RESUMEN
Positive end-expiratory pressure (PEEP) is used to improve gas exchange, increase functional residual capacity, recruit air spaces, and decrease pulmonary shunt in patients suffering from respiratory failure. The effect of PEEP on extravascular lung water (EVLW), however, is still not fully understood. This study was designed as a prospective laboratory experiment to evaluate the effects of PEEP on EVLW and pulmonary lymph flow (QL) under physiologic conditions. Twelve adult sheep were operatively prepared to measure haemodynamics of the systemic and pulmonary circulation, and to assess EVLW In addition, the lung lymphatic duct was cannulated and a tracheostomy performed. The animals were then mechanically ventilated in the awake-state without end-expiratory pressure (PEEP 0). After a two-hour baseline period, PEEP was increased to 10 cmH2O for the duration of two hours, and then reduced back to 0 cmH2O. Cardiopulmonary variables, QL, and arterial blood gases were recorded intermittently; EVLW was determined two hours after each change in PEEP. The increase in PEEP resulted in a decrease in QL (7 +/- 1 vs 5 +/- 1 ml/h) and an increase in EVLW (498 +/- 40 vs 630 +/- 58 ml; P<0.05 each) without affecting cardiac output. As PEEP was decreased back to baseline, QL increased significantly (5 +/- 1 vs 10 +/- 2 ml/h), whereas EVLW returned back to baseline. This study suggests that institution of PEEP produces a reversible increase in EVLW that is linked to a decrease in QL.
Asunto(s)
Agua Pulmonar Extravascular/fisiología , Pulmón , Linfa/fisiología , Respiración con Presión Positiva , Animales , Femenino , Hemodinámica , OvinosRESUMEN
UNLABELLED: We evaluated the vasomotor effects of clonidine in awake subjects with an intact central cardiovascular regulatory system. To determine the lower limit of the vasoconstrictive effect of clonidine in awake volunteers, we blocked sympathetic innervation to the left arm by anesthetizing the brachial plexus. We then measured arterial blood pressure and vasoconstriction via finger volume plethysmography measuring infrared light transmitted through a fingertip (LTF). LTF values obtained from the left arm were compared with those from the neurally intact right arm during four progressively increasing IV doses of clonidine, targeting plasma clonidine concentrations of 0.3, 0.45, 0.68, and 1.0 ng/mL. Clonidine decreased systolic blood pressure (P < 0.004) from 135 +/- 8 mm Hg to 115 +/- 8 mm Hg and heart rate (P = 0.0017) from 68 +/- 7 mm Hg to 61 +/- 10 mm Hg. Clonidine decreased LTF by -12% +/- 11% (P < 0.0001) less than preinfusion values at the 0.68 ng/mL target concentration in the right hand. In contrast, in the left hand, clonidine increased LTF significantly more than (P < 0.0001) preinfusion values at all target concentrations, with a maximal increase of 30% +/- 7%. We conclude that IV clonidine, at doses that decrease arterial blood pressure, causes arterial vasoconstriction in awake subjects. IMPLICATIONS: IV clonidine, at doses that decrease blood pressure, causes arterial vasoconstriction in awake subjects. These data suggest that an alpha-2 agonist with a high alpha-2a/alpha-2b selectivity should provide more profound sedative and analgesic effects with less undesirable vasoconstrictive effects.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Clonidina/farmacología , Vasoconstricción/efectos de los fármacos , Adulto , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Masculino , Piel/irrigación sanguínea , Temperatura Cutánea/efectos de los fármacos , VigiliaRESUMEN
