Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2 ), and, in some protocols, brain tissue PO2 , by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2 , rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg-1 min-1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO2 , but increased renal cortical and medullary PO2 . Increasing blood haemoglobin concentration increased rSO2 , but not renal PO2 . We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.

Repurposing old drugs as novel inhibitors of human MIF from structural and functional analysis.

Human macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine that plays multiple pleiotropic functions. It is considered as a promising therapeutic target for the infectious, autoimmune, and cardiovascular diseases and cancers. The development of MIF inhibitors has not been translated into clinical success despite decades of research. Given the time and cost of developing new drugs, existing drugs with clarified safety and pharmacokinetics are explored for their potential as novel MIF inhibitors. This study identified five known drugs that could inhibit MIF's tautomerase activity and MIF-mediated cell chemotaxis in RAW264.7 cells. It was found that compounds D2 (histamine), D5 (metaraminol), and D8 (nebivolol) exhibited micromolar-range inhibition potency close to the positive control ISO-1. Kinetics and the mechanism for inhibition were subsequently determined. Moreover, the detailed inhibitor-binding patterns were investigated by X-ray crystallography, computational molecular docking, and structure-based analysis. Therefore, this study elucidates the molecular mechanism of repurposed drugs acting on MIF and provides a structural foundation for lead optimization to promote the clinical development of MIF-targeted drugs.

Strategies that improve renal medullary oxygenation during experimental cardiopulmonary bypass may mitigate postoperative acute kidney injury.

Renal medullary hypoxia may contribute to cardiac surgery-associated acute kidney injury (AKI). However, the effects of cardiopulmonary bypass (CPB) on medullary oxygenation are poorly understood. Here we tested whether CPB causes medullary hypoxia and whether medullary oxygenation during CPB can be improved by increasing pump flow or mean arterial pressure (MAP). Twelve sheep were instrumented to measure whole kidney, medullary, and cortical blood flow and oxygenation. Five days later, under isoflurane anesthesia, CPB was initiated at a pump flow of 80 mL kg-1min-1 and target MAP of 70 mm Hg. Pump flow was then set at 60 and 100 mL kg-1min-1, while MAP was maintained at approximately 70 mm Hg. MAP was then increased by vasopressor (metaraminol, 0.2-0.6 mg/min) infusion at a pump flow of 80 mL kg-1min-1. CPB at 80 mL kg-1min-1 reduced renal blood flow (RBF), -61% less than the conscious state, perfusion in the cortex (-44%) and medulla (-40%), and medullary Po2 from 43 to 27 mm Hg. Decreasing pump flow from 80 to 60 mL kg-1min-1 further decreased RBF (-16%) and medullary Po2 from 25 to 14 mm Hg. Increasing pump flow from 80 to 100 mL kg-1min-1 increased RBF (17%) and medullary Po2 from 20 to 29 mm Hg. Metaraminol (0.2 mg/min) increased MAP from 63 to 90 mm Hg, RBF (47%), and medullary Po2 from 19 to 39 mm Hg. Thus, the renal medulla is susceptible to hypoxia during CPB, but medullary oxygenation can be improved by increasing pump flow or increasing target MAP by infusion of metaraminol.

Chronic stress accelerates the development of endometriosis in mouse through adrenergic receptor ß2.

