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Biomedical subjects

J P Rathmell

Publications and source records attributed to J P Rathmell.

At least 19 recordsLinked to original sources
PubMed2001

Effects of infusion rate of intravenously administered morphine on physiological, psychomotor, and self-reported measures in humans.

Although the rate of onset of a drug effect is commonly believed to contribute to a drug's abuse liability, only a few systematic experimental studies have been conducted examining this notion. The present study determined the profile of physiological, psychomotor, and self-reported effects of infusion rate (a key means of manipulating onset of drug action) of intravenously administered morphine, the prototypical analgesic with a known abuse liability in human participants. Two doses of morphine sulfate (5 and 10 mg/70 kg, i.v.) and a placebo dose (0 mg/70 kg, i.v.) were administered to healthy volunteers under three infusion rates (2 min bolus, 15 min, and 60 min). Faster infusions of morphine produced greater positive subjective effects than slower infusions on visual analog scale measures of good drug effect, drug liking, and high. Faster infusions also resulted in greater self-reported drug effects and opioid agonist effects, without producing significant physiological or psychomotor impairment. Importantly, faster rates of drug infusion produced significantly higher morphine plasma levels than slower rates, and morphine plasma levels followed a similar pattern and timing of peak effect as the self-reported effects of the drug. Moreover, morphine produced dose-dependent increases in self-reported drug effects, opioid agonist effects, and morphine plasma levels in the study. Results suggest that the pharmacokinetic properties of a drug, including the dosage administered and the rate of at which it is administered may function to jointly affect the abuse liability of the drug.

Adolescent↗
PubMed1998

A multicenter, randomized, blind comparison of amrinone with milrinone after elective cardiac surgery.

UNLABELLED: Amrinone and milrinone are phosphodiesterase inhibitors with positive inotropic effects useful for the treatment of ventricular dysfunction after cardiac surgery. Forty-four patients undergoing elective cardiac surgery at four centers received either amrinone (n = 22) or milrinone (n = 22) in a randomized, blind fashion. Immediately after separation from cardiopulmonary bypass (CPB), two bolus doses of either amrinone 0.75 mg/kg or milrinone 25 microg/kg were administered over 30 s, separated by 5 min. Hemodynamic measurements were recorded before each dose and at the end of the 10-min study. Both amrinone and milrinone increased the cardiac index (48% vs 52%, P = not significant [NS] for amrinone and milrinone, respectively). There was a small increase in mean arterial pressure (MAP) after amrinone administration (from 68 +/- 3 to 72 +/- 3 mm Hg at 10 min, P < 0.05) with no significant change in MAP after milrinone administration. Central venous pressure was significantly higher in the amrinone group at baseline and 5 min (12 vs 10 mm Hg and 11 vs 10 mm Hg, respectively; P < 0.05). Systemic and pulmonary vascular resistances decreased significantly and to a similar extent after either amrinone or milrinone administration. Phenylephrine was required in 11 of 22 patients receiving amrinone and in 11 of 22 patients receiving milrinone to maintain arterial blood pressure. The proportion of patients requiring an intravascular volume infusion (15 of 22 vs 17 of 22, P = NS) and the total fluid volume infused were similar (402 +/- 57 vs 350 +/- 49 mL, P = NS for amrinone and milrinone, respectively). Amrinone and milrinone seem to have similar hemodynamic effects after CPB, with the exception of blood pressure, although the need for vasopressor support of blood pressure did not differ. Selection between these two drugs may include nonhemodynamic considerations such as cost. IMPLICATIONS: Amrinone and milrinone are drugs that improve cardiac contraction. Their effects have never been directly compared in patients. We found that amrinone and milrinone produced similar hemodynamic effects in adult patients undergoing cardiac surgery. Choice between the two drugs can be based on nonhemodynamic considerations such as cost.

Adult↗
PubMed1997

Duration of intrathecal labor analgesia: early versus advanced labor.

