A romifidine and morphine combination for epidural analgesia of the flank in cattle

PubMed Central

2004-01-01

Abstract The objective of the study reported here was to determine the onset, duration, and degree of analgesia achieved with a combination of romifidine (50 μg/kg body weight [BW]) and morphine (0.1 mg/kg BW) administered epidurally. Ten adult Holstein Friesen cows were assigned to either a treatment group receiving the romifidine and morphine combination or a control group receiving 0.9% saline in a randomized, blinded, crossover design. Cows were assessed for degree of flank analgesia and systemic sedation at various time intervals over a period of 24 hours. The romifidine and morphine combination, compared with saline, provided significant analgesia for at least 10 minutes (P = 0.016) and up to 12 hours (P = 0.004) after epidural administration. Treated cows were sedate between 10 minutes (P = 0.016) and 6 hours (P = 0.002) after epidural administration. These results provide evidence for a potential cost-effective intra- and postoperative method of analgesia; however, the sedation seen in this study could be detrimental to patients expected return to the farm shortly after surgery. Further research into withdrawal times, systemic effects, and potential adverse effects are needed before an opiod and α2-adrenergic agonist combination can be used safely in a clinical setting PMID:15600157

Involvement of peripheral mechanism in the verapamil-induced potentiation of morphine analgesia in mice.

PubMed

Shimizu, Norifumi; Kishioka, Shiroh; Maeda, Takehiko; Fukazawa, Yohji; Dake, Yoshihiro; Yamamoto, Chizuko; Ozaki, Masanobu; Yamamoto, Hiroyuki

2004-08-01

Morphine's analgesic actions are thought to be mediated through both the central and peripheral nervous systems. L-type calcium channel blockers have been reported to potentiate the analgesic effects of morphine, but the locus of this interaction is not known. In this experiment, we examined the site of verapamil-induced potentiation of morphine analgesia in mice using the quaternary opioid receptor antagonist naloxone-methiodide (NLX-M). Subcutaneous injections of morphine increased locomotor activity and serum corticosterone level, which are mediated by the central nervous system. These central effects were not antagonized by 0.1 mg/kg of NLX-M, whereas this dose of NLX-M partially antagonized the analgesic effect of morphine. Treatment with verapamil potentiated morphine analgesia in a dose-dependent manner. The verapamil-induced potentiation of morphine analgesia was abolished by pretreatment with NLX-M (0.1 and 1 mg/kg). These findings suggest that peripheral mechanisms partially contribute to morphine analgesia and mediate the potentiation of morphine analgesia by verapamil.

A Subanalgesic Dose of Morphine Eliminates Nalbuphine Anti-analgesia in Postoperative Pain

PubMed Central

Gear, Robert W.; Gordon, Newton C.; Hossaini-Zadeh, Mehran; Lee, Janice S.; Miaskowski, Christine; Paul, Steven M.; Levine, Jon D.

2008-01-01

The agonist-antagonist kappa-opioid nalbuphine administered for postoperative pain produces greater analgesia in females than in males. In fact, males administered nalbuphine (5 mg) experience pain greater than those receiving placebo, suggesting the existence of an anti-analgesic effect. These sexually dimorphic effects on postoperative pain can be eliminated by co-administration of a fixed ratio of the prototypical opioid receptor antagonist naloxone with nalbuphine, implying a role for opioid receptors in the anti-analgesic as well as analgesic effects of nalbuphine. In the present study, we further evaluated the role of opioid receptors in the sex-specific effects on pain produced by nalbuphine by co-administering a dose of morphine low enough that it does not produce analgesia. Following extraction of bony impacted third molar teeth, nalbuphine (5 mg) was administered alone or in combination with either of two low doses of morphine (2 mg or 4 mg). Both doses of morphine reversed nalbuphine-induced anti-analgesia in males, but only the lower dose (2 mg) reached statistical significance. Neither dose affected nalbuphine-induced analgesia in females, and when administered alone in either males or females, morphine (2 mg) had no analgesic effect. Though not observed in females, the effect of morphine in males argues that, like naloxone, low dose morphine may act as an anti-analgesia opioid receptor antagonist. Perspective Previously we reported that the nalbuphine produces both analgesic and anti-analgesic effects, and that the opioid antagonist naloxone can enhance nalbuphine analgesia by selectively antagonizing the anti-analgesic effect. Here we show that morphine, given in a subanalgesic dose, reverses nalbuphine-induced anti-analgesia in males, perhaps by a similar mechanism. PMID:18201935

Ketamine Patient Controlled Analgesia for Acute Pain in Trauma Patients: A Randomized, Active Comparator Controlled, Blinded, Pilot Trial

DTIC Science & Technology

2017-01-11

patient- controlled analgesia per the primary treating team. Four subjects in the ketamine group and one subject in the hydromorphone group withdrew...occurred more frequently in the ketamine group , although this was not statistically significant (40% vs. 0%, P=0.090). Ketamine patient- controlled ...breakthrough IV morphine equivalents between groups . 4.0 RESULTS 4.1 Participants Due to unanticipated barriers to enrollment, including a

Parecoxib Supplementation to Morphine Analgesia Decreases Incidence of Delirium in Elderly Patients After Hip or Knee Replacement Surgery: A Randomized Controlled Trial.

PubMed

Mu, Dong-Liang; Zhang, Da-Zhi; Wang, Dong-Xin; Wang, Geng; Li, Chun-Jing; Meng, Zhao-Ting; Li, Ya-Wei; Liu, Chao; Li, Xue-Ying

2017-06-01

Severe pain and high-dose opioids are both associated with increased risk of postoperative delirium. The authors investigated whether parecoxib-supplemented IV morphine analgesia could decrease the incidence of delirium in elderly patients after total hip or knee replacement surgery. In a randomized, double-blind, 2-center trial, patients of 60 years or older who underwent elective total hip or knee replacement surgery were assigned in a 1:1 ratio to receive either parecoxib (40 mg at the end of surgery and then every 12 hours for 3 days) or placebo (normal saline). All patients received combined spinal-epidural anesthesia during surgery and IV morphine for postoperative analgesia. The primary outcome was the incidence of delirium within 5 days after surgery. Between January 2011 and May 2013, 620 patients were enrolled and were included in the intention-to-treat and safety analyses. The incidence of delirium was significantly reduced from 11.0% (34/310) with placebo to 6.2% (19/310) with parecoxib (relative risk 0.56, 95% confidence interval 0.33-0.96, P = .031). The severity of pain and the cumulative consumptions of morphine at 24, 48, and 72 hours after surgery were significantly lower with parecoxib than with placebo (all P < .001), although the differences were small. There was no difference in the incidence of postoperative complications between the 2 groups (12.3% [38/310] with placebo versus 11.6% [36/310] with parecoxib; P = .80). For low-risk elderly patients undergoing elective total hip or knee replacement surgery, multidose parecoxib supplemented to IV morphine decreased the incidence of postoperative delirium without increasing adverse events.

Oral oxycodone offers equivalent analgesia to intravenous patient-controlled analgesia after total hip replacement: a randomized, single-centre, non-blinded, non-inferiority study.

PubMed

Rothwell, M P; Pearson, D; Hunter, J D; Mitchell, P A; Graham-Woollard, T; Goodwin, L; Dunn, G

2011-06-01

To determine if oral oxycodone (OOXY) could provide equivalent postoperative analgesia and a similar side-effect profile to i.v. patient-controlled morphine in patients undergoing elective primary total hip replacement (THR) under spinal anaesthesia. We studied 110 consecutive patients aged 60-85 yr. After operation, patients were randomly allocated to receive either oral controlled- and immediate-release OOXY or i.v. patient-controlled analgesia (IVPCA) with morphine. Both groups received regular co-analgesia and antiemetics. The primary outcome measures were: (i) postoperative pain at rest and movement and (ii) nausea score recorded 12 hourly. The secondary outcome measures were: (i) time to first mobilization, (ii) total amount of opioid consumed, (iii) number of additional antiemetic doses, and (iv) time to analgesic discontinuation. There were no statistically significant differences in the primary outcome measures of pain at rest and movement (P>0.05, 95% confidence intervals -0.41, +0.96) or nausea score (P>0.5). The secondary outcome measures showed no significant difference in the total amount of opioid consumed (102 vs 63 mg; P>0.05) or time to mobilization (24.45 vs 26.6 h, P=0.2). The number of antiemetic doses required in the first 24 h was significantly lower in the OOXY group (1.1 vs 1.4, P<0.05). The time to analgesic discontinuation was significantly shorter in the OOXY group (50.5 vs 56.6 h, P<0.05). Oral analgesia with OOXY was approximately GBP 10 less expensive per patient than IVPCA. Oral analgesia with OOXY after THR offers non-inferior analgesia to IVPCA and may offer some logistical and cost advantages.

Stress antagonizes morphine-induced analgesia in rats

NASA Technical Reports Server (NTRS)

Vernikos, J.; Shannon, L.; Heybach, J. P.

1981-01-01

Exposure to restraint stress resulted in antagonism of the analgesic effect of administered morphine in adult male rats. This antagonism of morphine-induced analgesia by restraint stress was not affected by adrenalectomy one day prior to testing, suggesting that stress-induced secretion of corticosteroids is not critical to this antagonism. In addition, parenteral administration of exogenous adrenocorticotropin (ACTH) mimicked the effect of stress in antagonizing morphine's analgesic efficacy. The hypothesis that ACTH is an endogenous opiate antagonist involved in modulating pain sensitivity is supported.

A randomised controlled trial comparing three analgesia regimens following total knee joint replacement: continuous femoral nerve block, intrathecal morphine or both.

PubMed

Olive, D J; Barrington, M J; Simone, S A; Kluger, R

2015-07-01

This randomised controlled trial compared three analgesia regimens following primary unilateral total knee joint replacement: continuous femoral nerve block (CFNB), intrathecal morphine (ITM), and both. The primary outcome was pain ratings over the first 24 hours. Secondary outcomes included morphine consumption, nausea, pruritus and sedation ratings, oxygen saturation (SpO2) ratings, and ability to mobilise postoperatively. All patients received a spinal anaesthetic and a postoperative patient-controlled morphine pump. Patients were randomised to receive CFNB, ITM, or both. In patients with no CFNB, the use of ITM was blinded. Eighty-one patients were randomised and there were no withdrawals. At 24 hours, the ITM-only group had higher pain ratings than either of the other groups (P=0.04 versus CFNB, P=0.01 versus combination). In the 18 to 24 hour period, the ITM group used more morphine than either of the other groups. There were no statistically significant differences in pain ratings or morphine consumption at earlier time intervals. The ITM group were less likely to be able to sit out of bed on day one. Patients who received ITM were more likely to have pruritus. There were no statistically significant differences in nausea, SpO₂or sedation ratings. This study showed that a CFNB resulted in reduced pain and was also associated with less morphine consumption and improved mobilisation at 24 hours compared to ITM. This study did not show any statistically significant differences between CFNB alone and CFNB+ITM.

Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice.

PubMed

Kambur, Oleg; Männistö, Pekka T; Viljakka, Kaarin; Reenilä, Ilkka; Lemberg, Kim; Kontinen, Vesa K; Karayiorgou, Maria; Gogos, Joseph A; Kalso, Eija

2008-10-01

Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.

Comparison of extended-release epidural morphine with femoral nerve block to patient-controlled epidural analgesia for postoperative pain control of total knee arthroplasty: a case-controlled study.

PubMed

Sugar, Scott L; Hutson, Larry R; Shannon, Patrick; Thomas, Leslie C; Nossaman, Bobby D

2011-01-01

Because newer anticoagulation strategies for total knee replacement present potentially increased risk of neuraxial analgesia, there is movement away from using patient-controlled epidural analgesia (PCEA) for pain control. This concern opens the door for other regional modalities in postoperative analgesia, including the use of extended-release epidural morphine (EREM) combined with a femoral nerve block (FNB). This study was a prospective observational chart review with the use of recent historical controls in patients undergoing unilateral total knee replacement. Outcomes of interest were 0-, 24-, and 48-hour postoperative pain scores using the visual analog scale (VAS); incidence of side effects; and time spent in the postanesthesia care unit (PACU). Postoperative pain scores at 24 and 48 hours in the EREM and FNB group (n  =  14; 2.6 ± 0.6 and 5.0 ± 0.9, respectively) were comparable to the PCEA group (n  =  14; 3.8 ± 0.6 and 4.2 ± 0.9). The PACU time was shorter in the EREM and FNB group (2.4 ± 0.3 hours) compared with PCEA (3.6 ± 0.3 hours, P  =  .02). No statistically significant difference was found in the incidence of side effects between the 2 groups. The VAS scores at 24 and 48 hours indicate that EREM and FNB provide comparable analgesia to PCEA. The trend toward shorter PACU times represents an opportunity for cost-identification analysis. The study data are limited by their observational nature and the small number of patients involved; nevertheless, this study demonstrates a therapeutic equivalence to PCEA that may be more cost effective.

Gastric pentadecapeptide BPC 157 counteracts morphine-induced analgesia in mice.

PubMed

Boban Blagaic, A; Turcic, P; Blagaic, V; Dubovecak, M; Jelovac, N; Zemba, M; Radic, B; Becejac, T; Stancic Rokotov, D; Sikiric, P

2009-12-01

Previously, the gastric pentadecapeptide BPC 157, (PL 14736, Pliva) has been shown to have several beneficial effects, it exert gastroprotective, anti-inflammatory actions, stimulates would healing and has therapeutic value in inflammatory bowel disease. The present study aimed to study the effect of naloxone and BPC 157 on morphine-induced antinociceptive action in hot plate test in the mouse. It was found that naloxone and BPC 157 counteracted the morphine (16 mg/kg s.c.) - analgesia. Naloxone (10 mg/kg s.c.) immediately antagonised the analgesic action and the reaction time returned to the basic values, the development of BPC 157-induced action (10 pg/kg, 10 ng/kg, 10 microg/kg i.p.) required 30 minutes. When haloperidol, a central dopamine-antagonist (1 mg/kg i.p.), enhanced morphine-analgesia, BPC 157 counteracted this enhancement and naloxone reestablished the basic values of pain reaction. BPC 157, naloxone, and haloperidol per se failed to exert analgesic action. In summary, interaction between dopamine-opioid systems was demonstrated in analgesia, BPC 157 counteracted the haloperidol-induced enhancement of the antinociceptive action of morphine, indicating that BPC acts mainly through the central dopaminergic system.

Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial.

PubMed

Berger, J S; Gonzalez, A; Hopkins, A; Alshaeri, T; Jeon, D; Wang, S; Amdur, R L; Smiley, R

2016-12-01

The appropriate dose of intrathecal morphine for post-cesarean analgesia is unclear. With the inclusion of routine non-steroidal anti-inflammatory drugs, the required dose of morphine may be significantly less than the 200-300μg common a decade ago. We performed a two-center, prospective, randomized, blinded trial comparing three doses of intrathecal morphine, combined with routine intravenous ketorolac, in 144 healthy women undergoing elective cesarean delivery. Patients received an intrathecal injection of hyperbaric bupivacaine 12mg, fentanyl 15μg and a randomized dose of 50, 100, or 150μg morphine in a volume of 2.2mL. Patients received intravenous ketorolac 30mg before leaving the operating room and 15mg intravenously every 6h for the duration of the study (24h). All received postoperative patient-controlled intravenous morphine. The primary endpoint was total intravenous morphine administered postoperatively over 24h, analyzed using mixed model regression. There were no differences between dose groups (or institutions) in intravenous morphine use over 24h. Visual analog scale scores for pain and nausea did not differ. Pruritus was greater in the 100 and 150μg groups than the 50μg group at 6h and 12h, but there was no difference between groups in nausea or pruritus treatments. Respiratory depression or significant sedation did not occur. The dose-response relationship of intrathecal morphine for multimodal post-cesarean analgesia suggests that 50μg produces analgesia similar to that produced by either 100μg or 150μg. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of intrathecal and local infiltration analgesia by morphine for pain management in total knee and hip arthroplasty: A meta-analysis of randomized controlled trial.

PubMed

Jia, Xu-Feng; Ji, Yong; Huang, Guang-Ping; Zhou, Yu; Long, Miao

2017-04-01

We performed a meta-analysis from randomized controlled trials to evaluate the efficiency and safety between local infiltration analgesia and intrathecal morphine for pain control in total knee and hip arthroplasty. We systemically searched electronic databases including Embase (1980-2016.7), Medline (1966-2016.7), PubMed (1966-2016.7), ScienceDirect (1985-2016.7), web of science (1950-2016.7) and Cochrane Library for relevant articles. All calculation was carried out by Stata 11.0. Four randomized controlled trials (RCTs) involving 242 patients met the inclusion criteria. The meta-analysis showed that there were significant differences in terms of postoperative pain scores at 24 h during rest (P = 0.008) and mobilization (P = 0.049) following total knee and hip arthroplasty. Significant difference was found regarding the incidence of nausea (P = 0.030), vomiting (P = 0.005), and pruritus (P = 0.000) between two groups. There was no significant difference between groups in terms of morphine equivalent consumption at postoperative 24 or 48 h. Local infiltration analgesia (LIA) provided superior analgesic effects within the first 24 h compared to intrathecal morphine (ITM) following total knee and hip arthroplasty. There were fewer adverse effects in LIA. Doses of morphine consumption were similar in the two groups. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

[Postoperative pain management by intravenous patient-controlled analgesia in patients undergoing upper abdominal gastrointestinal surgery].

PubMed

Kajiyama, Seiji; Niihata, Tomoko; Sugimoto, Yuki; Kawamoto, Masashi

2012-10-01

We conducted a retrospective study to evaluate the effectiveness of intravenous patient-controlled analgesia (IVPCA) in the early postoperative period after upper abdominal gastrointestinal surgery. We also evaluated the postoperative effects of intraoperative analgesic dosage in patients after this surgery. A total of 59 adult patients classified as ASA 1-3 were allocated to one of two groups: Group A, 23 patients who requested IVPCA more than 50 times, and Group B, 36 patients with fewer than 50 requests. IVPCA was induced using morphine 1 mg x ml(-1) without a base dose. The bolus dose was 1 ml and the lock-out time was 5 min. There was no significant difference between the two groups in the total intraoperative remifentanil dosage/body weight/surgical duration, predicted effect-site concentration of fentanyl during extubation, and utilization of flurbiprofen. The doses of morphine were significantly higher, and the visual analogue scale scores for pain at rest and during movement tended to be lower in group A than in group B. The results of this study suggest that the effects of intraoperative analgesics may not be significant. Patients who had received the above mentioned anesthetic regimen intraoperatively also required full postoperative analgesia as well.

Intrathecal morphine for postoperative pain control following robot-assisted prostatectomy: a prospective randomized trial.

PubMed

Bae, Junyeol; Kim, Hyun-Chang; Hong, Deok Man

2017-08-01

Robot-assisted laparoscopic prostatectomy (RALP) is minimally invasive surgery, but also causes moderate to severe pain during the immediate postoperative period. We evaluated the efficacy and safety of intrathecal morphine (ITM) for postoperative pain control in patients undergoing RALP. Thirty patients scheduled for RALP were randomly assigned into one of two groups. In the ITM group (n = 15), postoperative pain was managed using 300 µg intrathecal morphine with intravenous patient-controlled analgesia (IV-PCA). In the IV-PCA group (n = 15), only intravenous patient-controlled analgesia was used. The numerical pain score (NPS; 0 = no pain, 100 = worst pain imaginable), postoperative IV-PCA requirements and opioid-related complications including nausea, vomiting, dizziness, headache and pruritus were compared between the two groups. The NPSs on coughing were 20 (IQR 10-50) in the ITM group and 60 (IQR 40-80) in the IV-PCA group at postoperative 24 h (p = 0.001). The NPSs were significantly lower in the ITM group up to postoperative 24 h. The ITM group showed less morphine consumption at postoperative 24 h in the ITM group than in the IV-PCA group [5 (IQR 3-15) mg vs 17 (IQR 11-24) mg, p = 0.001]. Complications associated with morphine were comparable between the two groups and respiratory depression was not reported in either group. Intrathecal morphine provided more satisfactory analgesia without serious complications during the early postoperative period in patients undergoing RALP.

Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences.

