RESUMEN
A 5-week-old infant with congenital chylothorax required long-term intravenous access for parenteral nutrition. Cannulation of the inferior vena cava via the left femoral vein was attempted, but the catheter was misplaced into the left ascending lumbar vein. Catheter removal is advised when such malposition is identified. We were able successfully to redirect the catheter into the inferior vena cava using ultrasonographic guidance. This procedure has not been described previously in children. We propose that repositioning of incorrectly placed vascular catheters can be achieved using ultrasound guidance at the bedside.
Asunto(s)
Cateterismo Venoso Central , Catéteres de Permanencia , Errores Médicos , Ultrasonografía Intervencional , Humanos , Lactante , Masculino , Sistemas de Atención de PuntoRESUMEN
Induction of the heat shock response protects animals from either endotoxemia or peritonitis. In endotoxemia, heat shock protein (HSP) induction is associated with reversal of vascular hyporeactivity and inhibition of iNOS expression. Recent studies suggest differences in the inflammatory mechanisms during endotoxemia and peritonitis animal models and their response to therapeutic interventions. We therefore studied the effect of the HSP inducer sodium arsenite (SA) on vascular reactivity and iNOS expression in rats undergoing cecal ligation and puncture (CLP). CLP resulted in suppression of the pressor effect of norepinephrine (NE) in vivo (measured by changes in blood pressure in response to NE boluses) and ex vivo (changes in contraction force in isolated mesenteric arteries in response to NE concentrations), and in the expression of iNOS protein. Pretreatment of the rats with SA resulted in reversal of CLP-induced vascular hyporeactivity in vivo and ex vivo, and inhibition of iNOS expression after 22 h. SA pretreatment improved 7-day survival after CLP from 18.2% to 70% (P < 0.005). Glucocorticoid receptor inhibition did not affect the effect of HSP induction on iNOS expression. The similarity of the effect of HSP on vascular reactivity and iNOS expression in two distinct sepsis models suggests that this effect may be clinically important and that a causative relationship between HSP induction, iNOS inhibition, and reversal of vascular reactivity is likely.
Asunto(s)
Arsenitos/farmacología , Óxido Nítrico Sintasa/metabolismo , Sepsis/metabolismo , Compuestos de Sodio/farmacología , Vasoconstricción/efectos de los fármacos , Animales , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/fisiología , Ciego/cirugía , Inhibidores Enzimáticos/farmacología , Proteínas de Choque Térmico/efectos de los fármacos , Proteínas de Choque Térmico/metabolismo , Ligadura , Masculino , Mesenterio , Óxido Nítrico Sintasa/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II , Norepinefrina/farmacología , Punciones , Ratas , Ratas Wistar , Sepsis/mortalidad , Sepsis/fisiopatología , Tasa de Supervivencia , Vasoconstrictores/farmacologíaRESUMEN
Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinal fluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus who experienced multiple shunt failures, and who had externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. The effects of increasing doses of ACTZ on CSF production and subsequent tolerance to ventriculopleural shunts were evaluated. The patients had a 48% and a 39% decrease in their EVD CSF output when compared to baseline with maximum ACTZ dose of 75 mg/kg/day and 50 mg/kg/day, respectively (p < 0.05). This is the first report of change in CSF volume in children after extended treatment with ACTZ. ACTZ treatment in mechanically ventilated paediatric patients with hydrocephalus may improve tolerance of ventriculopleural shunts and minimise respiratory compromise. Potassium and bicarbonate supplements are required to correct metabolic disturbances.
Asunto(s)
Acetazolamida/uso terapéutico , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Derivaciones del Líquido Cefalorraquídeo , Hidrocefalia/tratamiento farmacológico , Líquido Cefalorraquídeo/efectos de los fármacos , Líquido Cefalorraquídeo/fisiología , Resultado Fatal , Femenino , Estudios de Seguimiento , Humanos , Hidrocefalia/líquido cefalorraquídeo , Lactante , Recién Nacido , Masculino , Respiración Artificial , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: Presentation of a case report describing the use of a mobile computed tomography (CT) scanner in the pediatric intensive care unit (PICU) to radiographically evaluate tracheobronchial stenting and lung volumes while using different levels of positive end-expiratory pressure (PEEP) and positioning in a critically ill infant. DESIGN: Case report of a single patient. SETTING: Pediatric intensive care unit in a University Hospital. PATIENT: A 6-month-old premature infant with bronchopulmonary dysplasia, tracheobronchomalacia, and progressive respiratory failure. INTERVENTIONS: CT scans of the chest were performed by using a mobile CT scanner in the PICU. Serial CT scans were performed at PEEP levels of 5, 10, 15, and 20 cm H(2)O in both the supine and prone position. Scheduled medical care and standard monitoring were continued during the course of the CT scans. MEASUREMENTS AND MAIN RESULTS: Identical anatomic levels demonstrating the trachea, bronchi, and lung parenchyma were compared while different levels of PEEP and supine or prone positioning were used. From these comparisons, the level of PEEP in which lung volumes were optimized was radiographically determined. No significant changes in large airway caliber were observed. There was no difference noted between prone and supine positioning. CT scans were completed with minimal disruption to the patient's care. CONCLUSIONS: Mobile CT scanners can be used in the PICU for the diagnostic evaluation of critically ill children. This option allows for the continuation of medical therapies and monitoring in the intensive care setting while avoiding the potential complications of transporting a critically ill child to the radiology department. The use of mobile CT scanners may disrupt PICU routine and is more expensive than use of fixed CT scanners. Mobile CT scanners may be useful in radiographically determining the optimal level of PEEP in infants with tracheobronchomalacia and bronchopulmonary dysplasia.
