothelial dependent vasodilatation, decreased FCD (11.3 ± 1.3 vs. 6.8 ± 1.2/field) and capillary recruitment during hyperinsulinemia and increased macromolecular permeability after ischemia/reperfusion (86.4 ± 5.2 vs.105.2 ± 5.1 leaks/cm(2)), iNOS expression and insulin resistance. MAP, HR, endothelial independent vasodilatation and eNOS expression were not different between groups. Our results have shown that HFD elicits an increase on visceral fat deposition, microvascular dysfunction and insulin resistance in hamsters.

Improved resuscitation from hemorrhagic shock with Ringer's lactate with increased viscosity in the hamster window chamber model.

BACKGROUND: Infusion of large volume of fluid is practiced in the treatment of hemorrhagic shock although resuscitation with small fluid volumes reduces the risks associated with fluid overload. We explored the hypothesis that reduced Ringer's lactate (RL) volume restoration in hemorrhage is significantly improved by increasing its viscosity, leading to improved microvascular conditions. METHODS: Awake hamsters were subjected to a hemorrhage of 50% of blood volume followed by a shock period of 1 hour. They were resuscitated with conventional RL (n = 6) or with RL whose viscosity was increased by the addition of 0.3% alginate (RL-HV) (n = 6). In both cases, the volume infused was 200% of shed blood. RESULTS: After resuscitation, blood and plasma viscosities were 1.9 cp ± 0.18 cp and 1.0 cp ± 0.03 cp in RL and 2.5 cp ± 0.34 cp and 1.6 cp ± 0.05 cp in RL-HV. Mean arterial pressure was lower than baseline in RL. Arteriolar diameter and arteriolar and venular flow were significantly higher in RL-HV. Functional capillary density was significantly higher in RL-HV than RL. After 90 minutes of resuscitation, functional capillary density was lower than baseline in RL, whereas it was maintained in RL-HV. Arteriolar PO2 was higher in RL-HV than RL. Microcirculation O2 delivery and tissue PO2 were significantly higher in RL-HV. CONCLUSIONS: Increasing blood and plasma viscosities in resuscitation from hemorrhagic shock with increased viscosity RL improves microvascular hemodynamics and oxygenation parameters.

The role of KATP channels on propofol preconditioning in a cellular model of renal ischemia-reperfusion.

BACKGROUND: Propofol (2,6-diisopropylphenol) has been shown to protect several organs, including the kidneys, from ischemia-reperfusion (I-R)-induced injury. Although propofol affects adenosine triphosphate-sensitive potassium (K(ATP)) channels in nonrenal tissues, it is still not clear by which mechanisms propofol protects renal cells from such damage. In this study, we investigated whether propofol induces renal preconditioning through renal K(ATP) channels. METHODS: A reversible ATP depletion (antimycin A) followed by restoration of substrate supply in LLC-PK1 cells was used as an in vitro model of renal I-R. Cell viability was assessed by dimethylthiazol-diphenyltetrazol bromide and trypan blue dye exclusion test assays. Apoptosis was evaluated by annexin V-fluorescein isothiocyanate staining by flow cytometry and immunofluorescence. Propofol treatments were initiated at various time intervals: 1 or 24 h before ischemia, only during ischemia, or only during reperfusion. To evaluate the mechanisms of propofol protection, specific K(ATP) channel inhibitors or activators were used in some experiments during propofol pretreatment. RESULTS: Propofol attenuated I-R injury on LLC-PK1 cells when present either 1 or 24 h before initiated I-R, and also during the recovery period, but not when added only during ischemia. Propofol pretreatment significantly protected LLC-PK1 from I-R-induced apoptosis. The protective effect of propofol was prevented by glibenclamide (a sarcolemmal ATP-dependent K(+) channel blocker) and decreased by 5-hydroxidecanoic acid (a mitochondrial ATP-dependent K(+) channel blocker), but it was not modified by diazoxide (a selective opener of ATP-sensitive K(+) channel). CONCLUSION: Propofol protected cells against apoptosis induced by I-R. This protection was probably due to a preconditioning effect of propofol and was, at least in part, mediated by K(ATP) channels.

