RESUMO
OBJECTIVES: The integrity of the parathyroid axis was tested in 18 infants and young children undergoing repair of congenital heart disease with cardiopulmonary bypass. BACKGROUND: Infants are believed to have an immature parathyroid hormone response to hypocalcemia. Whereas adults are known to respond appropriately to hypocalcemia during cardiopulmonary bypass, children have not been studied carefully. METHODS: Calcium, magnesium, parathyroid hormone, phosphate and total protein were measured in blood samples withdrawn at defined times before, during and after cardiopulmonary bypass. RESULTS: At the initiation of cardiopulmonary bypass, ionized calcium decreased markedly in 12 infants less than or equal to 24 months old (mean +/- SEM 1.11 +/- 0.04 to 0.29 +/- 0.05 mM) and decreased significantly in 6 young children greater than 24 months old (1.19 +/- 0.02 to 0.42 +/- 0.12 mM). In response to hypocalcemia, parathyroid hormone concentration increased significantly in both the infants (from 42 +/- 8 to 103 +/- 29 and 85 +/- 22 pg/ml) and the young children (from 39 +/- 8 to 44 +/- 20 and 92 +/- 30 pg/ml). Before separation from cardiopulmonary bypass, increased parathyroid hormone concentration restored ionized calcium concentration to 0.75 +/- 0.03 mM in the infants and to 0.92 +/- 0.07 mM in the young children. There was no significant influence of either age or the use of deep hypothermia and circulatory arrest on either calcium or parathyroid hormone responses. Total magnesium and total protein concentrations decreased on initiation of cardiopulmonary bypass and thereafter remained stable. Phosphate concentrations were unchanged during the study. CONCLUSIONS: In infants and young children undergoing cardiac surgery, the parathyroid hormone response to both hypocalcemia and to rising ionized calcium concentrations was at least as great as that of adults. Thus, the calcium-parathyroid-vitamin D axis functions in infants and young children as it does in adults.
Assuntos
Cálcio/sangue , Ponte Cardiopulmonar/efeitos adversos , Cardiopatias Congênitas/cirurgia , Hipocalcemia/sangue , Hormônio Paratireóideo/sangue , Proteínas Sanguíneas/análise , Criança , Pré-Escolar , Feminino , Homeostase , Humanos , Hipocalcemia/etiologia , Lactente , Recém-Nascido , Íons , Magnésio/sangue , Masculino , Glândulas Paratireoides/fisiopatologia , Fosfatos/sangueRESUMO
A 58-year-old man was initially seen with fatigue and weight loss. Laboratory examination detected hypercalcemia, elevated 1,25-dihydroxycholecalciferol levels, low parathyroid hormone (PTH) concentrations, and subperiosteal bone resorption. The patient underwent subtotal parathyroidectomy for presumed hyperparathyroidism, but serum calcium and 1,25-dihydroxycholecalciferol levels remained elevated following surgery. Search for another cause of the hypercalcemia disclosed enlarged para-aortic lymph nodes, biopsy specimens of which demonstrated Hodgkin's disease. After treatment of the patient with two cycles of chemotherapy with mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone, serum calcium, 1,25-dihydroxycholecalciferol, and PTH levels normalized. We speculate that the humoral hypercalcemia in this patient resulted from tumor production of 1,25-dihydroxycholecalciferol.
Assuntos
Doença de Hodgkin/complicações , Hipercalcemia/complicações , Reabsorção Óssea/complicações , Calcitriol/sangue , Doença de Hodgkin/metabolismo , Humanos , Hipercalcemia/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
We measured serum angiotensin-converting enzyme (ACE) activity radiometrically as a possible indicator of reduced thyroid function in 57 euthyroid controls, 27 patients in a noncardiac intensive care unit (13 with medical and 14 with surgical disorders), and 29 patients having coronary artery bypass grafting. In the last group, blood was obtained preoperatively and one day and one month after surgery (group 1; n = 18) or preoperatively and six hours and one day after surgery (group 2; n = 11). Patients in group 1 had significant reductions in levels of serum thyroxine (T4), triiodothyronine (T3), and thyrotropin response to protirelin one day postoperatively. The ACE activity fell significantly. Patients in group 2 had low levels of T4, T3, thyrotropin, and ACE six hours postoperatively. All these levels remained low the next day, and free T4 and free T3 levels were also reduced; the reverse T3 level became elevated. Changes in ACE significantly paralleled changes in T3. The 27 patients without coronary artery bypass grafting also had significant reductions in serum T4, T3, and ACE levels. Dilution studies and dialysis of serum with low ACE activity failed to demonstrate an inhibitor to explain the reduced enzyme function.