RESUMEN
The dependence of the critical steps in the sepsis cascade on the transcription factor NF-kappaB andation to nitric oxide (NO) production are controversial. Tyrosine kinase (TK) is involved in several of the steps, and TK inhibitors (TKI) inhibit lipopolysaccharide (LPS)-induced vascular hyporesponsiveness in septic animals. We studied the relationship of TK inhibition, hemodynamics, vascular contraction, iNOS mRNA expression and NF-kappaB translocation in anesthetized endotoxic rats. The TKI AG556 (2.5 mg/kg i.p.), given 1 h before i.v. endotoxin (LPS) resulted in attenuation of early (<60 min) and late (60-120 min) hypotension, improved contraction of mesenteric arteries to norepinephrine 4 h after LPS, and attenuated tissue iNOS mRNA expression. LPS-induced NF-kappaB translocation was unaffected. The observed dissociation between NF-kappaB translocation and the salutary effect of TKI in vivo and ex vivo and its effect on iNOS mRNA expression suggest that although NF-kappaB may be involved in the sepsis cascade, it may not be essential for some of the molecular and vascular consequences of septic shock.
Asunto(s)
Hemodinámica/fisiología , FN-kappa B/metabolismo , Óxido Nítrico Sintasa/genética , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Choque Séptico/fisiopatología , Circulación Esplácnica/fisiología , Transcripción Genética , Tirfostinos/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Núcleo Celular/metabolismo , Endotoxinas/toxicidad , Inhibidores Enzimáticos/farmacología , Escherichia coli , Hemodinámica/efectos de los fármacos , Técnicas In Vitro , Lipopolisacáridos/toxicidad , Masculino , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/fisiología , Arterias Mesentéricas/fisiopatología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Músculo Liso Vascular/fisiopatología , Óxido Nítrico Sintasa de Tipo II , Norepinefrina/farmacología , Transporte de Proteínas/efectos de los fármacos , ARN Mensajero/genética , Ratas , Ratas Wistar , Circulación Esplácnica/efectos de los fármacos , Vasoconstricción/efectos de los fármacosRESUMEN
OBJECTIVES: To evaluate our experience with propofol anesthesia delivered by pediatric intensivists in the pediatric intensive care unit (PICU) to facilitate elective oncology procedures in children performed by pediatric oncologists. METHODS: Elective oncology procedures performed with propofol anesthesia in our multidisciplinary, university-affiliated PICU were prospectively evaluated over a 7-month period. Ambulatory and hospitalized children were prescheduled for their procedure, underwent a medical evaluation, and met fasting requirements before the start of anesthesia. Continuous cardiorespiratory and neurologic monitoring was performed by a pediatric intensivist and a PICU nurse, while the procedure was performed by a pediatric oncologist. Propofol was delivered in intermittent boluses to achieve the desired level of anesthesia. Information studied included patient demographics, procedures performed, induction and total doses of propofol used, the duration of the different phases of the patient's PICU stay, the occurrence of side effects, the need for therapeutic interventions, and the incidence of recall of the procedure. RESULTS: Fifty procedures in 28 children (mean age: 7.5 +/- 4.3 years) were evaluated. Sixty-one percent of patients had established diagnoses. Fifty-four percent of procedures were lumbar puncture with intrathecal chemotherapy administration and 26% of procedures were bone marrow aspirations with biopsy. Induction propofol doses were 2. 0 +/-.8 mg/kg for ambulatory and hospitalized patients, while total propofol doses were 6.6 +/- 2.3 mg/kg and 7.9 +/- 2.4 mg/kg for ambulatory and hospitalized patients, respectively. Induction time was 1.5 +/-.7 minutes, recovery time was 23.4 +/- 11.5 minutes, and total PICU time was 88.8 +/- 27.7 minutes. Transient decreases in systolic blood pressure less than the fifth percentile for age occurred in 64% of procedures, with a mean decrease of 25% +/- 10%. Intravenous fluids were administered in 31% of these cases. Hypotension was more common in ambulatory patients but was not predicted by propofol dose, anesthesia time, or age. Partial airway obstruction was noted in 12% of procedures while apnea requiring bag-valve-mask ventilation occurred in 2% of procedures. Neither was associated with age, propofol dose, or the duration of anesthesia. All procedures were successfully completed and there were no incidences of recall of the procedure. CONCLUSIONS: Propofol anesthesia is effective in achieving patient comfort and amnesia, while optimizing conditions for elective oncology procedures in children. Although transient hypotension and respiratory depression may occur, propofol anesthesia seems to be safe to use for these procedures in the PICU setting. Recovery from anesthesia was rapid and total stay was brief. Under the proper conditions, propofol anesthesia delivered by pediatric intensivists in the PICU is a reasonable option available to facilitate invasive oncology procedures in children.
