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Biomedical subjects

R L Carpenter

Publications and source records attributed to R L Carpenter.

At least 37 records · Page 2Linked to original sources
PubMed1997

A comparison of oral ketorolac and hydrocodone-acetaminophen for analgesia after ambulatory surgery: arthroscopy versus laparoscopic tubal ligation.

This multicenter study compared the analgesic efficacy and side effects of ketorolac and hydrocodone-acetaminophen when administered orally after ambulatory arthroscopic or laparoscopic tubal ligation procedures. After awakening from general anesthesia, 252 patients experiencing moderate or severe postoperative pain were randomly assigned to receive one of three analgesic treatments according to a placebo-controlled, double-blind protocol. Group 1 (n = 83) received oral ketorolac 10 mg every 6 h for up to 3 days, Group 2 (n = 82) received hydrocodone 7.5 mg plus acetaminophen 750 mg every 6 h for up to 3 days, and Group 3 (n = 87) received placebo capsules followed by ketorolac 10 mg every 6 h for up to 3 days. Severity of pain was recorded using a 4-point categorical score and visual analog scale (VAS) at 0.5 h and subsequently at hourly intervals for 6 h, as well as daily for up to 3 days. Pain relief was recorded using a 5-point categorical scale at the same time points. In the patients undergoing arthroscopic surgery, both ketorolac and hydromorphone-acetaminophen provided superior pain relief compared with the placebo. Although the categorical summed pain intensity difference (SPID), VAS SPID, and total pain relief scores were higher in the ketorolac group compared with the hydrocodone-acetaminophen group, the differences were not statistically significant. In the patients undergoing laparoscopic tubal ligation surgery, the three treatment groups displayed similar responses to the study medications. However, the ketorolac group scored higher in terms of overall tolerability than the hydrocodone-acetaminophen group. In conclusion, there was no difference in the efficacy between oral ketorolac and hydrocodone-acetaminophen combination in controlling pain after outpatient arthroscopic surgery procedures. Neither oral analgesic proved to be very effective after laparoscopic tubal ligation.

Acetaminophen↗
PubMed1997

A proposed approach to study the toxicology of complex mixtures of petroleum products: the integrated use of QSAR, lumping analysis and PBPK/PD modeling.

Mixture toxicity is a topic that has become a matter of concern during the last two decades. One of the major problems with assessing the toxicity of mixtures and the associated human and environmental risk is the large number of possible mixtures, as well as the fact that the actual mixture effect for a given set of constituents might strongly depend on the actual composition of the mixture, i.e., the ratios of the constituent, as well as their nature. This paper presents a possible approach to describe and thereby better understand the pharmacokinetics and dynamics of complex mixtures by combining quantitative structure-activity relationships to predict needed parameters, lumping to reduce the complexity of the problem, and physiologically based pharmacokinetic/pharmacodynamic modeling to integrate all this information into a complete toxicological description of the mixture. It is our hope that by presenting this conceptual approach we might be able to stimulate some criticisms and discussions in the toxicology community regarding this complex and yet very important area of research.

Animals↗
PubMed1996

The effects of electrical stimulation at different frequencies on perception and pain in human volunteers: epidural versus intravenous administration of fentanyl.

The study was performed to determine whether epidural fentanyl produced segmental sensory changes to electrical stimulation at different frequencies. Eight healthy volunteers received fentanyl 1 microgram/kg both intravenously and epidurally in a randomized, double-blind, cross-over fashion. Perception thresholds and amount of current required to elicit a predetermined level of moderate pain (Cmp) at 5,250, and 2000 Hz stimulation were measured at ipsilateral dermatomes C2 and L2 at 0, 5, 15, 30, 45, and 60 min after injection. Perceptions to 5,250, and 2000 Hz stimulation were unaffected by either intravenous or epidural fentanyl (P > 0.08). Intravenous fentanyl increased Cmp at both 5 and 250 Hz at both dermatomes (P < 0.004) and thus did not produce segmental analgesia. In contrast, epidural fentanyl increased Cmp only at the L2 dermatome and only at 5 Hz (P = 0.005). We conclude that an epidural bolus of fentanyl results in segmental spinal analgesia to transcutaneous electrical stimulation only at specific frequencies. Furthermore, pain produced by stimulation at 5 Hz may have a different pharmacology than pain produced by 250 Hz stimulation.

Adult↗
PubMed1996

Hemodynamic responses to intravascular injection of epinephrine-containing epidural test doses in adults during general anesthesia.