Assuntos
Hipotireoidismo/diagnóstico , Peptidil Dipeptidase A/sangue , Adulto , Idoso , Ensaios Enzimáticos Clínicos , Ponte de Artéria Coronária , Cuidados Críticos , Feminino , Humanos , Hipotireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Tiroxina/sangue , Fatores de Tempo , Tri-Iodotironina/sangue , Tri-Iodotironina Reversa/sangueRESUMO
While performing thyroid function tests, we noticed that protirelin (TRH) raised BP, and, therefore, we investigated the effect of diagnostic dosages of protirelin (500 micrograms) on plasma catecholamine levels and cardiovascular function in eight patients one day before, one day after, and four weeks following heart surgery. Mean arterial pressure (MAP), heart rate (HR), plasma norepinephrine (NE), epinephrine (EPI), dopamine (DA), thyroid hormone (triiodothyronine [T3], thyroxine), and thyrotropin (TSH) levels were measured before and after the intravenous injection of protirelin. Protirelin increased MAP transiently from 88 +/- 2 to 103 +/- 3 mm Hg (before surgery), 86 +/- 4 to 102 +/- 4 mm Hg (one day after surgery), and 86 +/- 4 to 104 +/- 5 mm Hg (four weeks after surgery). There were no notable changes in HR or plasma NE, EPI, or DA levels. The T3 and TSH response to protirelin was normal on all three study days. Protirelin raised MAP by an effect on systemic vascular resistance (SVR) rather than an increase in cardiac output. We conclude the following: (1) diagnostic dosages of protirelin transiently elevate MAP and SVR by a noncatecholamine mechanism, (2) clinicians who perform protirelin tests should be aware of protirelin's transient pressor effects.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hormônio Liberador de Tireotropina/farmacologia , Adulto , Idoso , Ponte de Artéria Coronária , Dopamina/sangue , Epinefrina/sangue , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Testes de Função Tireóidea , Hormônios Tireóideos/sangue , Hormônio Liberador de Tireotropina/administração & dosagemRESUMO
Inotropic support of the failing myocardium may combine calcium with adrenaline in an attempt to augment the haemodynamic actions of each drug. We have previously shown, however, that calcium blunts adrenaline induced increases in blood pressure and cardiac output in animals and man. The mechanisms by which calcium may interfere with the haemodynamic actions of adrenaline are not well understood. Adrenaline is known to stimulate adenylate cyclase and increase levels of cellular cyclic adenosine monophosphate (cAMP), a crucial second messenger in cell regulation. We evaluated the effect of increased circulating calcium levels on adrenaline stimulated cAMP production in laboratory animals. Calcium infusion in rats nearly doubled the circulating ionised calcium concentration, from 1.27 (SEM 0.03) mM to 2.3(0.18) mM. Adrenaline infusion significantly increased plasma cAMP in saline infused control animals, from 26(6) pmol.ml-1 to 98(22) pmol.ml-1, whereas there was no increase in cAMP plasma levels in the calcium infused rats. The apparent inhibition of adenylate cyclase by calcium may participate in a negative feedback system which helps protect cells from harmful intracellular calcium overload.
