Rectal methohexital: concentration and length of the rectal catheters

In the study, the authors evaluated the concentration of rectal methohexital (1% vs 10%) and the length of the rectal catheter (3.8 vs 12.7 cm), on sleep-success rate, administration-sleep time, methohexital plasma concentrations, and recovery time in 85 healthy children scheduled for elective ophthalmic or ear, nose, or throat operations lasting approximately 1 h. At a dose of 25 mg/kg, the 1% solution of rectal methohexital was associated with a significant (P less than 0.05) higher sleep-success rate (95% vs 70%), shorter administration-sleep time (5.7 +/- 1.9 vs 7.0 +/- 2.0 min), higher methohexital plasma concentrations at 20 min (6.5 vs 4.7 ng/mL) and at 30 min (5.3 vs 3.7 ng/mL), and prolonged recovery time (53.2 +/- 31.1 vs 32.4 +/- 18.5 min). The length of the rectal catheters did not significantly affect sleep-success rate, administration-sleep time, methohexital plasma concentrations, or recovery time. The use of 25 mg/kg of 1% rectal methohexital solution to induce anesthesia in children is superior to the use of 25 mg/kg of 10% methohexital solution for induction of anesthesia in children, particularly in operations 1 h or longer in duration.     

The Influence of Body Weight on Plasma Concentration of Atropine after Rectal Administration in Children

To avoid an unpleasant injection, the rectal administration of drugs to children is often to be preferred. Very little has been published on plasma concentrations of atropine given rectally. To determine whether body weight has any influence on the plasma concentrations of atropine, 18 children weighing 7.5-55.0 kg were given 0.02 mg atropine sulphate per kg rectally, and the plasma levels of atropine were determined. The mean peak plasma concentration of atropine was 1.17 ng/ml and it was reached after 33 min. In the group of smaller children (b.w. less than 15 kg) the peak plasma concentration was (0.83 ng/ml) lower than that observed in older children (1.26-1.36 ng/ml), but this difference was not statistically significant. Plasma concentrations in the group of smaller children declined significantly faster than in the other weight groups.     

Comparison of two and ten per cent rectal methohexitone for induction of anaesthesia in children

Plasma methohexitone concentrations were determined in 30 children, aged one to six years, who received 25 mg.kg-1 rectal methohexitone as either a two per cent or ten per cent solution for induction of anaesthesia. Venous blood samples were obtained 15, 30, 45 and 120 minutes following drug administration. Twenty-six of 30 children were asleep within fifteen minutes. Mean plasma methohexitone concentrations were 5.39, 4.42, 3.40 and 1.54 micrograms.ml-1 at 15, 30, 45 and 120 minutes following administration of two per cent methohexitone. Use of the ten per cent solution resulted in mean plasma methohexitone concentrations of 3.81, 3.12, 2.31 and 1.07 micrograms.ml-1 at the same time intervals. Plasma methohexitone concentrations were significantly higher at 15, 30 and 45 minutes following administration of two per cent methohexitone, when compared to the ten per cent solution.     

A basic study on cefpirome

The antibacterial activity of cefpirome (CPR), a new parenteral cephalosporin antibiotic having a cyclopentenopyridine group in the 3-position side chain, was evaluated against Neisseria gonorrhoeae and concentrations in human kidney and prostate was determined. The minimum inhibitory concentrations (MICs) of CPR against N. gonorrhoeae isolated clinically in our out-clinic (34 strains of non-PPNG and 20 of PPNG) were less than or equal to 0.003-0.1 microgram/ml in non-PPNG group and 0.006-0.1 microgram/ml in PPNG group. The 90% of MICs (MIC90s) was 0.1 microgram/ml in the non-PPNG group and 0.05 microgram/ml in the PPNG group. The concentration in the prostate was determined in 30 cases with benign prostatic hypertrophy. The maximum values was 52.8 micrograms/g at 15 minutes after administration of 1 g of CPR. The levels of CPR were gradually decreased with the lapse of time. The prostatic tissue concentration was 17.9 micrograms/g at 60 min., 10.1 micrograms/g at 180 min., 7.22 micrograms/g at 320 min. and 2.70 micrograms/g at 360 min. There was a positive correlation between concentration of the prostate and plasma collected at the time of the prostate. The concentration of CPR in human kidney, 90-100 min. after administration of 1 g to 4 cases with renal tumor, was 107-148 micrograms/g in the renal cortex, and 80.6-88.6 micrograms/g in the renal medulla. The concentration in kidney was higher than that in the plasma in all cases. In conclusion, CPR is suggested to be a useful drug for urological infection.     