PubMed

Romberg, Raymonda; Olofsen, Erik; Sarton, Elise; den Hartigh, Jan; Taschner, Peter E M; Dahan, Albert

2004-01-01

Morphine-6-glucuronide (M6G) is a metabolite of morphine and a micro-opioid agonist. To quantify the potency and speed of onset-offset of M6G and explore putative sex dependency, the authors studied the pharmacokinetics and pharmacodynamics of M6G in volunteers using a placebo-controlled, randomized, double-blind study design. Ten men and 10 women received 0.3 mg/kg intravenous M6G and placebo (two thirds of the dose as bolus, one third as a continuous infusion over 1 h) on separate occasions. For 7 h, pain tolerance was measured using gradually increasing transcutaneous electrical stimulation, and blood samples were obtained. A population pharmacokinetic (inhibitory sigmoid Emax)-pharmacodynamic analysis was used to analyze M6G-induced changes in tolerated stimulus intensity. The improvement in model fits by inclusion of covariate sex was tested for significance. P values less than 0.01 were considered significant. Taking into account previous morphine data, a predictive pharmacokinetic-pharmacodynamic model was constructed to determine the contribution of M6G to morphine analgesia. M6G concentrations did not differ between men and women. M6G caused analgesia significantly greater than that observed with placebo (P < 0.01). The M6G analgesia data were well described by the pharmacokinetic-pharmacodynamic model. The M6G effect site concentration causing a 25% increase in current (C25) was 275 +/- 135 nm (population estimate +/- SE), the blood effect site equilibration half-life was 6.2 +/- 3.3 h, and the steepness parameter was 0.71 +/- 0.18. Intersubject variability was 167% for C25 and 218% for the effect half-life. None of the model parameters showed sex dependency. A cumulative dose of 0.3 mg/kg M6G, given over 1 h, produces long-term analgesia greater than that observed with placebo, with equal dynamics (potency and speed of onset-offset) in men and women. Possible causes for the great intersubject response variability, such as genetic polymorphism of the

Simultaneous measurement and integrated analysis of analgesia and respiration after an intravenous morphine infusion.

PubMed

Dahan, Albert; Romberg, Raymonda; Teppema, Luc; Sarton, Elise; Bijl, Hans; Olofsen, Erik

2004-11-01

To study the influence of morphine on chemical control of breathing relative to the analgesic properties of morphine, the authors quantified morphine-induced analgesia and respiratory depression in a single group of healthy volunteers. Both respiratory and pain measurements were performed over single 24-h time spans. Eight subjects (four men, four women) received a 90-s intravenous morphine infusion; eight others (four men, four women) received a 90-s placebo infusion. At regular time intervals, respiratory variables (breathing at a fixed end-tidal partial pressure of carbon dioxide of 50 mmHg and the isocapnic acute hypoxic response), pain tolerance (derived from a transcutaneous electrical acute pain model), and arterial blood samples were obtained. Data acquisition continued for 24 h. Population pharmacokinetic (sigmoid Emax)-pharmacodynamic models were applied to the respiratory and pain data. The models are characterized by potency parameters, shape parameters (gamma), and blood-effect site equilibration half-lives. All collected data were analyzed simultaneously using the statistical program NONMEM. Placebo had no systematic effect on analgesic or respiratory variables. Morphine potency parameter and blood-effect site equilibration half-life did not differ significantly among the three measured effect parameters (P > 0.01). The integrated NONMEM analysis yielded a potency parameter of 32 +/- 1.4 nm (typical value +/- SE) and a blood-effect site equilibration half-life of 4.4 +/- 0.3 h. Parameter gamma was 1 for hypercapnic and hypoxic breathing but 2.4 +/- 0.7 for analgesia (P < 0.01). Our data indicate that systems involved in morphine-induced analgesia and respiratory depression share important pharmacodynamic characteristics. This suggests similarities in central mu-opioid analgesic and respiratory pathways (e.g., similarities in mu-opioid receptors and G proteins). The clinical implication of this study is that after morphine administration, despite lack

Patient-controlled analgesia versus intramuscular analgesic therapy.

PubMed

Smythe, M; Loughlin, K; Schad, R F; Lucarroti, R L

1994-06-01

The pharmacy and nursing time requirements, quality of postoperative pain control, and cost of patient-controlled analgesia (PCA) and intramuscular (i.m.) analgesic therapy were studied. All timings were conducted with a stopwatch on a single nursing unit that primarily receives gynecologic surgery patients. The various work elements involved in each type of therapy were timed individually. Both quality of analgesia and cost were evaluated in a prospective, randomized study in hysterectomy patients. I.M. patients received meperidine hydrochloride 75-100 mg every three to four hours as needed. PCA patients had access to morphine sulfate 1 mg or meperidine hydrochloride 10 mg, with a six-minute lockout period. The patients scored their pain every four hours. Direct costs for PCA were calculated as drug cost plus tubing cost plus form cost plus maintenance cost plus depreciation cost. Direct costs for i.m. therapy consisted of the cost of drugs. The total mean nursing time per patient was 16.9 minutes for PCA and 10.7 minutes for i.m. therapy. Pharmacy time per patient was 5.1 minutes longer for PCA than for i.m. therapy. Thirty-six hysterectomy patients (17 i.m. and 19 PCA) were enrolled in the study of pain control and cost. Among i.m. patients, 64% of the pain scores were mild or worse, compared with 40% for PCA patients. The median pain scores were moderate for i.m. patients and mild for PCA patients. Scores tended to be lower for PCA patients at 16 and 20 hours. Although equal numbers of patients in the two groups experienced nausea, i.m. patients needed more doses of antiemetics than PCA patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Central neuraxial opioid analgesia after caesarean section: comparison of epidural diamorphine and intrathecal morphine.

PubMed

Caranza, R; Jeyapalan, I; Buggy, D J

1999-04-01

In a prospective, randomized, double-blind study in 55 women undergoing elective caesarean section under spinal anaesthesia, we compared epidural diamorphine 3 mg (2 distinct boluses, group ED) with single-dose intrathecal morphine 0.2 mg (group SM), in terms of analgesic efficacy, patient satisfaction and side-effects at 2, 3, 4, 8, 12, 16, 24 and 28 h postoperatively. There were no significant differences between groups in pain (assessed by 100 mm visual analogue scale), incidence of pruritus, sedation or respiratory depression measured by continuous pulse oximetry. However, time to first request for supplementary oral analgesia was longer in SM than in ED (mean +/- SD: 22.3+/-12.0 h vs. 13.8+/-6.5 h, P=0.04). The incidence of nausea or vomiting was significantly higher in SM than ED (73% vs. 41%, P=0.01). In ED, the mean +/- SD time to requirement of the second bolus was 6.7+/-3.2 h. There was a high level of satisfaction in both groups. We conclude that two boluses of epidural diamorphine 3 mg and single-dose intrathecal morphine 0.2 mg provide satisfactory analgesia after caesarean section, but spinal morphine was associated with both delayed requirement for supplementary analgesia and a higher incidence of nausea and vomiting.

Modulation by alpha-difluoromethyl-ornithine and aminoguanidine of pain threshold, morphine analgesia and tolerance.

PubMed

Lu, Gang; Su, Rui-Bin; Li, Jin; Qin, Bo-Yi

2003-10-08

The effects of alpha-difluoromethyl-ornithine (DFMO) and aminoguanidine, which might influence the metabolism of endogenous agmatine, on pain threshold, morphine analgesia and tolerance were investigated in mice. In the mouse acetic acid writhing test, intracerebroventricular (i.c.v.) injection of DFMO or aminoguanidine significantly elevated the pain threshold as indicated by a decrease in the number of writhings. DFMO or aminoguanidine obviously increased the analgesic effect of morphine in the mouse acetic acid writhing test and the mouse heat radiation tail-flick assay. These effects of DFMO and aminoguanidine were antagonized by idazoxan (3 mg/kg, i.p.), which is a selective antagonist of the imidazoline receptor. In the mouse heat radiation tail-flick assay, aminoguanidine significantly prolonged the tail-flick latency of animals, suggesting that the pain threshold was elevated. Furthermore, both DFMO and aminoguanidine enhanced morphine analgesia and inhibited acute morphine tolerance in the mouse heat radiation tail-flick assay. Neither DFMO nor aminoguanidine inhibited the activity of nitric oxide synthase in different brain areas in mice in vivo. These results indicate that the substances involved in the metabolism of endogenous agmatine could modulate the pain threshold, morphine analgesia and tolerance, indicating the possible role of endogenous agmatine in the pharmacological effects of morphine.

The effect of duration of dose delivery with patient-controlled analgesia on the incidence of nausea and vomiting after hysterectomy

PubMed Central

Woodhouse, Annie; Mather, Laurence E

1998-01-01

Aims Postoperative nausea and vomiting (PONV) may be exacerbated by postoperative opioid analgesics and may limit patients’ successful use of these medications when used with patient controlled analgesia (PCA). We tested the hypothesis that the rapid change in blood morphine concentration associated with PCA bolus delivery contributed to PONV, and that prolonging its delivery to a brief infusion would result in decreased PONV. Methods Patients, who were receiving morphine for pain relief via patient-controlled analgesia (PCA) after total abdominal hysterectomy, received 1 mg morphine sulphate incremental doses either over 40 s with a 5 min lockout interval or over 5 min delivery with a 1 min lockout interval. Episodes of nausea, retching and vomiting, along with the use of morphine and the pain relief obtained, were recorded. Results Data from 20 patients in each group were analysed. Contrary to expectations, most patients in both groups reported nausea postoperatively. Those patients receiving morphine over 5 min experienced more episodes of emesis (36) than those receiving the dose over 40 s (17). Most patients receiving the 40 s doses vomited in the first 12 h (median time 8 h), while those receiving the 5 min doses vomited between 12 and 24 h (median time 19 h) (P=0.01). There were no differences between groups in the visual analogue pain scores or use of morphine between groups. Conclusions Reasons for these unexpected findings remain speculative. The high incidence of PONV appears to be inherently high in gynaecological surgery patients and standard antiemetic medication regimens appear to be poorly efficacious. Reasons for the differences in the time-course of emetic episodes between the two groups may be related to differences in the time-course of central opioid receptor occupancy. PMID:9489595

Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients.

PubMed

Bendall, Jason C; Simpson, Paul M; Middleton, Paul M

2011-01-01

To compare the effectiveness of intravenous morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane for managing moderate to severe pain in pediatric patients in the out-of-hospital setting. We conducted a retrospective comparative study of 3,312 pediatric patients aged between 5 and 15 years who had moderate to severe pain (pain score ≥ 5) and who received intravenous morphine, IN fentanyl, or inhaled methoxyflurane, either alone or in combination, between January 1, 2004, and November 30, 2006. Multivariate logistic regression was used to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of ≥ 30% of initial pain score using an 11-point verbal numeric rating scale. Effective analgesia was achieved in 82.5% of cases overall. All analgesic agents were effective in the majority of patients (87.5%, 89.5%, and 78.3% for morphine, fentanyl, and methoxyflurane, respectively). There was evidence that methoxyflurane was less effective than both morphine (odds ratio [OR] 0.52; 95% confidence interval [CI] 0.36-0.74) and fentanyl (OR 0.43; 95% CI 0.29-0.62; p < 0.0001). There was no clinical or statistical evidence of difference in the effectiveness of fentanyl and morphine in this population (OR 1.22; 95% CI 0.74-2.01). There was no evidence that combination analgesia was better than either fentanyl or morphine alone. Intranasal fentanyl and intravenous morphine are equally effective analgesic agents in pediatric patients with moderate to severe acute pain in the out-of-hospital setting. Methoxyflurane is less effective in comparison with both morphine and fentanyl, but is an effective analgesic in the majority of children.

Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter

PubMed Central

Li, Yuting; Liu, Xing; Liu, Chang; Kang, Jiuhong; Yang, Jingyu; Pei, Gang; Wu, Chunfu

2009-01-01

Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance. PMID:19399231

Predicting the effectiveness of virtual reality relaxation on pain and anxiety when added to PCA morphine in patients having burns dressings changes.

PubMed

Konstantatos, A H; Angliss, M; Costello, V; Cleland, H; Stafrace, S

2009-06-01

Pain arising in burns sufferers is often severe and protracted. The prospect of a dressing change can heighten existing pain by impacting both physically and psychologically. In this trial we examined whether pre-procedural virtual reality guided relaxation added to patient controlled analgesia with morphine reduced pain severity during awake dressings changes in burns patients. We conducted a prospective randomized clinical trial in all patients with burns necessitating admission to a tertiary burns referral centre. Eligible patients requiring awake dressings changes were randomly allocated to single use virtual reality relaxation plus intravenous morphine patient controlled analgesia (PCA) infusion or to intravenous morphine patient controlled analgesia infusion alone. Patients rated their worst pain intensity during the dressing change using a visual analogue scale. The primary outcome measure was presence of 30% or greater difference in pain intensity ratings between the groups in estimation of worst pain during the dressing change. Of 88 eligible and consenting patients having awake dressings changes, 43 were assigned to virtual reality relaxation plus intravenous morphine PCA infusion and 43 to morphine PCA infusion alone. The group receiving virtual reality relaxation plus morphine PCA infusion reported significantly higher pain intensities during the dressing change (mean=7.3) compared with patients receiving morphine PCA alone (mean=5.3) (p=0.003) (95% CI 0.6-2.8). The addition of virtual reality guided relaxation to morphine PCA infusion in burns patients resulted in a significant increase in pain experienced during awake dressings changes. In the absence of a validated predictor for responsiveness to virtual reality relaxation such a therapy cannot be recommended for general use in burns patients having awake dressings changes.

Nefopam and Ketamine Comparably Enhance Postoperative Analgesia

PubMed Central

Kapfer, Barbara; Alfonsi, Pascal; Guignard, Bruno; Sessler, Daniel I.; Chauvin, Marcel

2005-01-01

Summary Opioids alone sometimes provide insufficient postoperative analgesia. Co-administration of drugs may reduce opioid use and to improve opioid efficacy. We therefore tested the hypothesis that administration of ketamine or nefopam, to postoperative patients with pain only partly alleviated by morphine, limits the amount of subsequent opioid necessary to produce adequate analgesia. Patients (n=77) recovering from major surgery were given up to 9 mg intravenous morphine. Those still suffering from pain were randomly assigned to blinded administration of: 1) isotonic saline (Control, n=21); 2) ketamine 10 mg (Ketamine, n=22); or, 3) nefopam 20 mg (Nefopam, n=22). Three-mg morphine boluses were subsequently given at 5-minute intervals until adequate analgesia was obtained, or 60 minutes elapsed after the beginning of the study drug administration, or ventilation became insufficient (respiratory rate < 10 breath/minute or saturation by pulse oxymetery < 95%). Supplemental morphine (i.e., after test drug administration) requirements were significantly greater in the Control group [17 ± 10 (SD) mg] than in the Nefopam (10 ± 5 mg, P < 0.005) or Ketamine (9 ± 5 mg, P < 0.001) groups. Morphine titration was successful in all Ketamine and Nefopam patients, but failed in four Control patients (two from respiratory toxicity and two from persistent pain). Tachycardia and profuse sweating were more frequent in patients given nefopam and sedation was greater with ketamine; however, the incidence of other potential complications did not differ between groups. Implications We conclude that ketamine 10 mg and nefopam 20 mg comparably potentiate opioid analgesia, each reducing opioid need by approximately 40%. Ketamine administration was associated with sedation whereas nefopam produced tachycardia and sweating. However, none of the side effects was serious. Either drug can thus be used to potentiate opioid analgesia. PMID:15616073

Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy.

PubMed

Dews, T E; Schubert, A; Fried, A; Ebrahim, Z; Oswalt, K; Paranandi, L

1996-03-01

Selective dorsal root rhizotomy is performed for relief of spasticity in children with cerebral palsy. Postoperative pain relief can be provided by intrathecal morphine administered at the time of the procedure. We sought to define an optimal dose of intrathecal morphine in children undergoing selective rhizotomy, through a randomized, double-blinded prospective trial. After institutional approval and parental written informed consent, 27 patients, ages 3-10 years, were randomized to receive 10, 20, or 30 micrograms.kg-1 (Groups A, B, and C, respectively) of preservative-free morphine administered intrathecally by the surgeon after dural closure. Postoperatively, vital signs, pulse oximetry, and pain intensity scores were recorded hourly for 24 hr. Supplemental intravenous morphine was administered postoperatively according to a predetermined schedule based on pain scores. There was considerable individual variability in the time to initial morphine dosing and cumulative supplemental morphine dose. Time to first supplemental morphine dose was not different between groups. When compared to Groups A and B, cumulative 6-hr supplemental morphine dose was significantly lower in Group C (38.6 +/- 47 micrograms versus 79.1 +/- 74 and 189.6 +/- 126 for Groups A and B, respectively). By 12 hr, cumulative supplemental morphine dose was similar in Groups A and C. Group B consistently had a higher supplemental dose requirement than Groups A and C at 6, 12, and 18 hr. By 24 hr, there was no difference in cumulative dose among groups. Postoperative pain scores and the incidence of respiratory events, nausea, vomiting and pruritus were comparable among groups. These data suggest that intrathecal morphine at 30 micrograms.kg-1 provides the most intense analgesia at 6 hr following selective dorsal root rhizotomy, but was otherwise comparable to the 10 micrograms.kg-1 dose.

Intrathecal Morphine for Laparoscopic Segmental Colonic Resection as Part of an Enhanced Recovery Protocol: A Randomized Controlled Trial.

PubMed

Koning, Mark V; Teunissen, Aart Jan W; van der Harst, Erwin; Ruijgrok, Elisabeth J; Stolker, Robert Jan

2018-02-01

Management of postoperative pain after laparoscopic segmental colonic resections remains controversial. We compared 2 methods of analgesia within an Enhanced Recovery After Surgery (ERAS) program. The goal of the study was to investigate whether administration of intrathecal bupivacaine/morphine would lead to an enhanced recovery. A single-center, randomized, double-blind controlled trial was performed (NL43488.101.13). Patients scheduled for laparoscopic segmental intestinal resections were considered. Exclusion criteria were patients in whom contraindications to spinal anesthesia were present, conversion to open surgery, and gastric and rectal surgery. The intervention group received single-shot intrathecal bupivacaine/morphine (12.5 mg/300 μg), with an altered dose for older patients. The control group received a sham procedure and a bolus of piritramide (0.1 mg/kg). Both groups received standardized general anesthesia and a patient-controlled intravenous analgesia pump as postoperative analgesia. All patients were treated according to an ERAS protocol. A decrease in days to "fit for discharge" was the primary outcome. Fifty-six patients were enrolled. Intervention group patients were fit for discharge earlier (median of 3 vs 4 days, P = 0.044). Furthermore, there was a significant decrease in opioid use and lower pain scores on the first postoperative day in the intervention group. There were no differences in adverse events (except for more pruritus), time to mobilization, fluid administration, or patient satisfaction. This randomized controlled trial shows that intrathecal morphine is a more effective method of postoperative analgesia in laparoscopic surgery than intravenous opioids within an ERAS program. Recovery is faster and less painful with intrathecal morphine. Other studies have confirmed these results, although data on faster recovery are new and require confirmation in future trials. This study was registered at ClinicalTrials.gov, identifier NCT

Comparison of morphine and carprofen administered alone or in combination for analgesia in dogs undergoing ovariohysterectomy.

PubMed

Dzikiti, T B; Joubert, K E; Venter, L J; Dzikiti, L N

2006-09-01

In this study the analgesic efficacy of the pure agonistic opioid morphine and the cyclo-oxygenase type-2-selective carprofen were compared since there is no previous specific comparative study for these two common analgesics. Forty-five bitches undergoing elective ovariohysterectomy were randomly assigned to one of three groups; receiving morphine 0.4 mg/kg bodyweight pre-operatively and 0.2 mg/kg every 4-6 hours thereafter (Morphine group), receiving a once-off carprofen 4 mg/kg injection (Carprofen group) or receiving both morphine and carprofen (MorphCarp group). The dogs were premedicated with acepromazine 0.01 mg/kg and induced with either thiopentone 5-10 mg/kg or propofol 4-6 mg/kg. General anaesthesia was maintained with halothane in oxygen. The degree of pain was assessed over a 24-hour period under blinded conditions using a pain scale modified from the University of Melbourne pain scale and the Glasgow composite pain tool. Physiological parameters such as respiratory rate, pulse rate and body temperature were also assessed over the same time period. There was no significant difference in pain-scores and thus analgesia offered by the three analgesia protocols at any assessment point across the three groups, but there were differences within groups across time points. Baseline total pain-scores were lower than scores at all post-operative points within all three groups. Both morphine and carprofen provided good analgesia without any obvious adverse effects. This study indicates that at the dosages indicated above, carprofen administered on its own produces analgesia equal to that produced by morphine and that the two drugs administered together do not produce better analgesia than either drug administered on its own.

