RESUMO
BACKGROUND: Photoplethysmographic pulse wave amplitude (PPGA) and heart rate (HR) can be used to measure cold, nociception-induced autonomic responses, or both. The aim of our study was to correlate the intensity of experimental pain to changes in physiological variables reflecting the autonomic nervous system response to pain. METHODS: PPGA, HR, and subjective measurements of pain intensity were measured in 29 healthy male volunteers during two heat stimuli (43°C and 48°C) and the cold pressor test (CPT). Surgical pleth index (SPI), autonomic nervous system state (ANSS), and ANSS index (ANSSi) were calculated using PPGA and HR. RESULTS: Pain intensity scores increased on the average by 1.6, 3.5, and 8.1 for the 43°C, 48°C, and CPT stimuli, respectively. The pain intensity scores for all three stimuli groups were significantly different from each other (P<0.001). All three stimuli changed HR, PPGA, SPI, ANSS, and ANSSi values significantly from their respective baseline values (P<0.001 for all). Heat stimuli-induced pain intensity did not correlate with the magnitude of the respective changes in HR, PPGA, SPI, ANSS, and ANSSi. CPT-induced pain intensity correlated with the magnitude of the respective changes in HR, PPGA, SPI, ANSS, and ANSSi. PPGA, ANSSi, ANSS, and SPI differentiated between heat and cold stimuli-induced pain. CONCLUSIONS: All three thermal stimuli produced a significant change in photoplethysmograph-derived parameters. All photoplethysmograph-derived parameters appear to be suitable to study autonomic nervous system activation.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Dor/fisiopatologia , Adolescente , Adulto , Temperatura Baixa , Frequência Cardíaca/fisiologia , Temperatura Alta , Humanos , Masculino , Dor/diagnóstico , Dor/etiologia , Medição da Dor/métodos , Fotopletismografia/métodos , Adulto JovemRESUMO
BACKGROUND: This study aimed to assess the contribution of endothelial nitric oxide synthesis to the net responses of human peripheral blood vessels in vivo to the selective alpha(2)-adrenoceptor agonist dexmedetomidine. METHODS: Two groups of healthy young men were studied. In the first experiment, after brachial plexus block, the responses of digital arteries to systemically administered dexmedetomidine (target plasma concentration 1.2 ng ml(-1)) were studied using a photoplethysmograph (n=10) during i.a. infusions of saline and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (8 micromol min(-1)). In a separate experiment, after pre-treatment with acetylsalicylic acid, responses to increasing doses of dexmedetomidine (0.01-164 ng min(-1)) in the presence and absence of L-NMMA were compared in dorsal hand veins (DHV) (n=10) using linear variable differential transformers. RESULTS: L-NMMA significantly augmented dexmedetomidine-induced vasoconstriction of digital arteries as assessed by an increase in light transmission through a finger and by a decrease in finger temperature. The mean (95% confidence interval) extent of the additional effect of L-NMMA over the constrictor effect of dexmedetomidine alone was 19% (14-24) (P<0.0001). In DHV, L-NMMA had variable effects on the dexmedetomidine-constriction dose-response curve. In three subjects, the curve was shifted significantly to the left (with a >10-fold difference in ED(50)), but ED(50) was only marginally affected by L-NMMA in the other subjects (difference in ED(50) Assuntos
Agonistas alfa-Adrenérgicos/farmacologia
, Dexmedetomidina/farmacologia
, Óxido Nítrico Sintase/antagonistas & inibidores
, Vasoconstrição/efeitos dos fármacos
, Adolescente
, Adulto
, Plexo Braquial
, Dexmedetomidina/antagonistas & inibidores
, Relação Dose-Resposta a Droga
, Inibidores Enzimáticos/farmacologia
, Dedos/irrigação sanguínea
, Humanos
, Hipnóticos e Sedativos/antagonistas & inibidores
, Hipnóticos e Sedativos/farmacologia
, Masculino
, Pessoa de Meia-Idade
, Bloqueio Nervoso
, Óxido Nítrico/fisiologia
, Óxido Nítrico Sintase/fisiologia
, Fluxo Sanguíneo Regional/efeitos dos fármacos
, Vasoconstrição/fisiologia
, Adulto Jovem
, ômega-N-Metilarginina/farmacologia
RESUMO
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.