Asunto(s)
Anestesia Intravenosa , Anestésicos Intravenosos , Técnicas y Procedimientos Diagnósticos/efectos adversos , Dolor/prevención & control , Pediatría , Propofol , Adolescente , Adulto , Anestésicos Intravenosos/efectos adversos , Biopsia con Aguja/efectos adversos , Biopsia con Aguja/psicología , Examen de la Médula Ósea/efectos adversos , Examen de la Médula Ósea/psicología , Niño , Preescolar , Técnicas y Procedimientos Diagnósticos/psicología , Femenino , Humanos , Hipotensión/inducido químicamente , Lactante , Unidades de Cuidado Intensivo Pediátrico , Masculino , Oncología Médica , Dolor/etiología , Dolor/psicología , Propofol/efectos adversos , Estudios Prospectivos , Punción Espinal/efectos adversos , Punción Espinal/psicologíaRESUMEN
Tracheal extubation after laryngotracheal reconstruction in children may be complicated by postoperative tracheal edema and pulmonary dysfunction. The replacement of a tracheal tube in this situation may exacerbate the existing injury to the tracheal mucosa, complicating subsequent attempts at tracheal extubation. We present two cases where noninvasive positive-pressure ventilation was employed to treat partial airway obstruction and respiratory failure in two children following laryngotracheal reconstruction. Noninvasive positive-pressure ventilation served as a bridge between mechanical ventilation via a tracheal tube and spontaneous breathing, providing airway stenting and ventilatory support while tracheal edema and pulmonary dysfunction were resolved. Under appropriate conditions, noninvasive positive-pressure ventilation may be useful in the management of these patients.
Asunto(s)
Intubación Intratraqueal , Laringoestenosis/cirugía , Respiración con Presión Positiva , Preescolar , Femenino , Humanos , Lactante , Laringe/cirugía , Masculino , Máscaras , Complicaciones Posoperatorias/terapia , Procedimientos de Cirugía Plástica , Insuficiencia Respiratoria/terapia , Tráquea/cirugíaRESUMEN
OBJECTIVES: To describe our experience with propofol anesthesia to facilitate invasive procedures for ambulatory and hospitalized children in the pediatric intensive care unit (PICU) setting. METHODS: We retrospectively reviewed the hospital records of 115 children who underwent 251 invasive procedures with propofol anesthesia in our multidisciplinary, university-affiliated PICU during a 20-month period. All patients underwent a medical evaluation and were required to fast before anesthesia. Continuous monitoring of the patient's cardiorespiratory and neurologic status was performed by a pediatric intensivist, who also administered propofol in intermittent boluses to obtain the desired level of anesthesia, and by a PICU nurse, who provided written documentation. Data on patient demographics, procedures performed, doses of propofol used, the occurrence of side effects, induction time, recovery time, and length of stay in the PICU were obtained. RESULTS: Propofol anesthesia was performed successfully in all children (mean age, 6.4 years; range, 10 days to 20.8 years) who had a variety of underlying medical conditions, including oncologic, infectious, neurologic, cardiac, and gastrointestinal disorders. Procedures performed included lumbar puncture with intrathecal chemotherapy administration, bone marrow aspiration and biopsy, central venous catheter placement, endoscopy, and transesophageal echocardiogram. The mean dose of propofol used for induction of anesthesia was 1.8 mg/kg, and the total mean dose of propofol used was 8.8 mg/kg. In 13% of cases, midazolam also was administered but did not affect the doses of propofol used. The mean anesthesia induction time was 3.9 minutes, and the mean recovery time from anesthesia was 28.8 minutes for all patients. The mean PICU stay for ambulatory and ward patients was 140 minutes. Hypotension occurred in 50% of cases, with a mean decrease in systolic blood pressure of 25%. The development of hypotension was not associated with propofol doses, the concomitant use of midazolam, or the duration of anesthesia, but was associated with older patient age. Hypotension was transient and not associated with altered perfusion. Intravenous fluid was administered in 61% of the cases in which hypotension was present. Respiratory depression requiring transient bag-valve-mask ventilation occurred in 6% of cases and was not associated with patient age, propofol doses, concomitant use of midazolam, or the duration of anesthesia. Transient myoclonus was observed in 3.6% of cases. Ninety-eight percent of procedures were completed successfully, and no procedure failures were considered secondary to the anesthesia. Patients, parents, and health care providers were satisfied with the results of propofol anesthesia. CONCLUSIONS: Propofol anesthesia can safely facilitate a variety of invasive procedures in ambulatory and hospitalized children when performed in the PICU and is associated with short induction and recovery times and PICU length of stay. Hypotension, although usually transient, is common, and respiratory depression necessitating assisted ventilation may occur. Therefore, appropriate monitoring and cardiorespiratory support capabilities are essential. Propofol anesthesia in the PICU setting is a reasonable therapeutic option available to pediatric intensivists to help facilitate invasive procedures in ambulatory and hospitalized children.