The effect of morphine added to bupivacaine in ultrasound guided transversus abdominis plane (TAP) block for postoperative analgesia following lower abdominal cancer surgery, a randomized controlled study.

PubMed

El Sherif, Fatma Adel; Mohamed, Sahar Abdel-Baky; Kamal, Shereen Mamdouh

2017-06-01

Transversus abdominis plane (TAP) block used for management of surgical abdominal pain by injecting local anesthetics into the plane between the internal oblique and transversus abdominis muscles. We aimed to explore the effect of adding morphine to bupivacaine in ultrasound guided TAP-block in patients undergoing lower abdominal cancer surgery. Randomized, double-blind, prospective study. Clinical trial identifier: NCT02566096. Academic medical center. Sixty patients were enrolled in this study after ethical committee approval. Patients divided into 2 groups (30 each): Bupivacaine group (GB): given ultrasound guided TAP-block 20ml 0.5% bupivacaine diluted in 20ml saline; Morphine group (GM): given ultrasound guided TAP-block with 20ml 0.5% bupivacaine+10mg morphine sulphate diluted in 20ml saline. Patients were observed for total morphine consumption, time for first request of rescue analgesia, sedation scores, hemodynamics and side effects for 24h postoperatively. Morphine added to bupivacaine in TAP block compared to bupivacaine alone reduced total morphine consumption (5.33±1.28mg) (10.70±3.09mg) respectively (p<0.001), prolonged the time to first request of analgesia (10.40±4.96h) (6.97±3.26h) respectively (p<0.008), with a statistically significant decrease in (VAS-M) in GM compared with GB at 12h postoperatively (p<0.002). No significant differences in hemodynamics, respiratory rate, oxygen saturation, sedation score, and side effects except for nausea were observed (p>0.05). Addition of morphine to bupivacaine in TAP block is effective method for pain management in patients undergoing major abdominal cancer surgery without serious side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial.

PubMed

Lockwood, Geoff G; Cabreros, Leilani; Banach, Dorota; Punjabi, Prakash P

2017-10-01

Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg -1 .hr -1 ) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l -1 . There were no adverse events as a consequence of the study. Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. ISRCTN13424423 ( https://www.isrctn.com ).

Extending Time Profile of Morphine-Induced Analgesia Using a Chitosan-Based Molecular Imprinted Polymer Nanogel.

PubMed

Hassanzadeh, Marjan; Ghaemy, Mousa; Ahmadi, Shamseddin

2016-10-01

Chitosan-based molecular imprinted polymer (CS-MIP) nanogel is prepared in the presence of morphine template, fully characterized and used as a new vehicle to extend duration of morphine analgesic effect in Naval Medical Research Institute mice. The CS-MIP nanogel with ≈25 nm size range exhibits 98% loading efficiency, and in vitro release studies show an initial burst followed by an extended slow release of morphine. In order to study the feasibility of CS-MIP nanogel as morphine carrier, 20 mice are divided into two groups randomly and received subcutaneous injection of morphine-loaded CS-MIP and morphine (10 mg kg -1 ) dissolved in physiologic saline. Those received injection of morphine-loaded CS-MIP show slower and long lasting release of morphine with 193 min effective time of 50% (ET50) analgesia compared to 120 min ET50 in mice received morphine dissolved in physiologic saline. These results suggest that CS-MIP nanogel can be a possible strategy as morphine carrier for controlled release and extension of its analgesic efficacy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain.

PubMed

Tan, Ene-choo; Lim, Eileen C P; Teo, Yik-ying; Lim, Yvonne; Law, Hai-yang; Sia, Alex T

2009-06-23

Morphine consumption can vary widely between individuals even for identical surgical procedures. As mu-opioid receptor (OPRM1) is known to modulate pain perception and mediate the analgesic effects of opioid compounds in the central nervous system, we examined the influence of two OPRM polymorphisms on acute post-operative pain and morphine usage in women undergoing elective caesarean delivery. Data on self-reported pain scores and amount of total morphine use according to patient-controlled analgesia were collected from 994 women from the three main ethnic groups in Singapore. We found statistically significant association of the OPRM 118A>G with self-administered morphine during the first 24-hour postoperative period both in terms of total morphine (p = 1.7 x 10(-5)) and weight-adjusted morphine (p = 6.6 x 10(-5)). There was also significant association of this OPRM variant and time-averaged self-rated pain scores (p = 0.024). OPRM 118G homozygotes used more morphine and reported higher pain scores than 118A carriers. Other factors which influenced pain score and morphine usage include ethnicity, age and paying class. Our results suggest that ethnicity and OPRM 118A>G genotype are independent and significant contributors to variation in pain perception and postoperative morphine use in patients undergoing cesarean delivery.

Spinal cord distribution of sup 3 H-morphine after intrathecal administration: Relationship to analgesia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishio, Y.; Sinatra, R.S.; Kitahata, L.M.

1989-09-01

The distribution of intrathecally administered {sup 3}H-morphine was examined by light microscopic autoradiography in rat spinal cord and temporal changes in silver grain localization were compared with results obtained from simultaneous measurements of analgesia. After tissue processing, radio-activity was found to have penetrated in superficial as well as in deeper layers (Rexed lamina V, VII, and X) of rat spinal cord within minutes after application. Silver grain density reached maximal values at 30 min in every region of cord studied. Radioactivity decreased rapidly between 30 min and 2 hr and then more slowly over the next 24 hr. In ratsmore » tested for responses to a thermal stimulus (tail flick test), intrathecal administration of morphine (5 and 15 micrograms) resulted in significant dose dependent analgesia that peaked at 30 min and lasted up to 5 hr (P less than 0.5). There was a close relationship between analgesia and spinal cord silver grain density during the first 4 hr of the study. It is postulated that the onset of spinal morphine analgesia depends on appearance of molecules at sites of action followed by the activation of anti-nociceptive mechanisms.« less

Acupuncture and pharmacopuncture are as effective as morphine or carprofen for postoperative analgesia in bitches undergoing ovariohysterectomy.

PubMed

Luna, Stelio Pacca Loureiro; Martino, Irene Di; Lorena, Silvia Elaine Rodolfo de Sá; Capua, Maria Luisa Buffo de; Lima, Alfredo Feio da Maia; Santos, Bianca Paiva Costa Rodrigues dos; Brondani, Juliana Tabarelli; Vesce, Giancarlo

2015-12-01

To investigate the analgesic effect of acupuncture (AP) or micro-dose pharmacopuncture (PA), using carprofen or morphine, in bitches undergoing ovariohysterectomy (OHE). Thirty five dogs were randomly assigned to five groups after sedation with acepromazine IM: AP, 0.5 mg.kg(-1) of morphine subcutaneously (SC), 4 mg.kg(-1) of carprofen SC, and PA with 0.05 mg.kg(-1) of morphine or 0.4 mg.kg(-1) of carprofen. Anaesthesia was induced with propofol and maintained with isoflurane. Pain was assessed after OHE by a blind observer for 24h, by dynamic visual analogue scale (DIVAS), Glasgow (CMPS-SF), Melbourne (UMPS) and Colorado University pain scale (CSU). Animals reaching 33% of the UMPS score received rescue analgesia with morphine IM. Non parametric data were analysed by Kruskal-Wallis or Friedman tests where applicable, followed by Dunn's test. Parametric data were analysed by two way ANOVA, followed by Tukey test. There were no differences among groups in number of rescue analgesia. Except for the DIVAS score where animals treated with morphine had the lowest score compared with AP and carprofen, at 1h after surgery, there were no other differences among groups. Acupuncture or pharmacopuncture were equally effective as morphine or carprofen to control postoperative pain in bitches undergoing ovariohysterectomy.

Cholinergic mechanisms of analgesia produced by physostigmine, morphine and cold water swimming.

PubMed

Romano, J A; Shih, T M

1983-07-01

This study concerns the cholinergic involvement in three experimental procedures which produce analgesia. Rats were given one of seven treatments: saline (1.0 ml/kg, i.p.); morphine sulfate (3.5, 6.0 or 9.0 mg/kg, i.p.); physostigmine salicylate (0.65 mg/kg, i.p.); warm water swim (3.5 min at 28 degrees C); and cold water swim (3.5 min at 2 degrees C). Each rat was tested on a hot plate (59.1 degrees C) once prior to and 30 min after treatment. Immediately after the last test the rats were killed with focussed microwave radiation. Levels of acetylcholine (ACh) and choline (Ch) in six brain areas (brain stem, cerebral cortex, hippocampus, midbrain, cerebellum and striatum) were analyzed by gas chromatograph-mass spectrometer. Morphine (9.0 mg/kg), physostigmine and cold water swimming caused significant analgesia. Morphine elevated the levels of ACh in the cerebellum and striatum, cold water swimming--in the cerebellum, striatum and cortex, and physostigmine--in the striatum and hippocampus. Levels of choline were elevated by morphine in the cerebellum, cortex and hippocampus, while cold water swimming elevated levels of choline in the cerebellum, cortex, striatum and hippocampus. Physostigmine did not change levels of choline in any of the brain areas studied. These data suggest that the analgetic effects of morphine or cold water swimming may be mediated by components of the cholinergic system that differ from those involved in the analgetic effects of physostigmine.

[Continuous subcutaneous morphine to patients with terminal cancer. Analgesia at home].

PubMed

Laursen, J O

1994-04-04

Since 1992 it has been possible for cancer patients in the county of Southern Jutland to receive terminal care in their own homes. An essential part of this management is effective pain relief; more than 60% of cancer patients have chronic pain. In cases where oral medication or epidural administration of morphine is insufficient or complicated by side-effects continuous subcutaneous morphine administration may be suitable. The patient may be treated in this latter manner for long periods of time. A case story is described where a cancer patient was treated with continuous subcutaneous morphine in his home for more than 257 days without complications or major side-effects.

A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

PubMed

Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

2016-11-15

Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .


Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study.

PubMed

Reif, Ingalill; Wincent, Anders; Stiller, Carl-Olav

2017-06-01

The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karo-linska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 - 7) at baseline (before catheter insertion) to 1 (0 - 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
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Analgesia Following Major Gynecological Laparoscopic Surgery - PCA versus Intermittent Intramuscular Injection

PubMed Central

Lam, Alan M.; Carlton, Mark A.; Cario, Gregory M.; McBride, Lindsay

1998-01-01

Background and Objectives: To compare the use of patient-controlled analgesia to intermittent intramuscular injections of morphine following major gynecological laparoscopic procedures in order to assess differences in level of pain, sedation, episodes of nausea and/or vomiting, hospitalization time and patient satisfaction with their postoperative analgesia. Methods: Seventy-two patients undergoing major gynecological laparoscopic surgery were randomized to receive either postoperative analgesia via intermittent intramuscular injection of morphine (Group 1) or patient controlled analgesia (PCA - Group 2). All patients received anesthesia via a standardized protocol. Postoperative pain levels were recorded via a 10 cm visual analogue scale, and sedation scores were recorded on a standard PCA form. Episodes of nausea and vomiting were also recorded on the same form. Results: There were no statistically significant differences between intramuscular analgesia and PCA for any of the factors studied. Most significantly it was found that most patients ceased to require either form of parenteral analgesia within 24 hours of their procedure, regardless of the operating time. Conclusion: It is important for the surgeon to be aware of the effects of postoperative analgesia on his or her patients' level of satisfaction. We do not recommend the use of PCA analgesia following major laparoscopic gynecological surgery. PMID:9876706

Effects of parecoxib on morphine analgesia after gynecology tumor operation: a randomized trial of parecoxib used in postsurgical pain management.

PubMed

Nong, Lidan; Sun, Yi; Tian, Yuke; Li, Hongying; Li, Haifeng

2013-08-01

The analgesic efficacy of parecoxib in postsurgical pain management has been confirmed in minimally invasive surgery. However, little is known about its effects used in combination with opioids and about its potential for opioid-sparing effects in complex operations. This study was performed to investigate the influence of parecoxib on morphine analgesia after gynecological tumor surgery. Eighty patients undergoing gynecological tumor resection were randomized to receive either intravenous parecoxib at a dose of 40 mg (Group P, n = 40) followed by 40 mg every 12 h for 48 h or saline as a control (Group C, n = 40) 30 min before induction of anesthesia, followed by saline at the same time points after the operation. All patients had access to patient-controlled analgesia with intravenous morphine. Patients were assessed with respect to pain score (visual analog scale from 0-10), cumulative morphine requirement, satisfaction score, and side effects at 2, 6, 12, 24, and 48 h after surgery. A total of 79 patients were evaluated. The cumulative dose of morphine administered at each time point was lower in Group P than in Group C (P < 0.05), at 2 h (3.81 ± 0.35 versus 4.13 ± 0.45; P = 0.01), 6 h (16.20 ± 1.49 versus 19.60 ± 0.35; P < 0.001), 12 h (26.29 ± 2.75 versus 32.49 ± 2.42; P < 0.001), 24 h (41.72 ± 2.70 versus 49.97 ± 4.53; P < 0.001), and 48 h (60.06 ± 4.00 versus 65.68 ± 3.23; P < 0.001). Compared with Group C, Group P had significantly lower visual analog scale scores at rest and with movement, respectively, at 2 h (4.2, P < 0.001 and 5.0, P < 0.001), 6 h (3.6, P < 0.001 and 4.5, P < 0.001), 12 h (3.0, P = 0.017 and 4.0, P < 0.001), 24 h (2.1, P < 0.001 and 3.4, P < 0.001), and 48 h (1.8, P < 0.001 and 2.6, P < 0.001). The satisfaction score was higher in Group P than in Group C (8.6 ± 0.3 versus 6.8 ± 0.7, P < 0.001). There were no significant differences in side effects between the two

Comparison of epidural oxycodone and epidural morphine for post-caesarean section analgesia: A randomised controlled trial

PubMed Central

Sng, Ban Leong; Kwok, Sarah Carol; Mathur, Deepak; Ithnin, Farida; Newton-Dunn, Clare; Assam, Pryseley Nkouibert; Sultana, Rehena; Sia, Alex Tiong Heng

2016-01-01

Background and Aims: Epidural morphine after caesarean section may cause moderate to severe pruritus in women. Epidural oxycodone has been shown in non-obstetric trials to reduce pruritus when compared to morphine. We hypothesised that epidural oxycodone may reduce pruritus after caesarean section. Methods: A randomised controlled trial was conducted in pregnant women at term who underwent caesarean section with combined spinal-epidural technique initiated with intrathecal fentanyl 15 μg. Women received either epidural morphine 3 mg or epidural oxycodone 3 mg via the epidural catheter after delivery. The primary outcome was the incidence of pruritus at 24 h after caesarean section. The secondary outcomes were the pruritus scores, treatment for post-operative nausea and vomiting (PONV), pain scores and maternal satisfaction. Results: One hundred women were randomised (group oxycodone O = 50, morphine M = 50). There was no difference between Group O and M in the incidence of pruritus (n [%] 28 [56%] vs. 31 [62%], P = 0.68) and the worst pruritus scores (mean [standard deviation] 2.6 (2.8) vs. 3.3 [3.1], P = 0.23), respectively. Both groups had similar pain scores at rest (2.7 [2.3] vs. 2.0 [2.7], P = 0.16) and sitting up (5.0 [2.3] vs. 4.6 [2.4], P = 0.38) at 24 h. Pruritus scores were lower at 4–8, 8–12 and 12–24 h with oxycodone, but pain scores were higher. Both groups had a similar need for treatment of PONV and maternal satisfaction with analgesia. Conclusion: There was no difference in the incidence of pruritus at 24 h between epidural oxycodone and morphine. However, pruritus scores were lower with oxycodone between 4 and 24 h after surgery with higher pain scores in the same period. PMID:27053782

Local infiltration analgesia for total knee arthroplasty: should ketorolac be added?

PubMed

Andersen, K V; Nikolajsen, L; Haraldsted, V; Odgaard, A; Søballe, K

2013-08-01

Adequate postoperative analgesia with minimal side-effects is essential for early mobilization and recovery in patients undergoing total knee arthroplasty (TKA). High-volume local infiltration analgesia (LIA) with ropivacaine has been introduced, but effects of adjuvants are still debated. We tested the hypothesis that the addition of ketorolac to LIA significantly improves analgesia after TKA. Sixty patients undergoing TKA were randomized to receive intraoperative LIA (ropivacaine 300 mg and epinephrine 0.5 mg) combined with either ketorolac 30 mg (ketorolac group) or saline (control group). After surgery, eight bolus doses of ropivacaine 100 mg combined with either ketorolac 15 mg (ketorolac group) or saline (control group) were administered every 6 h via an intra-articular catheter. The primary outcome was postoperative consumption of i.v. morphine patient-controlled analgesia (PCA). Secondary outcomes were time to first request of i.v. morphine PCA, pain intensity, side-effects, and readiness for hospital discharge. Consumption of i.v. morphine PCA was lower in the ketorolac group vs control group {0-6 h: 0 (0-0) vs 5 (0-10) mg, P<0.0001; 0-48 h: 10 (0-22.5) vs 48.75 (30-82.5) mg, P<0.0001 [median (inter-quartile range, IQR)]}. Time to first request of i.v. morphine PCA was longer in the ketorolac group vs the control group [490 (248-617) vs 223 (115-319) min, P=0.02, median (IQR)]. Early postoperative pain (<48 h) and readiness for hospital discharge were also significantly reduced in the ketorolac group. LIA with ketorolac results in reduced morphine consumption, reduced pain intensity, and earlier readiness for hospital discharge.

The effect of IVPCA morphine on post-hysterectomy bowel function.

PubMed

Chan, Kuang-Cheng; Cheng, Ya-Jung; Huang, Guang-Ta; Wen, Yuan-Jui; Lin, Chen-Jung; Chen, Li-Kuei; Sun, Wei-Zen

2002-06-01

Although morphine has been shown to induce bowel dysfunction in a dose-dependent fashion, in most relevant studies it was investigated in single bolus injection. Recently, intravenous morphine via patient-controlled analgesia (IVPCA) has been widely used to provide analgesia by divided bolus doses on patients' demand with satisfactory effects. This approach, by reducing the peak serum surge, largely resembles the pharmacokinetic and pharmacodynamic advantage of continuous infusion. There is yet no report on the investigation of its effect on post-operative bowel dysfunction. Fifty-one women who underwent abdominal total hysterectomy (ATH) due to uterine myoma were enrolled to investigate the association between the doses of morphine consumption by PCA and the time of first passage of flatus. In all patients morphine was administered intravenously via a PCA pump immediately after recovery from general anesthesia. We found that 49 out of 51 patients (96%) exhibited mild pain with IVPCA morphine. They had consumed an average dose of 16.9 mg morphine (range, 0-46 mg) upon the first passage of flatus which occurred 2036.4 min (average) post-operatively. There was no correlation between the dose of morphine and the time of first passage of flatus (r = 0.053, P > 0.05). The absence of suppression of bowel movement by IVPCA morphine for post-operative pain control suggests that favorable pharmacokinetic profile of IVPCA can help reduce the morphine-induced bowel dysfunction at its therapeutic level.

Blockade of phosphodiesterase 4 reverses morphine-induced ventilatory disturbance without loss of analgesia.