Pharmacokinetics of rapacuronium in infants and children with intravenous and intramuscular administration

BACKGROUND: A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability. METHODS: Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2-240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration. RESULTS: Plasma clearance was 4.77 ml x kg(-1) x min(-1) + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.0110 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot. CONCLUSIONS: In infants and children, rapacuronium's clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.     

S-ketamine and s-norketamine plasma concentrations after nasal and i.v. administration in anesthetized children

BACKGROUND: It has been suggested that nasal administration of s-ketamine may be used to improve sedation or premedication in combination with nasal midazolam in pediatric patients. In this study we measured and compared plasma concentrations of s-ketamine and its main metabolite s-norketamine after nasal and i.v. administration in preschool children. METHODS: During sevoflurane anaesthesia, 20 children, aged 1-7 years, weight 11-25 kg, received s-ketamine 2 mg x kg(-1) either intranasally (Group IN, n = 10), or i.v. (Group IV, n = 10). Six venous blood samples were obtained up to 60 min after drug administration for measurement of s-ketamine and s-norketamine plasma concentrations. RESULTS: Plasma concentrations [mean +/- sd] of s-ketamine in group IN peaked at 355 +/- 172 ng x ml(-1) within 18 +/- 13 min vs. 1860 +/- 883 ng x ml(-1) within 3 +/- 1 min in group IV (P < 0.01). Plasma concentrations of s-norketamine in group IN peaked at 90 +/- 128 ng x ml(-1) within 50 +/- 11 min vs. 429 +/- 277 ng x ml(-1) within 40 +/- 16 min in group IV (P < 0.01). One child in group IN experienced rapid and high level s-ketamine absorption with a peak plasma concentration of 732 ng x ml(-1) after 2 min, which decreased to 274 ng x ml(-1) after 60 min. Systolic blood pressure and heart rate remained unaltered in both study groups after s-ketamine administration. CONCLUSIONS: Nasal administration of s-ketamine 2 mg x kg(-1) results in a wide spread of plasma concentrations and absorption times. Rapid and high level drug absorption after nasal drug administration is possible. The use of a pulse oximeter and continuous observation after nasal administration of s-ketamine for pediatric premedication is recommended.     

Pharmacokinetics of two per cent rectal methohexitone in children

Plasma methohexitone concentrations were determined in 60 children, aged one to six years, following administration of 15 mg.kg-1, 20 mg.kg-1, 25 mg.kg-1 or 30 mg.kg-1 two per cent rectal methohexitone. Time to the onset of sleep was determined by a blinded observer and venous blood samples obtained 15, 30, 45 and 120 minutes following drug administration. Fifty of 60 children were asleep within 15 minutes. Nine of the ten children that did not fall asleep were sedate and could be separated easily from their parents to undergo inhalational induction of anesthesia. Time to the onset of sleep was inversely related to the dose of rectal methohexitone administered. Sleep was achieved more reliably following the use of 25 to 30 mg.kg-1 rectal methohexitone. In addition, plasma methohexitone concentrations following 30 mg.kg-1 rectal methohexitone were significantly higher for up to 120 minutes following drug administration than the plasma concentrations achieved after 15 mg.kg-1 or 20 mg.kg-1 methohexitone. There was no difference in the incidence of complications. The authors recommend that clinical circumstances be carefully considered and the dose of rectal methohexitone administered be individualized to meet the specific anaesthetic requirements of each child.     