Asunto(s)
Anestesia Intravenosa , Anestésicos Intravenosos , Propofol , Adulto , Factores de Edad , Procedimientos Quirúrgicos Ambulatorios , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Niño , Preescolar , Depresión Química , Hospitalización , Humanos , Hipotensión/inducido químicamente , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico , Propofol/administración & dosificación , Propofol/efectos adversos , Respiración/efectos de los fármacos , Estudios RetrospectivosRESUMEN
Neuropeptide Y (1-36), NPY, is a sympathetic vasoconstrictor whose activities in blood vessels is determined by the presence of vasoconstrictive Y1 receptors and the enzyme dipeptidyl peptidase IV (DPPIV), which converts NPY to non-vasoconstrictive peptides. While the role of the NPY system has been established during cold water stress, its role in hypotensive conditions has not; yet, exogenous NPY improves hemodynamics and survival in rats with endotoxic shock. We used a new selective non-peptidergic Y1 receptor antagonist, BIBP-3226, to determine the role of the endogenous NPY/Y1 system in endotoxic shock (induced by i.v. injection of 10 mg/kg of Escherichia coli lipopolysaccharide 0127:B8, LPS) and hemorrhagic shock (bleeding of 15 ml/kg over 1.5 min). Conscious rats received a bolus of BIBP-3226 or the vehicle 5 min before endotoxin challenge or induction of hemorrhage, followed by continuous infusion. Mean arterial pressure (MAP) at 5 min after LPS administration dropped in the control group by 15%, compared to 36% in the BIBP-3226-treated group (p < 0.01). Similarly, the hemorrhage-induced drop in MAP in the control group was 32% at 5 min, compared to 53% in the BIBP-treated rats (p < 0.01). Plasma NPY levels were unchanged in the endotoxic shock group, but were significantly elevated in the hemorrhagic shock group. BIBP-3226 pretreatment abrogated the increased plasma NPY levels after hemorrhagic shock. Endogenous NPY contributes to blood pressure recovery during endotoxic and hemorrhagic shock.
Asunto(s)
Neuropéptido Y/fisiología , Choque Hemorrágico/fisiopatología , Choque Séptico/fisiopatología , Vasoconstricción/fisiología , Animales , Arginina/análogos & derivados , Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Modelos Animales de Enfermedad , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Lipopolisacáridos/toxicidad , Masculino , Neuropéptido Y/sangre , Ratas , Ratas Wistar , Receptores de Neuropéptido Y/antagonistas & inhibidores , Receptores de Neuropéptido Y/fisiología , Choque Hemorrágico/etiología , Choque Séptico/etiología , Vasoconstricción/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate the relationship of perioperative levels of interleukin 6 (IL-6) in serum and bronchoalveolar fluid with morbidity and mortality in children undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective, noninterventional study. SETTING: Operating room and pediatric intensive care unit (PICU) of a university hospital. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: IL-6 levels were measured in serum and lung lavage fluid obtained before, during, and after CPB using the B9.9 bioassay. Alveolar epithelial lining fluid (AELF) volume was calculated using the urea correction method. Mean intraoperative AELF IL-6 levels increased fourfold compared to preoperative levels, and mean serum IL-6 levels increased fivefold after CPB. Mean intraoperative AELF IL-6 levels correlated with intraoperative blood transfusion (r2 = 0.18; p = 0.049) and duration of inotropic support (r2 = 0.29; p = 0.009), mechanical ventilation (r2 = 0.24; p = 0.019), and PICU stay (r2 = 0.29; p = 0.008). Mean serum IL-6 levels 2 h after CPB correlated with intraoperative blood transfusion (r2 = 0.3;p = 0.007), and with Pediatric Risk of Mortality score on postoperative day 3 (r2 = 0.24; p = 0.022), and were higher in patients with massive fluid retention (p = 0.014) and in nonsurvivors (p = 0.003). CONCLUSIONS: Serum and alveolar IL-6 levels increase after CPB, and correlate with postoperative morbidity. Serum IL-6 levels also correlate with mortality. They may be useful in assessing the severity of the systemic inflammatory response after CPB.
