Biomedical subjects

J W van Kleef

Publications and source records attributed to J W van Kleef.

At least 19 recordsLinked to original sources

PubMed2004

Effect of age on the clinical profile and systemic absorption and disposition of levobupivacaine after epidural administration.

BACKGROUND: Pharmacokinetic and/or pharmacodynamic changes, which may occur with increasing age, could alter the clinical profile of the new local anaesthetic levobupivacaine. We investigated the effect of age on the absorption and disposition kinetics and the neural block characteristics after epidural administration of levobupivacaine 0.75%. METHODS: Thirty-one patients were enrolled in one of three age groups (Group 1, 18-44 yr; Group 2, 45-70 yr; Group 3, >70 yr). Twenty-five minutes after epidural administration of levobupivacaine (127.5 mg), they received approximately 25 mg deuterium-labelled levobupivacaine (D(3)-levobupivacaine) intravenously. Arterial blood samples were collected until 24 h after the epidural administration. Plasma concentrations were determined using liquid chromatography mass spectrometry. Plasma concentration-time data were analyzed by compartmental and non-compartmental analysis. Assessments of analgesia and motor block were made at set intervals until complete regression of the block. RESULTS: The upper levels of analgesia in the two oldest groups of patients were 3 dermatomes (95% confidence interval (95% CI): 0.5-5.0 dermatomes) higher than in the youngest group. The fraction absorbed (F(1)) was 0.07 (95% CI: 0.02-013) smaller and the absorption half-life (t(1/2,a1)), characterizing the initial fast absorption phase, 3.6 min (95% CI: 0.8-6.4) shorter in the oldest group compared with the youngest group. CONCLUSIONS: Age influences the pharmacokinetics, in particular the early absorption kinetics, and the neural block characteristics after epidural administration of levobupivacaine. Changes in the upper level of analgesia are best explained by anatomical considerations and possibly pharmacodynamic changes in the elderly.

Adult↗

PubMed2004

The systemic absorption and disposition of levobupivacaine 0.5% after epidural administration in surgical patients: a stable-isotope study.

BACKGROUND AND OBJECTIVE: Absorption and disposition kinetics can be studied with a stable-isotope method. The aim of this study was to validate a stable-isotope method for levobupivacaine and to derive the relevant pharmacokinetics after epidural administration. METHODS: Eight volunteers (18-32 yr) received approximately 23 mg of both levobupivacaine and deuterium-labelled levobupivacaine simultaneously by intravenous infusion. Venous blood samples were taken for 8 h. Fifteen patients (23-85 yr) received 19 mL levobupivacaine 0.5% (including a 3 mL test dose) epidurally and, 25 min later, approximately 25 mg deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial blood samples were collected for 24 h. Plasma concentrations were determined using liquid chromatography-mass spectrometry. Plasma concentration-time data were analysed by compartmental and non-compartmental analysis. RESULTS: Based on the ratio of the normalized areas under the curve of unlabelled and deuterium-labelled levobupivacaine in volunteers, as determined by both compartmental (mean ratio: 1.02, 90% CI: 1.00-1.04) and non-compartmental analysis (mean ratio: 1.02, 90% CI: 1.00-1.03) the two formulations were considered equivalent. In surgical patients the elimination half-life (mean +/- SD: 196 +/- 65 min), total body clearanc (349 +/- 114 mL min(-1)) and volume of distribution at steady state (56 +/- 14 L), derived by compartmental analysis, were similar to those obtained by non-compartmental analysis. The absorption was bi-phasic. The fractio absorbed and half-life of the fast absorption process were 0.22 +/- 0.06 and 5.2 +/- 2.7 min, respectively. Th values for the slow absorption process were 0.84 +/- 0.14 and 386 +/- 91 min, respectively. CONCLUSIONS: D3-levobupivacaine is pharmacokinetically equivalent to unlabelled levobupivacaine and can be used to study the absorption and disposition kinetics after perineural administration of levobupivacaine in a single experiment.