Clonidine-induced analgesia in postoperative patients: epidural versus intramuscular administration

To compare the analgesic efficacy and plasma concentration of intramuscular (IM) versus epidural (EP) clonidine, 20 patients recovering from orthopedic or perineal surgery were randomly divided into two groups of ten. Clonidine (2 micrograms/kg) was administered epidurally in group 1 and intramuscularly in group 2. Analgesia was assessed using a visual analog scale (VAS) over a period of 6 h following clonidine administration. Venous blood samples were obtained at specific intervals for radioimmunoassay determination of plasma clonidine concentrations. The maximum reduction in VAS pain score was 78.5 +/- 20.6% in the EP group and 68.1 +/- 31.5% in the IM group (NS). Onset of analgesia was similar (within 15 min of injection), but duration tended to be longer after epidural than intramuscular administration (208 +/- 87 min vs. 168 +/- 95 min, mean +/- SD, P greater than 0.05). The peak plasma clonidine concentration after EP injection was 0.82 +/- 0.22 ng/ml and 1.02 +/- 0.76 ng/ml after IM injection. Hypotension, bradycardia, and drowsiness occurred with both methods of administration. None of these effects required treatment. Thus, in postoperative patients clonidine produces similar analgesia and side effects after parenteral or EP administration.     

Plasma concentrations of midazolam in children following intranasal administration

Nasally administered midazolam appears to be a useful method for rapidly sedating children prior to the induction of anesthesia. We determined the peak plasma concentrations after intranasal administration of midazolam and compared this to plasma concentrations achieved after intravenously administered midazolam in 18 children between the ages of 14 months and 5 yr, who underwent elective closure of an asymptomatic atrial septal or ventricular septal defect. Preanesthetic medication was at the discretion of the attending anesthesiologist. Induction of anesthesia was with halothane in N2O and O2 via mask, and tracheal intubation was performed after the administration of fentanyl or sufentanil plus pancuronium. Anesthesia was maintained with these agents, and augmented with halothane or isoflurane. As soon as arterial access was established, the patient received 0.1 mg/kg of either intranasal or intravenous midazolam. Midazolam concentrations were measured by gas chromatography-mass spectrometry. Intranasal midazolam achieved its peak plasma concentration of 72.2 +/- 27.3 ng/ml in 10.2 +/- 2 min. Ten minutes after the administration of midazolam, the mean plasma concentration in the intranasal midazolam group was 57% of the concentrations in the group receiving midazolam intravenously. These results confirm the clinical impression that intranasal administration of midazolam rapidly achieves sedative plasma concentrations in children.     

Cardiovascular effects of rectal methohexital in children.

STUDY OBJECTIVE: To define the cardiovascular effects of rectal methohexital in children with normal cardiac function. DESIGN: Cardiovascular evaluation of each patient was performed before and after medication. Each patient's predrug results were used as control measurements for comparison with measurements made after methohexital administration. SETTING: Inpatient operating room induction area in a privately endowed philanthropic children's hospital. PATIENTS: Forty-seven children age 35 +/- 22 months (mean +/- SD) scheduled for elective orthopedic or plastic surgery, free of cardiac or pulmonary disease, and receiving no medication with central nervous system activity. INTERVENTIONS: Control measurements of heart rate (HR), blood pressure (BP), and echocardiographic evaluations were obtained on the day before scheduled surgery. Repeat measurements were performed after the onset of methohexital-induced sleep. The time span of the measurements was designed to include the period of peak plasma methohexital concentration. In the preoperative holding area, 30 mg/kg of a 10% methohexital solution was administered rectally. If sleep did not occur in 15 minutes, an additional 15 mg/kg was given. MEASUREMENTS AND MAIN RESULTS: HR increased markedly after rectal methohexital [126 +/- 23 beats per minute (bpm) to 144 +/- 21 bpm, p less than 0.001], and stroke volume (SV) decreased (24 +/- 9 ml to 21 +/- 8 ml, p less than 0.01). There were no significant changes in BP or cardiac index. The shortening fraction and ejection fraction remained within the normal range for this age-group. CONCLUSIONS: Rectal methohexital induces sleep in healthy pediatric patients with minimal cardiovascular side effects. The primary effects are increased HR and decreased SV.     