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Líquido del Lavado Bronquioalveolar/química , Puente Cardiopulmonar , Interleucina-6/análisis , Complicaciones Posoperatorias/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/metabolismo , Adolescente , Análisis de Varianza , Bioensayo/métodos , Bioensayo/estadística & datos numéricos , Puente Cardiopulmonar/mortalidad , Puente Cardiopulmonar/estadística & datos numéricos , Niño , Preescolar , Cardiopatías Congénitas/metabolismo , Cardiopatías Congénitas/cirugía , Humanos , Lactante , Recién Nacido , Periodo Intraoperatorio , Complicaciones Posoperatorias/epidemiología , Periodo Posoperatorio , Estudios Prospectivos , Sobrevivientes/estadística & datos numéricos , Síndrome de Respuesta Inflamatoria Sistémica/epidemiologíaRESUMEN
Endotoxin (lipopolysaccharide, LPS)-induced hypotension is, in part, mediated via induction of nitric oxide synthase (iNOS), release of nitric oxide, and suppression of vascular reactivity (vasoplegia). Induction of heat shock proteins (HSP) or inhibition of iNOS expression improves survival in LPS-challenged rodents. We studied the effect of induction of HSP on LPS-mediated iNOS expression and on LPS-induced vasoplegia and hypotension. Rats were treated with the HSP inducer sodium arsenite (6 mg/kg iv) or saline control. Seventeen hours later, rats were challenged intravenously with 10 mg/kg of Escherichia coli LPS O127:B8 or saline control. Arsenite pretreatment resulted in expression of HSP 70 mRNA and of HSP 70 and heme oxygenase-1 proteins, inhibition of LPS-mediated iNOS mRNA induction, reversal of the LPS-induced hyporesponsiveness to norepinephrine ex vivo in isolated mesenteric arteries, and attenuation of LPS-induced hypotension in vivo. Our data suggest that induction of HSP expression protects rats from LPS by blocking LPS-induced iNOS expression, leading to inhibition of the overproduction of nitric oxide and thereby reversing LPS-induced vasoplegia and LPS-induced hypotension.
Asunto(s)
Endotoxinas/farmacología , Proteínas HSP70 de Choque Térmico/metabolismo , Hipotensión/fisiopatología , Óxido Nítrico Sintasa/genética , ARN Mensajero/metabolismo , Animales , Arsenitos/farmacología , Perros , Inducción Enzimática , Escherichia coli , Hemo Oxigenasa (Desciclizante)/metabolismo , Hemodinámica/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Norepinefrina/farmacología , Ratas , Ratas Wistar , Compuestos de Sodio/farmacología , Circulación Esplácnica/efectos de los fármacos , VasoconstricciónRESUMEN
OBJECTIVE: To evaluate the relationship between postoperative serum lactate levels and outcome in children undergoing open heart surgery. DESIGN: Prospective, noninterventional study. SETTING: Pediatric intensive care unit (PICU) of a university hospital. PATIENTS: 41 nonconsecutive children who had had cardiopulmonary bypass for repair of congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Serum lactate levels were measured on admission to the PICU immediately after open heart surgery. Lactate levels were correlated with bypass and cross clamp times, estimated intraoperative blood loss, lowest temperature on bypass, admission Pediatric Risk of Mortality score, anion gap, and measures of postoperative morbidity. Mean lactate levels on admission to the PICU were 6.86 +/- 0.79 mmol/l for nonsurvivors (n = 7) and 2.38 +/- 0.13 mmol/l for survivors (n = 34) (p < 0.0001), and 4.87 +/- 0.7 mmol/l and 2.35 +/- 0.19 mmol/l, for patients with (n = 11) and without (n = 30) multiple organ system failure, respectively (p < 0.0001). Admission lactate levels correlated with all measurements of postoperative morbidity. A serum lactate level of greater than 4.2 mmol/l had a positive predictive value of 100% and a negative predictive value of 97% for postoperative death. CONCLUSIONS: Initial postoperative serum lactate levels after pediatric open heart surgery may be predictive of outcome. Lactate levels are also higher in patients who go on to develop multiple organ system failure. Elevated postoperative lactate levels may reflect intraoperative tissue hypoperfusion, and measures aimed at increasing oxygen delivery, with normalization of lactate, may improve patient outcome.