BACKGROUND: Epidural anesthesia is sometimes initiated during general anesthesia, yet few data exist concerning efficacy of epinephrine-containing test doses. METHODS: Thirty-six patients were randomized to receive either 0.5 MAC isoflurane, 1 MAC isoflurane, or 0.5 MAC each (1 MAC total) of isoflurane and nitrous oxide. Each subject received intravenous saline followed by three test doses containing 45 mg lidocaine with 7.5, 15, and 30 micrograms epinephrine in a randomized, double-blind fashion. Heart rate and systolic, diastolic, and mean blood pressures were measured for 5 min after injection. Positive hemodynamic criteria identifying intravascular injection were determined from peak increases in hemodynamics during administration of saline. Dose-effect relationships between epinephrine and peak increases in hemodynamics were assessed with linear regression. Minimum required doses of epinephrine to produce peak positive hemodynamic increases on average were determined from linear regression. RESULTS: Positive hemodynamic criteria were identified as increases in heart rate > or = 8 beats/min, systolic blood pressure > or = 13 mmHg, diastolic blood pressure > or = 7 mmHg, and mean blood pressure > or = 9 mmHg. Significant dose-effect relationships were observed for epinephrine and peak increases in hemodynamics (correlation coefficients ranged from 0.61-0.91). Minimum required doses of epinephrine ranged from 6 to 19 micrograms depending on hemodynamic measurement and anesthetic group. CONCLUSIONS: Hemodynamic responses to intravascular injection of test doses vary with dose of epinephrine and depth and type of general anesthetic used. Thus, the 15 micrograms epinephrine contained in the standard test dose may not be sufficient during all anesthetic conditions.

Adult↗
PubMed1995

Fentanyl prolongs lidocaine spinal anesthesia without prolonging recovery.

Lidocaine spinal anesthesia is a popular anesthetic for short procedures due to its brief duration. The addition of fentanyl may improve the quality and duration of lidocaine spinal anesthesia. Eight volunteers received plain lidocaine 5% in dextrose (50 mg) both with and without 20 micrograms of fentanyl in a randomized, double-blind, cross-over fashion. Sensory analgesia was assessed with pinprick, cold, touch, transcutaneous electrical stimulation equivalent to surgical incision, and duration of tolerance of pneumatic thigh tourniquet. Motor block was assessed with isometric force dynamometry. Regression of pinprick, touch, and cold was prolonged with fentanyl. Duration of tolerance of electrical stimulation at the umbilicus, hip, knee, and ankle was increased with fentanyl (181% increase from plain lidocaine on average; P < 0.01). Duration of tolerance of tourniquet-induced pain was increased by an average of 48% with addition of fentanyl (P = 0.02). Neither motor block nor time to void was prolonged with fentanyl. Pruritus occurred in all subjects receiving fentanyl but was treated easily and were well tolerated. We recommend the addition of 20 micrograms of fentanyl to lidocaine spinal anesthesia as a means to improve duration of sensory anesthesia without prolonging recovery of motor function or time to micturition.

Adult↗
PubMed1995

The effects of epinephrine on lidocaine spinal anesthesia: a cross-over study.

The efficacy of epinephrine for prolonging the duration of lidocaine spinal anesthesia remains controversial. Seven volunteers were randomized in a double-blind manner to receive two 50-mg lidocaine (in dextrose 7.5%) spinal anesthetics with and without epinephrine (0.2 mg). Sensory analgesia was assessed with transcutaneous electrical stimulation (TES) equivalent to surgical incision and compared to standard pinprick dermatomal levels. Motor block was assessed with surface electromyography (EMG) and isometric force dynamometry. Intravenous fluids were administered by a standardized regimen, and time until ability to void was determined. Addition of epinephrine significantly prolonged duration of surgical anesthesia in the lumbar and sacral dermatomes by an average of 16-29 min (P = 0.03), but not in thoracic dermatomes. Although there was a trend toward prolongation of motor block with addition of epinephrine, this did not reach statistical significance. Epinephrine significantly prolonged duration until ability to void from 153 +/- 27 to 234 +/- 50 min (P = 0.0001). Thus, addition of epinephrine to lidocaine may be indicated to prolong duration of anesthesia for lower body operations. However, delayed recovery of ability to void may also prolong time until discharge after ambulatory surgery.

Adult↗
PubMed1995

Comparison of 5% with dextrose, 1.5% with dextrose, and 1.5% dextrose-free lidocaine solutions for spinal anesthesia in human volunteers.