Adolescent↗

PubMed2001

Mortality associated with anaesthesia: a qualitative analysis to identify risk factors.

From a prospectively defined cohort of patients who underwent either general, regional or combined anaesthesia from 1 January 1995 to 1 January 1997 (n = 869 483), all consecutive patients (n = 811) who died within 24 h or remained unintentionally comatose 24 h after anaesthesia were classified to determine a relationship with anaesthesia. These deaths (n = 119; 15%) were further analysed to identify contributing aspects of the anaesthetic management, other factors and the appropriateness of care. The incidence of 24-h peri-operative death per 10 000 anaesthetics was 8.8 (95% CI 8.2-9.5), of peri-operative coma was 0.5 (0.3-0.6) and of anaesthesia-related death 1.4 (1.1-1.6). Of the 119 anaesthesia-related deaths, 62 (52%) were associated with cardiovascular management, 57 (48%) with other anaesthetic management, 12 (10%) with ventilatory management and 12 (10%) with patient monitoring. Inadequate preparation of the patient contributed to 30 (25%) of the anaesthesia-related deaths. During induction of anaesthesia, choice of anaesthetic technique (n = 18 (15%)) and performance of the anaesthesiologist (n = 8 (7%)) were most commonly associated with death. During maintenance, the most common factors were cardiovascular management (n = 43 (36%)), ventilatory management (n = 12 (10%)) and patient monitoring (n = 12 (10%)). In both the recovery and the postoperative phases, patient monitoring was the most common factor (n = 12 (10%) for both). For cardiovascular, ventilatory and other anaesthetic management, human failure contributed to 89 (75%) deaths and organisational factors to 12 (10%). For inadequate patient monitoring, human factors contributed to 71 (60%) deaths and organisational factors to 48 (40%). Other contributing factors were inadequate communication (30 deaths (25%) for all four aspects of the anaesthetic management) and lack of supervision (particularly for ventilatory management). Inadequate care was delivered in 19 (16%) of the anaesthesia-related deaths with respect to cardiovascular management, in 20 (17%) with respect to ventilatory management, in 18 (15%) with respect to patient monitoring and in 23 (19%) with respect to other anaesthetic management.

Anesthesia↗

PubMed2001

Spinal anaesthesia with 0.5% hyperbaric bupivacaine in elderly patients: effects of duration spent in the sitting position.

Sixty patients, aged 65-84 yr, undergoing minor urological surgery under spinal anaesthesia remained sitting for 2 (group 1, n = 15), 5 (group 2, n = 15), 10 (group 3, n = 15), or 20 (group 4, n = 15) min after completion of the subarachnoid administration of 3 ml of a 0.5% hyperbaric bupivacaine solution. They were then placed in the supine position. Analgesia levels were assessed bilaterally using pinprick. Motor block was scored using a 12-point scale. Systolic and diastolic arterial pressures and heart rate were also recorded. Twenty minutes after the injection the upper analgesia levels were lower (P<0.05) in group 4 (median T9.0) than in the groups 1-3 (medians T6.6-T8.5). The highest obtained levels (medians T5.7-T8.0) did not differ between the groups, but occurred later (P<0.05) in group 4 (median 35 min) than in groups 1-3 (medians 19-24 min). There were no significant differences in the maximum degree of motor block or haemodynamic changes between the four study groups.

Aged↗

PubMed2000

Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery: pharmacokinetic evaluation.

BACKGROUND: Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia. METHODS: Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of alpha1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured. RESULTS: Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2) after 72 h infusion. alpha1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values. CONCLUSIONS: Postoperative increases in plasma alpha1-acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, causing divergence of total and unbound plasma concentrations.

Adult↗

PubMed1999

Target-controlled infusion of alfentanil for postoperative analgesia: contribution of plasma protein binding to intra-patient and inter-patient variability.