AIMS: To test the hypothesis that the alpha2-adrenergic agonist, dexmedetomidine, dilates the pupil and does not alter the pupillary light reflex of anaesthetized patients. METHODS: Eight volunteers were administered general anaesthesia with propofol, nitrous oxide and alfentanil. One hour and 25 min after induction of anaesthesia, a 45 min infusion of dexmedetomidine was begun, targeting a plasma concentration of 0.6 ng x ml(-1). Pupil size, pupillary light reflex amplitude, light reflex recovery time, and reflex dilation were measured before and during dexmedetomidine infusion. RESULTS: Dexmedetomidine produced no change in pupil size and light reflex recovery time, increased the light reflex from 0.30 +/- 0.14 to 0.37 +/- 0.12 mm and significantly reduced pupillary reflex dilation by 72 +/- 62%. CONCLUSIONS: These pupillary effects of dexmedetomidine in humans are difficult to reconcile with the findings obtained in cats and rats that have demonstrated a direct inhibitory effect of alpha2-adrenergic agonists on the pupilloconstrictor nucleus. The increase in the magnitude of the light reflex in response to dexmedetomidine does not necessarily involve an anxiolytic mechanism.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2 , Agonistas alfa-Adrenérgicos/farmacología , Anestesia General , Dexmedetomidina/farmacología , Reflejo Pupilar/efectos de los fármacos , Adulto , Presión Sanguínea/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , MasculinoRESUMEN
1. Increase in myocardial sympathetic activity contributes markedly to the pathophysiology of conditions such as congestive heart failure and is also associated with myocardial infarction. However, measurement of myocardial sympathetic activity in vivo is difficult. 2. The present study assesses the effectiveness of metaiodobenzylguanidine (MIBG) imaging to characterize modulation of sympathetic activity, as induced by dexmedetomidine, a highly specific alpha-2 adrenoceptor agonist. 3. We imaged washout of [125I]-MIBG from rabbit heart before and during two consecutive 45-min intravenous infusions of dexmedetomidine (10 microg kg(-1) followed by 16 microg kg(-1)) (n=9) or of saline (n=9). 4. Heart rate (HR), and mean blood pressure (BP) were measured before and at the end of each study period. Plasma noradrenaline (NA) was measured before and after study drug infusion. The hearts were then excised and biopsied for MIBG tissue concentration [MIBG] (% kg-dose g(-1)). 5. Relative to saline controls, dexmedetomidine significantly decreased HR, BP, plasma NA and MIBG washout. There was an inverse correlation between MIBG washout and residual [MIBG] in the myocardium (r= -0.75, P < 0.01). 6. These data suggest that a reduction of sympathetic nervous system activity causes a decrease in myocardial MIBG washout in vivo in rabbits, and confirms the usefulness of MIBG scintigraphy as a non-invasive tool to measure changes in myocardial sympathetic activity.
Asunto(s)
3-Yodobencilguanidina/farmacocinética , Inhibidores Enzimáticos/farmacocinética , Miocardio/metabolismo , Sistema Nervioso Simpático/fisiología , Agonistas alfa-Adrenérgicos/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Norepinefrina/sangre , Conejos , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismoRESUMEN
Large concentrations of alpha(2) agonists cause vasoconstriction. However, the threshold of the vasoconstrictive effect in humans is not known. We studied seven volunteers to determine the lower limit of the vasoconstrictive effect of clonidine. Subjects were studied while they were awake, and they were anesthetized with propofol/alfentanil/N(2)O. Arterial blood pressure was continuously monitored via radial arterial catheter and vasoconstriction via finger volume plethysmography measuring infrared light transmitted through a fingertip (LTF). Clonidine was administered, targeting plasma clonidine concentrations of 0.3, 0.45, 0.68, 1.0, 1.5, and 2.25 ng/mL. The maximum change from preclonidine values for systolic blood pressure (SBP) and LTF was analyzed by using repeated measures analysis of variance. In awake subjects, clonidine (2.25 ng/mL) decreased LTF by 14%+/-13% and SBP from 141+/-7 to 110+/-15 mm Hg (P<0.0001). In contrast, clonidine (2.25 ng/mL) increased LTF in anesthetized subjects by 21%+/-16% and SBP from 91+/-7 to 106+/-19 mm Hg (P<0.0001). We conclude that the same dose of clonidine that decreased blood pressure and caused vasodilation in awake subjects had the opposite effect in anesthetized subjects with reduced sympathetic tone, increasing blood pressure and causing vasoconstriction in human digital vasculature. Our findings suggest that the lower threshold for clonidine-induced vasoconstriction in human digital vasculature is 1.0 ng/mL.