PubMed

Kimura, Satoko; Ohi, Yoshiaki; Haji, Akira

2015-04-15

Ventilatory disturbance is a fatal side-effect of opioid analgesics. Separation of analgesia from ventilatory depression is important for therapeutic use of opioids. It has been suggested that opioid-induced ventilatory depression results from a decrease in adenosine 3',5'-cyclic monophosphate content in the respiratory-related neurons. Therefore, we examined the effects of caffeine, a methylxanthine non-selective phosphodiesterase (PDE) inhibitor with adenosine antagonistic activity, and rolipram, a racetam selective PDE4 inhibitor, on ventilatory depression induced by morphine. Spontaneous ventilation and paw withdrawal responses to nociceptive thermal stimulation were measured in anesthetized rats simultaneously. The efferent discharge of the phrenic nerve was recorded in anesthetized, vagotomized, paralyzed and artificially ventilated rats. Rolipram (0.1 and 0.3 mg/kg, i.v.) and caffeine (3.0 and 10.0 mg/kg, i.v.) relieved morphine (1.0 mg/kg, i.v.)-induced ventilatory depression but had no discernible effect on its analgesic action. Rolipram (0.3 and 1.0 mg/kg, i.v.) and caffeine (10.0 and 20.0 mg/kg, i.v.) recovered morphine (3.0 mg/kg, i.v.)-induced prolongation and flattening of inspiratory discharge in the phrenic nerve. Inhibition of PDE4 may be a possible approach for overcoming morphine-induced ventilatory depression without loss of analgesia. Copyright © 2015 Elsevier Inc. All rights reserved.

Analgesic activity of ZC88, a novel N-type voltage-dependent calcium channel blocker, and its modulation of morphine analgesia, tolerance and dependence.

PubMed

Meng, Ge; Wu, Ning; Zhang, Cheng; Su, Rui-Bin; Lu, Xin-Qiang; Liu, Yin; Yun, Liu-Hong; Zheng, Jian-Quan; Li, Jin

2008-05-31

ZC88 is a novel non-peptide N-type voltage-sensitive calcium channel blocker synthesized by our institute. In the present study, the oral analgesic activity of ZC88 in animal models of acute and neuropathic pain, and functional interactions between ZC88 and morphine in terms of analgesia, tolerance and dependence were investigated. In mice acetic acid writhing tests, ZC88 (10-80 mg/kg) administered by oral route showed significant antinociceptive effects in a dose-dependent manner. The ED50 values of ZC88 were 14.5 and 14.3 mg/kg in male and female mice, respectively. In sciatic nerve chronic constriction injury rats, mechanical allodynia was ameliorated by oral administration of ZC88 at doses of 14, 28 and 56 mg/kg, suggesting ZC88 relieved allodynic response of neuropathic pain. When concurrently administered with morphine, ZC88 (20-80 mg/kg) dose-dependently potentiated morphine analgesia and attenuated morphine analgesic tolerance in hot-plate tests. ZC88 also prevented chronic exposure to morphine-induced physical dependence and withdrawal, but not morphine-induced psychological dependence in conditioned place preference model. These results suggested that ZC88, a new non-peptide N-type calcium channel blocker, had notable oral analgesia and anti-allodynia for acute and neuropathic pain. ZC88 might be used in pain relief by either application alone or in combination with opioids because it enhanced morphine analgesia while prevented morphine-induced tolerance and physical dependence.

Ultrasound-guided rectus sheath and transversus abdominis plane blocks for perioperative analgesia in upper abdominal surgery: A randomized controlled study.

PubMed

Abdelsalam, Khaled; Mohamdin, O W

2016-01-01

Regional anesthetic techniques can be used to alleviate postoperative pain in patients undergoing major upper abdominal surgery. Our aim was to evaluate the efficacy of bilateral ultrasound (US)-guided rectus sheath (RS) and transversus abdominis plane (TAP) blocks for better perioperative analgesia. It is a prospective, observer-blinded, randomized clinical study. 40 eligible patients undergoing elective liver resection or Whipple procedure were included. All patients received a standardized anesthetic technique. Group 1 (n = 20) received preincisional US-guided bilateral RS and TAP blocks using 20 ml volume of bupivacaine 0.25% for each, and group 2 (n = 20) received local wound infiltration at end of surgery with 40 ml of bupivacaine 0.25%. A standardized postoperative analgesic regimen composed of intravenous paracetamol and a morphine patient-controlled analgesia (PCA). The use of intraoperative fentanyl and recovery room morphine boluses, PCA-administered morphine, pain scores as well as number of patients' experienced postoperative nausea and vomiting in the ward at 6 and 24 h were recorded. Group 1 patients received a significantly lower cumulative intraoperative fentanyl, significantly lesser boluses of morphine in postanesthesia care unit, as well, significantly lower cumulative 24 h postoperative morphine dosage than the group 2 patients. Pain visual analog scale scores were significantly lower at both 6 and 24 h postoperatively in TAP group when compared with the no-TAP group. There were no complications related to the TAP block procedures. No signs or symptoms of local anesthetic systemic toxicity were detected. The combination of bilateral US-guided RS and TAP blocks provides excellent perioperative analgesia for major upper abdominal surgery.

Effect of preemptive intra-articular morphine and ketamine on pain after arthroscopic rotator cuff repair: a prospective, double-blind, randomized controlled study.

PubMed

Khashan, M; Dolkart, O; Amar, E; Chechik, O; Sharfman, Z; Mozes, G; Maman, E; Weinbroum, A A

2016-02-01

Rotator cuff tear is a leading etiology of shoulder pain and disability. Surgical treatment is indicated in patients with persistent pain who fail a trial of non-surgical treatment. Pain reduction following rotator cuff repair, particularly within the first 24-48 h, is a major concern to both doctors and patients. This study aimed to compare the postoperative antinociceptive additive effects of pre-incisional intra-articular (IA) ketamine when combined with morphine with two times the dose of morphine or saline. In this prospective, randomized, double blind, controlled trial patients undergoing arthroscopic rotator cuff tear repair (ARCR) under general anesthesia were enrolled. Patients were randomly assigned to one of the three intervention groups. Twenty minutes prior to incision, morphine (20 mg/10 ml), ketamine (50 mg + morphine 10 mg/10 ml), or saline (0.9 % 10 ml) (n = 15/group), were administered to all patients. First 24 h postoperative analgesia consisted of intravenous patient controlled analgesia (IV-PCA) morphine and oral rescue paracetamol 1000 mg or oxycodone 5 mg. 24-h, 2-week and 3-month patient rated pain numeric rating scale (NRS) and analgesics consumption were documented. Patients' demographic and perioperative data were similar among all groups. The 24-h and the 2-week NRSs were significantly (p < 0.05) lower in both treatment groups compared to placebo, but were not significantly different between the two intervention groups. PCA-morphine and oral analgesics were consumed similarly among the groups throughout the study phases. Pre-incisional intra-articular morphine reduced pain in the first 2 weeks after arthroscopic rotator cuff repair. Further research is warranted to elucidate the optimal timing and dosing of IA ketamine and morphine for postoperative analgesic effects.

Assessment of patient-controlled analgesia versus intermittent opioid therapy to manage sickle-cell disease vaso-occlusive crisis in adult patients.

PubMed

Al-Anazi, Alaa; Al-Swaidan, Lowloa; Al-Ammari, Maha; Al-Debasi, Tariq; Alkatheri, Abdulmalik M; Al-Harbi, Shmeylan; Obaidat, Aiman A; Al-Bekairy, Abdulkareem M

2017-01-01

Vaso-occlusive crisis (VOC) is one of the acute complications of sickle-cell disease (SCD). Treatment mainly relies on hydration and pain control by analgesics. The specific aim of this study was to assess potential health outcomes within the first 72 h of admission between intermittent and patient-controlled analgesia (PCA) by opioids among VOC patients. A retrospective chart review study was conducted to determine SCD patients with VOC. Using the hospital electronic system, the following data were collected: patient's age, gender, blood pressure, heart rate, respiratory rate, oxygen saturation, and pain score on admission and daily for 3 days as well as the cumulative opioid analgesic dose for 72 h which is reported as morphine equivalent. One hundred and seventeen patients were screened over a period of 5 years. Of those, 99 (84.6%) met the study inclusion criteria, and 18 patients (15.4%) were excluded from the study. During the first 72 h of admission, a significant reduction in pain score was observed in patients on intermittent intravenous (IV) administration compared to those in the PCA group ( P < 0.0004) where the mean pain scores were 3 and 5, respectively. The total amount of morphine administered over 72 h of admission was significantly higher in PCA group (777 ± 175 mg) as compared to the intermittent IV administration group (149 ± 74 mg) ( P < 0.000003). Clinically significant hypotension or respiratory depression was not observed in both groups over the 72 h of admission. During the first 72 h of admission, intermittent IV administration of morphine was more effective than PCA infusion in pain control.

Spinal antinociception of synthetic omega-conotoxin SO-3, a selective N-type neuronal voltage-sensitive calcium channel blocker, and its effects on morphine analgesia in chemical stimulus tests in rodent.

PubMed

Yan, Ling-Di; Liu, Yan-Li; Zhang, Lei; Dong, Hua-Jin; Zhou, Pei-Lan; Su, Rui-Bin; Gong, Ze-Hui; Huang, Pei-Tang

2010-06-25

SO-3, a novel Omega-superfamily conotoxin derived from Conus striatus, selectively inhibits N-type neuronal voltage-sensitive calcium channels. In current study, antinociception of SO-3 compared with MVIIA or morphine and its effects on morphine analgesia were investigated in rodent chemical stimulus tests after acute or repeated intrathecal administration. In mice acetic acid writhing test, similar to MVIIA, SO-3 caused dose- and time-dependent spinal antinociception with ED(50) of 0.25 microg/kg and t(1/2) of 4h, which was more potent and longer-acting than morphine. In rat formalin test after intrathecal bolus injection, SO-3 produced dose- and time-dependent antinociception by suppressing acute (ED(50), 1.79 microg/kg) and tonic phases (ED(50), 0.41 microg/kg), which was similar to MVIIA and approximately 10-fold potency and twice longer-acting of morphine in blocking tonic phase responses. After repeated intrathecal injections twice daily for 5 consecutive days, SO-3 produced analgesia without loss of potency whereas morphine produced analgesia tolerance in rat formalin test; further, SO-3 still produced potent analgesia in morphine-tolerant rats. SO-3 co-administered with morphine left-shift the dose-response curve of morphine in mice acetic acid writhing test and significantly potentiated morphine analgesia in rat formalin test. No changes in motor function were seen in mice or rats receiving antinociceptive doses of SO-3 whereas MVIIA caused motor dysfunction at doses of 1.0-2.0 microg/kg in rats. This study showed that (1) novel SO-3 produced potent and long-acting spinal antinociception without observable motor dysfunction, (2) SO-3 significantly potentiated morphine analgesia, (3) After repeated intrathecal administration, SO-3 produced neither tolerance nor cross-tolerance to morphine analgesia. (c) 2010 Elsevier B.V. All rights reserved.

Patient-controlled analgesia after coronary bypass: Remifentanil or sufentanil?

PubMed

Alavi, Seyed Mostafa; Ghoreishi, Seyed Mohammadmehran; Chitsazan, Mitra; Ghandi, Iman; Fard, Alireza Jahangiri; Hosseini, Seyed Saeed; Mahjoobifard, Maziar; Fani, Kamal

2014-07-01

adequate pain control after cardiac surgery is mandatory to reduce its remarkable morbidity. In this study, we aimed to compare the efficacy of patient-controlled analgesia with remifentanil or sufentanil for pain management after coronary artery bypass grafting. 249 patients who underwent coronary artery bypass were randomly assigned to receive patient-controlled analgesia with remifentanil or sufentanil during the first 24 h postoperatively. Pain intensity during patient-controlled analgesia was assessed using 4 different pain rating scales. patients given remifentanil had lower Visual Analog Scale scores at 24 h compared to those given sufentanil (p = 0.002). The Numeric Rating Scale at 24 h was also significantly lower in patients using remifentanil (p = 0.004). The Faces Pain Scale scores at 4, 18, and 24 h were significantly lower in patients using remifentanil compared to those using sufentanil (p = 0.045, 0.036, and 0.011, respectively). No significant differences between groups were seen in the pain intensity assessed by the Behavior Rating Scale at any time point during the first 24 h postoperatively. our study showed that both remifentanil and sufentanil patient-controlled analgesia can provide acceptable analgesia after coronary artery bypass. The difference between their efficacies was inconspicuous until 24 h postoperatively. Remifentanil seems to result in better pain relief at 24 h postoperatively. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Comparing the Effectiveness of Patient Control Analgesia Pump and Bolus Morphine in Controlling Pain After Cardiopulmonary Bypass Graft Surgery.

PubMed

Imantalab, Vali; Mirmansouri, Ali; Mohammadzadeh Jouryabi, Ali; Naderi Nabi, Bahram; Kanani, Gholamreza; Nassiri Sheikhani, Nassir; Atrkarroushan, Zahra; Ghazanfar Tehran, Samaneh; Samadpour, Nastaran

2017-10-01

Postoperative pain is a complex process commonly caused by surgical trauma. It is one of the major concerns of patients undergoing heart surgery. Despite new techniques and modern analgesic treatments, postoperative pain is still one of the most important controversial issues. 68 patients scheduled for elective CABG with CPB were included in a prospective, double-blind clinical trial. They were randomly divided into two groups. One group received PCA pump including morphine (group P) with underlying infusion of 0.02 mg/kg/Qh, bolus dose of 1 mg, lockout time of 15 minutes, and a maximum of 4 bolus of 0.02 mg/kg for one hour and the other group received morphine bolus (group B). Three patients were excluded from the study, and 33 and 32 patients participated in the groups P and B, respectively. Variables including age, gender, pump time, aortic clamp time, duration of surgery, complications (nausea and vomiting, GI Bleeding, and hypoxia), level of pain based on VAS, opioid consumption, hemodynamic, and sedation status were measured in both groups. There was no significant difference between the groups regarding age, gender, pump time, clamp time, duration of surgery, complication, sedation score, and hemodynamic status in most of the assessment periods. By assessing the pain severity in the groups at different periods, results showed a significant difference between the groups except at enrollment, and a lower severity of pain was noted in the group P compared to the group B. The consumed opioid was significantly higher in the group P than in the group B. However, higher doses of diclofenac and paracetamol were administered in the group B compared to the group P. Results showed that higher morphine would be used in patients with PCA pump after extubation following heart surgery, and this increased dose of opioid was associated with better pain control and lack of complication. Therefore, PCA pump with underlying infusion could be effectively used in patients

Comparing the Effectiveness of Patient Control Analgesia Pump and Bolus Morphine in Controlling Pain After Cardiopulmonary Bypass Graft Surgery

PubMed Central

Imantalab, Vali; Mirmansouri, Ali; Mohammadzadeh Jouryabi, Ali; Naderi Nabi, Bahram; Kanani, Gholamreza; Nassiri Sheikhani, Nassir; Atrkarroushan, Zahra; Ghazanfar Tehran, Samaneh; Samadpour, Nastaran

2017-01-01

Background Postoperative pain is a complex process commonly caused by surgical trauma. It is one of the major concerns of patients undergoing heart surgery. Despite new techniques and modern analgesic treatments, postoperative pain is still one of the most important controversial issues. Methods 68 patients scheduled for elective CABG with CPB were included in a prospective, double-blind clinical trial. They were randomly divided into two groups. One group received PCA pump including morphine (group P) with underlying infusion of 0.02 mg/kg/Qh, bolus dose of 1 mg, lockout time of 15 minutes, and a maximum of 4 bolus of 0.02 mg/kg for one hour and the other group received morphine bolus (group B). Three patients were excluded from the study, and 33 and 32 patients participated in the groups P and B, respectively. Variables including age, gender, pump time, aortic clamp time, duration of surgery, complications (nausea and vomiting, GI Bleeding, and hypoxia), level of pain based on VAS, opioid consumption, hemodynamic, and sedation status were measured in both groups. Results There was no significant difference between the groups regarding age, gender, pump time, clamp time, duration of surgery, complication, sedation score, and hemodynamic status in most of the assessment periods. By assessing the pain severity in the groups at different periods, results showed a significant difference between the groups except at enrollment, and a lower severity of pain was noted in the group P compared to the group B. The consumed opioid was significantly higher in the group P than in the group B. However, higher doses of diclofenac and paracetamol were administered in the group B compared to the group P. Conclusions Results showed that higher morphine would be used in patients with PCA pump after extubation following heart surgery, and this increased dose of opioid was associated with better pain control and lack of complication. Therefore, PCA pump with underlying infusion could

Postoperative pain after laparoscopic sleeve gastrectomy: comparison of three analgesic schemes (isolated intravenous analgesia, epidural analgesia associated with intravenous analgesia and port-sites infiltration with bupivacaine associated with intravenous analgesia).

PubMed

Ruiz-Tovar, Jaime; Muñoz, Jose Luis; Gonzalez, Juan; Zubiaga, Lorea; García, Alejandro; Jimenez, Montiel; Ferrigni, Carlos; Durán, Manuel

2017-01-01

Although bariatric surgery is actually mainly performed laparoscopically, analgesic optimization continues being essential to reduce complications and to improve the patients' comfort. The aim of this study is to evaluate the postoperative pain after analgesia iv exclusively, or associated with epidural analgesia or port-sites infiltration with bupivacaine. A prospective randomized study of patients undergoing laparoscopic sleeve gastrectomy between 2012 and 2014 was performed. Patients were divided into three groups: Analgesia iv exclusively (Group 1), epidural analgesia + analgesia iv (Group 2) and port-sites infiltration + analgesia iv (Group 3). Pain was quantified by means of a Visual Analogic Scale, and morphine rescue needs were determined 24 h after surgery. A total of 147 were included. Groups were comparable in age, gender and BMI. There were no differences in operation time, complications, mortality or hospital stay between groups. Median pain 24 h after surgery was 5 in Group 1, 2.5 in Group 2 and 2 in Group 3 (P = 0.01), without statistically significant differences between Groups 2 and 3. In Group 1, morphine rescue was necessary in 16.3 % of the cases, 2 % in Group 2 and 2 % in Group 3 (P = 0.014), without statistically significant differences between Groups 2 and 3. Epidural analgesia and port-sites infiltration with bupivacaine, associated with analgesia iv, reduce the postoperative pain, when compared with analgesia iv exclusively. ClinicalTrials.gov Identifier: NCT02662660.

Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats.

PubMed

Esmaeili-Mahani, Saeed; Rezaeezadeh-Roukerd, Maryam; Esmaeilpour, Khadije; Abbasnejad, Mehdi; Rasoulian, Bahram; Sheibani, Vahid; Kaeidi, Ayat; Hajializadeh, Zahra

2010-10-28

Olive (Olea europaea) leaves are used as anti-rheumatic, anti-inflammatory, antinociceptive, antipyretic, vasodilatory, hypotensive, antidiuretic and hypoglycemic agents in traditional medicine. Recently, it has been shown that olive leaf extract (OLE) has calcium channel blocker property; however, its influences on nociceptive threshold and morphine effects have not yet been clarified. All experiments were carried out on male Wistar rats. The tail-flick, hot-plate and formalin tests were used to assess the effect of OLE on nociceptive threshold. To determine the effect of OLE on analgesic and hyperalgesic effects of morphine, OLE (6, 12 and 25 mg/kg i.p.) that had no significant nociceptive effect, was injected concomitant with morphine (5 mg/kg and 1 μg/kg i.p., respectively). The tail-flick test was used to assess the effect of OLE on anti- and pro-nociceptive effects of morphine. The data showed that OLE (50-200 mg/kg i.p.) could produce dose-dependent analgesic effect on tail-flick and hot-plate tests. Administration of 200 mg/kg OLE (i.p.) caused significant decrease in pain responses in the first and the second phases of formalin test. In addition, OLE could potentiate the antinociceptive effect of 5 mg/kg morphine and block low-dose morphine-induced hyperalgesia. Our results indicate that olive leaf extract has analgesic property in several models of pain and useful influence on morphine analgesia in rats. Therefore, it can be used for the treatment and/or management of painful conditions. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Relative Contributions of Adductor Canal Block and Intrathecal Morphine to Analgesia and Functional Recovery After Total Knee Arthroplasty: A Randomized Controlled Trial.