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Procedimientos Quirúrgicos Cardíacos/mortalidad , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/cirugía , Ácido Láctico/sangre , Adolescente , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Insuficiencia Multiorgánica/etiología , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
Neuropeptide-Y (NPY) is a sympathetic cotransmitter, which causes vasoconstriction, decreases coronary blood flow and decreases cardiac output. Circulating immunoreactive NPY (ir-NPY) levels increase with exercise, in patients admitted to the coronary care unit, and during thoracic surgery, and may play a role in postoperative hemodynamics. We studied changes in ir-NPY, epinephrine (E) and norepinephrine (NE) arterial plasma levels, and their correlation to simultaneous hemodynamic measurements at 8 perioperative time points in 13 patients undergoing open heart surgery. Changes in circulating ir-NPY negatively correlated with changes in systemic vascular resistance index (SVRI), mean arterial pressure (MAP) and mean pulmonary arterial pressure (MPAP) (P < 0.05), suggesting that the hemodynamic changes were the cause of the changes in ir-NPY levels, inducing overflow of NPY into the circulation via sympathetic activation. Changes in NE and E levels positively correlated with changes in heart rate (HR), SVRI and MPAP. Changes in E levels also positively correlated with changes in stroke volume index (SVI), central venous pressure (CVP) and cardiac index (CI). NE levels correlated well with E levels, but catecholamine levels did not correlate with ir-NPY levels. These results suggest, that the elevation in circulating NPY levels previously noted in patients with heart failure and acute myocardial infarction may reflect changes in NPY overflow and/or clearance secondary to increased sympathetic activity and to hemodynamic changes.
Asunto(s)
Epinefrina/sangre , Hemodinámica , Neuropéptido Y/sangre , Norepinefrina/sangre , Presión Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/fisiologíaRESUMEN
The physiological role of neuropeptide Y (NPY), a sympathetic cotransmitter and vasoconstrictor, has not been determined yet. We used a specific nonpeptide antagonist to the NPY Y1 receptor [BIBP-3226; (R)-N2-(diphenacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginineamide] to study the involvement of NPY in stress-induced vasoconstriction in the mesenteric bed. In rats subjected to cold water stress (COLD), plasma NPY immunoreactivity levels increased progressively from 0.15 +/- 0.01 to 0.32 +/- 0.05 pmol/ml and remained elevated during recovery. Administration of BIBP-3226 (3 mg.kg-1.h-1 infusion) tended to decrease the stress-induced pressor response and significantly attenuated the post-COLD elevation of blood pressure. The COLD-induced fall in the superior mesenteric artery blood flow and the increase of up to 300% in the mesenteric vascular resistance were either reduced or eliminated by BIBP-3226. Conversely, the Y1 antagonist had no effect on the COLD-induced tachycardia. This study provides the first evidence of the physiological role of NPY. The peptide is released during stress and increases mesenteric vascular resistance via activation of its Y1 receptors. Specific Y1-receptor antagonists may therefore be of potential benefit in prevention or treatment of stress-induced vasospasm.
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Arterias Mesentéricas/fisiología , Receptores de Neuropéptido Y/fisiología , Vasoconstricción/fisiología , Animales , Arginina/análogos & derivados , Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Frío , Hemodinámica , Masculino , Ratas , Ratas Wistar , Receptores de Neuropéptido Y/antagonistas & inhibidores , Flujo Sanguíneo Regional/efectos de los fármacos , Estrés Mecánico , Resistencia Vascular/efectos de los fármacosAsunto(s)
Medicina de Emergencia , Telemedicina , Triaje , Niño , Preescolar , Toma de Decisiones , Humanos , Pediatría , Telemedicina/métodos , Triaje/métodosRESUMEN
Studies of cardiovascular physiology are frequently performed under barbiturate anesthesia even though the effect of barbiturates on the pressor response to catecholamines is controversial, and their effect on the response to other agonists is unknown. The effect of pentobarbital (PB) anesthesia on the pressor and heart rate (HR) dose responses to norepinephrine (NE), angiotensin II (AII), vasopressin (VP) and neuropeptide Y (NPY) was studied in vivo in normal and endotoxemic rats. Four groups of rats (5-6 rats/group) were studied for each agonist: 1) anesthetized/endotoxemic, 2) anesthetized/control, 3) conscious/endotoxemic, and 4) conscious/control. Anesthesia was maintained with 10 mg/kg of PB i.v. q 45 minutes. Endotoxemia was established by infusion of a non-hypotensive dose of E. coli lipopolysaccharide 0127:B8, (LPS, 10 micrograms/10 microliters/min) throughout the experiment. One hour after the LPS (or saline control) infusion was started, dose response curves of the pressor and HR responses to agonists were established. LPS infusion resulted in marked suppression of the pressor response to NE, AII, and VP in both conscious and anesthetized rats. LPS infusion suppressed the response to NPY in conscious, but not in anesthetized rats. LPS did not affect the baroreceptor reflex. In both normal and endotoxemic rats, PB anesthesia suppressed the pressor response and attenuated the baroreceptor reflex to AII and NPY, enhanced the pressor response without affecting the heart rate response to NE, and attenuated the baroreceptor reflex to VP. The pressor response to VP was suppressed by anesthesia in normal, but not in endotoxemic rats. PB anesthesia interferes with the cardiovascular effects of different agonists in a variable manner, depending on the agonist tested and the presence or absence of endotoxemia, indicating their different modes of action. These effects should be considered when planning in vivo experiments with these and other agonists.
