摘要:

BackgroundRapacuronium is a new nondepolarizing muscle relaxant with rapid onset and offset. As part of a study to determine its neuromuscular effects, the authors sampled plasma sparsely to determine the influence of age, gender, and other covariates on its pharmacokinetic characteristics.MethodsOf 181 patients receiving a single bolus dose of 0.5‐2.5 mg/kg rapacuronium, 43 (aged 24‐83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed using a population approach (mixed‐effects modeling) to determine the influence of demographic characteristics and preoperative laboratory values on the pharmacokinetic parameters.ResultsRapacuronium's weight‐normalized plasma clearance was 7.03 [middle dot] (1 ‐ 0.0507 [middle dot] (HgB ‐ 13)) ml [middle dot] kg‐1[middle dot] min‐1, where HgB is the patient's preoperative value for hemoglobin (g/100 ml); however, rapacuronium's blood clearance (11.4 +/− 1.4 ml [middle dot] kg‐1[middle dot] min‐1, mean +/− SD) did not vary with hemoglobin. Rapacuronium's weight‐normalized pharmacokinetic parameters were not influenced by age, gender, or other covariates examined. Plasma concentrations of ORG9488 were typically less than 14% those of rapacuronium during the initial 30 min after rapacuronium administration.ConclusionsIn this patient population, neither age nor gender influence elimination of rapacuronium. This finding contrasts to an age‐related decrease in plasma clearance observed in a study of 10 healthy volunteers and in a pooled analysis of the pharmacokinetic data from 206 adults in multiple clinical studies. Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe tube of the intubating laryngeal mask (ILM) is more rigid than the standard laryngeal mask airway (LMA), and the authors have tested the hypothesis that pharyngeal mucosal pressures, airway sealing pressures, and fiberoptic position are different when the two devices are compared.MethodsTwenty anesthetized, paralyzed adults were randomly allocated to receive either the LMA or ILM for airway management. Microchip sensors were attached to the size 5 LMA or ILM at locations corresponding to the pyriform fossa, hypopharynx, base of tongue, posterior pharynx, and distal and proximal oropharynx. Mucosal pressures, airway sealing pressures, and fiberoptic positioning were recorded during inflation of the cuff from 0 to 40 ml in 10‐ml increments.ResultsAirway sealing pressures were higher for the ILM (30 vs. 23 cm H2O), but epiglottic downfolding was more common (56% vs. 26%). Pharyngeal mucosal pressures were much higher for the ILM at five of six locations. Mean mucosal pressures in the distal oropharynx for the ILM were always greater than 157 cm H2O, regardless of cuff volume. There was no correlation between mucosal pressures and airway sealing pressures at any location for the LMA, but there was a correlation at three of six locations for the ILM.ConclusionsThe ILM provides a more effective seal than the LMA, but pharyngeal mucosal pressures are higher and always exceed capillary perfusion pressure. The ILM is unsuitable for use as a routine airway and should be removed after its use as an airway intubator.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundOpioid‐related side effects associated with intravenous patient‐controlled analgesia can be reduced by a low‐dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid‐related side effects has not been evaluated. This study was designed to determine the dose‐response relation for nalmefene for the prevention of morphine‐related side effects in patients receiving intravenous patient‐controlled analgesia.MethodsOne hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 [micro sign]g nalmefene, or 25 [micro sign]g nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24‐h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation.ResultsThe need for antiemetic and antipruritic medications during the 24‐h study period was significantly lower in the patients receiving nalmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nalmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24‐h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h.ConclusionCompared with placebo, prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient‐controlled analgesia with morphine.