Early first-stage labor pain is primarily visceral in origin. Increasing pain intensity and transition to somatic nociceptive input characterizes late first- and second-stage labor pain. The effect of this change in nociceptive input on the duration of intrathecal labor analgesia has not been well studied. This prospective cohort observational study compares the duration of intrathecal labor analgesia after intrathecal injections made in early labor (3- to 5-cm cervical dilation) and those made in more advanced labor (7- to 10-cm cervical dilation). Forty-one parturients (18 in early labor and 23 in advanced labor) received intrathecal sufentanil (10 micrograms) and bupivacaine (2.5 mg) as part of a combined spinal-epidural technique. Patients rated their pain using a 0-10 verbal pain scale prior to intrathecal injection and every 20 min thereafter. Duration of analgesia was defined as the lesser of time until the pain score exceeded 5 or until a request for supplemental epidural analgesia was made. The duration of spinal analgesia was significantly less when intrathecal injection was made in advanced labor (120 +/- 26 min) compared with early labor (163 +/- 57 min, P < 0.01). We conclude that cervical dilation and stage of labor significantly impact the effective duration of intrathecal sufentanil/ bupivacaine labor analgesia.

Adult↗
PubMed1995

Labor epidural catheter reactivation or spinal anesthesia for delayed postpartum tubal ligation: a cost comparison.

STUDY OBJECTIVES: To evaluate the costs and resource consumption associated with utilizing epidural catheters placed during labor versus spinal anesthesia for postpartum tubal ligation. To examine maternal demographics, anesthetic management variables, and time interval from delivery until surgery for association with epidural catheter reactivation success rate. DESIGN: Retrospective study. SETTING: University hospital labor and delivery center. PATIENTS: 120 consecutive postpartum patients with tubal ligations performed between June 1991 and December 1993. INTERVENTIONS: Postpartum women scheduled for tubal ligation with labor epidural catheters in place either had local anesthetic injected via the epidural catheter (n = 45) or had the catheter removed without reinjection and spinal anesthetic administered (n = 20). Patients with inadequate epidural anesthesia went on to receive spinal anesthesia. Women without a labor epidural catheter received spinal anesthesia (n = 55). MEASUREMENTS AND MAIN RESULTS: Adequate anesthesia for tubal ligation was achieved in 78% of women after reinjection of their epidural catheter. Operating room (OR) and anesthesia times were highest when epidural catheter reactivation was unsuccessful, intermediate when epidural catheter reactivation was successful, and lowest with initial spinal anesthesia (p < 0.05). The longer OR and anesthesia provider times associated with epidural catheter reactivation increased patient charges on average of $176 compared with the initial use of spinal anesthesia. CONCLUSIONS: Spinal anesthesia for postpartum tubal ligation was associated with lower anesthesia professional fees and OR charges compared with attempted reactivation of epidural catheters placed during labor. Anesthesiologists should weigh the cost advantages of spinal anesthesia against the small, but increased probability of headache after dural puncture.

Analgesics, Opioid↗
PubMed1995

Spinal anesthesia for repair of meningomyelocele in neonates.

The use of spinal anesthesia for meningomyelocele repair in neonates has received minimal attention. Spinal anesthesia may lessen the stress response to surgery and decrease postoperative respiratory complications. We therefore examined the efficacy of spinal anesthesia in 14 neonates requiring repair of lumbar or sacral meningomyelocele. All neonates were positioned prone with a small chest roll. Hyperbaric 0.5% tetracaine with epinephrine was injected into the caudal end of the meningomyelocele sac. If necessary, supplemental tetracaine was administered directly into the intrathecal space by the surgeon during the operation. Blood pressure, heart rate, and oxyhemoglobin saturation were measured throughout surgery. Neonates were monitored with transthoracic impedance apnea monitors, electrocardiogram (ECG), and pulse oximetry for 36 h after surgery. Spinal anesthesia was successful in all cases. Seven patients received one supplemental tetracaine injection; one patient received two supplemental injections. Arterial blood pressure decreased an average of 5 mm Hg with the largest decrease being 10 mm Hg. Two postoperative respiratory events occurred in the first 8 h after surgery. Both neonates had received intraoperative midazolam for sedation. Neurologic function was assessed pre- and postoperatively. Twelve patients had no change in neurologic function after surgery, while two infants demonstrated improved function. We conclude that spinal anesthesia can be safely used for meningomyelocele repair.