Asunto(s)
Pentobarbital/farmacología , Presorreceptores/efectos de los fármacos , Toxemia/fisiopatología , Anestesia , Angiotensina II/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Interacciones Farmacológicas , Escherichia coli/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Neuropéptido Y/farmacología , Norepinefrina/farmacología , Presorreceptores/fisiología , Ratas , Ratas Wistar , Vasoconstrictores/farmacología , Vasopresinas/farmacologíaRESUMEN
Hypotension during endotoxic shock is related to reduced vascular responsiveness to vasoconstrictors. Neuropeptide Y (NPY) is known to potentiate the pressor response to some agonists, and NPY infusion has been shown to improve hemodynamics and survival in endotoxemic rats. We therefore studied the effect of NPY infusion on the suppressed pressor effect of norepinephrine (NE), angiotensin II (AII), vasopressin (VP), and endothelin (ET) in conscious endotoxemic rats. Chronically cannulated conscious rats were infused with a non-hypotensive dose of endotoxin (LPS, 10 micrograms/10 microliters/min) throughout the experiment. Infusion of NPY, 40 pmol/10 microliters/min was started 15 minutes before the LPS infusion, and continued for 65 minutes. Five minutes after the termination of NPY infusion, increasing agonist doses were administered i.v. to construct dose-response curves. Each experiment included one control group where saline replaced LPS, and one control group where saline replaced NPY. LPS infusion caused suppression of the pressor responses to all four agonists, as expressed by ED50 and by decreased pressor response to the individual agonist doses. In addition, LPS infusion altered the bradycardic response to AII and ET. NPY infusion prior to the administration of NE, AII and VP resulted in partial reversal of the LPS-induced suppressed responsiveness to these agonists. NPY infusion had no effect on the response to ET in either control or endotoxemic rats. Partial reversal of the suppressed responsiveness to the three agonists by NPY infusion may contribute to the observed NPY-induced improvement of blood pressure and survival rate during endotoxic shock.
Asunto(s)
Endotoxinas/antagonistas & inhibidores , Neuropéptido Y/farmacología , Choque Séptico/tratamiento farmacológico , Animales , Endotelinas/farmacología , Hemodinámica/efectos de los fármacos , Hipotensión/tratamiento farmacológico , Hipotensión/fisiopatología , Lipopolisacáridos , Masculino , Norepinefrina/farmacología , Presorreceptores/efectos de los fármacos , Ratas , Ratas Wistar , Choque Séptico/fisiopatología , Vasopresinas/farmacologíaRESUMEN
Neuropeptide Y (NPY), a sympathetic and platelet-derived vasoconstrictor, acts both directly and by potentiating adrenergic responsiveness and therefore may be beneficial in endotoxic shock, where suppressed vascular responsiveness to adrenergic agents is a key factor. This was studied in anesthetized rats. First, infusion of a nonhypotensive dose of endotoxin (lipopolysaccharide, LPS) markedly suppressed the pressor response to increasing doses of norepinephrine (NE), angiotensin II, and vasopressin but did not suppress the response to NPY. Second, in rats rendered hypotensive by intravenous LPS, continuous NE infusion (0.1-1.0 microgram.kg-1 x min-1 started 5 min after LPS for 1 h) did not alter hemodynamics. In contrast, 5 nmol.kg-1 x min-1 of NPY (equipotent to 0.1 microgram.kg-1 x min-1 of NE in normal rats) increased mean arterial pressure (MAP, from 64 to 114% of baseline), total peripheral resistance index (TPRI, from 64 to 154% of baseline), and left ventricular stroke work index (from 36 to 73% of baseline), without changing cardiac index (CI). Third, in a similar experimental protocol, pretreatment of the hypotensive rats with phentolamine blocked the pressor effect of NE infusion, but only partially attenuated the response to NPY. Finally, addition of low-dose NPY to NE infusion improved survival following a lethal dose of LPS compared with treatment with NE alone (P < 0.01). Thus, unlike other vasoconstrictors tested, NPY-mediated vasoconstriction is preserved during endotoxemia. The beneficial effect of NPY is mediated by increased TPRI without reduction in CI; both NPY receptor-mediated vasoconstriction and potentiation of adrenergic responsiveness may be involved.