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundMilrinone has been shown to increase cardiac output in children after cardiac surgery, but pharmacokinetic analysis has not been used to identify effective dose regimens. The purpose of this study was to characterize the pharmacokinetics of milrinone in infants and children and to apply the results of the issue of dosing.MethodsTwenty children were studied after they underwent repair of congenital cardiac defects. Control hemodynamic measurement was made after the children were separated from cardiopulmonary bypass, and each patient was given a loading dose of 50 [micro sign]g/kg progressively in 5 min. Hemodynamic measurements were recorded again at the end of the loading dose and when a blood sample was taken to determine milrinone plasma concentrations. Further blood samples were taken during the next 16 h for milrinone plasma concentration analysis. The pharmacokinetics of milrinone were analyzed using the population pharmacokinetic program NONMEM.ResultsThe loading dose of milrinone resulted in a mean decrease in mean blood pressure of 12% and a mean increase in cardiac index of 18% at a mean peak plasma concentration of 235 ng/ml. The pharmacokinetics of milrinone were best described by a three‐compartment model. In the optimal model, all volumes and distribution clearances were proportional to weight, and weight‐normalized elimination clearance was proportional to age; i.e., Cl1 = 2.5 [middle dot] weight [middle dot] (1 + 0.058 [middle dot] age) where Cl1 is expressed as ml/min, and the units of weight and age are kg and months, respectively.ConclusionsA loading dose of 50 [micro sign]g/kg effectively increases cardiac index in children after cardiac surgery. Simulations indicate that the peak plasma concentration can be maintained by following the loading dose of 50 [micro sign]g/kg with an infusion of approximately 3 [micro sign]g [middle dot] kg‐1[middle dot] min‐1for 30 min and then a maintenance infusion, which may require adjustment for age.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAn increase in masseter muscle tone in response to halothane or succinylcholine anesthesia (or both) can be observed in healthy persons. Thus the authors compared the fiber‐type halothane and succinylcholine sensitivities in human masseter and vastus lateralis muscles.MethodsMasseter and vastus lateralis muscle segments were obtained from 13 and 9 healthy persons, respectively. After chemical skinning of a single fiber and loading the sarcoplasmic reticulum with Ca++0.16 [micro sign]M solution, halothane (0.5‐4 vol% bubbled in the incubating solution), succinylcholine (0.1 [micro sign]M to 10 mM), or both sensitivities were defined as the concentration inducing more than 10% of the maximum tension obtained by application of 16 [micro sign]M Ca++solution. The myofilament response to Ca++was studied with and without halothane by observing the isometric tension of skinned masseter fibers challenged with increasing concentrations of Ca++. Muscle fiber type was determined by the difference in strontium‐induced tension measurements.ResultsA significant difference in halothane sensitivity was found between type 1 masseter fibers (0.6 +/− 0.2 vol%; mean +/− SD) versus type 1 (2.7 +/− 0.6 vol%) and type 2 vastus lateralis muscle (2.5 +/− 0.4 vol%). Succinylcholine did not induce Ca++release by the sarcoplasmic reticulum. In the masseter muscle, 0.75 vol% halothane decreased the maximal activated tension by 40% but did not change the Ca++concentration that yields 50% of the maximal tension.ConclusionsThe very low halothane threshold for Ca++release from the masseter muscle usually could be counteracted by a direct negative inotropic effect on contractile proteins. However, halothane may increase the sensitivity of the sarcoplasmic reticulum Ca++release to succinylcholine‐induced depolarization, leading to an increase in masseter muscle tone.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundMorphine is metabolized to two major metabolites, morphine‐3‐glucuronide and morphine‐6‐glucuronide (M6G). Under the conditions of long‐term oral morphine administration, the accumulation of M6G may contribute to the analgesic effects, but it may also cause respiratory depression.MethodsFive healthy male volunteers (ages 25‐34 yr) received 90 mg MST (morphine sulfate 5H2O sustained‐released tablet, equivalent to 67.8 mg oral morphine). Multiple plasma and urine samples were taken for as long as 14 and 36 h, respectively. Individual pharmacokinetics after intravenous administration of morphine and M6G were available from a previous investigation. A new model that considers the M6G‐plasma profile as a sum of the input from the first‐pass metabolism of morphine and the input from systemically available morphine was applied to the plasma concentration versus time curves of M6G. The concentrations of M6G at the effect site after