Assuntos
Cálcio/farmacologia , AMP Cíclico/sangue , Epinefrina/farmacologia , Animais , Cálcio/sangue , Interações Medicamentosas , Masculino , Distribuição Aleatória , Ratos , Ratos EndogâmicosRESUMO
FFAs are bound with calcium on the albumin molecule. We hypothesized that changes in circulating FFA levels during critical illness altered calcium-albumin binding. We found that serum from both normal subjects and critically ill patients contained an ether-extractable factor which lowered ionized calcium concentrations and increased albumin-calcium binding. This factor was found in higher concentrations in serum from ill patients. Oleic acid and palmitic acid increased albumin-calcium binding from 2-28% in a dose-dependent manner when added in vitro to calcium-albumin solutions. Scatchard analysis demonstrated that 0.1 mM oleic acid increased the number of calcium-binding sites on the albumin molecule (from three to five sites per molecule) without altering binding affinity. A similar effect was found when we performed Scatchard analyses of ether extracts in serum from three critically ill patients (number of calcium-binding sites increased from three to six). We also found that lipid infusions (during parenteral nutrition) lowered mean serum ionized calcium values in six critically ill patients [4.6 +/- 0.2 (+/- SEM) to 4.1 +/- 0.2 mg/dL; P less than 0.05]. These data support the concept that FFAs increase calcium binding to the albumin molecule. Alterations in FFA concentrations during critical illness may contribute to the poor correlation between corrected total serum calcium and ionized calcium concentrations in critically ill patients. In addition, acute elevations in circulating FFA concentrations may contribute to hypocalcemia in patients with defects in bone calcium mobilization.
Assuntos
Doença Aguda/sangue , Cálcio/sangue , Ácidos Graxos não Esterificados/sangue , Hipocalcemia/sangue , Albumina Sérica/metabolismo , Sítios de Ligação/efeitos dos fármacos , Sinergismo Farmacológico , Reações Falso-Negativas , Humanos , Ácido Oleico , Ácidos Oleicos/farmacologia , Ácido Palmítico , Ácidos Palmíticos/farmacologia , Ligação ProteicaRESUMO
Hypothyroidism is known to affect calcium homeostasis by decreasing bone turnover and serum calcium level, and by increasing parathyroid hormone and 1,25-dihydroxyvitamin D concentrations. A 52-year-old hypothyroid woman is described who had hypercalcemia associated with elevated parathyroid hormone and 1,25-dihydroxyvitamin D levels, but decreased 24-hour urinary calcium excretion and ratio of calcium to creatinine clearance. These parameters normalized following thyroid hormone replacement therapy. Hypercalcemia appeared to result from a combination of reduced renal calcium excretion and a change in the "set point" for calcium feedback inhibition of the parathyroid glands. These data suggest that thyroid hormone has a direct effect on the parathyroid glands, regulating parathyroid hormone secretion, and on the kidney's ability to excrete calcium. It is recommended that parathyroid hormone, 1,25-dihydroxyvitamin D, and urinary calcium excretion values be interpreted in light of thyroid hormone status.
Assuntos
Cálcio/urina , Hipercalcemia/etiologia , Hipotireoidismo/complicações , Tiroxina/uso terapêutico , Calcitriol/sangue , Cálcio/sangue , Creatinina/urina , Jejum , Feminino , Humanos , Hipercalcemia/urina , Hiperparatireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/urina , Pessoa de Meia-Idade , Glândulas Paratireoides/fisiologia , Hormônio Paratireóideo/sangue , Tiroxina/fisiologiaRESUMO
Liver injury is common in patients following hemorrhage and sepsis. There are multiple etiologies for this liver injury which involve both decreased nutrient blood flow and direct cellular injury. Enteral nutrients vasodilate gut blood vessels and increase blood flow to the intestines and liver. Since enteral nutrients vasodilate gut blood vessels, we wondered whether luminal nutrition would prevent hepatic injury during shock states. We randomized Sprague-Dawley rats to saline or enteral nutrition via duodenal feeding tubes. Animals were then subjected to 60 min of hemorrhagic hypotension or intraperitoneal injection of lipopolysaccharide (LPS). Liver injury was assessed by measuring levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) before and after hemorrhage or LPS. Enteral nutrients significantly decreased liver injury following hemorrhage. AST increased from 246 +/- 17 to 1605 +/- 593 U/L in saline animals and 283 +/- 39 to 551 +/- 94 U/L in enterally fed animals. ALT increased from 60 +/- 4 to 726 +/- 355 U/L in saline animals and 61 +/- 6 to 161 +/- 38 U/L in enterally fed animals. Enteral nutrients did not significantly alter the increase in AST/ALT following LPS. These results indicate that enteral nutrients can decrease liver injury following hemorrhagic hypotension.