The use of lidocaine in concentrations less than 5% for spinal anesthesia may be advantageous but has not been carefully studied. Lidocaine 50 mg (1.5% with dextrose and 1.5% dextrose-free) was administered to eight volunteers in a randomized, double blind, cross-over fashion. All of these subjects had previously received 5% lidocaine with dextrose using the same experimental protocol. Sensory analgesia was assessed with pinprick, transcutaneous electrical stimulation (TES) equivalent to surgical incision, and duration of tolerance of pneumatic thigh tourniquet. Motor block was assessed with isometric force dynamometry. Peak dermatomal level was the highest and duration until regression of pinprick the longest with the 5% solution (P < 0.05). Duration of tolerance to TES was increased (33 +/- 10 min) with the 5% solution (P < 0.04). Duration of tolerance to tourniquet pain was increased (11 +/- 3 min) with the 5% solution (P < 0.02). Duration of motor block was increased (45 +/- 9 min) with the 5% and the 1.5% without dextrose solutions (P < 0.04). Time to void was increased (33 +/- 5 min) with the 5% solution (P < 0.03). In conclusion, the use of different solutions of lidocaine for spinal anesthesia results in significant differences in sensory and motor block and time until recovery of micturition.

Adult↗
PubMed1995

Quantitative assessment of differential sensory nerve block after lidocaine spinal anesthesia.

BACKGROUND: Recent technology allows for quantitative and selective measurement of A beta, A delta, and C fiber nerve transmission. To gain further insight into the physiology of differential block after lidocaine spinal anesthesia, the function of these different fibers was quantitatively measured over time, and these measurements were correlated with regression of anesthesia to pinprick, touch, cold, and tolerance of tetanic electrical current (equivalent to surgical incision). METHODS: Six volunteers received lidocaine spinal anesthesia with 50 mg lidocaine (5% in dextrose). Cutaneous current perception thresholds at 2,000, 250, and 5 Hz, which stimulate A beta, A delta, and C fibers, respectively, were determined at L2-L3 (medial aspect above knee) before and every 10 min after spinal anesthesia. Dermatomal levels to pinprick, touch, and cold were assessed every 5 min after spinal anesthesia. Tolerance to tetanic electrical stimulus was assessed at L2-L3 every 10 min after spinal anesthesia. RESULTS: Differential block was demonstrated by the sequential return of sensation to touch, pinprick, and cold at L2-L3. Recovery of function of A beta, A delta, and C fibers correlated with return of sensation to touch (R2 = 0.7, p = 0.03), pinprick (R2 = 0.75, p = 0.02), and cold (R2 = 0.67, p = 0.04) respectively. Loss of tolerance of surgical anesthesia corresponded to return of A beta current perception thresholds to baseline, whereas current perception thresholds for A delta and C fibers were still increased to greater than baseline (p = 0.025). CONCLUSIONS: Differential sensory block during spinal anesthesia is due to different recovery profiles of A beta, A delta, and C fibers. Return of A beta current perception thresholds to baseline correlated with duration of surgical anesthesia as assessed with an electrical stimulation model.

Anesthesia Recovery Period↗
PubMed1995

Epidural and intravenous fentanyl produce equivalent effects during major surgery.

BACKGROUND: The benefit of epidural versus intravenous fentanyl administration for postoperative analgesia is controversial. In the current study, the intraoperative effects of epidural versus intravenous fentanyl administration were compared during major surgery. METHODS: Twenty elective patients scheduled for thoracoabdominal esophagectomy under general anesthesia with propofol infusion were randomly allocated to receive either intravenous or epidural boluses of 50-100 micrograms fentanyl in a double-blind fashion to maintain hemodynamic stability. Plasma cortisol and fentanyl, as well as total urinary catecholamines, were obtained at the end of the operations. RESULTS: Hemodynamic variations were similar except that patients receiving epidural fentanyl had a lower incidence of heart rate reduction (> 20% reduction from baseline, P < 0.05). There were no differences in mean intraoperative fentanyl (1,115 +/- 430 and 1,010 +/- 377 micrograms, epidural and intravenous, respectively) or propofol (2,281 +/- 645 and 2,452 +/- 1,169 mg) doses, number of boluses of fentanyl (nine in both groups), plasma fentanyl concentration (1.13 +/- 0.4 and 1.02 +/- 0.46 ng/ml), or number of anesthesiologists correctly identifying the site of fentanyl administration. Similarly, there were no differences in plasma glucose (8.9 +/- 1.8 and 9.3 +/- 1.8 mM) and cortisol (696 +/- 446 and 846 +/- 257 mM), or urinary epinephrine (12 +/- 3.7 and 13.1 +/- 9.2, micrograms/sample) and norepinephrine (42.7 +/- 26.7 and 39.1 +/- 27.6, micrograms/sample). CONCLUSIONS: There appears to be no clinical advantage to epidural administration of fentanyl over intravenous administration during anesthesia for major surgery.