Microcirculatory effects of intravenous fluids in critical illness: plasma expansion beyond crystalloids and colloids.

PURPOSE OF REVIEW: Plasma expanders are reviewed to determine their ability to restore microvascular function as a means for extending the transfusion trigger and delaying the use of blood transfusions. This outcome is currently achievable because of the emergence of a new understanding of optimal tissue function that prioritizes maintenance of functional capillary density, which results from the normalization of blood viscosity via the increase in plasma viscosity with new viscogenic colloids. RECENT FINDINGS: Use of viscous plasma expanders in experimental models of extreme hemodilution, hemorrhagic shock and endotoxemia shows that the limiting factor in anemia is not oxygen-carrying capacity but the decline of microvascular function due to the lowering of functional capillary density. In support of this hypothesis, we find that viscogenic colloids including high-molecular-weight starches, dextrans, polyvinylpyrrolidone, keratin and polyethylene glycol-conjugated albumin maintain or restore microvascular function in extreme hemodilution, polyethylene glycol-conjugated albumin yielding the best results. SUMMARY: Preclinical studies show that polyethylene glycol-conjugated albumin at concentrations in the range of 2-4% extends the transfusion trigger, providing the more extended and complete microvascular and systemic recovery from hemorrhagic shock, extreme hemodilution and endotoxemia, postponing the need of reestablish intrinsic blood oxygen-carrying capacity to hemoglobin concentrations lower than those associated with accepted transfusion triggers.

Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review. / Terapêutica anestésica para o alívio da dor aguda pós-colecistectomia videolaparoscópica: revisão sistemática.

Inappropriate therapy of postoperative pain in laparoscopic cholecystectomy may lead to late mobilization, patient dissatisfaction, delayed hospital discharge, and chronic pain development. Our objective was to identify the best therapeutic strategy available to the anesthesiologist for the acute postoperative pain of patients submitted to elective laparoscopic cholecystectomy. This is a systematic review that included 36 complete articles indexed in the Medline, Scopus, Web of Science and LILACS databases, with a five-year time cut (2012 to 2016), resulting from controlled and randomized studies that were submitted to qualitative analysis. In a proposal for multimodal analgesia, it is important to consider the contraindications, adverse effects, dose and optimal timing of interventions. Non-opioid drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase-2 (COX-2) inhibitors, gabapentin/pregabalin, N-methyl-D-aspartate (NMDA) receptor antagonists, and others. Opioids may be used at low doses associated with multimodal therapy or are restricted to cases where non-opioid multimodal analgesia is insufficient. We conclude that there is no consensus as to the best analgesic strategy to be implemented in the acute postoperative pain of laparoscopic cholecystectomy, which requires its applicability in an individualized way, based on the scientific evidence found in the literature. As contribution to medical learning and practice, we point out the theoretical enrichment of the analgesic drug options available for the therapy of postoperative pain in patients submitted to elective laparoscopic cholecystectomy, and alert the team to consider the adverse effects of the interventions implemented.