Asunto(s)
Clonidina/farmacología , Dedos/irrigación sanguínea , Vasoconstrictores/farmacología , Adulto , Alfentanilo/administración & dosificación , Análisis de Varianza , Anestesia General , Anestésicos por Inhalación/administración & dosificación , Anestésicos Intravenosos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Clonidina/administración & dosificación , Clonidina/sangre , Estado de Conciencia , Estudios Cruzados , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Rayos Infrarrojos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Óxido Nitroso/administración & dosificación , Pletismografía/métodos , Propofol/administración & dosificación , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiología , Vasoconstrictores/administración & dosificación , Vasoconstrictores/sangre , Vasodilatadores/administración & dosificación , Vasodilatadores/sangre , Vasodilatadores/farmacologíaRESUMEN
We investigated changes in cardiac output and organ blood flow induced by medetomidine in sheep and determined changes in cardiac output and organ blood flow after reversal of medetomidine-induced sedation by atipamezole. Eight sheep were chronically instrumented. Medetomidine was infused IV to target plasma levels of 0, 0.8, 1.6, 3.2, 6.4, and 12.8 ng/mL for 25 min each, followed by a 5-min infusion of atipamezole. Hemodynamic values and organ blood flow (using colored microspheres) were measured just before medetomidine infusion (baseline), at the end of each medetomidine infusion step, and 30 min after the administration of atipamezole. Medetomidine (12. 8 ng/mL) decreased cardiac output from 6.3 +/- 1.0 to 3.2 +/- 0.7 L/min (P < 0.0001) and increased systemic vascular resistance from 1310 +/- 207 to 3467 +/- 1299 dynes. s(-1). cm(-5) (P < 0.0001). Blood flow decreased in the cerebral cortex from 1.29 +/- 0.40 to 0. 66 +/- 0.12 mL. g(-1). min(-1) (P < 0.0001), left ventricle from 2. 11 +/- 0.61 to 1.40 +/- 0.40 mL. g(-1). min(-1) (P < 0.0001), kidney from 8.28 +/- 3.17 to 6.07 +/- 2.65 mL. g(-1). min(-1) (P < 0.0001), skin from 0.09 +/- 0.04 to 0.05 +/- 0.02 mL. g(-1). min(-1) (P < 0. 0001), intestine from 0.56 +/- 0.13 to 0.27 +/- 0.07 mL. g(-1). min(-1) (P < 0.0001), and skeletal muscle from 0.28 +/- 0.15 to 0.04 +/- 0.01 mL. g(-1). min(-1) (P < 0.0001). Blood flow in the liver (hepatic artery) increased from 0.05 +/- 0.03 to 0.24 +/- 0.16 mL. g(-1). min(-1) (P < 0.0001). After atipamezole infusion, cardiac output and systemic vascular resistance returned to baseline, but the cerebral cortex, left ventricle, and renal blood flows remained below baseline at 0.89 +/- 0.22, 1.37 +/- 0.50, and 6.25 +/- 2.76 mL. g(-1). min(-1), respectively; skeletal muscle blood flow increased above baseline to 0.44 +/- 0.27 mL. g(-1). min(-1), spleen blood flow decreased below baseline to 1.65 +/- 0.61 mL. g(-1). min(-1) (P < 0.0001), and liver, intestine, and lung blood flows returned to baseline values. In conclusion, medetomidine decreased and redistributed organ blood flow in sheep. Atipamezole reversed the medetomidine-induced hemodynamic changes, but redistributed blood flow from the brain, heart, and kidney to the skeletal muscle.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Sedación Consciente , Hemodinámica/efectos de los fármacos , Imidazoles/farmacología , Medetomidina/farmacología , Animales , Dióxido de Carbono/sangre , Gasto Cardíaco/efectos de los fármacos , Femenino , Colorantes Fluorescentes , Medetomidina/antagonistas & inhibidores , Microesferas , Oxígeno/sangre , Flujo Sanguíneo Regional/efectos de los fármacos , Ovinos , Resistencia Vascular/efectos de los fármacosRESUMEN
UNLABELLED: The neuromuscular effects of dexmedetomidine in humans are unknown. We evaluated the effect of dexmedetomidine on neuromuscular block and hemodynamics during propofol/alfentanil anesthesia. During propofol/alfentanil anesthesia, the rocuronium infusion rate was adjusted in 10 volunteers to maintain a stable first response (T1) in the train-of-four sequence at 50% +/- 3% of the pre-rocuronium value. Dexmedetomidine was then administered by computer-controlled infusion, targeting a plasma dexmedetomidine concentration of 0.6 ng/mL for 45 min. The evoked mechanical responses of the adductor pollicis responses (T1 response and T4/T1 ratio), systolic blood pressure (SBP), heart rate (HR), and transmitted light through a fingertip were measured during the dexmedetomidine infusion and compared with predexmedetomidine values using repeated-measures analysis of variance and Dunnett's test. Plasma dexmedetomidine levels ranged from 0.68 to 1.24 ng/mL. T1 values decreased during the infusion, from 51% +/- 2% to 44% +/- 9% (P < 0.0001). T4/T1 values did not change during the infusion. Plasma rocuronium concentrations increased during the infusion (P = 