The pharmacokinetics of bupivacaine when injected intra-articularly after knee arthroscopy

Bupivacaine pharmacokinetics were determined in 11 patients receiving the drug intra-articularly after knee arthroscopy performed under general anesthesia. Forty ml 0.25% bupivacaine was given at the end of surgery and the thigh tourniquet was released 2 to 3 minutes after injection. Blood samples were obtained up to 5 hours after tourniquet release and plasma bupivacaine concentrations were determined. Pharmacokinetic parameters determined were (mean +/- SD): volume of distribution (Vd beta) 206 +/- 88 L, clearance (Cl) 0.816 +/- 0.378 L/min, terminal half-life (T1/2) beta 189 +/- 84 minutes, absorption rate constant (ka) 9.92 +/- 6.79/min, estimated peak plasma concentrations (Cpmax) 0.48 +/- 0.20 micrograms/mL, and time to peak concentration (tmax) 43.4 +/- 23.1 minutes. Results indicate that injections of 100 mg bupivacaine intra-articularly after knee arthroscopy produce peak blood concentrations within the first hour after surgery, and that these will be well below concentrations associated with toxic reactions. Peak concentrations can be minimized with shorter tourniquet inflation times and with longer intervals between injection and tourniquet release.     

The chemical and physical stability of a 1:1 mixture of propofol and methohexital

Anesthetic drugs are frequently mixed or coadministered to optimize anesthetic effects while minimizing adverse effects. Methohexital advantages include its low cost and rapid onset, while propofol provides improved airway anesthesia and extremely rapid clearance from the plasma. Therefore, a mixture of these agents might well be superior to either drug given alone. We wished to determine whether a mixture of methohexital and propofol is chemically and physically stable. A 1:1 mixture of propofol 10 mg/ml and methohexital was prepared. At times varying from 0 to 48 hours, mixtures with an internal standard of thymol kept at room temperature were thrice extracted with a 2:1 v/v mixture of diethyl ether:pentane, dried under nitrogen, and treated overnight with bis-trimethylsilyl-trifluoroacetamide. The resultant derivatives were transferred to microsample vials and analyzed by GC-MS. Drug stability was quantified by electronic integration of peak areas representing characteristic ions for each drug. For each sample, the peak area of the methohexital ion (m/z 239) or propofol ion (m/z 235) relative to the corresponding thymol ion (m/z 207) served as an index of the concentration of the drug in the sample. At times varying from 0 to 48 hours, mixtures without thymol were used to determine mean droplet size of the particles. This was accomplished using both an Accusizer and a Nicomp 370 Particle Sizer. One way ANOVA tested for significant changes in drug concentrations and mean particle size as a function of time. There was no significant breakdown of propofol or methohexital when combined in a 1:1 mixture and allowed to stand for 48 hours, nor was there an increase in particle size suggestive of emulsion instability. We concluded that a 1:1 mixture of propofol and methohexital was stable up to 48 hours after mixing.     

Pharmacotherapy of ventricular fibrillation. A prospective study in an emergency medical service