We have examined the influence of plasma protein binding on inter-individual and intra-individual variability in the effective postoperative analgesic concentration (EAC) of alfentanil and on the performance of the target-controlled infusion system used. Ten patients received standardized anaesthesia and target-controlled alfentanil for postoperative analgesia. Analgesia was assessed using a visual analogue scale (VAS). Plasma protein binding of alfentanil was assessed at four different times (on arrival in the recovery room, at 21:00 on the day of surgery and at 09:00 and 21:00 on the first postoperative day). Bias and inaccuracy were examined on the day of surgery and on the first postoperative day. Unbound fractions of alfentanil varied from 5 to 15% and varied in time. In general, the unbound fractions on the day of surgery were higher than those on the first postoperative day. Thirty-nine percent of inter-individual variability in the EAC of alfentanil (range 33-140 ng ml-1) at the onset of therapy could be explained by protein binding. At the other observation times, correlations between unbound fraction and EAC were only moderate. Bias on the day of surgery was -19% and 12% on the first postoperative day (ns). Inaccuracy was 23% and 18%, respectively (ns). We conclude that inter-individual variations in plasma protein binding can explain a significant portion of inter-individual variability in the EAC of alfentanil in the early postoperative phase.

Adolescent↗

PubMed1999

The epidural "top-up" in combined spinal-epidural anesthesia: the effect of volume versus dose.

UNLABELLED: The reinforcement of anesthesia by an epidural "top-up" in combined spinal-epidural anesthesia may be explained by a dual mechanism: a volume effect compressing the dural sac and a local anesthetic effect. The purpose of our study was to investigate the relative importance of each of these factors. Fifty patients scheduled for lower limb orthopedic surgery under combined spinal-epidural anesthesia were randomly allocated to one of five groups comprising 10 patients each. Using a needle-through-needle technique, all patients received a subarachnoid injection of 10 mg of plain bupivacaine and an epidural catheter. After the maximal level of sensory blockade as a result of the subarachnoid injection had been established, an epidural top-up was given according to the randomization code. Patients in Group 1 received 10 mL of bupivacaine 0.25%; patients in Group 2 received 10 mL of saline; patients in Group 3 received 5 mL of bupivacaine 0.5%; patients in Group 4 received 5 mL of saline; and patients in Group 5 received no epidural top-up. The maximal level of sensory blockade was then assessed for an additional 30 min. In Groups 1-4, the maximal level of sensory blockade increased significantly, whereas there was no significant increase in Group 5. There was no significant difference in the increase in the maximal level of sensory blockade among Groups 1-4. We conclude that, under the conditions of our study, there is no difference between 5 and 10 mL with regard to the volume effect of an epidural top-up in combined spinal-epidural anesthesia and that to produce an additional local anesthetic effect with bupivacaine, the dose must be larger than 25 mg. IMPLICATIONS: In combined spinal-epidural anesthesia, an epidural "top-up" may increase the maximal level of sensory blockade by means of a volume effect and a local anesthetic effect. In this study, volumes of 5 and 10 mL produced a similar increase, and 25 mg of bupivacaine was insufficient to produce an additional local anesthetic effect.

Adolescent↗

PubMed1999

Pharmacokinetics of prilocaine after intravenous administration in volunteers: enantioselectivity.

BACKGROUND: Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous administration of the racemate. METHODS: Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis. RESULTS: The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P < 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P < 0.0001) than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min) was shorter (P < 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)-prilocaine (155+/-59 min; P < 0.005). CONCLUSIONS: The pharmacokinetics of prilocaine are enantioselective. The difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.

Adult↗

PubMed1998

Dutch case-control study of anaesthesia-related morbidity and mortality. Rationale and methods.