Adult↗
PubMed1995

Intravenous versus epidural administration of hydromorphone. Effects on analgesia and recovery after radical retropubic prostatectomy.

BACKGROUND: It remains unclear whether epidural administration of hydromorphone results in spinal analgesia or clinical benefit when compared with intravenous administration. Therefore, we undertook this study to determine whether epidural administration of hydromorphone resulted in decreased opioid requirement, improved analgesia, reduced side effects, more rapid return of gastrointestinal function, or shorter duration of hospital stay than intravenous administration. METHODS: Sixteen patients undergoing radical retropubic prostatectomy were randomized in a double-blind manner to receive either intravenous or epidural hydromorphone via patient-controlled analgesia (PCA) for postoperative analgesia. All patients underwent a standardized combined epidural and general anesthetic and all received ketorolac for 72 h postoperatively. To decrease variability, patients were cared for according to a standardized protocol and were deemed ready for discharge according to prospectively defined criteria. RESULTS: Patients in the intravenous PCA group required approximately twice as much opioid than the epidural PCA group (P < 0.008), but there were no differences between groups in pain scores or patient satisfaction. Epidural administration resulted in a greater incidence of pruritus (P = 0.02). Gastrointestinal function recovered quickly in all patients with little variation, and there were no differences between groups. All patients were deemed ready for discharge by the third postoperative day, and removal of surgical drains was the last discharge criterion reached in all patients. CONCLUSIONS: Our results indicate that epidural administration of hydromorphone results in spinally mediated analgesia. However, epidural administration did not provide significant benefits in terms of postoperative analgesia, recovery of gastrointestinal function, or duration of hospitalization. Furthermore, we suggest that radical retropubic prostatectomy no longer be used as a model to assess the effects of analgesic technique on postoperative recovery, because control of discharge criteria revealed that hospital discharge was primarily dependent on removal of surgical drains.

Aged↗
PubMed1995

Oral clonidine prolongs lidocaine spinal anesthesia in human volunteers.

BACKGROUND: Premedication with oral clonidine may improve the quality and duration of lidocaine spinal anesthesia, but this effect has not been examined in a quantitative fashion. METHODS: Eight volunteers received 50 mg lidocaine (1.5% dextrose free) both with and without 0.2 mg oral clonidine 1.5 h before spinal anesthesia in a randomized, double-blind, placebo-controlled, crossover fashion. Sensory block was assessed by pinprick, transcutaneous electric stimulation equivalent to surgical incision, and duration of tolerance to pneumatic thigh tourniquet. Motor block at the quadriceps and gastrocnemius muscles was assessed by isometric force dynamometry. Episodes of bradycardia, hypotension, and sedation were recorded. RESULTS: Regression of pinprick was unchanged with clonidine. However, duration of tolerance to electric stimulation was increased at the knee (28 +/- 24 min) and ankle (31 +/- 28 min) with clonidine (P < 0.05). The duration of tolerance to tourniquet-induced pain was increased with clonidine (14 +/- 12 min; P < 0.05). The duration of motor block was increased at the quadriceps (20 +/- 13 min) and gastrocnemius (33 +/- 24 min) muscle groups with clonidine (P < 0.05). Although clonidine decreased systolic blood pressure (13 +/- 4 mmHg, P < 0.003) and heart rate (13 +/- 5 beats/min; P = 0.02), no subjects had hypotension or bradycardia. The incidence of sedation was greater with clonidine than with plain lidocaine (50% vs. 0%, P < 0.04). DISCUSSION: Premedication with oral clonidine prolonged sensory and motor block from lidocaine spinal anesthesia. The exact mechanism whereby oral clonidine prolongs spinal anesthesia remains to be determined.

Administration, Oral↗
PubMed1995

Effects of perioperative analgesic technique on rate of recovery after colon surgery.