PubMed

Biswas, Abhijit; Perlas, Anahi; Ghosh, Meela; Chin, KiJinn; Niazi, Ahtsham; Pandher, Barjind; Chan, Vincent

2018-02-01

Effective postoperative analgesia may enhance early rehabilitation after orthopedic surgery. This randomized double-blind trial investigates the relative contributions of adductor canal block and low-dose intrathecal morphine (ITM) to postoperative analgesia and functional recovery after total knee arthroplasty. Two-hundred one patients undergoing elective unilateral total knee arthroplasty under spinal anesthesia were randomized to 3 groups. All patients received standardized intraoperative local infiltration analgesia and postoperative oral analgesics. Patients in group 1 received a "sham" adductor canal block with 30 mL of normal saline. Patients in group 2 received an adductor canal block with 30 mL of ropivacaine 0.5% with 1:400,000 epinephrine, whereas patients in group 3 received the adductor canal block with the active drug and 100 μg of ITM. The primary outcome measure was the Timed Up and Go (TUG) test on the second postoperative day. Secondary outcomes included postoperative pain scores and opioid requirements, distance walked, time to hospital discharge, and self-reported functional outcomes at 3 months. All 3 groups had similar values of TUG test on postoperative day (POD) 2 (46 [36-62], 45 [33-61], and 52 [41-69]; P = 0.166) as well as other short-term and 3-month functional outcomes. Patients in group 3 showed a favorable analgesic profile as evidenced by 3 positive secondary outcomes. These positive outcomes were lower pain scores 12 hours postoperatively both at rest (4 [2-6.3], 4 [2.3-6], and 3 [1-4]; P = 0.007) and on movement (6 [4-8], 6 [3-8], and 4 [2-6]; P = 0.002), a lower incidence of "rescue" intravenous patient-controlled analgesia (42%, 34%, and 20%; P = 0.031), and the lowest cumulative opioid requirements for the first 48 hours postoperatively (86 ± 71, 68 ± 46, and 59 ± 39; P < 0.005, group 3 compared with group 1). Our data suggest that there is no difference in either the primary outcome of TUG test on POD 2, other immediate

Comparison of Transversus Abdominis Plane Infiltration with Liposomal Bupivacaine versus Continuous Epidural Analgesia versus Intravenous Opioid Analgesia.

PubMed

Ayad, Sabry; Babazade, Rovnat; Elsharkawy, Hesham; Nadar, Vinayak; Lokhande, Chetan; Makarova, Natalya; Khanna, Rashi; Sessler, Daniel I; Turan, Alparslan

2016-01-01

Epidural analgesia is considered the standard of care but cannot be provided to all patients Liposomal bupivacaine has been approved for field blocks such as transversus abdominis plane (TAP) blocks but has not been clinically compared against other modalities. In this retrospective propensity matched cohort study we thus tested the primary hypothesis that TAP infiltration are noninferior (not worse) to continuous epidural analgesia and superior (better) to intravenous opioid analgesia in patients recovering from major lower abdominal surgery. 318 patients were propensity matched on 18 potential factors among three groups (106 per group): 1) TAP infiltration with bupivacaine liposome; 2) continuous Epidural analgesia with plain bupivacaine; and; 3) intravenous patient-controlled analgesia (IV PCA). We claimed TAP noninferior (not worse) over Epidural if TAP was noninferior (not worse) on total morphine-equivalent opioid and time-weighted average pain score (10-point scale) within first 72 hours after surgery with noninferiority deltas of 1 (10-point scale) for pain and an increase less of 20% in the mean morphine equivalent opioid consumption. We claimed TAP or Epidural groups superior (better) over IV PCA if TAP or Epidural was superior on opioid consumption and at least noninferior on pain outcome. Multivariable linear regressions within the propensity-matched cohorts were used to model total morphine-equivalent opioid dose and time-weighted average pain score within first 72 hours after surgery; joint hypothesis framework was used for formal testing. TAP infiltration were noninferior to Epidural on both primary outcomes (p<0.001). TAP infiltration were noninferior to IV PCA on pain scores (p = 0.001) but we did not find superiority on opioid consumption (p = 0.37). We did not find noninferiority of Epidural over IV PCA on pain scores (P = 0.13) and nor did we find superiority on opioid consumption (P = 0.98). TAP infiltration with liposomal bupivacaine and

Effect of Parecoxib as an Adjunct to Patient-Controlled Epidural Analgesia after Abdominal Hysterectomy: A Multicenter, Randomized, Placebo-Controlled Trial.

PubMed

Liu, Wei-Feng; Shu, Hai-Hua; Zhao, Guo-Dong; Peng, Shu-Ling; Xiao, Jin-Fang; Zhang, Guan-Rong; Liu, Ke-Xuan; Huang, Wen-Qi

2016-01-01

This multicenter, randomized, placebo-controlled study evaluated the efficacy and side effects of parecoxib during patient-controlled epidural analgesia (PCEA) after abdominal hysterectomy. A total of 240 patients who were scheduled for elective abdominal hysterectomy under combined spinal-epidural anesthesia received PCEA plus postoperative intravenous parecoxib 40 mg or saline every 12 h for 48 h after an initial preoperative dose of parecoxib 40 mg or saline. An epidural loading dose of a mixture of 6 mL of 0.25% ropivacaine and 2 mg morphine was administered 30 min before the end of surgery, and PCEA was initiated using 1.25 mg/mL ropivacaine and 0.05 mg/mL morphine with a 2-mL/h background infusion and 2-mL bolus with a 15-min lockout. The primary end point of this study was the quantification of the PCEA-sparing effect of parecoxib. Demographic data were similar between the two groups. Patients in the parecoxib group received significantly fewer self-administrated boluses (0 (0, 3) vs. 7 (2, 15), P < 0.001) and less epidural morphine (5.01 ± 0.44 vs. 5.95 ± 1.29 mg, P < 0.001) but experienced greater pain relief compared with the control group (P < 0.001). Patient global satisfaction was higher in the parecoxib group than the control group (P < 0.001). Length of hospitalization (9.50 ± 2.1, 95% CI 9.12~9.88 vs. 10.41 ± 2.6, 95% CI 9.95~10.87, P = 0.003) and postoperative vomiting (17% vs. 29%, P < 0.05) were also reduced in the parecoxib group. There were no serious adverse effects in either group. Our data suggest that adjunctive parecoxib during PCEA following abdominal hysterectomy is safe and efficacious in reducing pain, requirements of epidural analgesics, and side effects. ClinicalTrials.gov (NCT01566669).

The effect of tramadol plus paracetamol on consumption of morphine after coronary artery bypass grafting.

PubMed

Altun, Dilek; Çınar, Özlem; Özker, Emre; Türköz, Ayda

2017-02-01

To compare the effects of oral tramadol+paracetamol combination on morphine consumption following coronary artery bypass grafting (CABG) in the patient-controlled analgesia (PCA) protocol. A prospective, double-blind, randomized, clinical study. Single-institution, tertiary hospital. Fifty cardiac surgical patients undergoing primary CABG surgery. After surgery, the patients were allocated to 1 of 2 groups. Both groups received morphine according to the PCA protocol after arrival to the coronary intensive care unit (bolus 1 mg, lockout time 15 minutes). In addition to morphine administration 2 hours before operation and postoperative 2nd, 6th, 12th, 18th, 24th, 30th, 36th, 42th, and 48th hours, group T received tramadol+paracetamol (Zaldiar; 325 mg paracetamol, 37.5 mg tramadol) and group P received placebo. Sedation levels were measured with the Ramsay Sedation Scale, whereas pain was assessed with the Pain Intensity Score during mechanical ventilation and with the Numeric Rating Scale after extubation. If the Numeric Rating Scale score was ≥3 and Pain Intensity Score was ≥3, 0.05 mg/kg morphine was administered additionally. Preoperative patient characteristics, risk assessment, and intraoperative data were similar between the groups. Cumulative morphine consumption, number of PCA demand, and boluses were higher in group P (P<.01). The amount of total morphine (in mg) used as a rescue analgesia was also higher in group P (5.06±1.0), compared with group T (2.37±0.52; P<.001). The patients who received rescue doses of morphine were 8 (32%) in group T and 18 (72%) in group P (P<.001). Duration of mechanical ventilation in group P was longer than group T (P<.01). Tramadol+paracetamol combination along with PCA morphine improves analgesia and reduces morphine requirement up to 50% after CABG, compared with morphine PCA alone. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation of opioid analgesia by agmatine.

PubMed

Kolesnikov, Y; Jain, S; Pasternak, G W

1996-01-18

Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, agmatine enhances morphine analgesia in a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater effect is observed when morphine is given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to the potentiation of morphine analgesia, agmatine (10 mg/kg) has no effect on morphine's inhibition of gastrointestinal transit. delta-Opioid receptor-mediated analgesia also is potentiated by agmatine, but kappa1-receptor-mediated (U50,488H; trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetemide) and kappa3-opioid receptor-mediated (naloxone benzoylhydrazone) analgesia is not significantly enhanced by any dose of agmatine tested in this acute model. In chronic studies, agmatine at a low dose (0.1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days. A higher agmatine dose (10 mg/kg) has a similar effect. Agmatine also blocks tolerance to the delta-opioid receptor ligand [D-Pen2,D-Pen5]enkephalin given intrathecally, but not to the kappa3-opioid receptor agonist naloxone benzoylhydrazone. Despite its inactivity on kappa1-opioid analgesia in the acute model, agmatine prevents kappa1-opioid receptor-mediated tolerance. These studies demonstrate the dramatic interactions between agmatine and opioid analgesia and tolerance.

The Effects of Ketorolac Injected via Patient Controlled Analgesia Postoperatively on Spinal Fusion

PubMed Central

Park, Si-Young; Moon, Seong-Hwan; Park, Moon-Soo; Oh, Kyung-Soo

2005-01-01

Lumbar spinal fusions have been performed for spinal stability, pain relief and improved function in spinal stenosis, scoliosis, spinal fractures, infectious conditions and other lumbar spinal problems. The success of lumbar spinal fusion depends on multifactors, such as types of bone graft materials, levels and numbers of fusion, spinal instrumentation, electrical stimulation, smoking and some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January 2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal stenosis or spondylolisthesis, were retrospectively enrolled in this study. One surgeon performed all 88 posterolateral spinal fusions with instrumentation and autoiliac bone graft. The patients were divided into two groups. The first group (n=30) was infused with ketorolac and fentanyl intravenously via patient controlled analgesia (PCA) postoperatively and the second group (n=58) was infused only with fentanyl. The spinal fusion rates and clinical outcomes of the two groups were compared. The incidence of incomplete union or nonunion was much higher in the ketorolac group, and the relative risk was approximately 6 times higher than control group (odds ratio: 5.64). The clinical outcomes, which were checked at least 1 year after surgery, showed strong correlations with the spinal fusion status. The control group (93.1%) showed significantly better clinical results than the ketorolac group (77.6%). Smoking had no effect on the spinal fusion outcome in this study. Even though the use of ketorolac after spinal fusion can reduce the need for morphine, thereby decreasing morphine related complications, ketorolac used via PCA at the immediate postoperative state inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs such as ketorolac, should be avoided after posterolateral spinal fusion. PMID:15861498

Patient-controlled Intermittent Epidural Bolus Versus Epidural Infusion for Posterior Spinal Fusion After Adolescent Idiopathic Scoliosis: Prospective, Randomized, Double-blinded Study.

PubMed

Erdogan, Mehmet Ali; Ozgul, Ulku; Ucar, Muharrem; Korkmaz, Mehmet Fatih; Aydogan, Mustafa Said; Ozkan, Ahmet Selim; Colak, Cemil; Durmus, Mahmut

2017-06-15

A prospective, randomized, double-blinded study. The aim of this study was to compare the efficacy and side effects of patient-controlled intermittent bolus epidural analgesia (PCIEA) and patient-controlled continuous epidural analgesia (PCCEA) for postoperative pain control in adolescent idiopathic scoliosis. Epidural analgesia is an accepted efficacious and safe procedure for postoperative pain management in scoliosis surgery. However, the PCIEA has not been adequately investigated for postoperative pain control in adolescent idiopathic scoliosis. Forty-seven patients, 8 to 18 years of age, who were undergoing posterior spinal fusion for idiopathic scoliosis were randomized to either the PCIEA or PCCEA group. An epidural catheter was inserted by a surgeon under direct visualization. The PCIEA group received 0.2 mg/mL of morphine, 0.25 mL/kg of morphine bolus, additional doses of 0.25 mL/kg morphine with a 1-hour lockout given by patient-controlled demand, and no infusion. The PCCEA group received the following: 0.2 mg/mL morphine, an initial morphine loading set at 0.1 mL/kg, followed by a 0.05 mL/kg/h continuous infusion of morphine, and a 0.025 mL/kg bolus dose of morphine. There was a 30-minute lockout interval. The primary outcome was morphine usage. The secondary outcomes were pain score, postoperative nausea and vomiting, and pruritus. Cumulative morphine consumption was lower in the PCIEA group than in the PCCEA group. Both methods provided effective pain control. There were no differences in pain scores between the groups. Postoperative nausea, vomiting, and pruritus were lower in the PCIEA group. The two epidural analgesia techniques studied are both safe and effective methods for postoperative pain control after posterior spinal fusion in idiopathic scoliosis. Nausea, vomiting and pruritus were considerably higher in the PCCEA group. Concerns regarding side effects associated with epidural opioids can be avoided by an intermittent bolus

The Analgesic Efficiency of Ultrasound-Guided Rectus Sheath Analgesia Compared with Low Thoracic Epidural Analgesia After Elective Abdominal Surgery with a Midline Incision: A Prospective Randomized Controlled Trial.

PubMed

Yassin, Hany Mahmoud; Abd Elmoneim, Ahmed Tohamy; El Moutaz, Hatem

2017-06-01

Ultrasound-guided rectus sheath blockade has been described to provide analgesia for midline abdominal incisions. We aimed to compare thoracic epidural analgesia (TEA) and rectus sheath analgesia (RSA) with respect to safety and efficacy. Sixty patients who underwent elective laparotomies through a midline incision were assigned randomly to receive either continuous TEA (TEA group, n = 31) or intermittent RSA (RSA group, n = 29). The number of patients who required analgesia, the time to first request analgesia, the interval and the cumulative morphine doses consumption during 72 hours postoperatively, and pain intensity using visual analog score (VAS) at rest and upon coughing were reported in addition to any side effects related to both techniques or administered drugs. While 17 (54.84 %) patients were in the TEA group, 25 (86.21%) patients in the RSA group required analgesia postoperatively, P = 0.008. Cumulative morphine consumed during the early 72 hours postoperatively median (interquartile range) = 33 mg (27 - 39 mg), 95% confidence interval (28.63 - 37.37 mg) for the TEA group. While in the RSA group, it was 51 mg (45 - 57 mg), 95% CI (47.4 - 54.6 mg), P < 0.001. The time for the first request of morphine was 256.77 ± 73.45 minutes in the TEA group versus 208.82 ± 64.65 min in the RSA group, P = 0.031. VAS at rest and cough were comparable in both groups at all time points of assessment, P > 0.05. The time to the ambulation was significantly shorter in the RSA group (38.47 ± 12.34 hours) as compared to the TEA group (45.89 ± 8.72 hours), P = 0.009. Sedation scores were significantly higher in the RSA group, only at 12 hours and 24 hours postoperatively than in TEA group, with P = 0.041 and 0.013, respectively. The incidence of other morphine-related side effects, time to pass flatus, and patients satisfaction scores were comparable between both groups. Continuous TEA had better opioid sparing effects markedly during the early 72 hours postoperatively

The Analgesic Efficiency of Ultrasound-Guided Rectus Sheath Analgesia Compared with Low Thoracic Epidural Analgesia After Elective Abdominal Surgery with a Midline Incision: A Prospective Randomized Controlled Trial

PubMed Central

Yassin, Hany Mahmoud; Abd Elmoneim, Ahmed Tohamy; El Moutaz, Hatem

2017-01-01

Background Ultrasound-guided rectus sheath blockade has been described to provide analgesia for midline abdominal incisions. We aimed to compare thoracic epidural analgesia (TEA) and rectus sheath analgesia (RSA) with respect to safety and efficacy. Methods Sixty patients who underwent elective laparotomies through a midline incision were assigned randomly to receive either continuous TEA (TEA group, n = 31) or intermittent RSA (RSA group, n = 29). The number of patients who required analgesia, the time to first request analgesia, the interval and the cumulative morphine doses consumption during 72 hours postoperatively, and pain intensity using visual analog score (VAS) at rest and upon coughing were reported in addition to any side effects related to both techniques or administered drugs. Results While 17 (54.84 %) patients were in the TEA group, 25 (86.21%) patients in the RSA group required analgesia postoperatively, P = 0.008. Cumulative morphine consumed during the early 72 hours postoperatively median (interquartile range) = 33 mg (27 - 39 mg), 95% confidence interval (28.63 - 37.37 mg) for the TEA group. While in the RSA group, it was 51 mg (45 - 57 mg), 95% CI (47.4 - 54.6 mg), P < 0.001. The time for the first request of morphine was 256.77 ± 73.45 minutes in the TEA group versus 208.82 ± 64.65 min in the RSA group, P = 0.031. VAS at rest and cough were comparable in both groups at all time points of assessment, P > 0.05. The time to the ambulation was significantly shorter in the RSA group (38.47 ± 12.34 hours) as compared to the TEA group (45.89 ± 8.72 hours), P = 0.009. Sedation scores were significantly higher in the RSA group, only at 12 hours and 24 hours postoperatively than in TEA group, with P = 0.041 and 0.013, respectively. The incidence of other morphine-related side effects, time to pass flatus, and patients satisfaction scores were comparable between both groups. Conclusions Continuous TEA had better opioid sparing effects markedly

Supraspinally administered agmatine prevents the development of supraspinal morphine analgesic tolerance.

PubMed

Kitto, Kelley F; Fairbanks, Carolyn A

2006-04-24

We have determined the effect of intracerebroventricularly (i.c.v.) administered decarboxylated arginine (agmatine) on supraspinally induced chronic morphine analgesic tolerance. Mice pre-treated with a schedule of chronic i.c.v administration of morphine (10 nmol, b.i.d. 3 days) show a 12-fold reduction in the potency of acutely administered i.c.v morphine compared to saline injected controls. Co-administration of agmatine (10 nmol) with one of the two daily morphine injections completely prevents the reduction in i.c.v morphine analgesia. Mice injected with agmatine once daily (but no morphine) do not show a increase in morphine analgesic potency relative to saline controls, indicating that a mere potentiation of acute morphine analgesia cannot account for the agmatine-mediated anti-tolerance effect in those mice subjected to the morphine tolerance induction schedule. These observations agree with previous reports that systemically and intrathecally administered agmatine prevent opioid tolerance, and extend these results to include a supraspinal site of action.

Stability of piritramide in patient-controlled analgesia (PCA) solutions.

PubMed

Remane, D; Scriba, G; Meissner, W; Hartmann, M

2009-06-01

For patient controlled analgesia, syringes with solutions of 1.5 mg/ml piritramide in 0.9% aqueous sodium chloride are used. The physical and chemical stability for dilutions of the commercially available preparation of piritramide is limited up to 72 hours by the manufacturer. Since application duration for patient-controlled analgesia can exceed that limited time, stability was investigated by HPLC. Our results show that these solutions are chemically stable over a time period of 60 days.

A role for heterodimerization of mu and delta opiate receptors in enhancing morphine analgesia.

PubMed

Gomes, Ivone; Gupta, Achla; Filipovska, Julija; Szeto, Hazel H; Pintar, John E; Devi, Lakshmi A

2004-04-06

Opiates such as morphine are the choice analgesic in the treatment of chronic pain. However their long-term use is limited because of the development of tolerance and dependence. Due to its importance in therapy, different strategies have been considered for making opiates such as morphine more effective, while curbing its liability to be abused. One such strategy has been to use a combination of drugs to improve the effectiveness of morphine. In particular, delta opioid receptor ligands have been useful in enhancing morphine's potency. The underlying molecular basis for these observations is not understood. We propose the modulation of receptor function by physical association between mu and delta opioid receptors as a potential mechanism. In support of this hypothesis, we show that mu-delta interacting complexes exist in live cells and native membranes and that the occupancy of delta receptors (by antagonists) is sufficient to enhance mu opioid receptor binding and signaling activity. Furthermore, delta receptor antagonists enhance morphine-mediated intrathecal analgesia. Thus, heterodimeric associations between mu-delta opioid receptors can be used as a model for the development of novel combination therapies for the treatment of chronic pain and other pathologies.

The effect of short-term continuous epidural morphine on postoperative pain after laparoscopic cholecystectomy.