Assuntos
Água Extravascular Pulmonar/fisiologia , Pulmão , Linfa/fisiologia , Respiração com Pressão Positiva , Animais , Feminino , Hemodinâmica , OvinosRESUMO
BACKGROUND: When administered intrathecally, alpha-2 adrenergic agonists produce spinally mediated antinociception, but also rapidly redistribute to supraspinal sites. This investigation the compared EMG effects of intrathecally administered dexmedetomidine, MPV-2426 (fadolmidine), and tizanidine in Sprague-Dawley rats, which has not been previously described. METHODS: We studied electromyographic (EMG) responses of the head and gastrocnemius muscles, antinociception using the tail-flick test, and sedation by using observer assessment. Saline, dexmedetomidine (0.5 microg, 2.5 microg and 12.5 microg), MPV-2426 (2 microg, 10 microg and 50 microg) and tizanidine (2 microg, 10 microg and 50 microg) were administered intrathecally. RESULTS: Tizanidine 50 microg, MPV-2426 10 microg and 50 microg, and dexmedetomidine 2.5 microg and 12.5 microg, decreased EMG activity (P < 0.005). Dexmedetomidine 12.5 microg, MPV-2426 50 microg, and tizanidine 10 microg and 50 microg increased tail-flick latencies (P < 0.01). Dexmedetomidine alone significantly increased the magnitude of observer-assessed sedation (P < 0.0001). CONCLUSION: We conclude that in rats, intrathecally administered dexmedetomidine, MPV-2426 and tizanidine have dose-dependent effects on EMG. At antinociceptive doses, the EMG effects of these three alpha-2 adrenergic agonists differ (dexmedetomidine > MPV-2426 > tizanidine).
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Clonidina/análogos & derivados , Clonidina/farmacologia , Dexmedetomidina/farmacologia , Imidazóis/farmacologia , Indanos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Clonidina/administração & dosagem , Dexmedetomidina/administração & dosagem , Relação Dose-Resposta a Droga , Eletromiografia/efeitos dos fármacos , Hipnóticos e Sedativos , Imidazóis/administração & dosagem , Indanos/administração & dosagem , Injeções Espinhais , Atividade Motora/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Clonidina/farmacologia , Vasoconstrição/efeitos dos fármacos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pele/irrigação sanguínea , Temperatura Cutânea/efeitos dos fármacos , VigíliaRESUMO
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.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2 , Agonistas alfa-Adrenérgicos/farmacologia , Anestesia Geral , Dexmedetomidina/farmacologia , Reflexo Pupilar/efeitos dos fármacos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , MasculinoRESUMO
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.
Assuntos
3-Iodobenzilguanidina/farmacocinética , Inibidores Enzimáticos/farmacocinética , Miocárdio/metabolismo , Sistema Nervoso Simpático/fisiologia , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Norepinefrina/sangue , Coelhos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismoRESUMO
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.
Assuntos
Clonidina/farmacologia , Dedos/irrigação sanguínea , Vasoconstritores/farmacologia , Adulto , Alfentanil/administração & dosagem , Análise de Variância , Anestesia Geral , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Clonidina/administração & dosagem , Clonidina/sangue , Estado de Consciência , Estudos Cross-Over , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Raios Infravermelhos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Óxido Nitroso/administração & dosagem , Pletismografia/métodos , Propofol/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Vasoconstritores/administração & dosagem , Vasoconstritores/sangue , Vasodilatadores/administração & dosagem , Vasodilatadores/sangue , Vasodilatadores/farmacologiaRESUMO
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.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Sedação Consciente , Hemodinâmica/efeitos dos fármacos , Imidazóis/farmacologia , Medetomidina/farmacologia , Animais , Dióxido de Carbono/sangue , Débito Cardíaco/efeitos dos fármacos , Feminino , Corantes Fluorescentes , Medetomidina/antagonistas & inibidores , Microesferas , Oxigênio/sangue , Fluxo Sanguíneo Regional/efeitos dos fármacos , Ovinos , Resistência Vascular/efeitos dos fármacosRESUMO
UNLABELLED: We tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, blood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia. IMPLICATIONS: The alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Catecolaminas/metabolismo , Dexmedetomidina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Clonidina/farmacologia , Dexmedetomidina/efeitos adversos , Dexmedetomidina/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos VascularesRESUMO
BACKGROUND: The data on the effect of sevoflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that sevoflurane would increase intracranial pressure as compared to propofoL METHODS: In 20 patients with no evidence of mass effect undergoing transsphenoidal hypophysectomy, anesthesia was induced with intravenous fentanyl and propofol and maintained with 70% nitrous oxide in oxygen and a continuous propofol infusion, 100 microg x kg(-1) x min(-1). The authors assigned patients to two groups randomized to receive only continued propofol infusion (n = 10) or sevoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the sevoflurane group received, in random order, two concentrations (0.5 times the minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of sevoflurane for 10 min each. The authors continuously monitored lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations. RESULTS: Lumbar CSF pressure increased by 2+/-2 mmHg (mean+/-SD) with both 0.5 MAC and 1 MAC of sevoflurane. Cerebral perfusion pressure decreased by 11+/-5 mmHg with 0.5 MAC and by 15+/-4 mmHg with 1.0 MAC of sevoflurane. Systolic blood pressure decreased with both concentrations of sevoflurane. To maintain blood pressure within predetermined limits (within+/-20% of baseline value), phenylephrine was administered to 5 of 10 patients in the sevoflurane group (range = 50-300 microg) and no patients in the propofol group. Lumbar CSF pressure, cerebral perfusion pressure, and systolic blood pressure did not change in the propofol group. CONCLUSIONS: Sevoflurane, at 0.5 and 1.0 MAC, increases lumbar CSF pressure. The changes produced by 1.0 MAC sevoflurane did not differ from those observed in a previous study with 1.0 MAC isoflurane or desflurane.