To date, anaesthesia-related mortality, morbidity and risk factors have almost exclusively been studied qualitatively rather than quantitatively. Therefore, knowledge of the relative risk associated with many anaesthesia-related factors is still lacking. Recently, a quantitative study of the determinants and prevention of morbidity and mortality in anaesthesia was started in the Netherlands. Its objective is to study severe peri-operative morbidity and mortality as a function of anaesthesia-related risk factors. The study is designed as a case-control study within a prospectively defined cohort. The cohort comprises all patients undergoing an anaesthetic procedure, either general, regional or a combination, in one of 61 hospitals between 1 January 1995 and 1 January 1997. A 'case' is a patient who dies within 24 h of undergoing an anaesthetic procedure or who remains comatose 24 h after an anaesthetic procedure. A 'control' patient is a randomly chosen patient who has undergone anaesthesia and is matched for gender and age. The present report discusses the study protocol.

Anesthesia↗

PubMed1998

Pharmacokinetics of the enantiomers of bupivacaine and mepivacaine after epidural administration of the racemates.

UNLABELLED: We investigated the pharmacokinetics of the enantiomers of bupivacaine and mepivacaine after epidural injection of the racemate of each drug into six surgical patients. After epidural administration of either bupivacaine/HCl (115 mg) or mepivacaine/HCl (460 mg), blood samples were collected for 24 h. Unbound fractions were determined by using ultrafiltration for bupivacaine and equilibrium dialysis for mepivacaine. Concentrations in plasma, ultrafiltrate, and dialysate were determined by using stereoselective high-performance liquid chromatography. Peak plasma concentrations of R(+)-bupivacaine (389 +/- 93 ng/mL) and R(-)-mepivacaine (1350 +/- 430 ng/mL) were smaller than those of S(-)-bupivacaine (449 +/- 109 ng/mL, P < 0.0001) and S(+)-mepivacaine (1740 +/- 490 ng/mL, P < 0.002), respectively. However, the unbound peak concentrations of R(+)-bupivacaine (20 +/- 11 ng/mL) were larger than those of S(-)-bupivacaine (15 +/- 9 ng/mL, P < 0.005); unbound peak concentrations of R(-)-mepivacaine (485 +/- 158 ng/mL) and S(+)-mepivacaine (460 +/- 139 ng/mL) did not differ. These observations reflect differences in the systemic disposition (distribution and elimination) of the enantiomers, because the systemic absorption was not enantioselective with either drug. This study supports the opinion that the use of single enantiomers, rather than racemates, is preferable, particularly for bupivacaine. IMPLICATIONS: Measurements of the plasma concentrations of the enantiomers of bupivacaine and mepivacaine after epidural administration of the racemates demonstrated that the systemic disposition, but not the systemic absorption, of these drugs is enantioselective and supports the opinion that the use of single enantiomers, rather than racemates, is preferable.

Adult↗

PubMed1998

Alfentanil as an adjuvant to epidural bupivacaine in the management of postoperative pain after laparotomies: lack of evidence of spinal action.

UNLABELLED: In this double-blind study, we compared the efficacy of epidural versus i.v. administration of alfentanil in combination with small-dose bupivacaine for postoperative pain relief. Thirty-two patients were randomly allocated to one of two study groups. Patients from both groups received an epidural loading dose of 60 mg of bupivacaine (12 mL of 0.5%). Subsequently, patients in the epidural (EPI) group received an infusion (8 mL/h) of 0.125% bupivacaine (10 mg/h) plus alfentanil (0.36 mg/h) and an i.v. infusion (8 mL/h) of NaCl 0.9%. Patients in the i.v. group received an epidural infusion (8 mL/h) of 0.125% bupivacaine (10 mg/h) and an i.v. infusion (8 mL/h) of alfentanil (0.36 mg/h). Infusions were maintained for 24 h. These dose regimens were such that equivalent subanalgesic plasma concentrations of alfentanil were obtained. Patient-controlled analgesia with morphine was available to both groups. Time to onset of postoperative pain and morphine consumption were used as variables to compare the two regimens. Measured plasma concentrations of alfentanil during the postoperative observation period were similar (< 20 ng/mL) in both groups. Median times to onset of postoperative pain (EPI 600 min, i.v. 360 min) and total morphine consumption (EPI 11 mg, i.v. 10 mg) did not differ between the groups (P > 0.2). We conclude that, in combination with epidural bupivacaine 0.125%, an i.v. infusion of alfentanil is equally effective as an epidural infusion of alfentanil if the plasma concentrations are the same. The study did not demonstrate a spinal mechanism of action for alfentanil. IMPLICATIONS: This randomized, double-blind study showed that, when combined with small-dose bupivacaine (0.125%), epidurally administered alfentanil is not more effective than i.v. administered alfentanil for postoperative pain management when the regimens are such that equivalent subanalgesic plasma alfentanil concentrations are obtained. A spinal mechanism of action for alfentanil could therefore not be demonstrated.

