RESUMEN
OBJECTIVE: Insulin is a vasodilating agent and it was hypothesized that insulin (GIK) could improve systemic and regional oxygenation in cardiac surgery with cardiopulmonary bypass (CPB). Two questions were addressed: 1) Does insulin improve central mixed and hepatic venous oxygenation during CPB? and 2) Does this treatment reduce systemic levels of the proinflammatory mediators C3a and IL-6? DESIGN: Prospective, randomized, controlled study at a university hospital. Thirty patients were included and 16 of these received an infusion of insulin, glucose and potassium (GIK) using an euglycemic clamp technique. The insulin infusion was started during hypothermia, 15 min before rewarming. Blood gases and hemodynamic parameters were measured during hypothermia (before the insulin infusion was started), during rewarming at 35 degrees C, and 30 min after CPB was discontinued. Inflammatory markers were measured: preoperatively, during hypothermia and 2 h after CPB. RESULTS: GIK was associated with reduced systemic vascular resistance (p = 0.02 vs the control group), higher bypass pump flow (p = 0.001). higher central mixed oxygen saturation (p = 0.036) and oxygen tension (p = 0.001) and higher hepatic venous oxygen saturation (p = 0.04) and oxygen tension (p = 0.006). C3a and IL-6 increased during surgery in both groups but there were no differences between the groups. CONCLUSION: 1) GIK infusion improved central mixed and hepatic venous oxygenation in patients undergoing heart surgery. 2) During the conditions of this study, this had no effect on the proinflammatory mediators C3a and IL-6.
Asunto(s)
Puente Cardiopulmonar/métodos , Glucosa/uso terapéutico , Insulina/uso terapéutico , Cuidados Intraoperatorios/métodos , Hígado/irrigación sanguínea , Oxígeno/sangre , Potasio/uso terapéutico , Anciano , Procedimientos Quirúrgicos Cardiovasculares/métodos , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
We investigated analgesia and the adverse effects of epidural sufentanil infusion in a double-blind randomized study of 37 patients undergoing thoracic surgery. Sufentanil 1 microgram/mL was administered at a thoracic (Ts, n = 12) or lumbar level (Ls, n = 11), or combined with bupivacaine 1 mg/mL at a thoracic level (Tsb, n = 14). Postoperatively, the epidural infusion rate was titrated (4-20 mL/h) according to the visual analog pain scale when assessed during function (VAS-F) or the occurrence of side effects. When epidural analgesia failed, nonsteroidal antiinflammatory drugs (NSAIDs) were given. VAS-F was lowest in the Tsb group (Tsb < Ts = Ls) despite its having both the lowest rate of epidural infusion (Tsb < Ts < Ls) and need of additional NSAIDs (Tsb < Ts = Ls). Sedation (Tsb < Ts < Ls) and hypercapnia (Tsb = Ts < Ls) occurred most frequently in the Ls group. Vital capacity (VC) was reduced in all groups by 43%-58% (Ls > Ts) and had recovered only partially at 24 h after discontinuation of the epidural infusion. The slopes of the ventilatory response (minute ventilation [VE], inspiratory flow, and mouth occlusion pressure at 0.1 s [P0.1]) to 7% CO2 decreased during treatment in Ls, Ts, and Tsb groups at the most by 73%, 55%, and 52% (not significant [NS] between groups), 59%, 45%, and 38% (NS between groups), and 81%, 43%, and 18% (Ls > Tsb), respectively. Twenty-four hours after discontinuation of the epidural infusion, there was a complete recovery of the VE, inspiratory flow, and P0.1 response to CO2 in the Tsb group only. The study shows that, after thoracotomy, epidural sufentanil analgesia is optimal when tailored to the site of nociceptive input and combined with bupivacaine.