Asunto(s)
Neuropéptido Y/farmacología , Choque Séptico/mortalidad , Choque Séptico/fisiopatología , Antagonistas Adrenérgicos alfa/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Endotoxinas/sangre , Hemodinámica/efectos de los fármacos , Infusiones Intravenosas , Masculino , Norepinefrina/farmacología , Fentolamina/farmacología , Ratas , Ratas Wistar , Análisis de SupervivenciaRESUMEN
OBJECTIVES: To study the hypothesis that endotoxin and tumor necrosis factor-alpha (TNF) are released into the circulation during the perioperative period in children undergoing open-heart surgery, and to assess the possible role of these factors in postoperative morbidity. DESIGN: Prospective study. SETTING: Operating room and ICU of a children's hospital. PATIENTS: Twenty-four consecutive patients undergoing open-heart surgery for repair of congenital heart disease. METHODS: Endotoxin and TNF concentrations were measured in blood samples withdrawn from patients at predetermined time points in the perioperative period. These concentrations were also measured in samples from all fluids and drugs administered to patients. Clinical variables were measured throughout the perioperative period, and the Pediatric Risk of Mortality score was calculated daily. RESULTS: All of the preoperative control samples were negative for endotoxin and TNF. Endotoxin or TNF was detected in the blood of 21 (88%) of 24 patients during or after surgery. Endotoxin (ranging in concentrations from 0.32 to 438 pg/mL) was detected in the blood of 16 (67%) of the 24 patients. The majority of the samples positive for endotoxin were withdrawn during cardiopulmonary bypass and were associated with positive samples from the pump, from cardiotomy suction specimens, and from autotransfused blood. Blood cultures of all patients, except one, were negative for bacterial growth. TNF (ranging in concentrations from 3 to 132 U/mL) was detected in the blood of nine (37%) of the 24 patients. Patients positive for TNF had significantly (p less than .05) lower mean central venous pressures at 20 hrs after surgery and higher mean heart rates postoperatively compared with patients negative for TNF. No differences in other indicators of perioperative morbidity and intraoperative conditions were found, when the groups positive for endotoxin or TNF were compared with the groups negative for endotoxin or TNF, respectively. CONCLUSIONS: Endotoxin and TNF are released into the circulation during and after pediatric open-heart surgery. TNF release may be related to some of the hemodynamic changes observed after open-heart surgery.
Asunto(s)
Endotoxinas/sangre , Bacterias Gramnegativas , Cardiopatías Congénitas/sangre , Factor de Necrosis Tumoral alfa/análisis , Niño , Preescolar , Oxigenación por Membrana Extracorpórea , Infecciones por Bacterias Gramnegativas/epidemiología , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/fisiopatología , Cardiopatías Congénitas/cirugía , Hemodinámica , Humanos , Lactante , Recién Nacido , Periodo Intraoperatorio , Prueba de Limulus , Medicación Preanestésica , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To study the effect of open- and closed-heart surgery on the immune status of infants and children. DESIGN: Prospective study. Data collected before anesthesia and surgery and 2 and 24 hrs after surgery. SETTING: Operating room and pediatric ICU in a children's hospital. PATIENTS: Children undergoing surgery for correction of congenital heart disease (age 3 months to 12 yrs). A total of 31 patients were studied (open-heart surgery, n = 25; closed-heart surgery, n = 6). MEASUREMENTS AND MAIN RESULTS: Increased neutrophil counts and lymphopenia were observed after both open- and closed-heart surgery. Serum levels of the complement components C3 and C4 were depressed after open-heart surgery, but not after closed procedures. The percentage of T3+ and T4+ lymphocytes, proliferative responses of the lymphocytes and serum immunoglobulin (Ig)G and IgM were decreased from preoperative levels after open-heart surgery. The percentage of T8+ lymphocytes and serum IgA levels did not change. Intraoperative variables and postoperative severity of illness (Pediatric Risk of Mortality score) did not correlate with immune suppression. CONCLUSIONS: The immune system is affected after pediatric cardiac surgery, particularly after open-heart surgery.