Adult↗

PubMed1997

Pharmacokinetics of the enantiomers of mepivacaine after intravenous administration of the racemate in volunteers.

The pharmacokinetics of R(-)-mepivacaine and S(+)-mepivacaine were investigated in 10 healthy volunteers. The volunteers received racemic mepivacaine, hydrochloride (dose 60 mg) via a 10-min intravenous infusion. Blood samples were collected at gradually increasing intervals until 8 h after the start of the infusion. Plasma concentrations of the enantiomers were determined with a stereoselective high-performance liquid chromatographic (HPLC) method. Unbound fractions of the enantiomers were determined using equilibrium dialysis. The unbound fraction of R(-)-mepivacaine (mean +/- SD: 35.6% +/- 4.5%) was larger (P < 0.0001) than that of S(+)-mepivacaine (25.1% +/- 4.6%). The total plasma clearance and steady-state volume of distribution of R(-)-mepivacaine, based on total plasma concentrations (total plasma clearance [CL] = 0.79 +/- 0.12 L/min; volume of distribution at steady state [VSS] = 103 +/- 14 L) as well as on unbound plasma concentrations (plasma clearance of unbound drug [CLu] = 2.24 +/- 0.30 L/min; volume of distribution of unbound drug at steady state [Vuss] = 290 +/- 32 L), were larger (P < 0.0001) than those of S(+)-mepivacaine (CL = 0.35 +/- 0.06 L/min; Vss = 57 +/- 7 L; CLu = 1.43 +/- 0.24 L/ min; Vuss = 232 +/- 30 L). The terminal half-life (t1/2,Z) and mean residence time (MRT) of R(-)-mepivacaine (t1/2,Z = 113 +/- 17 min; MRT = 131 +/- 15 min) were shorter than those of S(+)-mepivacaine (t1/2,Z = 123 +/- 20 min, P < 0.02; MRT = 165 +/- 24 min, P < 0.0001). This study demonstrated a marked difference in the pharmacokinetics of the enantiomers of mepivacaine. The stereoselectivity can be partially explained by a difference in the plasma protein binding of the enantiomers.

Adult↗

PubMed1996

High-performance liquid chromatographic assay of mepivacaine enantiomers in human plasma in the nanogram per milliliter range.

A method enabling quantification of R-(-)- and S-(+)-mepivacaine in human plasma in the low nanogram per milliliter range is described. The procedure involves extraction from plasma with diethyl ether, centrifugation, back-extraction into an acidified aqueous solution, washing with a mixture of pentane and isoamylalcohol, alkalinisation, followed by extraction with a mixture of n-pentane and isoamylalcohol. After evaporation of the organic phase, the residue is redissolved in the mobile phase used for the HPLC analysis, which consists of a 6.8:93.2 (v/v) isopropanol-sodium hydrogenphosphate buffer solution with the pH adjusted to 6.8 using phosphoric acid. The HPLC method has been described previously. Separation of the enantiomers is achieved with an alpha 1-AGP column and the UV detection wavelength is 210 nm. The minimal detectable concentration is ca. 3 ng/ml and the lower limit of quantification is 5 ng/ml for each enantiomer. For both enantiomers r is > 0.9995 over the plasma enantiomeric concentration range of 10.5-1053 ng/ml.