Asunto(s)
Analgesia Epidural , Analgésicos Opioides/uso terapéutico , Anestesia Epidural , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Sufentanilo/uso terapéutico , Toracotomía , Adulto , Anciano , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Anestésicos Locales/efectos adversos , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Bupivacaína/efectos adversos , Estado de Conciencia/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Hipercapnia/inducido químicamente , Hipercapnia/fisiopatología , Inhalación/efectos de los fármacos , Masculino , Persona de Mediana Edad , Nociceptores/efectos de los fármacos , Dimensión del Dolor , Dolor Postoperatorio/prevención & control , Presión , Respiración/efectos de los fármacos , Sufentanilo/administración & dosificación , Sufentanilo/efectos adversos , Capacidad Vital/efectos de los fármacosRESUMEN
In a double-blind, randomized study in patients undergoing thoracic surgery the plasma and cerebrospinal fluid (CSF) pharmacokinetics of the epidural sufentanil were studied by using radioimmunoassay analysis. Sufentanil was given as an infusion (1 microgram/mL) at the lumbar (Ls; n = 11), or thoracic (Ts; n = 12) level, or epidural sufentanil combined with bupivacaine (1 mg/ mL) at the thoracic level (Tsb; n = 14). Postoperatively, the infusion was adjusted to optimize analgesia. During the infusion, the sufentanil plasma concentrations were related to the rate of epidural infusion and unrelated both to the epidural infusion regimen and to the postoperative pain scores. The elimination half-life in plasma (mean +/- SEM) was 9.9 +/- 1.7 h (Ls), 8.6 +/- 0.7 h (Ts), and 11.7 +/- 2.2 h (Tsb). The distribution volume was 15.2 +/- 3.5 l/kg (Ls), 14.8 +/- 2.4 L/kg (Ts), and 12.9 +/- 1.2 L/kg (Tsb). Total sufentanil clearance was 17.8 +/- 1.4 and 16.9 +/- 2.0 mL.kg-1.min-1 (Ls), 22.9 +/- 3.5 and 20.0 +/- 2.6 mL.kg-1.min-1 (Ts), and 22.4 +/- 3.0 and 14.5 +/- 1.3 mL.kg-1.min-1 (Tsb). The terminal elimination half-life of sufentanil in CSF was 7.2 +/- 0.6 h. During steady state the CSF concentrations were not homogeneously distributed and they were higher than those in plasma. These pharmacokinetic findings support the concept that epidural sufentanil analgesia is optimal when administered segmentally and tailored to the surgical incision.
Asunto(s)
Analgesia Epidural , Analgésicos Opioides/farmacocinética , Anestesia Epidural , Anestésicos Locales/farmacocinética , Bupivacaína/farmacocinética , Sufentanilo/farmacocinética , Toracotomía , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/sangre , Analgésicos Opioides/líquido cefalorraquídeo , Anestésicos Locales/administración & dosificación , Anestésicos Locales/sangre , Anestésicos Locales/líquido cefalorraquídeo , Bupivacaína/administración & dosificación , Bupivacaína/sangre , Bupivacaína/líquido cefalorraquídeo , Método Doble Ciego , Semivida , Humanos , Tasa de Depuración Metabólica , Dimensión del Dolor , Dolor Postoperatorio/prevención & control , Sufentanilo/administración & dosificación , Sufentanilo/sangre , Sufentanilo/líquido cefalorraquídeoRESUMEN
The cerebrospinal fluid (CSF) and plasma pharmacokinetics of sufentanil were studied in 29 adult patients undergoing thoracotomy under general anesthesia. Sufentanil, 75 micrograms, diluted in 10 mL saline, was given preoperatively in either the lumbar or thoracic epidural space to 14 and 15 patients, respectively. Lumbar CSF and plasma were frequently sampled for 10 h and analyzed for sufentanil concentration by radioimmunoassay. In plasma, the area under the concentration curve (AUC) did not differ between the groups. The fraction of the lumbar epidural dose found in CSF was calculated to be 2.7%. The time to peak CSF sufentanil concentration differed (P < 0.01) after epidural administration in the lumbar (0.76 +/- 0.50 h) and thoracic (2.1 +/- 1.4 h) region. In the lumbar group, the AUC and Cmax values in CSF were 19 (P < 0.01) and 45 (P < 0.01) times higher than in plasma, and 4.7 (P < 0.01) and 8.2 (P < 0.001) times higher than in CSF in the thoracic group. The decline in sufentanil concentration was more rapid in CSF than plasma; in the lumbar group the CSF/plasma concentration-ratio was eight and five at 6 and 10 h, respectively, after sufentanil administration. This study shows that after epidural administration sufentanil concentrations are higher in CSF than in plasma, and are highly localized within CSF to the site of administration.