long‐term morphine administration were simulated.ResultsThe fraction of morphine absorbed from the gut was 82 +/− 14%. Of this, 42 +/− 8% passed through the liver, resulting in an oral bioavailability of morphine of 34 +/− 9%. Of the total amount of M6G, 71 +/− 7% was formed during the first‐pass metabolism, and 29 +/− 7% was formed by metabolism of systemic morphine. After 36 h, the amounts of M6G and morphine excreted in the urine were 92 +/− 17% and 9 +/− 3%, respectively. Simulation of effect‐site concentrations of M6G indicated that after multiple oral dosing of morphine in patients with normal liver and renal function, M6G might reach concentrations two times greater than that of morphine.ConclusionsM6G may contribute to the analgesic and side effects seen with long‐term morphine treatment. The current model of morphine and M6G pharmacokinetics after oral administration of morphine may serve as a pharmacokinetic basis for experiments evaluating the analgesic contribution of M6G with long‐term oral dosing of morphine.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundRapid cervical dilation reportedly accompanies lumbar sympathetic blockade, whereas epidural analgesia is associated with slow labor. The authors compared the effects of initial lumbar sympathetic block with those of epidural analgesia on labor speed and delivery mode in this pilot study.MethodsAt a hospital not practicing active labor management, full‐term nulliparous patients whose labors were induced randomly received initial lumbar sympathetic block or epidural analgesia. The latter patients received 10 ml bupivacaine, 0.125%; 50 [micro sign]g fentanyl; and 100 [micro sign]g epinephrine epidurally and sham lumbar sympathetic blocks. Patients to have lumbar sympathetic blocks received 10 ml bupivacaine, 0.5%; 25 [micro sign]g fentanyl; and 50 [micro sign]g epinephrine bilaterally and epidural catheters. Subsequently, all patients received epidural analgesia.ResultsCervical dilation occurred more quickly (57 vs. 120 min/cm cervical dilation; P = 0.05) during the first 2 h of analgesia in patients having lumbar sympathetic blocks (n = 17) than in patients having epidurals (n = 19). The second stage of labor was briefer in patients having lumbar sympathetic blocks than in those having epidurals (105 vs. 270 min; P < 0.05). Nine patients having lumbar sympathetic block and seven having epidurals delivered spontaneously, whereas seven patients having lumbar sympathetic block and seven having epidurals had instrument‐assisted vaginal deliveries. Cesarean delivery for fetal bradycardia occurred in one patient having lumbar sympathetic block. Cesarean delivery for dystocia occurred in five patients having epidurals compared with no patient having lumbar sympathetic block (P = not significant). Visual analog pain scores differed only at 60 min after block.ConclusionsNulliparous parturients having induced labor and receiving initial lumbar sympathetic blocks had faster cervical dilation during the first 2 h of analgesia, shorter second‐stage labors, and a trend toward a lower dystocia cesarean delivery rate than did patients having epidural analgesia. The effects of lumbar sympathetic block on labor need to be determined in other patient groups. These results may help define the tocodynamic effects of regional labor analgesia.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundIntra‐ and postoperative clinical properties of sciatic‐femoral nerve block performed with either ropivacaine at different concentrations or mepivacaine have been evaluated in a multicenter, randomized, blinded study.MethodsAdult patients scheduled for foot and ankle surgery were randomized to receive combined sciatic‐femoral nerve block with 225 mg of either 0.5% (n = 83), 0.75% (n = 87), or 1% (n = 86) ropivacaine, or with 500 mg of 2% mepivacaine (n = 84). A thigh tourniquet was used in all patients. Onset time, adequacy of surgical anesthesia, time to offset of nerve block, and time until first postoperative requirement for pain medication were evaluated by a blinded observer.ResultsThe adequacy of nerve block was similar in the four treatment groups (the ratios between adequate:inadequate: failed blocks were 74:9:0 with 0.5% ropivacaine, 74:13:0 with 0.75% ropivacaine, 78:8:0 with 1% ropivacaine, and 72:12:0 with 2% mepivacaine). The onset of the block was slower with 0.5% ropivacaine than with other anesthetic solutions (P < 0.001). Regardless of the concentration, ropivacaine produced a longer motor blockade (10.5 +/− 3.8 h, 10.3 +/− 4.3 h, and 10.2 +/− 5.1 h with 0.5%, 0.75%, and 