Assuntos
Nutrição Enteral , Fígado/fisiopatologia , Choque Hemorrágico/fisiopatologia , Choque Hemorrágico/terapia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Pressão Sanguínea/efeitos dos fármacos , Humanos , Lipopolissacarídeos/toxicidade , Fígado/patologia , Testes de Função Hepática , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Bedside testing offers a unique opportunity for earlier and more specific diagnosis, faster and more frequent monitoring, and the opportunity to improve patient care and reduce hospital costs. However, if abused it may not improve patient care and may increase hospital costs. In the future, more clinical studies will need to be performed to determine which tests are cost-effective.
Assuntos
Técnicas de Laboratório Clínico , Instalações de Saúde , Unidades de Terapia Intensiva , Quartos de Pacientes , Glicemia/análise , Cálcio/sangue , Dióxido de Carbono/sangue , Técnicas de Laboratório Clínico/economia , Técnicas de Laboratório Clínico/instrumentação , Custos e Análise de Custo , Cuidados Críticos , Erros de Diagnóstico , Estudos de Avaliação como Assunto , Humanos , Concentração de Íons de Hidrogênio , Unidades de Terapia Intensiva/economia , Tempo de Internação , Monitorização Fisiológica , Oxigênio/sangue , Potássio/sangue , Sódio/sangue , Fatores de Tempo , Urina/análiseRESUMO
Enteral delivery of nutrients is important for optimal treatment of critically ill patients. It maintains gut digestive and barrier functions, decreases gut bacterial translocation, decreases the incidence of sepsis, and improves outcome. Gastric emptying is impaired in many critically ill patients and feeding into a gastroparetic stomach leads to large gastric residuals and aspiration. We describe a simple bedside technique for placement of small bowel feeding tubes. Using this technique, we successfully placed 213/231 (92 percent) of feeding tubes in critically ill patients. Three percent were in the first portion of the duodenum, 25 percent in the second portion, 47 percent in the third portion, and 17 percent in the proximal jejunum. The average time for placement of small bowel feeding tubes was 40 +/- 14 min (mean +/- SD). Abdominal roentgenograms failed to properly locate 13 (6 percent) tubes. The most accurate and cheapest methods for confirming small bowel location of feeding tubes were bile aspiration, pH change from acidic to basic, and blue dye injection.
Assuntos
Nutrição Enteral/métodos , Intestino Delgado , Intubação Gastrointestinal/métodos , Humanos , Unidades de Terapia Intensiva , Estudos ProspectivosRESUMO
Pine oil is a common component of household cleaning solutions. We present the case of an elderly woman with dementia who ingested a household cleaning solution that contained pine oil and review the treatment of pine oil ingestion. The patient developed CNS depression and respiratory failure that required intubation and mechanical ventilation. A chest radiograph revealed diffuse alveolar interstitial infiltrates consistent with pneumonitis. The patient improved with supportive care. However, she developed nosocomial pneumonia, sepsis, and multiple organ failure and subsequently died. This case is illustrative of the increased risk for ingestion of toxic household compounds in the growing population of elderly and demented individuals, who are being cared for in the home. Pine oil ingestions are one of the most common accidental ingestions encountered in clinical practice. Clinical features of ingestion include depressed mentation, respiratory failure, and GI dysfunction. The treatment is supportive, and the ingestions are rarely fatal.
Assuntos
Detergentes/intoxicação , Acidentes Domésticos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer , Evolução Fatal , Feminino , HumanosRESUMO
To contrast the effect of increasing blood calcium concentrations on the cardiovascular actions of intravenous beta-adrenergic agonists and phosphodiesterase inhibitors, 46 patients recovering from aortocoronary bypass surgery received either dobutamine or amrinone both in the presence and absence of a calcium infusion. Cardiac output, systemic arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary artery occlusion pressure, heart rate, and blood ionized calcium concentration were measured before and during infusions of dobutamine (2.5 and 5.0 micrograms/kg/min) and amrinone (0.75 mg/kg bolus + 10 micrograms/kg/min or 2.25 mg/kg bolus + 20 micrograms/kg/min). After the initial dobutamine infusion period, patients were randomly and blindly assigned to receive either a calcium or placebo infusion, and the dobutamine infusions were repeated. Because of the long duration of amrinone's actions, the amrinone maintenance infusion was continued while randomized, blinded infusion of either calcium or placebo was added. Dobutamine (5 micrograms/kg/min) increased cardiac output from 7.1 +/- 0.3 L/min to 9.1 +/- 0.4 L/min, and increased heart rate from 93 +/- 4 beats/min to 107 +/- 4 beats/min. Systemic vascular resistance decreased and stroke volume increased. Dobutamine had no significant effects on other hemodynamic values. Amrinone (2.25 mg/kg bolus + 20 micrograms/kg/min) increased cardiac output from 5.6 +/- 0.4 L/min to 6.9 +/- 0.5 L/min, and increased heart rate from 87 +/- 3 beats/min to 98 +/- 3 beats/min. Amrinone decreased mean arterial pressure, systemic vascular resistance, pulmonary artery occlusion pressure, central venous pressure, and pulmonary artery pressure. Calcium infusion increased arterial pressure (8 to 13 percent) but had no significant effects on any other hemodynamic parameters. Calcium reduced the increase in cardiac output produced by dobutamine by 30 percent, but it did not alter the cardiotonic actions of amrinone. Thus, calcium inhibits the cardiotonic actions of certain beta-adrenergic agonists, most likely by interfering with signal transduction through the beta-adrenergic receptor complex.
Assuntos
Amrinona/farmacologia , Cálcio/farmacologia , Dobutamina/farmacologia , Hemodinâmica/efeitos dos fármacos , Amrinona/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Cálcio/sangue , Débito Cardíaco/efeitos dos fármacos , Dobutamina/administração & dosagem , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação QuímicaRESUMO
The hemodynamic and oxygen transport effects of low-dose (0.75 mg/kg loading dose + 10 micrograms/kg/min infusion, n = 12) and high-dose (2.25 mg/kg loading dose + 20 micrograms/kg/min infusion, n = 12) amrinone were evaluated in extubated patients 24 h after CABG. At both doses, amrinone significantly (p less than 0.05) increased HR, but decreased mean arterial, mean pulmonary artery, central venous and pulmonary artery occlusion pressures. High-dose amrinone significantly decreased systemic vascular resistance. Arterial oxygen saturation decreased significantly following both low- (97.8 +/- 0.4 to 95.6 +/- 0.9 percent) and high- (98.8 +/- 3.4 to 93.9 +/- 1.2 percent) dose amrinone. Pulmonary shunt increased significantly following low-dose amrinone and markedly increased Qs/Qt after high-dose amrinone. Although amrinone significantly increased cardiac index in a dose-dependent fashion (low:3.0 +/- 0.2 to 3.3 +/- 0.3 L/min/m2; high:2.7 +/- 0.2 to 3.4 +/- 0.2 L/min/m2), mixed venous oxygen saturation did not change. Thus, mixed venous oxygen saturation may not predict the hemodynamic response to amrinone infusion in postoperative surgical patients.
Assuntos
Amrinona/farmacologia , Débito Cardíaco/efeitos dos fármacos , Ponte de Artéria Coronária , Oxigênio/sangue , Amrinona/administração & dosagem , Cálcio/farmacologia , Relação Dose-Resposta a Droga , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-OperatórioRESUMO
In experimental animals, coadministration of calcium (Ca) salts with beta-adrenergic receptor agonists reduces the increased blood pressure and cyclic AMP (cAMP) produced by beta-adrenergic receptor agonists alone. In patients, coadministration of these drugs reduces the increased cardiac output and blood glucose produced by selective administration of beta-adrenergic agonists. The mechanism by which Ca might produce catecholamine resistance remains unclear. Healthy volunteers donated venous blood from which lymphocytes were isolated. The cAMP production was measured by radioimmunoassay under control conditions and after incubation with epinephrine or colforsin (forskolin) in the presence and absence of inhibitors. Epinephrine and colforsin produced concentration-dependent increases in cAMP production. Extracellular Ca concentration over the range from 0 to 8 mM did not inhibit basal cAMP production or that stimulated by either colforsin or epinephrine. The calcium channel agonist Bay K 8644 (50 microM) combined with normal extracellular Ca concentration significantly attenuated colforsin-induced increases in cAMP production. When barium was substituted for Ca in the extracellular fluid, the cAMP response to colforsin was restored, despite Bay K 8644. Inhibition of Ca channel permeability with cadmium or cobalt ions partially restored colforsin-stimulated cAMP production, despite the presence of extracellular Ca and Bay K 8644. These results suggest that entry of Ca ions through Ca channels attenuates adenylyl cyclase. The inhibition appears specific for Ca ions over other permeant divalent cations, and favors a possible physiologic role for the recently cloned Ca-inhibited adenylyl cyclase.