This prospective study investigated the effects of standard pharmacotherapy in out-of-hospital ventricular fibrillation (VF) after i.v. or endobronchial (e.b.) administration of epinephrine and lidocaine. METHODS. Only patients presenting with out-of-hospital VF were included in this study, whereby VF of noncardiac origin was excluded. Cardiopulmonary resuscitation (CPR) was performed according to the guidelines of the American Heart Association. Basic life support was initiated by Emergency Medical Service (EMS) technicians. The first step of advanced life support was immediate defibrillation by the EMS physician. Epinephrine was given in doses of 2.5 mg e.b. or 1.0 mg i.v. If indicated, patients received 200-500 mg lidocaine e.b. or 100 mg i.v. The course of CPR was tape-recorded and 2-3 blood samples were taken from each patient for drug monitoring. Plasma levels of epinephrine and lidocaine were measured by high-pressure liquid and gas chromatography, respectively, and then correlated to the course of CPR. RESULTS. Forty-seven patients presented VF on arrival of the EMS physician. Restoration of spontaneous circulation was achieved in 64% (Table 3), and 30% of the patients were discharged from hospital without major neurologic deficits. Immediate defibrillation before initiation of pharmacotherapy produced a success rate of 15.8%, whereas defibrillation after drug therapy was successful in 61.5% of cases. Following e.b. instillation of 2.5 mg epinephrine (Fig. 1), median peak concentrations of epinephrine (40.2, range 4.0-79.8 ng/ml) were reached after 3-4 min and plasma levels greater than or equal to 10 ng/ml were seen for 20 min. After i.v. injection of 1.0 mg epinephrine (Fig. 2) maximum concentrations (71.6, range 4.7-104.2 ng/ml) were measured after 1-2 min and plasma levels decreased below 10 ng/ml after 10 min. Following e.b. instillation of 400-500 mg lidocaine mean lidocaine concentrations within the therapeutic range (2-5 micrograms/ml) were reached after 4-5 min and remained within these limits for 20-30 min. Peak concentrations were obtained after 12 min. Doses of 200-320 mg lidocaine e.b. failed to achieve therapeutic plasma levels (Fig. 3). Regarding the pharmacodynamic aspects of drug therapy, 22.5% of the initial survivors were resuscitated from VF without therapeutic epinephrine, presenting with mean endogenous epinephrine concentrations of 7.1 ng/ml, 51.6% of patients were resuscitated after epinephrine therapy with plasma concentrations greater than 20 ng/ml. In only 1 case could a relationship be demonstrated between the administration of lidocaine and resuscitation success. CONCLUSION. In CPR, the e.b. administration of epinephrine and lidocaine is a reliable alternative to the i.v. injection route of these drugs. Recommended doses are 2.5 mg for epinephrine and 400-500 mg for lidocaine. Resuscitation from VF requires immediate epinephrine therapy if initial defibrillation is not successful. Lidocaine has no effect on resuscitation from VF and therefore should be used specifically for antiarrhythmic therapy after restoration of spontaneous circulation.     

A randomised double-blind study of interpleural analgesia after cholecystectomy

Continuous interpleural analgesia provided by 4 hourly injections of 20 ml bupivacaine 0.5% with adrenaline 5 micrograms/ml was compared with placebo in a randomised, double-blind study after cholecystectomy. All patients self-administered intravenous morphine using a patient-controlled analgesia device. There was a highly significant difference in mean morphine consumption between the groups (72 mg as compared with 22 mg). Visual analogue pain scores tended to be lower in the bupivacaine group throughout and this was significant at 2 hours. Respiratory function measurements were not significantly different between the groups. The mean peak venous plasma bupivacaine concentration after the sixth dose was 3.03 micrograms/ml and no symptoms suggestive of local anaesthetic toxicity occurred. It is concluded that this regimen can provide effective and continuous analgesia after cholecystectomy and that combined administration of interpleural bupivacaine and systemic morphine is more effective than morphine alone in the immediate postoperative period. The doses of bupivacaine required for optimal use of the technique lead to significant total plasma bupivacaine concentrations within 24 hours.     

Pharmacokinetics of Rapacuronium in Infants and Children with Intravenous and Intramuscular Administration

Background: A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability.

Methods: Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2-240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration.

Results: Plasma clearance was 4.77 ml [middle dot] kg-1 [middle dot] min-1 + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min-1 (72.4% of absorbed drug) and 0.0110 min-1 (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot.     

Fentanyl does not alter the "sleep" plasma concentration of thiopental.