STUDY QUESTION: Does chronic stress in mice accelerate the development of endometriosis, and, if so, through what mechanism? SUMMARY ANSWER: Exposure to chronic stress accelerates the development of endometriosis and exacerbates the endometriosis-associated generalized hyperalgesia, most likely through activation of the adrenoceptor ß2 (ADRB2) and cAMP responsive element-binding protein (CREB). WHAT IS KNOWN ALREADY: Women with endometriosis tend to have higher levels of psychological stress, which is known to impact negatively on health in general and to promote tumor growth and metastasis in particular. Exposure to chronic stress before and after the induction of endometriosis is reported to increase lesion sizes in rodents, but it is unclear whether adrenoceptors are involved or not in the stress-promoted development of endometriosis. STUDY DESIGN, SIZE, DURATION: Three independent, prospective, randomized mouse experimentations. A total of 184 virgin female Balb/C mice were used. PARTICIPANTS/MATERIALS, SETTING, METHODS: In Experiment 1, the mice were randomly divided into four groups: the control group, which received no stress; the before, after and both groups, which received immobilization stress before, after and both before and after the induction of endometriosis, respectively. In Experiment 2, mice were randomly divided into four groups one day after the induction of endometriosis: phosphate buffer saline (PBS) and propranolol (PROP) groups, which received the mini-pump containing, respectively, PBS only and propranolol (a non-selective ADRB antagonist) but no stress, STR+PROP and STR+PBS groups, which received stress and the mini-pump containing, respectively, propranolol and PBS. The immobilization stress started after the insertion of mini-pumps. In Experiment 3, mice were induced with endometriosis. Three days after the induction, they were randomly divided into four groups: control, ADRAa, ADRB2a, and ADRBa, which received the mini-pump containing solution only, metaraminol (a non-specific α adrenoceptor agonist), tebutaline (a specific ADRB2 agonist), or isoproterenol (a non-specific ADRB agonist), respectively. In all three experiments, the bodyweight and hotplate latency were evaluated before sacrifice 14 days after the induction. In all experimentations, the lesion weight was evaluated and the harvested ectopic endometrial tissue samples were subjected to immunohistochemistry analysis of vascular endothelial growth factor (VEGF), CD31-positive microvessels, proliferating cell nuclear antigen (PCNA), phosphorylated CREB, ADRB1, ADRB2, ADRB3, adrenergic receptor α1 (ADRA1) and ADRA2. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to chronic stress accelerated the development of endometriosis and exacerbated the endometriosis-associated generalized hyperalgesia. This promotional effect is likely to be mediated through the systemic activation of the sympatho-adreno-medullary (SAM) axis, which results in subsequent release of catecholamines. The surging catecholamines may activate ADRB2 and CREB, yielding increased angiogenesis and cellular proliferation in ectopic endometrium in mice with induced endometriosis. In addition, ß adrenergic receptor blockade completely abolished the promotional effect of chronic stress, likely through suppression of ADRB2 and CREB activation, thus suppressing angiogenesis and proliferation. Moreover, a non-specific adrenergic ß agonist and a specific adrenergic ß2 agonist, but not non-specific adrenergic α agonist, acted similarly to chronic stress, accelerating the development of endometriosis and exacerbating the generalized hyperalgesia in mice with pre-existing endometriosis. LARGE SCALE DATA: NA. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of immunohistochemistry analyses only and the lack of molecular data. WIDER IMPLICATIONS OF THE FINDINGS: The present study provides the experimental evidence that chronic stress can promote the development of endometriosis through the activation of ADRB2. Given ADRB2 is also expressed in human endometriosis and appears to be functional, and in light of recent awareness that adrenergic signaling plays critical roles in tumorigenesis, it is likely that adrenergic signaling may play important roles in the development of endometriosis and is potentially a target for intervention. STUDY FUNDING/COMPETING INTERESTS: This research was supported in part by grants (81270676,  81471434 and 81530040  to S.W.G.;  81370695 and 81671436  to X.S.L.) from the National Natural Science Foundation of China, and grant (2013ZYJB0019 to X.S.L.) from Shanghai Municipal Commission of Health and Family Planning. None of the authors has anything to disclose.

Minimally invasive cardiac output monitoring: agreement of oesophageal Doppler, LiDCOrapid™ and Vigileo FloTrac™ monitors in non-cardiac surgery.

There is lack of data about the agreement of minimally invasive cardiac output monitors, which make it impossible to determine if they are interchangeable or differ objectively in tracking physiological trends. We studied three commonly used devices: the oesophageal Doppler and two arterial pressure-based devices, the Vigileo FloTrac™ and LiDCOrapid™. The aim of this study was to compare the agreement of these three monitors in adult patients undergoing elective non-cardiac surgery. Measurements were taken at baseline and after predefined clinical interventions of fluid, metaraminol or ephedrine bolus. From 24 patients, 131 events, averaging 5.2 events per patient, were analysed. The cardiac index of LiDCOrapid versus FloTrac had a mean bias of -6.0% (limits of agreement from -51% to 39%) and concordance of over 80% to the three clinical interventions. The cardiac index of Doppler versus LiDCOrapid and Doppler versus FloTrac, had an increasing negative bias at higher mean cardiac outputs and there was significantly poorer concordance to all interventions. Of the preload-responsive parameters, Doppler stroke volume index, Doppler systolic flow time and FloTrac stroke volume variation were fair at predicting fluid responsiveness while other parameters were poor. While there is reasonable agreement between the two arterial pressure-derived cardiac output devices (LiDCOrapid and Vigileo FloTrac), these two devices differ significantly to the oesophageal Doppler technology in response to common clinical intraoperative interventions, representing a limitation to how interchangeable these technologies are in measuring cardiac output.

Prewarming neurosurgical patients to minimize hypotension on induction of anesthesia: a randomized trial.

PURPOSE: Prewarming prior to surgery is effective in preventing perioperative hypothermia. There is a paucity of evidence, however, regarding the hemodynamic effects of prewarming. We hypothesized that the nadir mean arterial pressure during anesthesia induction would be higher after prewarming than after no prewarming. METHODS: We randomized 32 patients prior to elective neurosurgery to receive either one hour of forced-air convective warming at 46°C or routine care (full body blanket with convective warmer attached but not turned on). All patients had invasive blood pressure, heart rate, and core temperature monitoring before and during warming and underwent a protocolized intravenous anesthetic induction with propofol and remifentanil target-controlled infusions. The primary endpoint was the nadir mean arterial blood pressure (MAP) during induction. Hypotension was defined as systolic blood pressure (SBP) < 90 mmHg, MAP < 60 mmHg, or a reduction in either SBP or MAP > 20% from baseline values. RESULTS: No difference was found in the mean (SD) nadir MAP between the prewarmed group and the control group [64 (11) mmHg vs 68 (16) mmHg, respectively; mean difference, 5 mmHg; 95% confidence interval (CI), -6 to 15; P = 0.36]. Similarly, there was no difference between groups in the incidence of hypotension (100% of prewarmed vs 93% of control patients; relative risk, 1.07; 95% CI, 0.94 to 1.23; P = 0.32) or in the requirement for vasopressors during induction (four patients in each group required metaraminol; P = 1.00). CONCLUSION: Prewarming with convective forced air for one hour prior to intravenous anesthetic induction did not prevent hypotension during the induction period (Australian New Zealand Clinical Trials Registry [ANZCTR] ACTRN12615000431527).

Comparison of metaraminol, phenylephrine and ephedrine in prophylaxis and treatment of hypotension in cesarean section under spinal anesthesia / Avaliação comparativa entre metaraminol, fenilefrina e efedrina na profilaxia e no tratamento da hipotensão em cesarianas sob raquianestesia / Evaluación comparativa entre el metaraminol, la fenilefrina y la efedrina en la profilaxis y en el tratamiento de la hipotensión en cesáreas bajo anestesia espinal

Maternal hypotension is a common complication after spinal anesthesia for cesarean section, with deleterious effects on the fetus and mother. Among the strategies aimed at minimizing the effects of hypotension, vasopressor administration is the most efficient. The aim of this study was to compare the efficacy of phenylephrine, metaraminol, and ephedrine in the prevention and treatment of hypotension after spinal anesthesia for cesarean section. Ninety pregnant women, not in labor, undergoing cesarean section were randomized into three groups to receive a bolus followed by continuous infusion of vasopressor as follows: phenylephrine group (50 μg + 50 μg/min); metaraminol group (0.25 mg + 0.25 mg/min); ephedrine group (4 mg + 4 mg/min). Infusion dose was doubled when systolic blood pressure decreased to 80% of baseline and a bolus was given when systolic blood pressure decreased below 80%. The infusion dose was divided in half when systolic blood pressure increased to 120% and was stopped when it became higher. The incidence of hypotension, nausea and vomiting, reactive hypertension, bradycardia, tachycardia, Apgar scores, and arterial cord blood gases were assessed at the 1st and 5th minutes. There was no difference in the incidence of hypotension, bradycardia, reactive hypertension, infusion discontinuation, atropine administration or Apgar scores. Rescue boluses were higher only in the ephedrine group compared to metaraminol group. The incidence of nausea and vomiting and fetal acidosis were greater in the ephedrine group. The three drugs were effective in preventing hypotension; however, fetal effects were more frequent in the ephedrine group, although transient.

Hipotensão materna é uma complicação comum após raquianestesia em cirurgia cesariana, trazendo efeitos deletérios para o feto e a mãe. Entre as estratégias com o objetivo de minimizar os efeitos da hipotensão, a administração de vasopressores é a mais eficiente. O objetivo deste estudo foi comparar a eficácia da fenilefrina, metaraminol e efedrina na prevenção e tratamento de hipotensão após raquianestesia em cirurgia cesariana. Noventa gestantes que não estavam em trabalho de parto submetidas à cesariana eletiva foram randomizadas em três grupos para receber um bolus, seguido de infusão contínua de vasopressor da seguinte forma: Grupo Fenilefrina (50 μg + 50 μg/min); Grupo Metaraminol (0,25 mg + 0,25 mg/min); Grupo Efedrina (4 mg + 4 mg/min). A dose da infusão foi dobrada quando a pressão arterial sistólica (PAS) decresceu até 80% dos valores basais e um bolus foi dado quando a PAS decresceu para valores abaixo de 80%. A dose da infusão foi dividida ao meio quando a PAS aumentou até 120% e foi interrompida quando mais elevada. Foram analisadas as incidências de hipotensão, náuseas e vômitos, hipertensão reativa, bradicardia, taquicardia e escores de Apgar no primeiro e quinto minutos e gases de sangue arterial do cordão umbilical. Não houve diferenças nas incidências de hipotensão, bradicardia, hipertensão reativa, interrupção da infusão, administração de atropina ou escores de Apgar. A administração de bolus de resgate foram superiores apenas no Grupo Efedrina em comparação com Metaraminol. A incidência de náuseas e vômitos e acidose fetal foram superiores no Grupo Efedrina. Os três fármacos foram eficazes na prevenção de hipotensão, mas repercussões fetais foram mais frequentes no Grupo Efedrina, embora transitórias.

La hipotensión materna es una complicación común posterior a la anestesia espinal en cirugía de cesárea, lo que trae efectos perjudiciales para el feto y la madre. Entre las estrategias cuyo objetivo es minimizar los efectos de la hipotensión, la administración de vasopresores es la más eficaz. El objetivo de este estudio fue comparar la eficacia de la fenilefrina, del metaraminol y de la efedrina en la prevención y el tratamiento de la hipotensión posterior a la aplicación de la anestesia espinal en cirugía de cesárea. Noventa gestantes que no estaban de parto y sometidas a la cesárea electiva, fueron aleatorizadas en 3 grupos para recibir un bolo, seguido de infusión continua de vasopresor de la siguiente forma: grupo fenilefrina (50 μg + 50 μg/min); grupo metaraminol (0,25 mg + 0,25 mg/min); grupo efedrina (4 mg + 4 mg/min). La dosis de la infusión se duplicó cuando la presión arterial sistólica cayó al 80% de los valores basales y un bolo se administró cuando la presión arterial sistólica cayó a valores por debajo del 80%. La dosis de la infusión se dividió en 2 cuando la presión arterial sistólica aumentó alcanzando los 120% y fue interrumpida cuando se elevó. Se analizaron las incidencias de hipotensión, náuseas y vómitos, hipertensión reactiva, bradicardia, taquicardia y puntuaciones de Apgar en el primer y en el quinto minutos, y gases de sangre arterial del cordón umbilical. No hubo diferencias en las incidencias de hipotensión, bradicardia, hipertensión reactiva, interrupción de la infusión, administración de atropina o puntuaciones de Apgar. La administración de bolos de rescate fue superior solo en el grupo efedrina en comparación con el metaraminol. La incidencia de náuseas y vómitos y la acidosis fetal fueron superiores en el grupo efedrina. Los 3 fármacos fueron eficaces en la prevención de la hipotensión y las repercusiones fetales fueron más frecuentes en el grupo efedrina, aunque hayan sido transitorias.

A comparison of three minimally invasive cardiac output devices with thermodilution in elective cardiac surgery.

This study compared the cardiac output responses to haemodynamic interventions as measured by three minimally invasive monitors (Oesophageal Doppler Monitor the VigileoFlotrac and the LiDCOrapid) to the responses measured concurrently using thermodilution, in cardiac surgical patients. The study also assessed the precision and bias of these monitors in relation to thermodilution measurements. After a fluid bolus of at least 250 ml, the measured change in cardiac output was different among the devices, showing an increase with thermodilution in 82% of measurements, Oesophageal Doppler Monitor 68%, VigileoFlotrac 57% and LiDCOrapid 41%. When comparing the test devices to thermodilution, the kappa statistic showed at best only fair agreement, Oesophageal Doppler Monitor 0.34, LiDCOrapid 0.28 and VigileoFlotrac -0.03. After vasopressor administration, there was also significant variation in the change in cardiac output measured by the devices. Using Bland-Altman analysis, the precision of the devices in comparison to thermodilution showed minimal bias, but wide limits of agreement with percentage errors of Oesophageal Doppler Monitor 64.5%, VigileoFlotrac 47.6% and LiDCOrapid 54.2%. These findings indicate that these three devices differ in their responses, do not always provide the same information as thermodilution and should not be used interchangeably to track cardiac output changes.

Vasopressores em bloqueios do neuroeixo para cesariana / Vasopressors in neuraxial anesthesia at cesarean sections

Justificativa e objetivos: Os fármacos vasopressores sempre apresentaram um lugar de destaque no controle da hipotensão arterial relacionada aos bloqueios do neuroeixo em anestesia obstétrica. Este artigo tem o objetivo de discutir os diversos fármacos utilizados na prática clínica e as inúmeras estratégias descritas na literatura para a prevenção e tratamento da hipotensão arterial pós-raquianestesia para cesariana. Conteúdo: Com a popularização da raquianestesia como técnica mais utilizada em anestesia para cesariana, os vasopressores tornaram-se pedra angular para a melhoria dos resultados maternos e fetais. Várias mudanças de paradigmas se apresentam nos dias atuais, destacando-se a segurança na utilização de fármacos alfa-agonistas, particularmente a fenilefrina. A efedrina já não tem sido mais considerada a primeira escolha em anestesia obstétrica, pois pode causar redução no pH fetal. Conclusões: A administração pro-filática e/ou terapêutica de agonistas alfa-adrenérgicos mostra-se segura e eficaz para o controle da hipotensão arterial pós-raquianestesia, otimizando os resultados maternos e fetais. Portanto, sugere-se revisão de conceitos.

Justification and objectives: vasopressor drugs have always been highlighted for the control of hypotension related to neuraxial blockade in obstetrical anesthesia. This article purpose is arguing the several drugs used in the clinical practice and the countless strategies described in the literature for the prevention and treatment of arterial hypotension after spinal anesthesia for caesarian section. Content: With the popularization of spinal anesthesia as the technique most used in anesthesia for caesarian section, vasopressors became the angular stone for the improvement of the maternal and fetal outcomes. Several changes of paradigms are introduced currently, highlighting the safe use of alpha-agonist drugs, particularly phenylephrine. Ephedrine has no longer been considered the unique first choice in obstetrical anesthesia, because it may cause reduction in fetal pH. Conclusions: The alpha adrenergic prophylactic and/or therapeutic administration proved to be a safe and effective option for the hypotension control after spinal anesthesia, optimizing the maternal and fetal outcomes. Therefore, that is the time for reviewing old concepts.

Transient transmural ischaemia during endobronchial laser treatment: possible coronary artery embolism.

We report the case of a 51-year-old woman receiving endobronchial treatment with neodymium:yttrium garnet laser After 30 minutes of stable anaesthesia and laser treatment, sudden inferior myocardial ischaemia developed followed by haemodynamic collapse. Resuscitation with fluids, pressors, atropine and esmolol was successful, leading to rapid resolution of the ischaemia and full recovery. The sudden onset and time course of the ST segment elevation was consistent with coronary artery air embolism, as occurs occasionally during cardiac surgery. Systemic gas embolism during endobronchial laser treatment has been previously reported with poor outcomes and significant mortality. This complication can be avoided with awareness of the mechanism while appropriate monitoring may allow early detection and successful treatment.

Successful management of stuttering priapism using home self-injections of the alpha-agonist metaraminol

Low-flow priapism can result in impotence if treatment is delayed, yet patients with recurrent priapism often suffer delay before therapy. We describe management of recurrent priapism using self-administered injections of intracavernosal metaraminol (AramineÖ, Merck), a long-acting vasoconstricting amine that is considered safer than epinephrine. The patient injects as often as once daily using 5-10 mg of drug. Our patient reports rapid detumescence and has not required emergency room visits since starting injections. He denies complications. Treatment of priapism using metaraminol has been suggested in the hospital setting; however, this is the first report of successful home self-administration of the drug.

Expansão volêmica em raquianestesia para cesariana: como realizá-la? / Fluid preload in obstetric patients: how to do it?

JUSTIFICATIVA E OBJETIVOS: Em pacientes não obstétricas, demonstrou-se que a expansão volêmica rápida realizada imediatamente após a injeção subaracnóidea do anestésico local era mais efetiva que a expansão volêmica lenta, realizada previamente à instalação do bloqueio para se reduzir a incidência e a gravidade da hipotensão arterial após raquianestesia. O objetivo do estudo foi comparar a incidência de hipotensão arterial e o consumo de vasopressores em gestantes submetidas à cesariana sob raquianestesia com diferentes regimes de expansão volêmica. MÉTODO: Foram avaliadas prospectivamente 60 gestantes de termo submetidas à cesariana sob raquianestesia. As pacientes receberam expansão volêmica com 10 ml.kg-1 de solução de Ringer com lactato como segue: Grupo 1 (n = 20), antes da raquianestesia através de cateter 18G; Grupo 2 (n = 20), após a raquianestesia e com cateter 18G e Grupo 3 (n = 20) após a raquianestesia com cateter 16G sob ação de pressurizador. A pressão arterial (PA) foi monitorizada a cada minuto e administrou-se 0,2 mg de metaraminol para qualquer diminuição de PA, a partir do valor de controle e 0,4 mg para diminuição > 20 por cento. A PA controle foi definida como a média de três valores sucessivos de pressão arterial sistólica obtidos antes da expansão volêmica e do bloqueio. Estudou-se a velocidade de infusão de fluidos, incidência de hipotensão arterial materna, náusea e vômito, consumo de metaraminol, índice de Apgar e pH da artéria umbilical. RESULTADOS: A velocidade de administração de fluidos foi maior no Grupo 3 do que nos Grupos 1 e 2 (201 ± 61 vs 56 ± 13 e 59 ± 21 ml.min-1, p < 0,05). Os grupos foram semelhantes em relação à incidência de hipotensão arterial, náusea, vômito, consumo de metaraminol, índice de Apgar e pH da artéria umbilical. CONCLUSÕES: A expansão volêmica, realizada antes ou após a instalação da raquianestesia, de maneira rápida ou lenta, não modifica o consumo de vasopressor, a ocorrência de hipotensão arterial mat...