Anesthesia, Spinal↗
PubMed1993

Hemodynamic and pharmacodynamic comparison of doxacurium and pipecuronium with pancuronium during induction of cardiac anesthesia: does the benefit justify the cost?

We compared the pharmacodynamic effects and hospital costs of three long-acting neuromuscular blocking drugs in a prospective, randomized, double-blind manner. Each neuromuscular blocking drug was administered with fentanyl (50 micrograms/kg) for intravenous induction of anesthesia for coronary artery bypass surgery. Each patient received twice the 95% effective dose (ED95) of either pancuronium (0.14 mg/kg, n = 10), pipecuronium (0.10 mg/kg, n = 10), or doxacurium (0.05 mg/kg, n = 10). Hemodynamic measurements were recorded at baseline, 5 min after completion of anesthetic induction, immediately after endotracheal intubation, and 5 min after intubation. Only small hemodynamic differences between neuromuscular blocking drugs were observed. Doxacurium (but not pancuronium or pipecuronium) significantly decreased mean arterial blood pressure (from 94 +/- 4 mm Hg before induction to 83 +/- 3 mm Hg 5 min after intubation); nevertheless, there were no significant between-group differences at any time. Pancuronium increased heart rate (from 68 +/- 4 beats/min before induction to 76 +/- 5 beats/min 5 min after intubation); however, pancuronium differed significantly from doxacurium and pipecuronium only 5 min after induction and 5 min after intubation. Central venous pressure, pulmonary artery occlusion pressure, cardiac index, and systemic and pulmonary vascular resistance indices did not change. Electrocardiographic abnormalities were observed in two pipecuronium patients: ST segment depression in one and premature ventricular contractions in another. No other electrocardiographic changes were observed. There were no significant between-group differences in the need for hemodynamic interventions.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1989

Clinicopathologic review of 142 cases of lacrimal gland lesions.

A review of 142 lacrimal gland biopsies performed during a 25-year period at a major eye hospital showed that 78% of lacrimal gland lesions were of nonepithelial origin and only 22% were primary epithelial neoplasms. The nonepithelial lesions included inflammation (64%) and lymphoid tumors (14%), whereas the epithelial lesions included dacryops (6%), pleomorphic adenoma (12%), and malignant epithelial tumors (4%). These results contradict the much quoted dictum that 50% of lacrimal gland lesions are primary epithelial tumors and 50% are nonepithelial lesions.

Adenocarcinoma↗
PubMed1987

Membrane transport influences the rate of accumulation of cytosine arabinoside in human leukemia cells.

The role of membrane transport in the cellular accumulation of 1-beta-D-arabinofuranosylcytosine (ara-C) was studied in freshly isolated human acute leukemia cells. Patient cells had low rates for ara-C transport as compared with human and murine experimental cells and correspondingly low binding capacities for the nucleoside transport inhibitor, nitrobenzylmercaptopurine riboside (NBMPR). At 1 microM ara-C, the rate of net cellular accumulation was close to the membrane transport rate, and NBMPR inhibited transport and accumulation to the same extent. The rate of ara-C accumulation was half maximal at only 3-5 microM, a level much lower than that required for murine cells (67-85 microM). At concentrations below 1 microM the rate of ara-C accumulation was determined primarily by the transport rate, but at higher concentrations above 10 microM, phosphorylation capacity was the principal determinant of the net uptake rate. This difference in the role of transport at high and low ara-C concentrations may explain, in part, the efficacy of high-dose ara-C in patients refractory to standard dose protocols.