Thiopental and fentanyl are commonly combined for induction of anesthesia. The effect of an analgesic concentration of fentanyl on the plasma concentration of thiopental to induce sleep was studied in 46 unpremedicated patients. As a measure of drug effect, sleep (the lack of response to open eyes to a verbal command) was used. Forty-six patients were randomized to receive thiopental infused to one of several predetermined plasma concentrations. Twenty-two of these patients also received a fentanyl infusion to a desired analgesic concentration of 1 ng/mL. Thiopental and fentanyl were infused by means of a pharmacokinetic model-driven infusion device (computer-assisted continuous infusion, CACI). Venous blood samples were taken from the contralateral antecubital fossa at 5 and 10 min after the start of the infusion. At 10 min, the patients' names were firmly spoken, and they were instructed to open their eyes. If they did not respond to this command, they were considered to be asleep. Only patients in whom the 5- and 10-min measured plasma concentrations of thiopental and fentanyl, respectively, were within +/- 30% of each other were used for the determination of the Cp50(asleep), the plasma concentration at which 50% of the patients were asleep. The Cp50(asleep) with and without fentanyl was calculated by logistic regression. The Cp50(asleep) for patients in whom concentrations were maintained within +/- 30% for thiopental alone (n = 17) was 7.32 micrograms/mL (95% confidence interval, 5.53-10.95); for thiopental in the presence of fentanyl (n = 18 with a measured fentanyl concentration of 1.27 +/- 0.5 ng/mL), this was 7.22 micrograms/mL (95% confidence interval, 4.83-10.15).(ABSTRACT TRUNCATED AT 250 WORDS)     

Platinum distribution in malignant glioma following intraoperative intravenous infusion of carboplatin

The objective of this paper was to determine the time course and extent of platinum uptake into human malignant glioma tissue. An intraoperative, intravenous infusion of carboplatin was given to nine patients (seven glioblastoma and two anaplastic glioma) undergoing tumour excision. Carboplatin dosage was calculated individually to achieve a target systemic free carboplatin exposure. Tumour and peritumoural tissue was harvested at timed intervals following carboplatin administration. Plasma and tumour platinum concentrations were measured by graphite furnace flameless atomic absorption spectrophotometry. Histological examination was also performed on a piece of each tissue sample. The mean carboplatin dose administered was 783, SEM 56 mg (range 485-903). Plasma pharmacokinetics showed a typical elimination curve. The mean peak plasma platinum concentration was 44, SEM 5 micrograms/ml (range 27-74). The mean total elemental plasma platinum area under the curve (AUC) was 9.0, SEM 1.4 mg/ml/min. Platinum was detected in 61 tumour samples, the mean peak concentration being 13 SEM 2 micrograms/g (range 5-21). Platinum was also detected in peritumoural brain and necrotic tumour. No correlation was apparent between the degree of necrosis in each tumour specimen and tumour platinum concentration. Platinum concentrations achieved in tumour were similar to levels that would be cytotoxic for glioma cells in vitro. The results of this study have implications for future studies using capillary permeability modifying agents as adjuncts to brain tumour chemotherapy.     

Arterial and venous pharmacokinetics of ropivacaine with and without epinephrine after thoracic paravertebral block

BACKGROUND: Animal and volunteer studies indicate that ropivacaine is associated with less neurologic and cardiac toxicity than bupivacaine. Ropivacaine may offer advantages when used for thoracic paravertebral block. This study was designed to describe the pharmacokinetics of ropivacaine after thoracic paravertebral block. METHODS: Twenty female patients undergoing elective unilateral breast surgery were randomly assigned to receive a single bolus thoracic paravertebral injection of 2 mg/kg ropivacaine, with or without 5 mug/ml epinephrine. Simultaneous arterial and venous blood samples were obtained for plasma ropivacaine assay. Data were analyzed with NONMEM, using two possible absorption models: conventional first-order absorption and absorption following the inverse gaussian density function. RESULTS: Epinephrine reduced the peak plasma concentrations and delayed the time of peak concentration of ropivacaine in both the arterial and venous blood. The time course of drug input into the systemic circulation was best described by two inverse gaussian density functions. The median bioavailability of the rapid component was approximately 20% higher when epinephrine was not used. The mean absorption times were 7.8 min for the rapid absorption phase and 697 min for the slow absorption phase, with wide dispersion of the absorption function for the acute phase. The half-time of arterial-venous equilibration was 1.5 min. CONCLUSION: The absorption of ropivacaine after thoracic paravertebral block is described by rapid and slow absorption phases. The rapid phase approximates the speed of intravenous administration and accounts for nearly half of ropivacaine absorption. The addition of 5 mug/ml epinephrine to ropivacaine significantly delays its systemic absorption and reduces the peak plasma concentration.     