PubMed

Fujikawa, T; Nakamura, Y; Takeda, H; Matsusue, S; Kato, Y; Nishiwada, M

1998-01-01

This study was undertaken to determine whether short-term continuous epidural analgesia using morphine would relieve pain after laparoscopic cholecystectomy. The authors retrospectively reviewed the clinical data of 182 cases who had undergone a laparoscopic cholecystectomy. These cases were divided into four groups according to their anesthetic modes as follows: a control group with general anesthesia only (n = 37); group I, general anesthesia combined with one shot of epidural morphine (n = 78); and group II, general anesthesia combined with continuous epidural analgesia using morphine (IIa for 12 h (n = 33); IIb for 8 h (n = 34)). The pain score on a four-category verbal scale and the frequency of analgesic use were investigated. There were no differences in the background characteristics of the patients among the groups, except for the duration of surgery (I vs IIa; P = 0.006). The pain scores were significantly different between the control group and the other groups. The frequency of analgesic use in the control group was also significantly higher than in the other groups. A tendency toward a higher frequency of analgesic use in group I, compared with that in groups IIa and IIb, was observed. These findings thus suggest that short-term continuous epidural analgesia using morphine can effectively relieve postoperative pain after a laparoscopic cholecystectomy.

Involvement of protein kinase C in the modulation of morphine-induced analgesia and the inhibitory effects of exposure to 60-hz magnetic fields in the land snail, Cepaea nemoralis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kavaliers, M.; Ossenkopp, K.P.

1990-02-26

One of the more consistent and dramatic effects of exposure to magnetic fields is the attenuation of morphine-induced analgesia. Results of previous studies have implicated alterations in calcium channel functioning and Ca{sup ++} flux in the mediation of these effects. It is generally accepted that Ca{sup ++}-activated-phospholipid-dependent protein kinase (Protein kinase C; PKC) plays an important role in relaying trans-membrane signaling in diverse Ca{sup ++} dependent cellular processes. In experiment 1 we observed that morphine-induced analgesia in the land snail, Cepaea nemoralis, as measured by the latency of an avoidance behavior to a warmed surface, was reduced by the PKCmore » activator, SC-9, and was enhanced by the PKC inhibitors, H-7 and H-9. In contrast, HA-10004, a potent inhibitor of other protein kinases, but only a very weak inhibitor of PKC, had no effect on morphine-induced analgesia. In experiment 2 exposure of snails for 30 minutes to a 1.0 gauss (rms) 60-Hz magnetic field reduced morphine-induced analgesia. This inhibitory effect of the magnetic field was reduced by the PKC inhibitors, H-7 and H-9, and was augmented by the PKC activator SC-9. These results suggest that: (i) PKC is involved in the modulation of morphine-induced analgesia and, (ii) the inhibitory effects of magnetic fields involve PKC.« less

Effect of Parecoxib as an Adjunct to Patient-Controlled Epidural Analgesia after Abdominal Hysterectomy: A Multicenter, Randomized, Placebo-Controlled Trial

PubMed Central

Liu, Wei-Feng; Shu, Hai-Hua; Zhao, Guo-Dong; Peng, Shu-Ling; Xiao, Jin-Fang; Zhang, Guan-Rong; Liu, Ke-Xuan; Huang, Wen-Qi

2016-01-01

Objective This multicenter, randomized, placebo-controlled study evaluated the efficacy and side effects of parecoxib during patient-controlled epidural analgesia (PCEA) after abdominal hysterectomy. Methods A total of 240 patients who were scheduled for elective abdominal hysterectomy under combined spinal-epidural anesthesia received PCEA plus postoperative intravenous parecoxib 40 mg or saline every 12 h for 48 h after an initial preoperative dose of parecoxib 40 mg or saline. An epidural loading dose of a mixture of 6 mL of 0.25% ropivacaine and 2 mg morphine was administered 30 min before the end of surgery, and PCEA was initiated using 1.25 mg/mL ropivacaine and 0.05 mg/mL morphine with a 2-mL/h background infusion and 2-mL bolus with a 15-min lockout. The primary end point of this study was the quantification of the PCEA-sparing effect of parecoxib. Results Demographic data were similar between the two groups. Patients in the parecoxib group received significantly fewer self-administrated boluses (0 (0, 3) vs. 7 (2, 15), P < 0.001) and less epidural morphine (5.01 ± 0.44 vs. 5.95 ± 1.29 mg, P < 0.001) but experienced greater pain relief compared with the control group (P < 0.001). Patient global satisfaction was higher in the parecoxib group than the control group (P < 0.001). Length of hospitalization (9.50 ± 2.1, 95% CI 9.12~9.88 vs. 10.41 ± 2.6, 95% CI 9.95~10.87, P = 0.003) and postoperative vomiting (17% vs. 29%, P < 0.05) were also reduced in the parecoxib group. There were no serious adverse effects in either group. Conclusion Our data suggest that adjunctive parecoxib during PCEA following abdominal hysterectomy is safe and efficacious in reducing pain, requirements of epidural analgesics, and side effects. Trial Registration ClinicalTrials.gov (NCT01566669) PMID:27622453

Pavlovian second-order conditioned analgesia.

PubMed

Ross, R T

1986-01-01

Three experiments with rat subjects assessed conditioned analgesia in a Pavlovian second-order conditioning procedure by using inhibition of responding to thermal stimulation as an index of pain sensitivity. In Experiment 1, rats receiving second-order conditioning showed longer response latencies during a test of pain sensitivity in the presence of the second-order conditioned stimulus (CS) than rats receiving appropriate control procedures. Experiment 2 found that extinction of the first-order CS had no effect on established second-order conditioned analgesia. Experiment 3 evaluated the effects of post second-order conditioning pairings of morphine and the shock unconditioned stimulus (US). Rats receiving paired morphine-shock presentations showed significantly shorter response latencies during a hot-plate test of pain sensitivity in the presence of the second-order CS than did groups of rats receiving various control procedures; second-order analgesia was attenuated. These data extend the associative account of conditioned analgesia to second-order conditioning situations and are discussed in terms of the mediation of both first- and second-order analgesia by an association between the CS and a representation or expectancy of the US, which may directly activate endogenous pain inhibition systems.

A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

PubMed Central

Wang, Yi-lun; Li, Yu-sheng; Wei, Jie; Li, Hui; Yang, Tuo; Yang, Tu-bao; Lei, Guang-hua

2015-01-01

Objectives The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery. Methods Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software. Results Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone. Conclusion The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone. Level of Evidence Level I, meta-analysis of Level I studies. PMID:26474401

Duloxetine reduces morphine requirements after knee replacement surgery.

PubMed

Ho, K-Y; Tay, W; Yeo, M-C; Liu, H; Yeo, S-J; Chia, S-L; Lo, N-N

2010-09-01

Multimodal analgesia is advocated for perioperative pain management to reduce opioid use and its associated adverse effects. Serotonin and norepinephrine are involved in the modulation of endogenous analgesic mechanisms via descending inhibitory pain pathways in the brain and spinal cord. An increase in serotonin and norepinephrine may increase inhibition of nociceptive input and improve pain relief. Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, has demonstrated efficacy in chronic pain conditions such as painful diabetic neuropathy and post-herpetic neuralgia. The objective of the study was to evaluate the efficacy of duloxetine in reducing morphine requirements in patients after knee replacement surgery. Fifty patients received either two doses of oral duloxetine 60 mg (2 h before surgery and on first postoperative day) or placebo. All patients received patient-controlled analgesia with morphine for 48 h after operation. Pain and adverse effects were assessed at 0.5, 1, 2, 6, 12, 24, and 48 h after surgery on an 11-point numeric rating scale. Twenty-three patients in the duloxetine group and 24 patients in the placebo group completed the study. Morphine requirements during the 48 h after surgery were significantly lower in the duloxetine group [19.5 mg, standard deviation (sd) 14.5 mg] compared with the placebo group (30.3 mg, sd 18.1 mg) (P=0.017). There were no statistically significant differences between the groups in pain scores (at rest and on movement) or in adverse effects. Perioperative administration of duloxetine reduced postoperative morphine requirements during the first 48 h after knee replacement surgery, without significant adverse effects.

Etoricoxib - preemptive and postoperative analgesia (EPPA) in patients with laparotomy or thoracotomy - design and protocols

PubMed Central

2010-01-01

Background and Objective Our objective was to report on the design and essentials of the Etoricoxib protocol- Preemptive and Postoperative Analgesia (EPPA) Trial, investigating whether preemptive analgesia with cox-2 inhibitors is more efficacious than placebo in patients who receive either laparotomy or thoracotomy. Design and Methods The study is a 2 × 2 factorial armed, double blinded, bicentric, randomised placebo-controlled trial comparing (a) etoricoxib and (b) placebo in a pre- and postoperative setting. The total observation period is 6 months. According to a power analysis, 120 patients scheduled for abdominal or thoracic surgery will randomly be allocated to either the preemptive or the postoperative treatment group. These two groups are each divided into two arms. Preemptive group patients receive etoricoxib prior to surgery and either etoricoxib again or placebo postoperatively. Postoperative group patients receive placebo prior to surgery and either placebo again or etoricoxib after surgery (2 × 2 factorial study design). The Main Outcome Measure is the cumulative use of morphine within the first 48 hours after surgery (measured by patient controlled analgesia PCA). Secondary outcome parameters include a broad range of tests including sensoric perception and genetic polymorphisms. Discussion The results of this study will provide information on the analgesic effectiveness of etoricoxib in preemptive analgesia and will give hints on possible preventive effects of persistent pain. Trial registration NCT00716833 PMID:20504378

PolyMorphine: an innovative biodegradable polymer drug for extended pain relief.

PubMed

Rosario-Meléndez, Roselin; Harris, Carolyn L; Delgado-Rivera, Roberto; Yu, Lei; Uhrich, Kathryn E

2012-09-28

Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed "PolyMorphine", was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge. Copyright © 2012 Elsevier B.V. All rights reserved.

Patient-controlled oral analgesia for postoperative pain management following total knee replacement

PubMed Central

Kastanias, Patti; Gowans, Sue; Tumber, Paul S; Snaith, Kianda; Robinson, Sandra

2010-01-01

PURPOSE: To investigate whether patient-controlled oral analgesia (PCOA) used by individuals receiving a total knee replacement could reduce pain, increase patient satisfaction, reduce opioid use and/or reduce opioid side effects when compared with traditional nurse (RN)-administered oral analgesia. METHODS: Patients who underwent an elective total knee replacement at a quaternary care centre (Toronto Western Hospital, Toronto, Ontario) were randomly assigned to either PCOA or RN-administered short-acting oral opioids on postoperative day 2. Subjects in the RN group called the RN to receive their prescribed short-acting opioid. Subjects in the PCOA group kept a single dose of their prescribed oral opioid at their bedside and took this dose when they felt they needed it, to a maximum of one dose every 2 h. Study outcomes, collected on postoperative day 2, included pain (measured by the Brief Pain Inventory – Short Form), patient satisfaction (measured by the Pain Outcome Questionnaire Satisfaction sub-scale – component II), opioid use (oral morphine equivalents), opioid side effects (nausea, pruritis and/or constipation) and knee measures (maximum passive knee flexion and pain at maximum passive knee flexion, performed on the operative knee). RESULTS: Study outcomes were analyzed twice. First, for a subset of 73 subjects who remained in their randomly assigned group (PCOA group, n=36; RN group, n=37), randomized analyses were performed. Second, for the larger sample of 88 subjects who were categorized by their actual method of receiving oral opioids (PCOA group, n=41; RN group, n=47), as-treated analyses were performed. There were no differences in study outcomes between the PCOA and RN groups in either analysis. CONCLUSION: PCOA was not superior to RN administration on study outcomes. However, PCOA did not increase opioid use or pain. PCOA remains an important element in the patient-centred care facility. PMID:20195553

Patient-controlled oral analgesia for postoperative pain management following total knee replacement.

PubMed

Kastanias, Patti; Gowans, Sue; Tumber, Paul S; Snaith, Kianda; Robinson, Sandra

2010-01-01

To investigate whether patient-controlled oral analgesia (PCOA) used by individuals receiving a total knee replacement could reduce pain, increase patient satisfaction, reduce opioid use and/or reduce opioid side effects when compared with traditional nurse (RN)-administered oral analgesia. Patients who underwent an elective total knee replacement at a quaternary care centre (Toronto Western Hospital, Toronto, Ontario) were randomly assigned to either PCOA or RN-administered short-acting oral opioids on postoperative day 2. Subjects in the RN group called the RN to receive their prescribed short-acting opioid. Subjects in the PCOA group kept a single dose of their prescribed oral opioid at their bedside and took this dose when they felt they needed it, to a maximum of one dose every 2 h. Study outcomes, collected on postoperative day 2, included pain (measured by the Brief Pain Inventory - Short Form), patient satisfaction (measured by the Pain Outcome Questionnaire Satisfaction subscale - component II), opioid use (oral morphine equivalents), opioid side effects (nausea, pruritus and/or constipation) and knee measures (maximum passive knee flexion and pain at maximum passive knee flexion, performed on the operative knee). Study outcomes were analyzed twice. First, for a subset of 73 subjects who remained in their randomly assigned group (PCOA group, n=36; RN group, n=37), randomized analyses were performed. Second, for the larger sample of 88 subjects who were categorized by their actual method of receiving oral opioids (PCOA group, n=41; RN group, n=47), as-treated analyses were performed. There were no differences in study outcomes between the PCOA and RN groups in either analysis. PCOA was not superior to RN administration on study outcomes. However, PCOA did not increase opioid use or pain. PCOA remains an important element in the patient-centred care facility.

Analgesia with interfascial continuous wound infiltration after laparoscopic colon surgery: A randomized clinical trial.

PubMed

Telletxea, S; Gonzalez, J; Portugal, V; Alvarez, R; Aguirre, U; Anton, A; Arizaga, A

2016-04-01

For major laparoscopic surgery, as with open surgery, a multimodal analgesia plan can help to control postoperative pain. Placing a wound catheter intraoperatively following colon surgery could optimize the control of acute pain with less consumption of opioids and few adverse effects. We conducted a prospective, randomized, study of patients scheduled to undergo laparoscopic colon surgery for cancer in Galdakao-Usansolo Hospital from January 2012 to January 2013. Patients were recruited and randomly allocated to wound catheter placement plus standard postoperative analgesia or standard postoperative analgesia alone. A physician from the acute pain management unit monitored all patients for pain at multiple points over the first 48 hours after surgery. The primary outcome variables were verbal numeric pain scale scores and amount of intravenous morphine used via patient controlled infusion. 92 patients were included in the study, 43 had a wound catheter implanted and 49 did not. Statistically significant differences in morphine consumption were observed between groups throughout the course of the treatment period. The mean total morphine consumption at the end of the study was 5.63±5.02mg among wound catheter patients and 21. 86±17.88mg among control patients (P=.0001). Wound catheter patients had lower pain scale scores than control patients throughout the observation period. No adverse effects associated with the wound catheter technique were observed. The wound catheter group showed lower hospital stays with statistically significant difference (P=.02). In patients undergoing laparoscopic colon surgery, continuous infusion of local anaesthetics through interfascial wound catheters during the first 48h aftersurgery reduced the level of perceived pain and also reduced parenteral morphine consumption with no associated adverse effects and lower hospital stays. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor

The evolution of analgesia in an 'accelerated' recovery programme for resectional laparoscopic colorectal surgery with anastomosis.

PubMed

Zafar, N; Davies, R; Greenslade, G L; Dixon, A R

2010-02-01

The study set out to analyse the outcomes of an evolving accelerated recovery programme after laparoscopic colorectal resection (LCR). The results of a prospective electronic database (March 2000 - April 2008) were analysed. There were 353 consecutive patients undergoing 'three port' high anterior resection (AR) (237 without covering stoma) and 166 a right hemicolectomy (RHC). One hundred thirty-eight had postoperative analgesia using paracetamol IV and oral analgesia (IVP); 27 (16.3%) received additional parenteral morphine and were excluded. Patient controlled morphine analgesia (PCA) was used in 138. Transversus abdominis plane (TAP) blocks, supplemented by IV paracetamol and oral analgesia were used in the last 50 patients. The time to the resumption of diet was significantly reduced with TAP analgesia (median 12 h) and IVP (median 12 h) compared with PCA median (36 h) (chi(2) = 143; 4df: P < 0.001). The postoperative hospital stay was significantly reduced with TAP analgesia (median 2 days) and IVP (median 3 days) compared with PCA (median 5 days); chi(2) = 73; 2df: P < 0.001. Seventeen (34%) TAP and nine (6.5%) IVP patients were discharged within 24 h of surgery compared with no patient in the PCA group. Ninety-three per cent of PCA, 35% IVP and 10% TAP patients were discharged in more than 3 days. The movement towards 'accelerated recovery' was not associated with any increased risk of urinary retention, return to theatre, readmission and/or 30 day mortality. Laparoscopic surgery utilizing IV paracetamol and TAP blocks for postoperative analgesia aids safe effective 'accelerated recovery' in an unselected patient population undergoing right hemicolectomy and high anterior resection. Routine epidural anaesthesia is unnecessary for LCR. Morphine PCA is associated with delayed recovery.

Prehospital analgesia in New South Wales, Australia.

PubMed

Bendall, Jason C; Simpson, Paul M; Middleton, Paul M

2011-12-01

With at least 20% of ambulance patients reporting pain of moderate to severe intensity, pain management has become a primary function of modern ambulance services. The objective of this study was to describe the use of intravenous morphine, inhaled methoxyflurane, and intranasal fentanyl when administered in the out-of-hospital setting by paramedics within a large Australian ambulance service. A retrospective analysis was conducted using data from ambulance patient health care records (PHCR) for all cases from 01 July 2007 through 30 June 2008 in which an analgesic agent was administered (alone or in combination). During the study period, there were 97,705 patients ≤ 100 years of age who received intravenous (IV) morphine, intranasal (IN) fentanyl, or inhaled methoxyflurane, either alone or in combination. Single-agent analgesia was administered in 87% of cases. Methoxyflurane was the most common agent, being administered in almost 60% of cases. Females were less likely to receive an opiate compared to males (RR = 0.83, 95% CI, 0.82-0.84, p <0.0001). Pediatric patients were less likely to receive opiate analgesia compared to adults (RR = 0.65, 95% CI, 0.63-0.67, p <0.0001). The odds of opiate analgesia (compared to pediatric patients 0-15 years) were 1.47; 2.10; 2.56 for 16-39 years, 40-59 years, and ≥ 60 years, respectively. Pediatric patients were more likely to receive fentanyl than morphine (RR = 1.69, 95% CI, 1.64-1.74, p < 0.0001). In this ambulance service, analgesia most often is provided through the use of a single agent. The majority of patients receive non-opioid analgesia with methoxyflurane, most likely because all levels of paramedics are authorized to administer that analgesic. Females and children are less likely to receive opiate-based analgesia than their male and adult counterparts, respectively. Paramedics appear to favor intranasal opiate delivery over intravenous delivery in children with acute pain.

Managing Postoperative Analgesic Failure: Tramadol Versus Morphine for Refractory Pain in the Post-Operative Recovery Unit.

PubMed

Byrne, Kelly; Nolan, Aoife; Barnard, John; Tozer, Megan; Harris, David; Sleigh, Jamie

2017-02-01

This study aimed to discover whether co-analgesia with tramadol or additional morphine was more effective for patients who still had severe pain despite being given 10 mg intravenous morphine in the post-anesthesia care unit (PACU). All eligible patients were consented and recruited to the trial pre-operatively, but only a small subgroup – whose pain was not successfully controlled (pain score 6/10 or more) after receiving 10 mg of morphine in the PACU—were then randomized to enter the trial and receive, in a double blinded fashion, the analgesic study drug; which consisted of either a further 10 mg of morphine, or 100 mg of tramadol, titrated intravenously to control their pain. The groups were compared as to: the time to readiness for discharge, the patient’s pain scores over time, and the presence of side effects. There was no statistically significant difference in any of the outcomes measured. The time to readiness for discharge from PACU was 119 minutes in the morphine group and 120 minutes in the tramadol group. However in approximately half the cases who entered the trial (i.e., where pain had not been controlled with the pre-enrollment baseline 10 mg of morphine in PACU) neither a further 10 mg of morphine nor 100 mg of tramadol effectively relieved the patient’s pain. We found no difference between additional morphine and co-analgesia with tramadol in this study. Patients who don’t respond to reasonable doses of opioids in PACU are very likely to be unresponsive to further opioids, and other non-opioid analgesic techniques (such as regional anesthesia) should be considered early in this group of patients.