Assuntos
Adenilil Ciclases/metabolismo , Cálcio/fisiologia , AMP Cíclico/biossíntese , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Adenilil Ciclases/efeitos dos fármacos , Cálcio/análise , Células Cultivadas , Colforsina/farmacologia , Epinefrina/farmacologia , Espaço Extracelular/química , Humanos , Linfócitos/metabolismoRESUMO
To determine how intraoperative hypothermia associated with coronary bypass surgery (CABS) alters sympathetic nervous system (SNS) activity, we prospectively studied 21 adult CABS patients and measured preoperative, intraoperative, and postoperative circulating catecholamine concentrations. Because thyroid hormone levels change rapidly following CABS, we also serially measured these hormone levels. The measured plasma concentrations for each of the above variables were corrected for hemodilution during CABS by using serum albumin changes as a reference. It was concluded that important alterations in SNS activity and thyroid hormone homeostasis occur in humans during CABS and deep hypothermia, and that changes in core temperature may contribute to these findings. We speculate that these hormonal changes may influence the response to adrenergic receptor therapy in hypothermic patients and may contribute to arrhythmias during rewarming and the immediate postoperative period.
Assuntos
Ponte de Artéria Coronária , Hipotermia Induzida , Sistema Nervoso Simpático/metabolismo , Acetilcolinesterase/sangue , Pressão Sanguínea , Epinefrina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Radioimunoensaio , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
POC testing provides an opportunity for clinicians and laboratorians to work together to consider how best to serve the patients within an individual institution. Each health system has unique characteristics relative to patient population, as well as a unique laboratory structure. If physicians, nurses, laboratorians, and pathologists work collaboratively, the best interests of patients will be served. In some institutions that cater to specific patient groups, POC testing may offer clear and distinct advantages. In other institutions with sophisticated transport systems and established rapid response capabilities, the quality resulting from central laboratory testing may outweigh any advantages of bedside testing. Clearly, attention to regulatory issues, QC issues, the importance of proper documentation, proficiency testing, performance enhancement, and cost-effectiveness is requisite. As the technology for diagnostic testing advances through more microcomputerization, microchemistry, and enhanced test menus, the concept of POC testing will need perpetual revisiting. We hope that the information provided here will aid clinicians, laboratorians, and administrators in their quest to best serve their patients.
Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Custos e Análise de Custo , Humanos , Laboratórios/normas , Sistemas Automatizados de Assistência Junto ao Leito/economia , Sistemas Automatizados de Assistência Junto ao Leito/normas , Garantia da Qualidade dos Cuidados de SaúdeRESUMO
BACKGROUND: As the proportion of the population that is older continues to rise, infection in older people has become an important healthcare problem. Although aging is associated with multiple abnormalities in immune function, the effect of aging on the production of proinflammatory cytokines has not been well studied under conditions of clinical stress. OBJECTIVES: The aim of this study was to examine the effect of aging on circulating levels of the proinflammatory cytokines in a large cohort of septic shock patients. We hypothesized that aging would be associated with a diminished proinflammatory cytokine response to sepsis. DESIGN: Patients with septic shock who were enrolled in the placebo limb of the North American Sepsis Trial (NORASEPT II) study were analyzed. SETTING: The intensive care units of 105 hospitals in the United States and Canada. PARTICIPANTS: Nine hundred and thirty patients presenting to hospital within 12 hours of the onset of septic shock. MEASUREMENTS: Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble tumor necrosis factor-receptor-55 (sTNF-R55), and soluble tumor necrosis factor-receptor-75 (sTNF-R75) concentrations were measured at enrollment. The study population was broken down into five age groups as follows: less than 50 years (group one), 50 to 64 years (group two), 65 to 74 years (group three), 75 to 84 years (group four), and 85 or older (group five). Clinical, demographic, and cytokine data were extracted to describe each age group. RESULTS: Data were available for 930 patients. The patients' mean age (+/- SD) was 59 +/- 17 years (range, 18 to 102). There were 280 patients in group one, 242 in group two, 210 in group three, 150 in group four, and 48 in group five. The primary diagnoses; clinical characteristics; and IL-6, sTNF-R55, and sTNF-R75 levels were similar among the five age groups. The TNF-alpha levels were significantly higher, however, in the oldest group of patients (group five). The 28-day survival was 49% in patients over the age of 75 and 58% in those under 75 years (P = .03). There was no gender difference in survival or cytokine levels. CONCLUSIONS: Contrary to our expectations, we found that aging was not associated with a decline in the circulating levels of proinflammatory cytokines.
Assuntos
Envelhecimento , Citocinas/sangue , Choque Séptico/sangue , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Anticorpos Monoclonais/uso terapêutico , Estudos de Coortes , Método Duplo-Cego , Humanos , Interleucina-1/sangue , Interleucina-1/imunologia , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/análise , Choque Séptico/imunologia , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: Hypothermic patients with sepsis have been reported to have a higher mortality than febrile septic patients. The failure to mount a febrile response in sepsis is poorly understood. Since the proinflammatory cytokines play a crucial role in the genesis of fever, we postulated that hypothermic patients with sepsis would have lower circulating levels of these cytokines than febrile patients. METHODS: Patients with septic shock who were enrolled into the placebo limb of the North American study of the safety and efficacy of murine monoclonal antibody to tumor necrosis factor for the treatment of septic shock (NORASEPT II) were analyzed. Body temperature, interleukin-6, tumor necrosis factor alpha, soluble tumor necrosis factor receptor-55, and soluble tumor necrosis factor receptor-75 concentrations were measured at enrollment. The study population was divided into a hypothermic (temperature < 35.6 degrees C) and a febrile group (temperature > or = 38.3 degrees C) according to the core temperature at enrollment (normothermia was an exclusion criteria). Clinical, demographic, and cytokine data were extracted, allowing for comparisons between these two groups of patients. In addition, the correlation between the core body temperature and cytokine levels at enrollment was determined. RESULTS: A complete data set was available for 930 patients; 195 patients (21%) were hypothermic at enrollment. The 28-day survival of these patients was significantly lower than that of the febrile patients (34% vs. 59%, p < 0.001). Hypothermia (and enrollment temperature) were independent predictors of mortality. The hypothermic patients had a higher incidence of organ dysfunction at enrollment than the febrile patients. There was no significant difference in the cytokine profile between the two groups of patients. In addition, there was no correlation between the core body temperature at enrollment and the circulating levels of cytokines measured. CONCLUSION: Hypothermic patients with septic shock have a significantly higher mortality with a higher incidence of organ dysfunction than febrile septic shock patients. The hypothermia in these patients cannot be explained by lower levels of circulating proinflammatory cytokines.