BACKGROUND AND OBJECTIVES: In has been shown in non-obstetric patients, that a fast acute fluid preload immediately after spinal anesthesia was more effective than a slow preload before regional block to decrease the incidence and severity of arterial hypotension after spinal anesthesia. This study aimed at comparing the incidence of arterial hypotension and vasopressants consumption in parturients submitted to C-section under spinal anesthesia with different fluid preload regimens. METHODS: Sixty term pregnant women submitted to C-section under spinal anesthesia. Patients were randomly distributed in three groups receiving acute preload (10 ml.kg-1 lactated Ringer's) as follows: Group 1 (n = 20), before spinal anesthesia through 18G catheter; Group 2 (n = 20), after spinal anesthesia through 18G catheter and Group 3 (n = 20), after spinal anesthesia through 16G catheter with pressurizer. Blood pressure (BP) was monitored at 1-minute intervals until delivery and 0.2 mg bolus metaraminol was administered for any BP decrease from baseline values; 0.4 mg was administered for BP decrease > 20%. Control blood pressure was defined as the mean of three successive SBP values obtained before acute preload and spinal block. Variables studied were: preload rate, incidence of maternal arterial hypotension, nausea, vomiting, vasopressants consumption, Apgar scores and umbilical artery pH. RESULTS: Acute preload was faster in Group 3 as compared to Groups 1 and 2 (201 ± 61 vs 56 ± 13 and 59 ± 21 ml.min-1, p < 0.05). Groups were similar regarding the incidence of arterial hypotension, nausea and vomiting, metaraminol consumption, Apgar scores and umbilical artery pH. CONCLUSIONS: Acute preload before or after spinal anesthesia performance, in a slow or fast rate, does not change vasopressants consumption, the incidence of maternal arterial hypotension, nausea and vomiting, as well as fetal wellbeing.

JUSTIFICATIVA Y OBJETIVOS: En pacientes no obstétricas, se demostró que la expansión volémica rápida realizada inmediatamente después de la inyección subaracnoidea del anestésico local era más efectiva que la expansión volémica lenta, realizada previamente a la instalación del bloqueo para reducir la incidencia y la gravedad de la hipotensión arterial después de raquianestesia. El objetivo del estudio fue comparar la incidencia de hipotensión arterial y el consumo de vasopresores en embarazadas sometidas a cesárea bajo raquianestesia con diferentes regímenes de expansión volémica. MÉTODO: Fueron evaluadas prospectivamente 60 embarazadas de término sometidas a cesárea bajo raquianestesia. Las pacientes recibieron expansión volémica con 10 ml.kg-1 de solución de Ringer con lactato como sigue: Grupo 1 (n = 20), antes de la raquianestesia a través de catéter 18G; Grupo 2 (n = 20), después de raquianestesia y con catéter 18G y Grupo 3 (n = 20) después de raquianestesia con catéter 16G bajo acción de un presurizador. La presión arterial (PA) fue monitorizada a cada minuto y se administró 0,2 mg de metaraminol para cualquier diminución de PA, a partir del valor de control y 0,4 mg para diminución > 20%. La PA control fue definida como la media de tres valores sucesivos de PAS obtenidos antes de la expansión volémica y del bloqueo. Se estudió la velocidad de infusión de fluidos, incidencia de hipotensión arterial materna, náusea y vómito, consumo de metaraminol, índice de Apgar y pH de la arteria umbilical. RESULTADOS: La velocidad de administración de fluidos fue mayor en el Grupo 3 de que en los Grupos 1 y 2 (201 ± 61 vs 56 ± 13 y 59 ± 21 ml.min-1, p < 0,05). Los grupos fueron semejantes en relación a la incidencia de hipotensión arterial, náusea, vómito, consumo de metaraminol, índice de Apgar y pH de la arteria umbilical. CONCLUSIONES: La expansión volémica, realizada antes o después de la instalación de la raquianestesia, de manera rápida o lenta, no modifica el...