Acute Disease↗
PubMed1985

Inhibition of 1-beta-D-arabinofuranosylcytosine transport and net accumulation by teniposide and etoposide in Ehrlich ascites cells and human leukemic blasts.

The interactions of the epipodophyllotoxins, teniposide (VM-26) and etoposide (VP-16), with the nucleoside carrier were examined with emphasis on their effects on 1-beta-D-arabinofuranosylcytosine (ara-C) transport and net accumulation. VM-26 inhibited ara-C transport by Ehrlich ascites cells within 1 min of exposure, and inhibition was only partially reversed after 45 min in VM-26-free medium. ara-C transport was slowed by 50% by 7 microM VM-26 or by 35 microM VP-16. Since epipodophyllotoxins were noncompetitive inhibitors, fractional inhibition was independent of the ara-C concentration. Analysis of ara-C transport kinetics revealed only a single saturable transport route, and there was no indication of VM-26-insensitive transport. VM-26, VP-16, and ara-C were competitive inhibitors of the specific binding of nitrobenzylthioinosine to the nucleoside carrier with Ki values of 7.4 microM, 23 microM, and 2.2 microM, respectively. The rate of dissociation of nitrobenzylthioinosine (t 1/2 = 20.6 min) was accelerated by 5 microM ara-C (t 1/2 = 18.5 min) but slowed by 100 microM VM-26 (t 1/2 = 34.6). By these criteria, the interaction of VM-26 with the nucleoside carrier was qualitatively similar to that of dipyridamole. Although VM-26 inhibited ara-C transport, it did not significantly slow the rate of net intracellular accumulation of ara-C by Ehrlich cells, presumably because transport capacity far exceeds the capacity for phosphorylation in these cells. In freshly isolated human leukemic blasts, which have far less nucleoside transport activity, inhibition of ara-C accumulation by VM-26 was dependent on the ara-C concentration. At 1 microM ara-C, a concentration where transport was rate limiting for net uptake, VM-26 inhibited accumulation of ara-C over a 60-min time course. At 50 microM ara-C, transport was in excess, and VM-26 did not slow ara-C metabolism.

Animals↗
PubMedDate not supplied

Detection of intravascular epidural catheters using 2-chloroprocaine. Influence of local anesthetic dose and nalbuphine premedication.

BACKGROUND AND OBJECTIVES: Detecting the intravascular placement of epidural catheters is essential to avoid local anesthetic toxicity. Small doses of intravenous local anesthetics produce changes in sensorium and are often used to test newly placed epidural catheters. Many parturients receive nalbuphine for analgesia prior to epidural catheter placement. This study examines how nalbuphine premedication influences symptoms following intravenous 2-chloroprocaine. METHODS: Thirty-one volunteers were randomized to receive premedication with placebo or 0.15 mg/kg of nalbuphine intravenously. Starting 10 minutes later, intravenous injections of 0.0, 0.3, 0.6, 0.9, 1.2, and 1.5 mg/kg of 2-chloroprocaine were given in random order at 10 minute intervals. After each injection, volunteers were asked to report changes in hearing, taste, or other symptoms. RESULTS: Symptoms reported (in decreasing order of frequency) were auditory changes, taste changes, dizziness/ lightheadedness, tingling in the extremities, and visual changes. The probability that volunteers will report symptoms is proportional to the dose of 2-chloroprocaine administered (auditory symptoms, P < .001; taste symptoms, P = .01; any symptoms, P < .001). Nalbuphine-premedicated volunteers were more likely to report symptoms (auditory symptoms, P = .004; taste symptoms, P = .004; any symptoms, P = .02). A dose of at least 1.5 mg/kg appears to be necessary to produce a 90% probability that patients will report symptoms when they receive 2-chloroprocaine intravenously. CONCLUSIONS: This study suggests that patients who receive nalbuphine for analgesia prior to epidural placement will be more likely to report symptoms after receiving intravenous 2-chloroprocaine during epidural test dosing.

Adult↗