BACKGROUND: Choice of perioperative analgesia may affect the rate of recovery of gastrointestinal function and thus duration and cost of hospitalization after colonic surgery. METHODS: Fifty-four patients undergoing partial colectomy surgery were randomized into four groups. All groups received a standardized general anesthetic. Group MB received a preoperative bolus of epidural bupivacaine and morphine followed by an infusion of morphine and bupivacaine. Group M received a preoperative bolus of epidural morphine followed by an infusion of morphine. Group B received a preoperative bolus of bupivacaine followed by an infusion of bupivacaine. Group P received a preoperative bolus of intravenous morphine followed by intravenous patient-controlled morphine postoperatively. All patients participated in a standardized recovery program to minimize the influence of nonanalgesic factors on recovery of gastrointestinal function. All epidural groups were double-blinded. All patients were deemed ready for discharge according to prospectively defined criteria. RESULTS: Groups B and MB reported superior analgesia with activity (P < 0.01). Group M had a greater incidence of pruritus (P < 0.05). Group B had a greater incidence of orthostatic hypotension (P = 0.04). Groups B and MB recovered gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier than groups M and P (P < 0.005). CONCLUSIONS: Epidural analgesia with bupivacaine and morphine provided the best balance of analgesia and side effects while accelerating postoperative recovery of gastrointestinal function and time to fulfillment of discharge criteria after colon surgery in relatively healthy patients within the context of a multimodal recovery program.

Analgesia, Epidural↗
PubMed1994

Pharmacokinetics of ropivacaine and bupivacaine for bilateral intercostal blockade in healthy male volunteers.

BACKGROUND: Intercostal blockade produces the highest serum local anesthetic concentrations of all regional anesthetic techniques. The purpose of this study was to determine the pharmacokinetic properties of ropivacaine and bupivacaine after bilateral intercostal blockade. METHODS: The pharmacokinetics of ropivacaine (n = 7) and bupivacaine (n = 7) were determined in adult human volunteers from venous samples drawn over 24 h after bilateral intercostal blockade of T5-T11 with 140 mg of either drug (0.25% plain solutions, 56 ml). Sensory (pinprick, temperature, and touch) and motor blockade (RAM-test and integrated electromyography) were assessed every 2 h. RESULTS: There was no significant difference between the maximum plasma concentrations (Cmax) obtained for either drug (ropivacaine 1.1 +/- 0.4 microgram/ml, bupivacaine 0.9 +/- 0.2 microgram/ml, P = 0.39), and there were no toxic signs observed in the obtained plasma concentration ranges. Plasma concentrations tended to peak (tmax) earlier with ropivacaine (21 +/- 9 versus 30 +/- 8 min, P = 0.09). The terminal half-life (t1/2 beta) of ropivacaine (2.3 +/- 0.8 h) was significantly less than that for bupivacaine (4.6 +/- 2.6 h, P = 0.04). Sensory blockade measured by pinprick was of shorter duration with ropivacaine (6.0 +/- 2.5 h versus bupivacaine 10.0 +/- 3.0 h; P < 0.001). Likewise, motor blockade was less intense and of shorter duration for ropivacaine by RAM-test (P = 0.02). CONCLUSIONS: The results of this pharmacokinetic study indicate that 0.25% ropivacaine and 0.25% bupivacaine (56 ml, 140 mg) produce peak plasma levels less than those considered toxic when used in bilateral intercostal blockade. Studies of ropivacaine for intercostal blockade in surgical patients are necessary before the optimum concentration for efficacy and anesthetic/analgesic duration is identified.

Adult↗
PubMed1994

Sensitivity of physiologically based pharmacokinetic models to variation in model parameters: methylene chloride.

The parameters in a physiologically based pharmacokinetic (PBPK) model of methylene chloride were varied systematically, and the resulting variation in a number of model outputs was determined as a function of time for mice and humans at several exposure concentrations. The importance of the various parameters in the model was highly dependent on the conditions (concentration, species) for which the simulation was performed and the model output (dose surrogate) being considered. Model structure also had a significant impact on the results. For sensitivity analysis, particular attention must be paid to conservation equations to ensure that the variational calculations do not alter mass balance, introducing extraneous effects into the model. All of the normalized sensitivity coefficients calculated in this study ranged between -1.12 and 1, and most were much less than 1 in absolute value, indicating that individual input errors are not greatly amplified in the outputs. In addition to ranking parameters in terms of their impact on model predictions, time-dependent sensitivity analysis can also be used as an aid in the design of experiments to estimate parameters by predicting the experimental conditions and sampling points which will maximize parameter identifiability.

Animals↗