A terapêutica inadequada da dor pós-operatória em colecistectomia videolaparoscópica pode levar a mobilização tardia, insatisfação do paciente, atraso na alta hospitalar e desenvolvimento de dor crônica. Objetivou-se identificar qual a melhor estratégia terapêutica disponível ao anestesiologista na terapia da dor aguda pós-operatória de pacientes submetidos à colecistectomia videolaparoscópica eletiva. Trata-se de revisão sistemática que incluiu 36 artigos completos indexados nas bases de dados Medline, Scopus, Web of Science e LILACS, com recorte temporal de cinco anos (2012 a 2016), resultantes de estudos controlados e randomizados que foram submetidos à análise qualitativa. Em uma proposta de analgesia multimodal, é importante considerar as contraindicações, os efeitos adversos, a dose e o momento ideal das intervenções. Utiliza-se fármacos não opioides, como anti-inflamatórios não esteroides (AINES)/inibidores da ciclo-oxigenase-2 (COX-2), gabapentina/pregabalina, antagonistas dos receptores N-methyl-D-aspartato (NMDA), entre outras. Os opioides podem ser utilizados em doses baixas associadas ou não a terapia multimodal e/ou ficarem restritos aos casos em que a analgesia multimodal não opioide for insuficiente. Conclui-se que não há consenso sobre qual a melhor estratégia analgésica a ser implementada na dor aguda pós-operatória da colecistectomia videolaparoscópica, o que requer sua aplicabilidade de forma individualizada, com base nas evidências científicas encontradas na literatura. Aponta-se como contribuições para o ensino e a prática profissional o enriquecimento teórico das opções medicamentosas analgésicas disponíveis para a terapêutica da dor pós-operatória de pacientes submetidos à colecistectomia videolaparoscópica eletiva, além de alertar a equipe para considerar os efeitos adversos das intervenções implementadas.

Prevalence of chronic pain in Brazil: A systematic review and meta-analysis

Abstract Objective This review synthesized existing studies on the prevalence of chronic pain in Brazil and its associated factors to produce a recent estimation to guide public health politics. Methods A search was carried out in the Ovid Medline, Embase, Web of Science, and BVS Regional/Lilacs databases to identify population-based cross-sectional studies from 2005 to 2020, which reported the prevalence of benign chronic pain in Brazil (more than three months). The risk of bias was assessed using design, sample size determination, and random selection as essential issues. Pooled prevalence estimates were calculated for chronic pain in the general and elderly populations. The protocol was registered on Prospero (CRD42021249678). Results Of the 682 identified, 15 macheted the authors' inclusion criteria. Chronic pain prevalence in the general adult population ranged from 23.02% to 41.4% (pooled estimate 35.70%, 95% Cis 30.42 to 41.17) and was described as moderate to intense. It was associated with female sex, old age, lower education, intense professional activity, excessive alcohol consumption, smoking, central obesity, mood disorder, and sedentarism. The Southeastern and Southern regions presented a higher prevalence. The prevalence in the elderly population ranged from 29.3% to 76.2% (pooled estimate 47.32%, 95% Cis 33.73 to 61.11). In addition, this population visited doctors more frequently, had more sleep disorders, and was more dependent on daily living activities. Almost fifty percent of both populations with chronic pain reported pain-induced disability. Conclusion Chronic Pain is highly prevalent in Brazil and associated with significant distress, disability, and poorly controlled.

Metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance.

OBJECTIVE: Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The study included 31 subjects (age 38.3 +/- 7.6 years and BMI 36.3 +/- 5.2 kg/m2), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n = 15) or metformin (n = 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 microg/min) and independent (sodium nitroprusside 2, 4, and 8 microg/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment. RESULTS: The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters. CONCLUSIONS: We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects.

[Microcirculation in diabetes: implications for chronic complications and treatment of the disease]. / A microcirculação no diabetes: implicações nas complicações crônicas e tratamento da doença.

Diabetic microangiopathy is responsible for an important rate of morbidity and mortality related to the disease. Endothelial damage seems to be the triggering factor in the pathogenesis of microvascular complications. Diabetes mellitus and other metabolic diseases are associated to endothelial dysfunction, the most precocious known marker of atherosclerosis. Changes on microvascular reactivity are present in patients with diabetes mellitus, as well as in individuals with risk factors for this disease. Evaluation of endothelial and microvascular functions is possible using different invasive or preferentially non-invasive methods. Adequate control of diabetes mellitus might postpone or perhaps even prevent the microvascular disease. Microvascular dysfunction, when seen only by changes on microvascular reactivity, could be ameliorated with correction of risk factors or drug treatment.