Anesthetics, Local↗

PubMed1996

Mechanism of action of an epidural top-up in combined spinal epidural anesthesia.

The purpose of this study was to elucidate the mechanism of action by which an epidural top-up reinforces anesthesia in combined spinal epidural anesthesia. Thirty patients scheduled to undergo lower limb orthopedic surgery were randomly allocated to three groups of 10 patients each. In all patients, a 16-gauge Tuohy needle was introduced into the epidural space. Using the needle through needle technique, each patient received a subarachnoid injection of 10 mg plain bupivacaine 0.5% through a long 27-gauge Whitacre spinal needle introduced into the subarachnoid space through the Tuohy needle. After withdrawal of the spinal needle, an epidural catheter was introduced into the epidural space. After the maximum level of sensory block after the subarachnoid injection had been established, an epidural top-up with 10 mL bupivacaine 0.5% (Group 1) or 10 mL saline (Group 2) was administered; patients in Group 3 received no epidural top-up. The maximum level of sensory block was then assessed for an additional 30 min. After the epidural top-up the maximum level of sensory block increased significantly by 4.8 +/- 1.6 segments in Group 1 and 2.0 +/- 2.0 segments in Group 2. In Group 3 there was a nonsignificant increase of 0.3 +/- 0.5 segments. Intergroup comparisons showed that this increase in Group 1 was significant compared with those in Groups 2 and 3, and that the increase in Group 2 was significant compared with that in Group 3. We conclude that the mechanism of action by which an epidural top-up reinforces anesthesia in combined spinal epidural anesthesia can be explained partly by an epidural volume effect and partly by an effect of the local anesthetic itself.

Adolescent↗

PubMed1996

Epidural vs. intravenous infusion of alfentanil in the management of postoperative pain following laparotomies.

BACKGROUND: This study was designed to compare the efficacy of epidural vs. intravenous administration of alfentanil for treatment of postoperative pain. METHODS: Twenty patients were randomly allocated to one of the two study groups to receive either an epidural bolus dose (0.75 mg) followed by an epidural infusion (0.36 mg/h) (EPI group) or an intravenous infusion (0.36 mg/h) of alfentanil (IV group) for 24 h. These dose regimens were chosen such that equivalent and subanalgesic plasma concentrations of alfentanil were obtained. PCA-morphine was available to both groups. Morphine consumption, pain scores measured on a Visual Analogue Scale (VAS) and the number of demands were used as variables to evaluate the efficacy of the postoperative analgesic therapy. In addition, plasma concentrations of alfentanil were measured. RESULTS: The mean plasma concentrations of alfentanil were similar and < 20 ng/ml in both groups. Total morphine consumption (EPI: 40 mg, i.v.: 43 mg), pain scores (time when the VAS-score > 3.0: EPI: median 215 min; i.v.: median 215 min) and number of valid demands (EPI: median 25; i.v.: median 34) did not differ between the groups. CONCLUSION: Compared to intravenous infusion of alfentanil epidural infusion resulting in the same plasma concentrations is not more effective in relieving postoperative pain. In view of this observation we were not able to demonstrate a spinal mechanism of alfentanil.

Adolescent↗

PubMed1995

Halothane affects ventilatory afterdischarge in humans.