1% ropivacaine, respectively) than with mepivacaine (4.3 +/− 2.6 h; P < 0.001). The duration of postoperative analgesia was shorter after mepivacaine (5.1 +/− 2.7 h) than after ropivacaine (12.2 +/− 4.1 h, 14.3 +/− 5 h, and 14.5 +/− 3.4 h, with 0.5%, 0.75%, or 1% ropivacaine, respectively; P < 0.001). Pain relief after 0.5% ropivacaine was 14% shorter than 0.75% or 1% ropivacaine (P < 0.05). During the first 24 h after surgery, 30‐37% of patients receiving ropivacaine required no analgesics compared with 10% of those receiving mepivacaine (P < 0.001).ConclusionsThis study suggests that 0.75% ropivacaine is the most suitable choice of local anesthetic for combined sciatic‐femoral nerve block, providing an onset similar to mepivacaine and prolonged postoperative analgesia.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAwareness during general anesthesia is a frightening experience, which may result in serious emotional injury and post‐traumatic stress disorder. We performed an in‐depth analysis of cases from the database of the American Society of Anesthesiologists Closed Claims Project to explore the contribution of intraoperative awareness to professional liability in anesthesia.MethodsThe database of the Closed Claims Project is composed of closed US malpractice claims that have been collected in a standardized manner. All claims for intraoperative awareness were reviewed by the reviewers to identify patterns of causation and standard of care. Logistic regression analysis was used to identify independent patient and anesthetic factors associated with claims for recall during general anesthesia compared to other general anesthesia malpractice claims.ResultsAwareness claims accounted for 79 (1.9%) of 4,183 claims in the database, including 18 claims for awake paralysis, i.e., the inadvertent paralysis of an awake patient, and 61 claims for recall during general anesthesia, i.e., recall of events while receiving general anesthesia. The majority of awareness claims involved women (77%), younger than 60 yr of age (89%), American Society of Anesthesiologists physical class I‐II (68%), who underwent elective surgery (87%). Most (94%) claims for awake paralysis represented substandard care involving errors in labeling and administration, whereas care was substandard in only 43% of the claims for recall during general anesthesia (P < 0.001). Claims for recall during general anesthesia were more likely to involve women (odds ratio [OR] = 3.08, 95% confidence interval [CI] = 1.58, 6.06) and anesthetic techniques using intraoperative opioids (OR = 2.12, 95% CI = 1.20, 3.74), intraoperative muscle relaxants (OR = 2.28, 95% CI = 1.22, 4.25), and no volatile anesthetic (OR = 3.20, 95% CI = 1.88, 5.46).ConclusionsDeficiencies in labeling and vigilance were common causes for awake paralysis. Claims for recall during general anesthesia were more likely in women and with nitrousnarcotic‐relaxant techniques.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundNerve injury associated with anesthesia is a significant source of morbidity for patients and liability for anesthesiologists. To identify recurrent and emerging patterns of injury we analyzed the current American Society of Anesthesiologists (ASA) Closed Claims Project Database and performed an in‐depth analysis of claims for nerve injury that were entered into the database since the authors' initial report of the subject.MethodsThe ASA Closed Claims Database is a standardized collection of case summaries derived from the closed claims files of professional liability insurance companies. Claims for nerve injury that were not included in the authors' 1990 report were reviewed in‐depth.ResultsSix hundred seventy (16% of 4,183) claims were for anesthesia‐related nerve injury. The most frequent sites of injury were the ulnar nerve (28%), brachial plexus (20%), lumbosacral nerve root (16%), and spinal cord (13%). Ulnar nerve (85%) injuries were more likely to have occurred in association with general anesthesia, whereas spinal cord (58%) and lumbosacral nerve root (92%) injuries were more likely to occur with regional techniques. Ulnar nerve injury occurred predominately in men (75%) and was also more apt to have a delayed onset of symptoms (62%) than other nerve injuries. Spinal cord injuries were the leading cause of claims for nerve injury that occurred in the 1990s.ConclusionNew strategies for prevention of nerve damage cannot be recommended at this time because the mechanism for most injuries, particularly those of the ulnar nerve, is not apparent.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID