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Biomedical subjects

D B Carr

Publications and source records attributed to D B Carr.

156 records · Page 9Linked to original sources

Hypercapneic ventilatory response in patients with panic disorder before and after alprazolam treatment and in pre- and postmenstrual women.

We tested the ventilatory and anxiety response to hypercapneic (CO2) challenge in women with panic disorder as well as in normal women in the premenstrual phase and mid-points of their menstrual cycles. Panic disorder patients were challenged on two occasions, each time while in the premenstrual phase of the menstrual cycle, receiving an open trial of alprazolam through the intervening 8 weeks between tests. This study confirms previous reports indicating increased sensitivity to CO2 in patients with panic disorder and that this sensitivity can be attenuated by treatment. We found a significant decrease in the ventilatory response of panic disorder patients comparing pre- and post-therapy. We also observed that normal females, while in the premenstrual phase of their menstrual cycle, have a heightened anxiety response to CO2 challenge.

Adult↗

Local increases of subcutaneous beta-endorphin immunoactivity at the site of thermal injury.

To examine interactions between exogenous opioid analgesia and endogenous opioid generation at a site of burn-induced tissue injury, we measured beta-endorphin (BE) and corticosterone (C) in aliquots of plasma and wound fluid withdrawn from subcutaneous wire mesh chambers beneath the site of a 3-5% surface area burn. After brief inhalational anesthesia at the time of thermal injury, rats received morphine (4 mg/kg, single dose), fentanyl (0.02 mg/kg hourly for 4 h), or no opioid. Systemic hormone responses and behavioral changes were minimal as expected for the minimal percentage burn. In all three groups intrachamber BE and C rose above baseline at 1, 2 and 4 h postburn, then returned to baseline at 24 h. Systemic opioid treatment produced analgesia (by tail flick latency testing) but did not reduce intrachamber hormone responses. Thus local BE and C responses at the site of thermal injury are regulated differently from systemic pituitary-adrenal responses.

Analgesics, Opioid↗

Postoperative patient-controlled analgesia: meta-analyses of initial randomized control trials.

STUDY OBJECTIVE: To compare outcomes during conventional analgesia (as-needed intramuscular dosing) and patient-controlled analgesia (PCA) in postoperative patients by analyzing data from published comparative trials. DESIGN: Meta-analyses of 15 randomized control trials. PATIENTS: Seven hundred eighty-seven adult patients (aged 16 to 65) undergoing various operative procedures. INTERVENTIONS: Either PCA or conventional analgesia for postoperative pain control. MEASUREMENTS AND MAIN RESULTS: Data were extracted on analgesic efficacy, analgesic use, patient satisfaction, length of hospital stay, and side effects. Meta-analyses of the data showed the following: (1) greater analgesic efficacy when PCA was used, with a mean additional benefit of 5.6 on a scale of 0 to 100 (SED, 2.2; p = 0.006); (2) a nonsignificant trend toward reduced analgesic use in PCA patients, based on a count of trials finding in one direction or the other (p = 0.092); (3) a 42% difference in the proportion of patients expressing satisfaction over dissatisfaction (SED, 20%; p = 0.02), with PCA being preferred; (4) a nonsignificant trend toward shortening of length of hospital stay with PCA use (mean, 0.15 days, SED, 0.13; p = 0.24); (5) no significant differences in the occurrence of any side effect. CONCLUSIONS: Patient preference strongly favors PCA over conventional analgesia. Patients using PCA also obtain better pain relief than those using conventional analgesia, without an increase in side effects. Favorable effect of PCA upon analgesic usage and length of hospital stay did not in the initial trials attain statistical significance. Nonetheless, the favorable trends in the mean effect sizes for both outcomes argue that further studies of both outcomes should be performed to determine whether the favorable impact of PCA upon either may become statistically significant if larger numbers of patients are enrolled.

Analgesia↗

Pain relief after knee arthroscopy: intra-articular morphine, intra-articular bupivacaine, or subcutaneous morphine?

BACKGROUND AND OBJECTIVES: This investigation was undertaken to compare analgesic effects, side effects, and requirements for supplemental analgesic therapy after knee arthroscopy in patients given intra-articular (IA) or subcutaneous (SC) morphine, intra-articular bupivacaine, or placebo. METHODS: In a randomized, double-blind controlled trial, 112 patients, 14-65 years old each received two solutions, one SC and the other IA. Group IAM (n = 30) received 10 mg IA morphine in 20 mL normal saline plus 1 mL of SC normal saline Group IAB (n = 27) received 20 mL IA bupivacaine 0.5% with IA epinephrine plus 1 mL SC normal saline Group SCM (n = 26) received 20 mL IA normal saline plus 10 mg SC morphine in 1 mL. Group P (n = 29) received 20 mL IA normal saline plus 1 mL SC normal saline. Pain was evaluated on arrival in the postanesthesia care unit (PACU), and 30, 45, 60, 90, and 120 minutes afterwards. If pain exceeded 4/10 on a visual analog pain scale in the PACU, 30 mg intravenous ketorolac was given, and if pain persisted, 0.4 mg hydromorphone was added every 7 minutes. After PACU discharge, patients whose pain exceeded 4/10 received oral ketorolac 10 mg every 6 hours; oral acetaminophen plus codeine was added every 4 hours if pain still exceeded 4/10. Analgesic requirements, along with visual analog pain score, sedation, and nausea were recorded every 6 hours for 72 hours. RESULTS: All three active (nonplacebo) pain treatments provided good pain control in the PACU. Side effects were similar in all groups. The placebo group had higher pain scores at 120 minutes (R = .02), higher supplemental analgesic requirements at 60 minutes (P = .04) and 90 minutes (P = .02) and the highest amount of total opioid rescue dose (P = .04). Patients in groups IAB and P had higher visual analog pain scores at 6 hours (P = .04) and 30 hours (P = .049) than those in Groups IAM and SCM. CONCLUSION: A single 10-mg dose of morphine given either IA or SC provides better and longer-lasting postoperative pain relief after knee arthroscopy than 20 mL IA bupivacaine 0.5% with epinephrine.

Adolescent↗

Dose effects of morphine and butorphanol alone and in combination after burn injury in the rat.

To test the effectiveness of analgesics after thermal trauma, butorphanol, a predominately opioid kappa-receptor agonist, and morphine, a mu-agonist, were administered alone and in combination 2 days after rats were subjected to scald burn or sham burn. After graded doses of morphine were administered, analgesia, assessed by tail flick latency and tail pinch latency, was similar in the sham-burn and scald-burn rats. With butorphanol alone analgesic effects were greater in the scald-burn than the sham-burn rats. When graded doses of butorphanol were given with a fixed dose of morphine (0.5 mg/kg), the tail pinch latency response was less in scald-burn rats and markedly less in sham-burn rats. The tail flick latency responses, however, moved in opposite directions in sham-burn and scald-burn rats receiving the drug combination: in sham-burn rats, tail flick latency effects were the same as with butorphanol alone; whereas in scald-burn rats, tail flick latency increases were suppressed except at the lowest dose.

Analgesics, Opioid↗

Vasopressin response to lactate infusion in normals and patients with panic disorder.

Infusions of sodium lactate evoke panic symptoms in patients with panic disorder but not in normal subjects. Although plasma vasopressin (AVP) is known to rise in response to other forms of stress, its response during this maneuver has not previously been reported. We measured plasma AVP in double-blind infusions of sodium lactate in 5 normal subjects, 6 patients with panic disorder, and, again in 4 patients after chronic alprazolam. In all groups administered lactate, AVP rose significantly above baseline values (p less than 0.05) though no change was seen in a control group of patients during D5NS infusion. No difference in AVP response to lactate was apparent between untreated patients (who experienced panic) and normals or chronically treated patients (who had minimal symptoms). Thus, the presence of panic symptoms induced by lactate is insufficient to provoke an abnormal pattern of AVP release.

Adult↗

Non-deterministic individual responses to receptor-selective opioid agonists.

To assess within a single rat strain individual variability of analgesic responses to sub-ED50 doses of receptor-selective opioids, we measured: 1) tail flick latency (TFL) responses after intrathecal (ith) injection of delta, mu, and kappa agonists administered serially; 2) TFL and tail pinch latencies (TPch) after intravenous (iv) mu and kappa agonists; and 3) TFL and TPch after iv agonists of mu or combined mu + delta selectivity. Mean values in each study confirmed an analgesic response, but individual TFL and TPch responses were chaotic and, within each study, rank order correlations between TFL and TPch values within or between drugs were insignificant. Our results suggest a hypothesis that such responses are intrinsically nondeterministic because--resembling other complex dynamic systems--they are generated by stochastic receptor-transmitter interactions that in turn evoke a series of nonlinearly coupled cellular and neural events.

Amino Acid Sequence↗

Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer.

BACKGROUND AND OBJECTIVES: Although rarely used, intracerebroventricular opioid therapy (ICV) is an option for the control of intractable pain due to cancer when systemic treatments have failed. The aim of the present study is to use available data from published trials to compare ICV with the more common epidural (EP) and subarachnoid (SA) opioid treatments in an attempt to establish the utility and safety of ICV. METHODS: Because there are no published controlled trials comparing these routes of administration, the combined data from multiple uncontrolled trials were used, with differences between the treatments analyzed statistically. Trials assessing ICV (13 trials, 268 patients). EPI (29 trials, 909 patients) and SA (21 trials, 410 patients) in cancer patients were identified; data on analgesic efficacy, common pharmacologic side effects, and complications were then extracted and the accumulated incidence data analyzed. RESULTS: The findings (weighted means) indicated ICV to be at least as effective against pain as other neuraxial treatments, with 75% of ICV-treated patients obtaining excellent pain relief as compared with 72% of EPI- and 58% of SA-treated patients (not significant). The failure rate of both spinal treatments tended to be greater than that of ICV and was significantly higher in the case of EPI (P = .045). In general, persistent side effects appeared to be more of a problem with the spinal treatments, while transient symptoms occur more often with ICV. Persistent nausea, urinary retention, and pruritus all were more frequent with the two spinal treatments than with ICV, but transient nausea and respiratory depression occurred more often with ICV. Sedation and confusion appeared to occur more often with ICV than with spinal therapy, while constipation and headache were rarely encountered with ICV. There were no real differences in infectious complication rates among the three treatments (except for a lower rate of infection when an implanted pump was used), but technical problems such as catheter blockage, misplacement, or leakage tended to occur less often with ICV. CONCLUSIONS: Intracerebroventricular therapy appears to be at least as effective against pain as other neuraxial treatments. The ICV technique is the only fixed system that is associated with fewer technical problems than the use of simple percutaneous epidural catheters (difference 9%, standard error of the difference 3.4). The present state of evidence indicates that ICV is a successful treatment for patients with intractable cancer pain and compares well with spinal opioid treatments in terms of efficacy, side effects, and complications.

Analgesia, Epidural↗