In awake humans, when ventilatory stimulation is suddenly removed, the subsequent change in minute ventilation (which remains at higher levels for longer times than expected from the dynamics of the chemoreceptors) is termed ventilatory after discharge. In this study we investigated the effects of subanaesthetic concentrations of halothane on afterdischarge. The ventilatory pattern after sudden termination of brief periods (90-180 s) of isocapnic hypoxia (PE'cO2 approximately 0.1 kPa above initial resting values; PE'O2 6.5 kPa) by normoxia (PE'O2 14 kPa) was determined in healthy volunteers. Six subjects underwent 13 studies without halothane (control) and six others 10 studies during inhalation of 0.22% halothane. Isocapnic hypoxia caused a mean increase in ventilation of 10.8 (SD 2.4) litre min-1 in the control and 4.2 (2.4) litre min-1 in the halothane studies (P < 0.01). The transition to normoxia caused a slow ventilatory decay in the control and a fast decay in the halothane groups: the interval that occurred between the "last hypoxic" breath and the time required for ventilation to return to 110% of baseline was 60.7 (23) s for the control and 12.3 (6.0) s for the halothane studies (P < 0.05). Taking into consideration the different factors that determine the pattern of breathing immediately after termination of a brief period of hypoxia by normoxia (PE'O2 waveform, transport delay time between lungs and carotid bodies, time constant of the peripheral chemoreflex loop and afterdischarge), the faster ventilatory decay observed with halothane is probably related to suppression of afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Ropivacaine 0.25% versus bupivacaine 0.25% for continuous epidural analgesia in labor: a double-blind comparison.

We compared the effects of continuous epidural infusion of ropivacaine 0.25% with bupivacaine 0.25% on pain relief and motor block during labor, and on the neonate. Seventy-six full-term parturients in active labor requiring epidural analgesia were randomly allocated to receive either bupivacaine 0.25% or ropivacaine 0.25%. Fifteen minutes after a loading dose of 10 mL of the study drug, an epidural infusion with the same drug was started at 6-12 mL/h to maintain an adequate block. Top-up doses of 6-10 mL were given as required. At full cervical dilation, the epidural infusion was discontinued. The onset of pain relief (verbal scale), contraction pain (visual analog scale), intensity of motor block (modified Bromage scale), and duration of motor block were not statistically different between the groups. Apgar scores at 1 and 5 min after delivery were comparable. There was a higher proportion of the neonates in the ropivacaine group (26/31 = 84%) who had a neurologic and adaptive capacity score (NACS) > or = 35 2 h after delivery than in the bupivacaine group (18/29 = 62%). We conclude that ropivacaine 0.25% and bupivacaine 0.25% are equally effective for epidural pain relief during labor. Ropivacaine may have an advantage over bupivacaine regarding neonatal neurobehavioral performance during the first few hours after delivery, although further studies will be required to substantiate this.

Adolescent↗

PubMed1995

Computer-controlled infusion of alfentanil versus patient-controlled administration of morphine for postoperative analgesia: a double-blind randomized trial.

This study compared the efficacy of computer-controlled infusion of alfentanil (CCiA) with patient-controlled administration of morphine (PCAM) for postoperative analgesia. Twenty patients were randomly allocated to one of the two study groups to receive either an intravenous CCiA or PCAM regimen. Pain scores measured on a visual analog scale (VAS) and the number of valid demands were used as variables to evaluate the efficacy of the postoperative analgesic therapy. In addition, the bias and inaccuracy of the pharmacokinetic data set of alfentanil used in the CCiA program were examined by determining the median performance error (MDPE), and the median absolute performance error (MDAPE). The onset of satisfactory analgesia was faster (P < 0.05) in the CCiA group (median: 20 min) than in the PCAM group (median: 50 min). The total number of demands was lower (21 vs 34, P < 0.05) and the time when the VAS score was > 3.0 was shorter (P < 0.05, 12% of the time) in the CCiA group than in the PCAM group (21% of the time). The MDPE and MDAPE were 8% and 22%, respectively. The maximum alfentanil concentrations associated with pain and the minimum effective analgesic concentrations of alfentanil varied considerably both inter- and intraindividually. In conclusion, compared to a standard intravenous PCAM regimen, a CCiA is faster in onset of analgesia and is as effective in providing postoperative analgesia.

Adolescent↗