Methohexital Impairs Osmoregulation: Studies in Conscious and Anesthetized Volume-expanded Dogs

Background: Anesthetic agents influence central regulations. This study investigated the effects of methohexital anesthesia on renal and hormonal responses to acute sodium and water loading in dogs in the absence of surgical stress.

Methods: Fourteen experiments (two in each dog) were performed in seven well-trained, chronically tracheotomized beagle dogs kept in highly standardized environmental and dietary conditions (2.5 mmol sodium and 91 ml water/kg body weight daily). Experiments lasted 3 h, while the dogs were conscious (7 experiments) or, after 1 h control, while they were anesthetized (7 experiments) with methohexital (initial dose 6.6 mg/kg body weight and maintenance infusion 0.34 mg *symbol* min sup -1 *symbol* kg sup -1 body weight) over a period of 2 h. In both experiments, extracellular volume expansion was performed by intravenous infusion of a balanced isoosmolar electrolyte solution (0.5 ml *symbol* min sup -1 *symbol* kg sup -1 body weight). Normal arterial blood gases were maintained by controlled mechanical ventilation. In another five dogs the same protocol was used, and vasopressin (0.05 mU *symbol* min sup -1 *symbol* kg sup -1 body weight) was infused intravenously during methohexital anesthesia.

Results: Values are given as means. During methohexital anesthesia, mean arterial pressure decreased from 108 to 101 mmHg, and heart rate increased from 95 to 146 beats/min. Renal sodium excretion decreased; urine volume increased; and urine osmolarity decreased from 233 to 155 mosm/l, whereas plasma osmolarity increased from 301 to 312 mosm/l because of an increase in plasma sodium concentration from 148 to 154 mmol/l. Plasma renin activity, plasma aldosterone concentration, plasma atrial natriuretic peptide, and plasma antidiuretic hormone concentrations (range 1.8-2.8 pg/ml) did not change in either protocol. In the presence of exogenous vasopressin (antidiuretic hormone 3.3 pg/ml), water diuresis did not occur, and neither plasma osmolarity nor the plasma concentration of sodium changed.     

Cumulation of bupivacaine, desbutylbupivacaine and 4-hydroxybupivacaine during and after continuous interscalene brachial plexus block

Desbutylbupivacaine (DBB) and 4-hydroxybupivacaine (4-OHB) are major metabolites of bupivacaine. They may cumulate during continuous infusion blocks. In the present study, all patients received an interscalene brachial plexus block with 20-28 ml of 0.75% bupivacaine plus adrenaline. A catheter was introduced into the interscalene space, and an infusion of 0.25% bupivacaine (5-9 ml/h) was started and continued with ten patients for 24 h and with another ten for 48 h. An infiltration block of the suprascapular and intercostobrachial nerves was performed using 0.5% bupivacaine. Before surgery, light general anaesthesia was induced. For measurement of plasma concentrations of bupivacaine, DBB and 4-OHB blood samples were taken before the block and 30 min, 3 h, 24 h and 48 h after the blocks as well as 30 min, 1 h, 2 h, 4 h and 6 h after the termination of the infusions. The highest plasma concentrations of bupivacaine, mean 1.84 micrograms/ml, were measured 30 min after the block. There was a slight but statistically significant rise in the bupivacaine concentrations between 24 and 48 h. The bupivacaine concentration decreased by 54% and 45%, on average, during the first 6 h following the 24- and 48-h infusions, respectively. On average, the highest DBB concentrations were measured 2 h after the 24-h infusion (0.31 +/- 0.18 micrograms/ml) and 30 min after the 48-h infusion (0.33 +/- 0.13 micrograms/ml). The highest 4-OHB concentrations were measured 1 h (0.18 +/- 0.09 micrograms/ml) and 30 min (0.20 +/- 0.05 micrograms/ml) after the 24- and 48-h infusions, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)