Asunto(s)
Anestesia Epidural , Sufentanilo/farmacocinética , Adulto , Anciano , Anestesia Epidural/métodos , Femenino , Humanos , Vértebras Lumbares , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Sufentanilo/sangre , Sufentanilo/líquido cefalorraquídeo , Vértebras Torácicas , ToracotomíaRESUMEN
Eight patients (7 men and 1 woman, 45-68 yr old) scheduled to undergo thoracotomy were given, preoperatively, 15 micrograms sufentanil in the lumbar intrathecal space for a study of cerebrospinal fluid (CSF) and plasma kinetics of sufentanil. Multiple samples of plasma and CSF from the lumbar region were obtained through indwelling catheters for 12 h and analyzed for sufentanil by radioimmunoassay. Pharmacokinetic parameters were derived by noncompartmental analysis. In plasma, the maximal concentration of sufentanil appeared after 0.65 +/- 0.17 h (mean +/- SEM). No equilibrium was reached between the sufentanil concentration in CSF and plasma, but the CSF/plasma concentration ratio declined from approximately 140 at 2 h to about 15 at 10 h. Extrapolation indicates that another 10 h would be required before the concentration in CSF would equal that in plasma. The mean residence time (MRT) of sufentanil in CSF was 0.92 +/- 0.08 h and in plasma was 6.8 +/- 0.6 h. The volume of distribution at steady state (Vss) in the subarachnoid compartment was 1.54 +/- 0.39 ml/kg, and the clearance from the CSF was 27 +/- 5 microliters.kg-1.min-1. The intrathecal administration of 15 micrograms sufentanil at the beginning of the operation did not produce analgesia that lasted into the postoperative period. Most patients had urinary retention, but none experienced any serious complications. This study demonstrates that the lipophilic opioid sufentanil undergoes rapid clearance from CSF and absorption to plasma after intrathecal administration. These pharmacokinetic characteristics are slower for the less lipophilic opioids meperidine and morphine. The rapid pharmacokinetics of sufentanil explain its rapid onset of action and short-lasting effects.
Asunto(s)
Analgésicos Opioides/farmacocinética , Fentanilo/análogos & derivados , Anciano , Analgésicos Opioides/sangre , Analgésicos Opioides/líquido cefalorraquídeo , Fentanilo/sangre , Fentanilo/líquido cefalorraquídeo , Fentanilo/farmacocinética , Humanos , Lactante , Inyecciones Espinales , Masculino , Persona de Mediana Edad , SufentaniloRESUMEN
The disposition of pethidine and its main metabolite, norpethidine, in cerebrospinal fluid (CSF) and plasma was studied in 11 thoracic surgery patients after lumbar epidural (100 mg; n = 6) or lumbar intrathecal (25 mg; n = 5) administration of pethidine. Pethidine appeared more slowly in plasma after intrathecal than after epidural administration (tmax 2.3 h and 14 min, respectively), but systemic bioavailability was similar. The CSF concentrations of pethidine were higher than those in plasma after both routes of administration. The maximal CSF/plasma concentration ratio was 6000 to 45,000 after intrathecal administration but was only 26 to 97 after the epidural route. Pethidine was rapidly distributed in CSF; nine to ten h after the intrathecal and epidural injections the CSF/plasma concentration ratios were 12 to 89 and 2 to 33, respectively. The calculated bioavailability in CSF of epidural pethidine was 10.3%. The terminal elimination half-life of pethidine was 6.0 h (CSF) and 5.4 h (plasma) after intrathecal administration and 8.6 h (CSF) and 8.8 h (plasma) after epidural injection. The volume of distribution of unchanged pethidine in the subarachnoid space was 13 ml.kg-1 and clearance from the CSF was 15 microliters.kg-1.min-1. In all patients receiving intrathecal pethidine and in some patients after epidural pethidine, CSF norpethidine concentrations were higher than those in plasma; the maximum CSF norpethidine was 102 to 1211 ng.ml-1 and 14 to 210 ng.ml-1 and the maximum CSF/plasma norpethidine concentration ratios were 21 to 652 and 0.6 to 14 times after intrathecal and epidural administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Meperidina/análogos & derivados , Meperidina/farmacocinética , Femenino , Humanos , Inyecciones Epidurales , Inyecciones Espinales , Masculino , Meperidina/administración & dosificación , Meperidina/sangre , Meperidina/líquido cefalorraquídeoRESUMEN
In order to determine the rate and degree of redistribution of morphine within the cerebrospinal fluid (CSF), and whether it was affected by the site of and volume of the injection, morphine was given to 23 elderly patients undergoing thoracotomy - in 10 ml saline in the lumbar epidural interspace (n = 5), in 10 ml saline in the thoracic epidural interspace (n = 5), in 2 ml saline in the thoracic interspace (n = 8) and in 10 ml saline in the lumbar epidural interspace (n = 5). The plasma concentration of morphine in all patients was comparable and was much lower than in the CSF. The CSF morphine concentration, measured as the area under the CSF concentration curve (AUC), the maximal CSF concentration (Cmax) and the time to reach maximal CSF concentration (tmax), varied between the four groups. The variation was related to the site of the injection; the AUC and Cmax were lower and tmax appeared later after thoracic than lumbar injection. Lumbar CSF morphine concentrations were further reduced by thoracic epidural injection of morphine in a small as compared to a large volume. The permeability of the dura to morphine was not influenced by the volume used. The results show that morphine is not homogeneously distributed within the CSF. The availability of morphine to CSF from the epidural space is not altered by the injection volume, but the drug remains more localized in CSF after epidural injection of morphine in a small volume.(ABSTRACT TRUNCATED AT 250 WORDS)