The incidence and management of priapism in Western Australia: a 16 year audit.

The objective of the study was to conduct a retrospective audit of patients who presented with priapism in Western Australia during the years 1985-2000. We searched the records of the teaching hospitals in metropolitan Perth and those of the Keogh Institute for Medical Research for the diagnostic code for priapism. A total of 82 episodes of priapism in 63 patients occurred over this 16 year period. In all, 62 episodes occurred after intracavernosal injections (ICI) and 20 were due to other causes. Treatment of priapism included simple aspiration of blood, intracavernosal injection of alpha-adrenergic agents and surgical shunt procedures. Priapism occurring outside the setting of ICI was more likely to require surgery; seven of 20 episodes. After ICI therapy, eight of 62 episodes required shunts. The use of prostaglandin E1 as the drug of choice in ICI therapy in 1989 led to a fall in the incidence of ICI-induced priapism. Priapism is a major side effect of ICI therapy and an uncommon, although important, side effect of other conditions. The incidence of priapism has fallen with the introduction of prostaglandin E1 monotherapy as the favoured drug for ICI therapy of erectile failure.

Prostaglandin synthesis inhibitor improves hypotension during normothermic cardiopulmonary bypass.

Hypotension is a major systemic side effect during cardiopu monary bypass (CPB), especially at normothermia. We previously reported that prostaglandin (PG) might play a substantial role in hypotension. The purpose of this study was to clarify whether a PG synthesis inhibitor (PGSI) could improve hypotension during CPB. Thirty-six patients undergoing cardiac surgery with normothermic CPB (35-37 degrees C) were divided into two groups: a PGSI group (n = 18), whose members wer given a PGSI before and during CPB, and a control group (n = 18). In both groups, perfusion flow was sufficient and pressure was maintained at above 45 mm Hg by infusion of metaraminol, a vasoconstrictor. The mean arterial pressure throughout CPB was significantly higher in the PGSI group than in the control group (57 +/- 4 vs. 48 +/- 3 mm Hg, p < 0.01), whereas the dose of infused metaraminol was significantly lower in the PGSI group (13 +/- 7 vs. 21 +/- 6 mg, p < 0.01). The blood base excess was not significantly different (1.0 +/- 1.6 vs. 1.7 +/- 1.9 mmol/L, p = 0.28), and urine output was significantly higher in the PGSI group (503 +/- 179 vs. 354 +/- 112 ml/hr, p < 0.01). In conclusion, PGSI can improve hypotension during CPB and increase urine output without impairing peripheral circulation.

Anaphylactic or anaphylactoid reactions in patients undergoing cardiac surgery.

OBJECTIVE: To examine the clinical features, treatment, and outcome of anaphylactic and anaphylactoid reactions during cardiac surgery. DESIGN: Retrospective descriptive study. SETTING: A specialized referral anesthetic allergy clinic at a university teaching hospital. PARTICIPANTS: Twenty-three cardiac surgical patients referred after reactions resembling anaphylaxis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The database of the anesthetic allergy clinic was examined, and the data for patients who developed anaphylactic or anaphylactoid reactions were collated and summarized. Twenty-three cardiac surgical patients who experienced signs of anaphylactic or anaphylactoid reactions during anesthesia and surgery from 8 cardiac surgical centers in a major city were referred to the clinic. Cephalosporin antibiotics (30%) and gelatin solutions (Hemaccel) (26%) were the most common (56%) causes of the reactions. Most reactions occurred before the start of cardiopulmonary bypass. Although metaraminol was the first vasopressor used in 18 of 23 patients, it was not effective in 14 patients. Response to epinephrine was immediate and effective in 88% of cases. Rapid placement onto cardiopulmonary bypass facilitated a good outcome and permitted all but one operation to proceed as planned. No intraoperative or postoperative deaths were recorded. CONCLUSION: Of the anaphylactic and anaphylactoid reactions, 60% occurred before cardiopulmonary bypass, and these were caused by antibiotics and gelatin solution. The results from this limited database showed that cardiac surgery proceeded without complications after cardiovascular collapse caused by anaphylactic or anaphylactoid reactions. Rapid institution of cardiopulmonary bypass may be life-saving and should be considered.