PAin SoluTions In the Emergency Setting (PASTIES)--patient controlled analgesia versus routine care in emergency department patients with pain from traumatic injuries: randomised trial.

PubMed

Smith, Jason E; Rockett, Mark; S, Siobhan Creanor; Squire, Rosalyn; Hayward, Chris; Ewings, Paul; Barton, Andy; Pritchard, Colin; Eyre, Victoria; Cocking, Laura; Benger, Jonathan

2015-06-21

To determine whether patient controlled analgesia (PCA) is better than routine care in patients presenting to emergency departments with moderate to severe pain from traumatic injuries. Pragmatic, multicentre, parallel group, randomised controlled trial. Five English hospitals. 200 adults (71% (n = 142) male), aged 18 to 75 years, who presented to the emergency department requiring intravenous opioid analgesia for the treatment of moderate to severe pain from traumatic injuries and were expected to be admitted to hospital for at least 12 hours. PCA (n = 99) or nurse titrated analgesia (treatment as usual; n = 101). The primary outcome was total pain experienced over the 12 hour study period, derived by standardised area under the curve (scaled from 0 to 100) of each participant's hourly pain scores, captured using a visual analogue scale. Pre-specified secondary outcomes included total morphine use, percentage of study period in moderate/severe pain, percentage of study period asleep, length of hospital stay, and satisfaction with pain management. 200 participants were included in the primary analyses. Mean total pain experienced was 47.2 (SD 21.9) for the treatment as usual group and 44.0 (24.0) for the PCA group. Adjusted analyses indicated slightly (but not statistically significantly) lower total pain experienced in the PCA group than in the routine care group (mean difference 2.7, 95% confidence interval -2.4 to 7.8). Participants allocated to PCA used more morphine in total than did participants in the treatment as usual group (mean 44.3 (23.2) v 27.2 (18.2) mg; mean difference 17.0, 11.3 to 22.7). PCA participants spent, on average, less time in moderate/severe pain (36.2% (31.0) v 44.1% (31.6)), but the difference was not statistically significant. A higher proportion of PCA participants reported being perfectly or very satisfied compared with the treatment as usual group (86% (78/91) v 76% (74/98)), but this was also not statistically significant. PCA

Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting.

PubMed

Middleton, Paul M; Simpson, Paul M; Sinclair, Gary; Dobbins, Timothy A; Math, B; Bendall, Jason C

2010-01-01

To compare the effectiveness of intravenous (IV) morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane when administered by paramedics to patients with moderate to severe pain. We conducted a retrospective comparative study of adult patients with moderate to severe pain treated by paramedics from the Ambulance Service of New South Wales who received IV morphine, IN fentanyl, or inhaled methoxyflurane either alone or in combination between January 1, 2004, and November 30, 2006. We used multivariate logistic regression to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of > or = 30% of initial pain score using an 11-point verbal numeric rating scale (VNRS-11). The study population comprised 52,046 patients aged between 16 and 100 years with VNRS-11 scores of > or = 5. All analgesic agents were effective in the majority of patients (81.8%, 80.0%, and 59.1% for morphine, fentanyl, and methoxyflurane, respectively). There was very strong evidence that methoxyflurane was inferior to both morphine and fentanyl (p < 0.0001). There was strong evidence that morphine was more effective than fentanyl (p = 0.002). There was no evidence that combination analgesia was better than either fentanyl or morphine alone. Inhaled methoxyflurane, IN fentanyl, and IV morphine are all effective analgesic agents in the out-of-hospital setting. Morphine and fentanyl are significantly more effective analgesic agents than methoxyflurane. Morphine appears to be more effective than IN fentanyl; however, the benefit of IV morphine may be offset to some degree by the ability to administer IN fentanyl without the need for IV access.

Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient-controlled analgesia.

PubMed

McInnes, Rhona J; Hillan, Edith; Clark, Diana; Gilmour, Harper

2004-10-01

To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour. Randomised controlled trial. The South Glasgow University Hospitals NHS Trust. Primigravidae and multigravidae in labour at term (37-42 weeks). Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks. Analgesia requirements during labour and women's satisfaction with the method of pain relief. Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS. Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.

The Effect of Adding Magnesium Sulfate to Epidural Bupivacaine and Morphine on Post-Thoracotomy Pain Management: A Randomized, Double-Blind, Clinical Trial.

PubMed

Farzanegan, Behrooz; Zangi, Mahdi; Saeedi, Kimia; Khalili, Ali; Rajabi, Mehdi; Jahangirifard, Alireza; Emami, Habib; Ali Mahboobipour, Amir; Baniasadi, Shadi

2018-05-22

Post-thoracotomy pain is very severe and may cause pulmonary complications. Thoracic epidural analgesia can greatly decrease the pain experience and its consequences. However, finding new methods to decrease the amount of administered opioids is an important issue of research. We aimed to evaluate the effect of adding epidural magnesium sulfate to bupivacaine and morphine on pain control and the amount of opioid consumption after thoracotomy. Eighty patients undergoing thoracotomy at a tertiary cardiothoracic referral centre were enrolled in a randomized, double-blind trial. Patients were randomly allocated to two groups. Bupivacaine (12.5 mg) plus morphine (2 mg) were administered epidurally to all patients at the end of operation. Patients in magnesium (Mg) group received epidural magnesium sulfate (50 mg) and patients in control (C) group received normal saline as an adjuvant. Visual analogue scale (VAS) score and the amount of morphine consumption were measured during 24 hr post-operation. Thirty-nine patients in Mg group and 41 patients in C group completed the study. Patients in Mg group had significantly less VAS score at recovery time (p<0.05), 2 h (p<0.01) and 4 hr (p<0.05) after surgery. The patients-controlled analgesia pump was started earlier in C group than in Mg group (p< 0.05). The amount of morphine needed in Mg group was significantly lower than C group (5.64±1.69 mg/24 hr versus 8.44±3.98 mg/24 hr; P<0.001). Pruritus was seen in C group (9.7%) and absent in Mg group (p<0.05). Co-administration of magnesium sulfate with bupivacaine and morphine for thoracic epidural analgesia after thoracotomy leads to reduction in post-operative pain score and the need for opioid administration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Decrease in serotonin concentration in raphe magnus nucleus and attenuation of morphine analgesia in two mice models of neuropathic pain.

PubMed

Sounvoravong, Sourisak; Nakashima, Mihoko N; Wada, Mitsuhiro; Nakashima, Kenichiro

2004-01-26

The alleviation of neuropathic pain cannot be satisfactorily achieved by treatment with opioids. There is much evidence to indicate that the active site of morphine for inducing effective analgesia is in the raphe magnus nucleus, where serotonin (5-HT, 5-hydroxytryptamine) acts as a primary transmitter. Therefore, we developed the hypothesis that 5-HT released in the raphe magnus nucleus could be related to the effectiveness of morphine in two mice models of neuropathic pain, diabetic (DM)-induced neuropathy and sciatic nerve ligation (SL). Two weeks after a single administration of streptozotocin, or 10 days after sciatic nerve ligation, mice were subcutaneously (s.c.) injected with morphine at 3, 5 and 10 mg/kg. The antinociceptive effect of morphine was estimated in the tail-pinch test; 5-HT content was measured after induction of neuropathic pain by microdialysis followed by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Morphine produced as insufficient antinociceptive effect in SL mice at all doses compared with that in sham-operated mice, while in DM mice, morphine given s.c. at 5 and 10 mg/kg produced antinociceptive effects compared with those in non-diabetic mice, but not at 3 mg/kg. The 5-HT content of dialysates, expressed as AUC for 75 min, in SL and DM mice was less than that in control mice. However, morphine given s.c. at 5 mg/kg did not significantly affect 5-HT levels in both mice models compared to their controls. These results suggest that the decrease in 5-HT levels in the raphe magnus nucleus may be related to attenuation of the analgesic effect of morphine caused by the abnormal pain state found in diabetes and partial peripheral nerve injury.

Antagonism of stress-induced analgesia by D-phenylalanine, an anti-enkephalinase.

PubMed

Bodnar, R J; Lattner, M; Wallace, M M

1980-12-01

Methionine- and leucine-enkephalin produce mild and transient analgesic effects, presumably because of enzymatic degradation. Administration of high (250 mg/kg) doses of D-phenylalanine retards the degradation process and elicits analgesia which is reversed by naloxone and which summates with electroacupuncture analgesia. The present study evaluated D-phenylalanine's dose-dependent effects upon a non-opioid analgesic treatment, cold-water swims (CWS), and compared this with morphine. following determination of flinch-jump baselines, three groups of rats received respectively either 25, 50 or 100 mg/kg of D-phenylalanine intraperitoneally in three conditions: alone, with CWS (2 degrees C for 3.5 min), and with morphine (5 mg/kg, SC). Parallel controls with saline were also tested. Simultaneous exposure with each minimally analgesic dose of D-phenylalanine reduced significantly the analgesic, but not hypothermic effects of CWS. By contrast, morphine analgesia was unaffected by D-phenylalanine. These data provide further support that different pain-inhibitory systems mediate CWS and morphine analgesia and suggest that activation of one system is capable of exerting collateral inhibition upon the other.

Small Dose Ketamine Improves Postoperative Analgesia and Rehabilitation After Total Knee Arthroplasty.

PubMed Central

Chauvin, Marcel; Manoir, Bertrand Du; Langlois, Mathieu; Sessler, Daniel I.; Fletcher, Dominique

2005-01-01

We designed this study to evaluate the effect of small-dose intravenous ketamine in combination with continuous femoral nerve block on postoperative pain and rehabilitation after total knee arthroplasty. Continuous femoral nerve block with ropivacaine was started before surgery and continued in the surgical ward for 48 h. Patients were randomly assigned to receive an initial bolus of 0.5 mg/kg ketamine followed by a continuous infusion of 3 μg·kg-1·min-1 during surgery and 1.5 μg·kg-1·min-1 for 48 h (Ketamine group) or an equal volume of saline (Control group). Additional postoperative analgesia was provided by patient-controlled intravenous morphine. Pain scores and morphine consumption were recorded over 48 hours. The maximal degree of active knee flexion tolerated was recorded daily until hospital discharge. Follow up was performed 6 weeks and 3 months after surgery. The Ketamine group required significantly less morphine than the Control group (45 ± 20 mg versus 69 ± 30 mg; P < 0.02). Patients in the Ketamine group reached 90° of active knee flexion more rapidly than those in the Control group (P < 0.02). Outcomes at 6 weeks and 3 months were similar in each group. These results confirm that ketamine is a useful analgesic adjuvant in perioperative multimodal analgesia with a positive impact on early knee mobilization. PMID:15673878

[N(omega)-nitro-L-arginine methyl ester inhibits the up-regulated expression of neuronal nitric oxide synthase/NMDA receptor in the morphine analgesia tolerance rats].

PubMed

Yu, Ling; Xue, Fu-Shan; Li, Cheng-Wen; Xu, Ya-Chao; Zhang, Guo-Hua; Liu, Kun-Peng; Liu, Yi; Sun, Hai-Tao

2006-12-25

The effect of systemic administration of nonspecific nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia tolerance was observed by using the thermal tail-flick method, and the roles of NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into six groups (6 rats per group). Group 1, control group, received a subcutaneous (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10 mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10 mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and 17:00). The tail-flick latency (TFL) was measured in each rat before the injection as a baseline value, and then TFL at 50 min after the 1st injection every day as the measuring values. The animals (except for groups 2 and 5) were decapitated at 80 min after the last injection on the 8th day. The spinal segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A mRNA expressions by the RT-PCR method. The results showed that TFL remained unchangeable in group 2 compared with baseline value during the 7-day observation, while increased significantly on the 7th day in group 3. In group 4, TFL was longest on the 1st day, then decreased gradually from the 2nd day to the 6th day, and restored to the baseline value on the 6th day. In group 5, TFL showed a decreasing tendency during the 7-day observation, but was still significantly longer than the baseline value on the 7th day. The changes of TFL obtained in group 6 were similar to those in group 5. The results of RT-PCR showed that as compared with group 1, nNOS mRNA expressions in spinal cord and midbrain were significantly down-regulated in

Multimodal Pain Management Protocol Versus Patient Controlled Narcotic Analgesia for Postoperative Pain Control after Shoulder Arthroplasty.

PubMed

Nicholson, Thema; Maltenfort, Mitchell; Getz, Charles; Lazarus, Mark; Williams, Gerald; Namdari, Surena

2018-05-01

Our institution's traditional pain management strategy after shoulder arthroplasty has involved the utilization of postoperative patient-controlled narcotic analgesia. More recently, we have implemented a protocol (TLC) that utilizes a multimodal approach. The purpose of this study was to determine whether this change has improved pain control and decreased narcotic utilization. Patients undergoing primary total shoulder or reverse arthroplasty were retrospectively studied. All patients underwent interscalene brachial plexus blockade. "Traditional" patients were provided a patient-controlled analgesic pump postoperatively. TLC patients were given preoperative and postoperative multimodal, non-narcotic analgesic medications and breakthrough narcotics. Morphine equivalent units (MEU) consumed and Visual Analog Scale (VAS) scores for pain (0, 8, 16, and 24 hours) were considered. There were 108 patients in each group. Total postoperative narcotic consumption in the first 24 postoperative hours was 38.5 +/- 81.1 MEU in the "Traditional group" compared to 59.3 +/- 59.1 MEU in the TLC group ( P<0.001 ). Of patients in the TLC group, 88% utilized breakthrough narcotics. VAS pain was significantly higher in the "Traditional group" at 16 hours (4.1 +/- 2.9 vs 3.2 +/- 2.7, P=0.020 ) and 24 hours (4.8 +/- 2.7 vs 3.7 +/- 2.6, P=0.004 ). Those treated with the TLC protocol had greater narcotic utilization but better VAS pain scores at 24 hours after surgery. Both groups experienced rebound pain. While the TLC protocol led to an improved pain experience, further modification of the currently protocol may be necessary to reduce overall narcotic utilization.

Effects of Shilajit on the development of tolerance to morphine in mice.

PubMed

Tiwari, P; Ramarao, P; Ghosal, S

2001-03-01

Effects of concomitant administration of Processed Shilajit (PS, 0.1 and 1 mg/kg, i.p.), in Swiss mice were evaluated on the development of tolerance to morphine induced analgesia in the hot plate test. Chronic administration of morphine (10 mg/kg, i.p., b.i.d.) to mice over a duration of 10 days resulted in the development of tolerance to the analgesic effect of morphine. Concomitant administration of PS with morphine, from day 6 to day 10, resulted in a significant inhibition of the development of tolerance to morphine (10 mg/kg, i.p.) induced analgesia. Processed Shilajit per se, in the doses used, did not elicit any significant analgesia in mice; nor did the chronic concomitant administration of Processed Shilajit alter the morphine-induced analgesia. These findings with Processed Shilajit indicate its potential as a prospective modifier of analgesic tolerance to morphine. Copyright 2001 John Wiley & Sons, Ltd.

Benefit and harm of adding ketamine to an opioid in a patient-controlled analgesia device for the control of postoperative pain: systematic review and meta-analyses of randomized controlled trials with trial sequential analyses.

PubMed

Assouline, Benjamin; Tramèr, Martin R; Kreienbühl, Lukas; Elia, Nadia

2016-12-01

Ketamine is often added to opioids in patient-controlled analgesia devices. We tested whether in surgical patients, ketamine added to an opioid patient-controlled analgesia decreased pain intensity by ≥25%, cumulative opioid consumption by ≥30%, the risk of postoperative nausea and vomiting by ≥30%, the risk of respiratory adverse effects by ≥50%, and increased the risk of hallucination not more than 2-fold. In addition, we searched for evidence of dose-responsiveness. Nineteen randomized trials (1349 adults, 104 children) testing different ketamine regimens added to various opioids were identified through searches in databases and bibliographies (to 04.2016). In 9 trials (595 patients), pain intensity at rest at 24 hours was decreased by 32% with ketamine (weighted mean difference -1.1 cm on the 0-10 cm visual analog scale [98% CI, -1.8 to -0.39], P < 0.001). In 7 trials (495 patients), cumulative 24 hours morphine consumption was decreased by 28% with ketamine (weighted mean difference -12.9 mg [-22.4 to -3.35], P = 0.002). In 7 trials (435 patients), the incidence of postoperative nausea and vomiting was decreased by 44% with ketamine (risk ratio 0.56 [0.40 to 0.78], P < 0.001). There was no evidence of a difference in the incidence of respiratory adverse events (9 trials, 871 patients; risk ratio 0.31 [0.06 to 1.51], P = 0.08) or hallucination (7 trials, 690 patients; odds ratio 1.16 [0.47 to 2.79], P = 0.70). Trial sequential analyses confirmed the significant benefit of ketamine on pain intensity, cumulative morphine consumption, and postoperative nausea and vomiting and its inability to double the risk of hallucination. The available data did not allow us to make a conclusion on respiratory adverse events or to establish dose-responsiveness.

Efficacy of pectoral nerve block versus thoracic paravertebral block for postoperative analgesia after radical mastectomy: a randomized controlled trial.

PubMed

Kulhari, S; Bharti, N; Bala, I; Arora, S; Singh, G

2016-09-01

Pectoral nerve (PecS) block is a recently introduced technique for providing surgical anaesthesia and postoperative analgesia during breast surgery. The present study was planned to compare the efficacy and safety of ultrasound-guided PecS II block with thoracic paravertebral block (TPVB) for postoperative analgesia after modified radical mastectomy. Forty adult female patients undergoing radical mastectomy were randomly allocated into two groups. Group 1 patients received a TPVB with ropivacaine 0.5%, 25 ml, whereas Group 2 patents received a PecS II block using same volume of ropivacaine 0.5% before induction of anaesthesia. Patient-controlled morphine analgesia was used for postoperative pain relief. The duration of analgesia was significantly prolonged in patients receiving the PecS II block compared with TPVB [mean (sd), 294.5 (52.76) vs 197.5 (31.35) min in the PecS II and TPVB group, respectively; P<0.0001]. The 24 h morphine consumption was also less in the PecS II block group [mean (sd), 3.90 (0.79) vs 5.30 (0.98) mg in PecS II and TPVB group, respectively; P<0.0001]. Postoperative pain scores were lower in the PecS II group compared with the TVPB group in the initial 2 h after surgery [median (IQR), 2 (2-2.5) vs 4 (3-4) in the Pecs II and TPVB group, respectively; P<0.0001]. Seventeen patients in the PecS II block group had T2 dermatomal spread compared with four patients in the TPVB group (P<0.001). No block-related complication was recorded. We found that the PecS II block provided superior postoperative analgesia than the TPVB in patients undergoing modified radical mastectomy without causing any adverse effect. CTRI/2014/06/004692. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Control of cancer pain by epidural infusion of morphine.

PubMed

Waterman, N G; Hughes, S; Foster, W S

1991-10-01

Pain that cannot be controlled by traditional oral and parenteral methods in those patients with advanced cancer can be alleviated by spinal administration of narcotics. Epidural and intrathecal infusion with morphine causes analgesia by blocking spinal receptors without significant long-term central nervous, gastrointestinal, and genitourinary system effects. Of the total of 33 patients, epidural catheters inserted in 20 patients then connected by a subcutaneous tunnel to a continuous infusion system. Implanted pumps were used in each of these patients. Because of the cost and limitations of the implanted pumps, epidural catheters were connected, either directly or by subcutaneous reservoirs, to external ambulatory infusion pumps in the remaining 13 patients. Patient assessment by a linear analogue scale to measure pain levels determined that 23 of the 33 total patients (70%) had excellent or good relief of pain. The delivery of spinal administration of narcotics to treat intractable cancer pain in patients is safe. Most importantly, this method of delivery can be used in community hospitals, in outpatient settings, and in home health care programs.

Chemical Stability of Morphine, Ropivacaine, and Ziconotide in Combination for Intrathecal Analgesia.