Assuntos
Anestésicos Inalatórios/farmacologia , Hipofisectomia , Pressão Intracraniana/efeitos dos fármacos , Éteres Metílicos/farmacologia , Humanos , SevofluranoRESUMO
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.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Anestesia Geral/métodos , Imidazóis/farmacologia , Bloqueio Neuromuscular , Junção Neuromuscular/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/sangue , Adulto , Alfentanil , Androstanóis/farmacocinética , Androstanóis/farmacologia , Anestésicos Intravenosos , Pressão Sanguínea/efeitos dos fármacos , Interações Medicamentosas , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Imidazóis/sangue , Masculino , Medetomidina , Fármacos Neuromusculares Despolarizantes/farmacocinética , Fármacos Neuromusculares Despolarizantes/farmacologia , Propofol , RocurônioRESUMO
OBJECTIVE: The intraoperative use of fluid warming devices has been recommended to avoid perioperative hypothermia and related adverse outcomes. To evaluate whether these devices might introduce risks of their own, we measured the volume of air escaping from a warmed intravenous solution that might be delivered to a patient. METHODS: In an operating room maintained at 19-19.5 degrees C, we tested an HL-90 Hotline fluid warmer with the L-70 fluid-warming set. One liter of lactated Ringer's solution was infused at flow rates of 150, 300, 500 and 3400 ml/h. The air that formed within the L-70 tubing during infusion was collected in a bubble trap placed at the end of the L-70 tubing. The volume of air in the bubble trap was measured. Twelve separate measurements were obtained at each flow rate. One additional study (n = 8) was performed using the L-10 Gas Vent to determine whether this equipment might reduce the volume of air infused when fluid flow rate was 300 mL/h. The volume of air collected at each flow rate was compared using ANOVA. RESULTS: Volume of air increased significantly from 1.0 +/- 0.2 mL to 2.9 +/- 0.4 ml as flow rate decreased from 3400 ml/h to 150 ml/h (p < 0.0001). The L-10 gas eliminator was ineffective in reducing the amount of air infused. CONCLUSIONS: We conclude that the use of the Hotline fluid warmer can result in infusion of air into the patient, introducing possible risk of air embolism.
Assuntos
Embolia Aérea/prevenção & controle , Hidratação , Temperatura Alta , Humanos , Infusões Intravenosas , Soluções Isotônicas , Lactato de Ringer , RiscoRESUMO
BACKGROUND: Clonidine decreases the vasoconstriction and shivering thresholds. It thus seems likely that the alpha2 agonist dexmedetomidine will also impair control of body temperature. Accordingly, the authors evaluated the dose-dependent effects of dexmedetomidine on the sweating, vasoconstriction, and shivering thresholds. They also measured the effects of dexmedetomidine on heart rate, blood pressures, and plasma catecholamine concentrations. METHODS: Nine male volunteers participated in this randomized, double-blind, cross-over protocol. The study drug was administered by computer-controlled infusion, targeting plasma dexmedetomidine concentrations of 0.0, 0.3, and 0.6 ng/ml. Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds were computed using established linear cutaneous contributions to control of sweating, vasoconstriction, and shivering. The dose-dependent effects of dexmedetomidine on thermoregulatory response thresholds were then determined using linear regression. Heart rate, arterial blood pressures, and plasma catecholamine concentrations were determined at baseline and at each threshold. RESULTS: Neither dexmedetomidine concentration increased the sweating threshold from control values. In contrast, dexmedetomidine administration reduced the vasoconstriction threshold by 1.61 +/- 0.80 degrees C x ng(-1) x ml (mean +/- SD) and the shivering threshold by 2.40 +/- 0.90 degrees C x ng(-1) x ml. Hemodynamic responses and catecholamine concentrations were reduced from baseline values, but they did not differ at the two tested dexmedetomidine doses. CONCLUSIONS: Dexmedetomidine markedly increased the range of temperatures not triggering thermoregulatory defenses. The drug is thus likely to promote hypothermia in a typical hospital environment; it is also likely to prove an effective treatment for shivering.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Imidazóis/farmacologia , Estremecimento/efeitos dos fármacos , Sudorese/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Adulto , Regulação da Temperatura Corporal/efeitos dos fármacos , Método Duplo-Cego , Humanos , Masculino , MedetomidinaRESUMO