A comparison of three fluid-vasopressor regimens used to prevent hypotension during subarachnoid anaesthesia in the elderly.

We aimed to compare the efficacy of fluid preloading with two recently recommended fluid-vasopressor regimens for maintaining blood pressure during subarachnoid anaesthesia in the elderly. Sixty elderly patients requiring surgery for traumatic hip fractures received subarachnoid anaesthesia using 0.05 ml/kg of 0.5% heavy bupivacaine. Hypotension, i.e. systolic arterial pressure < 75% of baseline, was prevented or treated by: A--normal saline 16 ml/kg plus intravenous ephedrine boluses (0.1 mg/kg); B--normal saline 8 ml/kg plus intramuscular depot ephedrine (0.5 mg/kg); or C--Haemaccel 8 ml/kg plus metaraminol infusion. Systolic arterial pressure and heart rate were recorded using custom-written computer software (Monitor, version 1.0). Systolic arterial pressure decreased in all groups after five minutes (P < 0.001). Decreases were greatest in group A (P < 0.05). Heart rate increased by 7% group A and decreased by 9% in group C (P < 0.05). During the first hour, hypotension was present for 47%, 25% and 20% of the time in groups A, B and C respectively and overcorrection of systolic arterial pressure occurred in 19% of the time in group C. We conclude that treatment A was inadequate in preventing hypotension. Treatments B and C were more effective but were associated with an increased heart rate and overcorrection of systolic arterial pressure respectively.

Alpha1-adrenoceptor stimulation enhances experimental gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged administration of the norepinephrine-mimicking agent metaraminol, the alpha1-adrenergic agonist phenylephrine and the alpha2-adrenergic agonist clonidine on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the ornithine decarboxylase activity of the gastric cancer and the labeling index of the gastric mucosa were investigated in Wistar rats. Rats received s.c. injections of metaraminol, phenylephrine or clonidine every other day after 20 weeks of oral treatment with MNNG. At week 52, administration of metaraminol and phenylephrine at the higher dose significantly increased the incidence of gastric cancers, the ornithine decarboxylase activity of the gastric cancers and the labeling index of the antral epithelial cells. Administration of phenylephrine at the lower dose and clonidine at both doses had no significant effect on the incidence of gastric cancers, the ornithine decarboxylase activity of the gastric cancers or the labeling index of the gastric mucosa. Our results suggest that adrenoreceptor stimulation enhances gastric carcinogenesis and that such enhancement is mediated through alpha1-adrenoceptors without alpha2-adrenoceptor involvement.

Biotransformation in monkey brain: coupling of sulfation to glutathione conjugation.

Phenol sulfotransferase (PST, EC 2.8.2.1) and glutathione-S-transferase (GST, EC 2.5.1.18), the phase II biotransformation enzymes inactivate many exo- and endogenous compounds. The effect of PST substrates (catecholamines, simple phenols, selected phenolic drugs) and PST products (phenolic sulfates) on GST activity was investigated to identify possible interactions between sulfation and glutathione conjugation in the brain. Two soluble forms of PST and two forms of GST were isolated from monkey (Rhesus macacus) brain cortex. Catecholamines, hypertensive and hypotensive drugs which are sulfated by monkey brain PSTs slightly inhibit the activity of brain GSTs. The greatest inhibitory effect was observed with neurotoxic compounds such as 6-OHDA and manganese. The commonly used analgesic drugs inhibit both GST forms. These enzymes are also inhibited by phenacetin, the precursor of paracetamol, and prototype salicylates such as sodium salicylate and acetylsalicylic acid. The effect of simple phenols and their sulfated metabolites on GST activity varies. The obtained results point to a possible interaction between sulfation and glutathione conjugation in vivo since many physiologically, therapeutically and toxicologically active compounds which are sulfated by brain phenol sulfotransferases may be bound by brain glutathione-S-transferases. These compounds may lose their activity (on being bound to GST) and expose the brain to the toxic electrophiles (by decreasing GST activity).

Effect of propofol infusion on the endocrine response to cardiac surgery.

The effect of propofol infusion on the stress response was studied in patients undergoing coronary artery bypass graft (CABG). Ten patients received propofol infusion during cardiopulmonary bypass (CPB) and ten controls received diazepam. Blood levels of cortisol, adrenaline and noradrenaline were sampled. There was a significant reduction in all three hormones (P < 0.05) in the study group. In addition, the amount of sodium nitroprusside used during CPB was significantly reduced (P < 0.05).