0.02). Dexmedetomidine increased SBP (P < 0.001) and decreased HR (P < 0.001) (5-min median values) during the infusion compared with values before the infusion. Dexmedetomidine increased the transmitted light through the fingertip by up to 41% +/- 8% during the dexmedetomidine infusion (P < 0.001).We demonstrated that dexmedetomidine (0.98 +/- 0.01 microg/kg) increased the plasma rocuronium concentration, decreased T1, increased SBP, and decreased finger blood flow during propofol/alfentanil anesthesia. We conclude that dexmedetomidine-induced vasoconstriction may alter the pharmacokinetics of rocuronium. IMPLICATIONS: We studied the effect of an alpha2-agonist (dexmedetomidine) on rocuronium-induced neuromuscular block during propofol/alfentanil anesthesia. We found that the rocuronium concentration increased and the T1 response decreased during the dexmedetomidine administration. Although these effects were statistically significant, it is unlikely that they are of clinical significance.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Anestesia General/métodos , Imidazoles/farmacología , Bloqueo Neuromuscular , Unión Neuromuscular/efectos de los fármacos , Agonistas alfa-Adrenérgicos/sangre , Adulto , Alfentanilo , Androstanoles/farmacocinética , Androstanoles/farmacología , Anestésicos Intravenosos , Presión Sanguínea/efectos de los fármacos , Interacciones Farmacológicas , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Imidazoles/sangre , Masculino , Medetomidina , Fármacos Neuromusculares Despolarizantes/farmacocinética , Fármacos Neuromusculares Despolarizantes/farmacología , Propofol , RocuronioRESUMEN
A relatively new H2-antagonist, famotidine, has become clinically available, but its effectiveness in decreasing gastric acidity and volume has not been compared in inpatients and outpatients. We reexamined the difference in gastric acidity and volume in inpatients and outpatients, and tested the effectiveness of different oral doses and dosage regimens of famotidine in reducing gastric acidity and volume in both groups of patients. Patients received either placebo or 20 mg or 40 mg of famotidine orally the night before surgery (HS) and on the morning of surgery (AM). One hundred forty-two inpatients and 180 outpatients were randomized to one of seven groups as follows: 1) placebo (HS)/placebo (AM); 2) 20 mg of famotidine (HS)/20 mg of famotidine (AM); 3) 20 mg of famotidine (HS)/placebo (AM); 4) placebo (HS)/20 mg of famotidine (AM); 5) 40 mg of famotidine (HS)/40 mg of famotidine (AM); 6) 40 mg of famotidine (HS)/placebo (AM); and 7) placebo (HS)/40 mg of famotidine (AM). We measured the gastric acidity and volume after induction of anesthesia and found no difference between the inpatients and outpatients, with or without famotidine. We found that famotidine given HS and AM or AM only was effective in reducing gastric acidity in both groups of patients, and that there was no difference between the 20-mg and 40-mg doses of famotidine. Gastric volume was not affected by any famotidine dose.
Asunto(s)
Atención Ambulatoria , Famotidina/administración & dosificación , Ácido Gástrico/metabolismo , Hospitalización , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Procedimientos Quirúrgicos Electivos , Famotidina/uso terapéutico , Determinación de la Acidez Gástrica , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: Monitoring of vital signs in critically ill patients during helicopter flight is difficult because of the noise and vibrations of the aircraft. We evaluated the use of a pulse oximeter to measure systolic BP intraflight. DESIGN: Systolic BP measured by pulse oximetry was compared with systolic BP measured by the direct intra-arterial and the arterial occlusion methods intraflight. Systolic BP by pulse oximetry was measured by observing the return of the plethysmographic waveform of the pulse oximeter as the BP cuff ipsilateral to the pulse oximeter probe was slowly deflated. Arterial occlusion pressure was measured by observing the return of the intraarterial waveform as the BP cuff ipsilateral to the arterial cannula was slowly deflated. SETTING: The study was performed during patient transport, intraflight. PATIENTS: Ten critically ill patients were studied. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Seventy-three sets of measurements were recorded. The best correlation (r2 = .99) was found between pulse oximetry and the arterial occlusion method. The indirect methods correlated better with each other than with direct intraarterial measurements. The noise and the vibrations of the helicopter did not significantly interfere with the operation of the pulse oximeter. CONCLUSIONS: We conclude that a pulse oximeter that displays a plethysmographic waveform can accurately measure systolic BP intraflight.