UNLABELLED: Dexmedetomidine is a selective alpha2-adrenoceptor agonist with centrally mediated sympatholytic, sedative, and analgesic effects. This study evaluated: 1) pharmacokinetics of dexmedetomidine in plasma and cerebrospinal fluid (CSF) in surgical patients; 2) precision of a computer-controlled infusion protocol (CCIP) for dexmedetomidine during the immediate postoperative period; and 3) dexmedetomidine's sympatholytic effects during that period. Dexmedetomidine was infused postoperatively by CCIP for 60 min to eight women, targeting a plasma concentration (Cp) of 600 pg/mL. Before, during, and after infusion, blood was sampled to determine plasma concentrations of norepinephrine, epinephrine, and dexmedetomidine, and CSF was sampled to determine dexmedetomidine concentrations (C[CSF]). Heart rate and arterial blood pressure were measured continuously from 5 min before until 3 h after the end of infusion. During the infusion, Cp values generally exceeded the target value: median percent error averaged 21% and ranged from -2% to 74%; median absolute percent error averaged 23% and ranged from 4% to 74%. After infusion, C(CSF) was 4% +/- 1% of Cp. Because C(CSF) barely exceeded the assay's limit of quantitation, CSF pharmacokinetics were not determined. During the infusion, norepinephrine decreased from 2.1 +/- 0.8 to 0.7 +/- 0.3 nmol/L; epinephrine decreased from 0.7 +/- 0.5 to 0.2 +/- 0.2 nmol/L; heart rate decreased from 76 +/- 15 to 64 +/- 11 bpm; and systolic blood pressure decreased from 158 +/- 23 to 140 +/- 23 mm Hg. We conclude that infusion of dexmedetomidine by CCIP using published pharmacokinetic parameters overshoots target dexmedetomidine concentrations during the early postoperative period. Hemodynamic and catecholamine results suggest that dexmedetomidine attenuates sympathetic activity during the immediate postoperative period. IMPLICATIONS: We studied the pharmacokinetic and sympatholytic effects of dexmedetomidine during the immediate postoperative period and found that during this period, the published pharmacokinetic data slightly overshoot target plasma dexmedetomidine concentrations. We also found that heart rate, blood pressure, and plasma catecholamine concentrations decrease during dexmedetomidine infusion.
Assuntos
Agonistas alfa-Adrenérgicos/farmacocinética , Agonistas alfa-Adrenérgicos/uso terapêutico , Imidazóis/farmacocinética , Imidazóis/uso terapêutico , Sistema Nervoso Simpático/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/líquido cefalorraquidiano , Adulto , Epinefrina/sangue , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipofisectomia , Imidazóis/líquido cefalorraquidiano , Infusões Intravenosas , Medetomidina , Norepinefrina/sangue , Cuidados Pós-OperatóriosRESUMO
BACKGROUND: Because patients may be taking clonidine chronically or may be receiving it as a premedication before surgery, the authors investigated its effect on cerebral hemodynamics. METHODS: In nine volunteers, middle cerebral artery mean blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography (TCD). CO2 vasoreactivity was measured before clonidine administration (preclonidine), 90 min after clonidine, 5 microg/kg orally, then following restoration of mean arterial pressure (MAP) to the preclonidine level. In addition, Vm was measured after a phenylephrine-induced 30-mmHg increase in MAP. RESULTS: After clonidine administration, Vm decreased from 62 +/- 9 to 48 +/- 8 cm/s (P < 0.01), and MAP decreased from 86 +/- 10 to 63 +/- 5 mmHg (P < 0.01; mean +/- SD). Clonidine decreased the CO2 vasoreactivity slope from 2.2 +/- 0.4 to 1.2 +/- 0.5 cm x s(-1) x mmHg(-1) (P < 0.05); restoring MAP to the preclonidine level increased the slope to 1.60 +/- 0.5 cm x s(-1) x mmHg(-1), still less than the preclonidine slope (P < 0.05). CO2 vasoreactivity expressed as a percentage change in Vm, decreased after clonidine, 3.5 +/- 0.8 versus 2.4 +/- 0.8 %/mmHg (P < 0.05); this difference disappeared after restoration of MAP, 3.1 +/- 1.2 %/mmHg. With a 30-mmHg increase in MAP, Vm increased by 13% before and after clonidine (P < 0.05). CONCLUSIONS: Clonidine, 5 microg/kg orally, decreases Vm and slightly attenuates cerebral CO2 vasoreactivity, therefore decreased cerebral blood flow and mildly attenuated CO2 vasoreactivity should be anticipated.