Assuntos
Citocinas/metabolismo , Hipotermia/etiologia , Hipotermia/imunologia , Choque Séptico/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Hipotermia/mortalidade , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Fatores de Risco , Taxa de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To evaluate the effects of propofol and propofol containing disodium edetate (ethylenediaminetetraacetic acid [EDTA]) on the parathyroid-calcium axis in normal subjects. DESIGN: Randomised, double-blind, age-stratified, crossover trial. SETTING: Single centre. PATIENTS: A total of 50 healthy subjects. INTERVENTIONS: Each subject was randomised to receive propofol or propofol containing EDTA on day 1 and the alternate treatment between days 15 and 29, with a 2-week wash-out period in between. On the day of treatment, subjects received a bolus of trial medication (1 or 2 mg/kg) followed by a 60-minute observation period. At the end of 60 minutes, subjects received trial medication infused for 60 minutes at 1 of 4 randomised infusion rates (25, 50, 100, or 200 microg/kg per min). Subjects were monitored for an additional 60 minutes following the infusion. MEASUREMENTS AND RESULTS: Blood pressure, heart rate, respiratory rate, oxygen saturation, blood ionised calcium concentration, serum total magnesium concentration, serum intact parathyroid hormone (PTH) level, and plasma EDTA level were assessed at periodic intervals during and following the bolus and continuous infusion of trial medication. Mean arterial pressure significantly decreased (p < 0.05) following the bolus injection of both trial medications and returned to baseline at 60 minutes; it significantly decreased again during the continuous infusion and returned to baseline during recovery. Heart rate and respiratory rate fluctuated in both groups with significant increases and decreases throughout the study period following the bolus injection; both returned to baseline during the recovery period in each group. Ionised calcium and total magnesium concentrations remained within normal limits and were unchanged in response to both study medications. PTH levels significantly increased following the bolus injection of both study drugs. The increase in PTH levels was greater with higher doses of study medication during the infusion period. There was no difference in the response of blood pressure, heart rate, respiratory rate, or PTH levels between propofol and propofol with EDTA. EDTA levels increased significantly during the infusion of propofol with EDTA, reaching mean levels of 240 ng/mL. CONCLUSIONS: The results of this study indicate that propofol increases PTH levels in normal subjects; however, propofol with EDTA does not alter ionised calcium or total magnesium concentrations.
Assuntos
Anestésicos Intravenosos/farmacologia , Quelantes/farmacologia , Ácido Edético/farmacologia , Hormônio Paratireóideo/sangue , Conservantes Farmacêuticos/farmacologia , Propofol/farmacologia , Adulto , Idoso , Cálcio/sangue , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Magnésio/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To compare the effects of propofol with and without disodium edetate (EDTA) on cation metabolism in intensive care unit (ICU) patients with renal insufficiency who received propofol or propofol plus EDTA (propofol EDTA) for sedation and mechanical ventilation. DESIGN: Double-blind, randomised, multicentre study. SETTING: Medical and surgical ICUs from 5 hospitals. PATIENTS: Thirty-nine ICU patients with acute and chronic renal impairment expected to require at least 24 hours of continuous sedation and respiratory failure necessitating mechanical ventilation. INTERVENTIONS: Propofol or propofol EDTA administered for sedation by continuous intravenous infusion. MEASUREMENTS AND RESULTS: The depth of sedation, as measured by the Modified Ramsay Sedation Scale, was similar in the 2 groups, when adjusted for dosing differences. The amount of propofol required to maintain adequate sedation was decreased in both groups compared to propofol requirements in ICU patients with normal renal function. EDTA levels were elevated at baseline in both groups. In the propofol EDTA group, the EDTA levels increased further by 20 % but decreased to below baseline EDTA levels at 48 hours after sedation. In the propofol group, EDTA levels decreased during sedation and remained below baseline levels at 48 hours after sedation. PATIENTS in both groups were hypocalcaemic and hyperphosphataemic at baseline with low levels of 1,25-dihydroxyvitamin D and elevated parathyroid hormone (PTH) levels. Other than a slight difference in ionised serum calcium levels at 4 h after the start of sedation, there were no significant differences observed in serum calcium levels between the two groups. There were no significant differences in 1,25-dihydroxyvitamin D or PTH levels over time between the two groups. There was no significant effect on renal function in either group. CONCLUSIONS: The results of this study suggest that adding EDTA to propofol does not adversely affect cation homeostasis or renal function when used for sedation of ICU patients with renal insufficiency. Although EDTA levels increased over time from baseline levels in patients with renal insufficiency who receive propofol EDTA, this increase does not appear to be clinically significant, and EDTA levels return to below baseline levels within 48 hours of discontinuing the propofol EDTA infusion. The efficacy of propofol with and without EDTA also appears comparable in these patients.