PubMed

Robert, Julien; Sorrieul, Jérémy; Rossignol, Elsa; Beaussart, Hélène; Kieffer, Hélène; Folliard, Caroline; Dupoiron, Denis; Devys, Catherine

2017-01-01

Pain is the most feared symptom amongst individuals living with cancer. In 15% to 20% of patients, conventional analgesic therapy either fails to relieve pain or induces adverse effects. Intrathecal drug delivery systems may present an effective alternative for pain management. The Cancerology Center Paul Papin protocol includes an admixture of morphine, ropivacaine, and ziconotide in intrathecal preparations. These drugs are administered by a fully implantable or an external pump. Syringes or polyolefin infusion bags are prepared for refill just before use. Few centers in France use the method of intrathecal analgesia. Therefore, for those patients receiving intrathecal preparations, each filling requires that the patients be transported from their local hospital (or their home) to a referral center where the patients are monitored. They sometimes must travel up to a hundred kilometers to have a pump filled. The preparation and the analytical control of the mixture are carried out only by those centers meeting the proper criteria, which includes the proper equipment. To spare the patient this travel, a peripheral center may be subcontracted to manage the patient's pump refill. No data are available concerning the chemical stability of admixtures in syringes or polyolefin infusion bags. The aim of this study was to evaluate, with a new analytical method using ultra high-performance liquid chromatography, the chemical stability of these admixtures in syringes or in polyolefin infusion bags. Ziconotide 1 µg/mL was combined with ropivacaine (7.5 mg/mL) and morphine (3.5 mg/mL) in syringes at 5°C, 21°C, and 31°C, and in polyolefin infusion bags at 21°C. Assays were performed using ultra high-pressure liquid chromatography. In syringes stored at 21°C and 31°C, concentrations after 6 hours were not in the acceptable criterion of 10% variability. When syringes were stored at 5°C, the residual concentration of ziconotide after 3 days was 100.5% +/- 2.6% [92.7% to

Is Subdissociative Ketamine As Safe and Effective As Morphine for Pain Management in the Emergency Department?

PubMed

Howard, Patricia Kunz; Gisness, Christine M

: Review of recent evidence with translation to practice for the advanced practice nurse (APN) role is presented using a case study module for "Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial." This prospective, randomized controlled inquiry enrolled 90 patients into 2 groups (ketamine vs. morphine) for patients seeking care in an emergency department with acute pain. Data regarding pain scores were collected at baseline, 15, 30, 60, 90, and 120 min. Study subjects reporting persistent pain could receive rescue analgesia with fentanyl. Initial pain scores for the subjects in each of the groups were comparable (ketamine: 8.6; morphine: 8.5). Pain management for the 2 groups revealed similar average doses (ketamine: 21.8 mg; morphine: 7.7 mg). Although subjects in both groups reported reduction in pain scores at 15 and 30 min, no clinical significance was found. Subjects experienced greater pain relief (pain score = 0) in the ketamine group at 15 min (percentage difference 31%; 95% confidence interval [13, 49]), yet this was not sustained at the 30-min interval. There were no serious or life-threatening adverse effects in either group. This study highlights the important role of the APN in providing quality care, communication about pain management, and related follow-up care.

The effects of preemptive intravenous versus preemptive epidural morphine on postoperative analgesia and surgical stress response after orthopaedic procedures.

PubMed

Kiliçkan, L; Toker, K

2000-09-01

The purpose of this study was to evaluate the effect of pre-emptive intravenous versus pre-emptive epidural morphine on both postoperative analgesic consumption and surgical stress response. Sixty patients, ASA I or II, aged 18-85, undergoing total hip or knee replacement were randomly assigned to three groups of 20 patients. In group pre-emptive epidural, patients were administered an epidural injection of 75 micrograms.kg-1 morphine about 45 minute before dermal incision. In group pre-emptive intravenous, patients were administered 0.15 mg.kg-1 of intravenous morphine following induction before dermal incision. In group control, patients were administered intravenous saline following induction before dermal incision. The pre-i.v. group used significantly less morphine than the pre-epi group (p < 0.0003). In all groups, plasma cortisol levels increased as compared to pre-op values, but plasma cortisol increased more significantly in the pre-i.v. and control groups within 4 hrs of surgery and was still significantly elevated at 7 am of the first postoperative morning compared to the pre-epi group (p < 0.001) and the increase persisted to the next morning in patients pre-i.v. and control groups. Although pre-emptive epidural morphine has failed to decrease postoperative analgesic consumption, it has been able to suppress the surgical stress more significantly than intravenous morphine and a saline control.

Continuous intravenous morphine infusion for postoperative analgesia following posterior spinal fusion for idiopathic scoliosis.

PubMed

Poe-Kochert, Connie; Tripi, Paul A; Potzman, Jennifer; Son-Hing, Jochen P; Thompson, George H

2010-04-01

A retrospective study of postoperative pain management. Evaluate the efficacy and safety of continuous intravenous morphine infusion for postoperative pain management in patients with idiopathic scoliosis (IS) undergoing posterior spinal fusion (PSF) and segmental spinal instrumentation (SSI). Postoperative pain is a common problem following surgery for IS. There are no published reports regarding the use of a continuous intravenous morphine infusion for this patient population. We retrospectively reviewed data regarding 339 consecutive patients with IS who underwent PSF and SSI between 1992 and 2006. All patients received intrathecal morphine after the induction of general anesthesia. Following surgery, preordered morphine infusion (0.01 mg/kg/h) was started at first reported pain. The infusion rate was titrated based on vital signs, visual analog scale (VAS) pain scores (0-10), and clinical status. It was continued until patients were able to take oral analgesics. We reviewed intrathecal morphine dosage, VAS pain scores through the third postoperative day, interval to start of morphine infusion, total morphine requirements in the first 48 hours, and any adverse reactions (nausea/vomiting, pruritus, respiratory depression, and pediatric intensive care unit admission). Mean intrathecal morphine dose was 15.5 +/- 3.9 microg/kg and mean interval to start of the intravenous morphine infusion was 17.5 +/- 5 hours. Mean VAS pain scores were 3.1, 4.5, 4.5, and 4.6 at 12 hours, 1, 2, and 3 days after surgery, respectively.The total mean morphine dose in the first 48 hours postoperatively was 0.03 +/- 0.01 mg/kg/h. Total morphine received was 1.44 +/- 0.5 mg/kg. Nausea/vomiting and pruritus, related to the morphine infusion occurred in 45 patients (13.3%) and 14 patients (4.1%), respectively. No patients had respiratory depression or required Pediatric Intensive Care Unit admission. A low frequency of adverse events and a mean postoperative VAS pain score of 5 or less

No Difference in Early Analgesia Between Liposomal Bupivacaine Injection and Intrathecal Morphine After TKA.

PubMed

Barrington, John W; Emerson, Roger H; Lovald, Scott T; Lombardi, Adolph V; Berend, Keith R

2017-01-01

Opioid analgesics have been a standard modality for postoperative pain management after total knee arthroplasty (TKA) but are also associated with increased risk of nausea, pruritus, vomiting, respiratory depression, prolonged ileus, and cognitive dysfunction. There is still a need for a method of anesthesia that can deliver effective long-term postoperative pain relief without incurring the high cost and health burden of opioids and nerve blocks. (1) Is liposomal bupivacaine-based periarticular injection (PAI) more effective than morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? (2) Do patients treated with liposomal bupivacaine-based PAI experience fewer opioid-related adverse events compared with patients treated with morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? This multicenter, blind trial randomized 119 patients undergoing TKA with spinal anesthesia to receive spinal anesthesia plus periarticular injection with liposomal bupivacaine (40 patients), spinal anesthesia with bupivacaine plus intrathecal morphine (41 patients) but no liposomal bupivacaine injection, or spinal anesthesia with bupivacaine (38 patients) and no liposomal bupivacaine injection. The two groups that did not receive periarticular liposomal bupivacaine did receive periarticular injection with ropivacaine, and all three groups had ketorolac (30 mg) plus epinephrine (1:1000) in the periarticular injections. Patients in all three groups received identical perioperative multimodal analgesic and antiemetic drugs. All patients were analyzed in the group to which they were randomized and no patients were lost to followup. The primary study endpoints were visual analog score (VAS) for pain and narcotic use during postoperative day 1. Secondary endpoints included side effects associated with narcotic administration during the hospital stay. Mean VAS pain in the liposomal bupivacaine PAI

Multi-Modal Preemptive Analgesia With Pregabalin, Acetaminophen, Naproxen, and Dextromethorphan in Radical Neck Dissection Surgery: A Randomized Clinical Trial

PubMed Central

Amiri, Hamid Reza; Mirzaei, Mojtaba; Beig Mohammadi, Mohammad Taghi; Tavakoli, Farhad

2016-01-01

Background Preemptive analgesia may be considered as a method not only to alleviate postoperative pain but also to decrease analgesic consumption. Different regimens are suggested, but there is currently no standard. Objectives The aim was to measure the efficacy of preemptive analgesia with pregabalin, acetaminophen, naproxen, and dextromethorphan in radical neck dissection surgery for reducing the intensity of pain and morphine consumption. Patients and Methods This study was conducted as a randomized double-blind clinical trial. Eighty adult patients (18 to 60 years of age) under the American society of anesthesiologists (ASA) physical status I and II undergoing elective radical neck dissection were enrolled. Patients were randomized into two groups of 40 with a simple randomization method. The case group received a combination of 15 mg/kg acetaminophen, 2.5 mg/kg pregabalin, 7 mg/kg naproxen, and 0.3 mg/kg dextromethorphan administered orally one hour prior to surgery. Postoperative pain was assessed with the universal pain assessment tool (UPAT) at 0, 2, 4, 6, 12, and 24 hours after surgery. Subjects received morphine based on postoperative pain control protocol. Total administered morphine doses were noted. Results Postoperative pain rates at 0, 2, 4, 6, 12, and 24 hours after surgery were significantly lower for the case group than the control group (P values = 0.014, 0.003, 0.00, 0.00, and 0.00, respectively). Total morphine doses for the preemptive analgesia group were 45% lower than those of the other group. Side effects were similar for both groups. Conclusions A single preoperative oral dose of pregabalin, acetaminophen, dextromethorphan, and naproxen one hour before surgery is an effective method for reducing postoperative pain and morphine consumption in patients undergoing radical neck dissection. PMID:27843771

Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial.

PubMed

Pathan, Sameer A; Mitra, Biswadev; Straney, Lahn D; Afzal, Muhammad Shuaib; Anjum, Shahzad; Shukla, Dharmesh; Morley, Kostantinos; Al Hilli, Shatha A; Al Rumaihi, Khalid; Thomas, Stephen H; Cameron, Peter A

2016-05-14

The excruciating pain of patients with renal colic on presentation to the emergency department requires effective analgesia to be administered in the shortest possible time. Trials comparing intramuscular non-steroidal anti-inflammatory drugs with intravenous opioids or paracetamol have been inconclusive because of the challenges associated with concealment of randomisation, small sample size, differences in outcome measures, and inadequate masking of participants and assessors. We did this trial to develop definitive evidence regarding the choice of initial analgesia and route of administration in participants presenting with renal colic to the emergency department. In this three-treatment group, double-blind, randomised controlled trial, adult participants (aged 18-65 years) presenting to the emergency department of an academic, tertiary care hospital in Qatar, with moderate to severe renal colic (Numerical pain Rating Scale ≥ 4) were recruited. With the use of computer-generated block randomisation (block sizes of six and nine), participants were assigned (1:1:1) to receive diclofenac (75 mg/3 mL intramuscular), morphine (0.1 mg/kg intravenous), or paracetamol (1 g/100 mL intravenous). Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants achieving at least a 50% reduction in initial pain score at 30 min after analgesia, assessed by intention-to-treat analysis and per-protocol analysis, which included patients where a calculus in the urinary tract was detected with imaging. This trial is registered with ClinicalTrials.gov, number NCT02187614. Between Aug 5, 2014, and March 15, 2015, we randomly assigned 1645 participants, of whom 1644 were included in the intention-to-treat analysis (547 in the diclofenac group, 548 in the paracetemol group, and 549 in the morphine group). Ureteric calculi were detected in 1316 patients, who were analysed as the per-protocol population (438 in

Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine.

PubMed

Altier, N; Stewart, J

1998-04-01

In the present study, we examined the effects of dopamine (DA) receptor antagonists infused into the nucleus accumbens septi (NAS) on analgesia induced by intra-ventral tegmental area (VTA) infusions of the substance P (SP) analog, DiMe-C7 or morphine and intra-NAS infusions of amphetamine. Rats received intra-NAS infusions of either the mixed DA receptor antagonist flupenthixol (1.5 or 3.0 microg/0.5 microl/side; DiMe-C7 only), the DA D1/D5 receptor antagonist SCH 23390 (0.1 microg/0.5 microl/side; DiMe-C7 only) or the DA D2-type receptor antagonist raclopride (1.0, 3.0 or 5.0 microg/0.5 microl/side). Ten minutes later, rats received intra-VTA infusions of DiMe-C7 (3.0 microg/0.5 microl/side) or morphine (3.0 microg/0.5 microl/side) or intra-NAS infusions of amphetamine (2.5 microg/0.5 microl/side). Animals were then administered the formalin test for tonic pain. Intra-NAS raclopride prevented analgesia induced by intra-VTA DiMe-C7, intra-VTA morphine and intra-NAS amphetamine. Similarly, intra-NAS flupenthixol or SCH 23390 attenuated the analgesia induced by intra-VTA DiMe-C7. These findings suggest that tonic pain is inhibited, at least in part, by enhanced DA released from terminals of mesolimbic neurons. Furthermore, the evidence that SP and opioids in the VTA mediate stress-induced analgesia suggests that the pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, pain or both.

Biphalin preferentially recruits peripheral opioid receptors to facilitate analgesia in a mouse model of cancer pain - A comparison with morphine.

PubMed

Lesniak, Anna; Bochynska-Czyz, Marta; Sacharczuk, Mariusz; Benhye, Sandor; Misicka, Aleksandra; Bujalska-Zadrozny, Magdalena; Lipkowski, Andrzej W

2016-06-30

The search for new drugs for cancer pain management has been a long-standing goal in basic and clinical research. Classical opioid drugs exert their primary antinociceptive effect upon activating opioid receptors located in the central nervous system. A substantial body of evidence points to the relevance of peripheral opioid receptors as potential targets for cancer pain treatment. Peptides showing limited blood-brain-barrier permeability promote peripheral analgesia in many pain models. In the present study we examined the peripheral and central analgesic effect of intravenously administered biphalin - a dimeric opioid peptide in a mouse skin cancer pain model, developed by an intraplantar inoculation of B16F0 melanoma cells. The effect of biphalin was compared with morphine - a golden standard in cancer pain management. Biphalin produced profound, dose-dependent and naloxone sensitive spinal analgesia. Additionally, the effect in the tumor-bearing paw was largely mediated by peripheral opioid receptors, as it was readily attenuated by the blood-brain-barrier-restricted opioid receptor antagonist - naloxone methiodide. On the contrary, morphine facilitated its analgesic effect primarily by activating spinal opioid receptors. Both drugs induced tolerance in B16F0 - implanted paws after chronic treatment, however biphalin as opposed to morphine, showed little decrease in its activity at the spinal level. Our results indicate that biphalin may be considered a future alternative drug in cancer pain treatment due to an enhanced local analgesic activity as well as lower tolerance liability compared with morphine. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of intraoperative dexmedetomidine on postoperative analgesia and sedation in pediatric patients undergoing tonsillectomy and adenoidectomy.

PubMed

Olutoye, Olutoyin A; Glover, Chris D; Diefenderfer, John W; McGilberry, Michael; Wyatt, Matthew M; Larrier, Deidre R; Friedman, Ellen M; Watcha, Mehernoor F

2010-08-01

The immediate postoperative period after tonsillectomy and adenoidectomy, one of the most common pediatric surgical procedures, is often difficult. These children frequently have severe pain but postoperative airway edema along with increased sensitivity to the respiratory-depressant effects of opioids may result in obstructive symptoms and hypoxemia. Opioid consumption may be reduced by nonsteroidal antiinflammatory drugs, but these drugs may be associated with increased bleeding after this operation. Dexmedetomidine has mild analgesic properties, causes sedation without respiratory depression, and does not have an effect on coagulation. We designed a prospective, double-blind, randomized controlled study to determine the effects of intraoperative dexmedetomidine on postoperative recovery including pain, sedation, and hemodynamics in pediatric patients undergoing tonsillectomy and adenoidectomy. One hundred nine patients were randomized to receive a single intraoperative dose of dexmedetomidine 0.75 microg/kg, dexmedetomidine 1 microg/kg, morphine 50 microg/kg, or morphine 100 microg/kg over 10 minutes after endotracheal intubation. There were no significant differences among the 4 groups in patient demographics, ASA physical status, postoperative opioid requirements, sedation scores, duration of oxygen supplementation in the postanesthetic care unit, and time to discharge readiness. The median time to first postoperative rescue analgesic was similar in patients receiving dexmedetomidine 1 microg/kg and morphine 100 microg/kg, but significantly longer compared with patients receiving dexmedetomidine 0.75 microg/kg or morphine 50 microg/kg (P < 0.01). In addition, the number of patients requiring >1 rescue analgesic dose was significantly higher in the dexmedetomidine 0.75 microg/kg group compared with the dexmedetomidine 1 microg/kg and morphine 100 microg/kg groups, but not the morphine 50 microg/kg group. Patients receiving dexmedetomidine had significantly

Postoperative morphine requirements of free TRAM and DIEP flaps.

PubMed

Kroll, S S; Sharma, S; Koutz, C; Langstein, H N; Evans GRD; Robb, G L; Chang, D W; Reece, G P

2001-02-01

In a review of the charts of 158 patients who had undergone breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps and who were treated for postoperative pain with morphine administered by a patient-controlled analgesia pump, the total dose of morphine administered during hospitalization for the flap transfer was measured. Patients whose treatment was supplemented by other intravenous narcotics were excluded from the study. The mean amount of morphine per kilogram required by patients who had reconstruction with DIEP flaps (0.74 mg/kg, n = 26) was found to be significantly less than the amount required by patients who had reconstruction with TRAM flaps (1.65 mg/kg; n = 132; p < 0.001). DIEP flap patients also remained in the hospital less time (mean, 4.73 days) than did free TRAM flap patients (mean, 5.21 days; p = 0.026), but the difference was less than one full hospital day. It was concluded that the use of the DIEP flap does reduce the patient requirement for postoperative pain medication and therefore presumably reduces postoperative pain. It may also slightly shorten hospital stay.

Overdose of opioid from patient-controlled analgesia pumps.

PubMed

Notcutt, W G; Knowles, P; Kaldas, R

1992-07-01

Two incidence have occurred in our hospital when a patient-controlled analgesia pump has accidentally delivered the whole contents of the syringe of diamorphine (60 mg) over a period of approximately 1 h. Electrical corruption of the pumps' program has been identified as the probable cause. All pumps of this type have been modified to prevent such occurrences.

Local infiltration analgesia with ropivacaine in acute fracture of thoracolumbar junction surgery.

PubMed

Swennen, C; Bredin, S; Eap, C; Mensa, C; Ohl, X; Girard, V

2017-04-01

Retrospective study. Local infiltration analgesia is effective in many surgeries as knee arthroplasty, but the analgesic efficacy of local infiltration analgesia with ropivacaine in trauma spine surgery in T10 to L2 has not been clarified. We conducted a trial to assess the analgesic efficacy of intraoperative local infiltration analgesia (LIA) with ropivacaine. The aim of the present study was to clarify the effect of intraoperative local infiltration analgesia with ropivacaine on postoperative pain for patients undergoing thoracolumbar junction fracture surgery. In a retrospective study, in 76 patients undergoing spine surgery for thoracolumbar junction fracture, 20ml of ropivacaine 7.5% (n R group=38) was infiltrated using a systematic technique, or no infiltration was realized (n M group=38). We assessed postoperative pain with Visual Analogue Scale (VAS) and morphine consumption in the 24 first hours. VAS pain score upon awakening and at 2hours postoperatively were significantly lower in the ropivacaine group (P=0.01 and P=0.002). Rescue opioid requirement during the 24 first hours were about 50% lower in the ropivacaine group (P=0.01). No local or systemic side effects were observed. Intraoperative LIA with ropivacaine in thoracolumbar junction fracture surgery may have an analgesic effect in postoperative pain control (24hours) with a reduction of VAS and morphine consumption. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Midazolam Plus Haloperidol as Adjuvant Analgesics to Morphine in Opium Dependent Patients: A Randomized Clinical Trial.

PubMed

Afzalimoghaddam, Mohammad; Edalatifard, Maryam; Nejati, Amir; Momeni, Mehdi; Isavi, Nader; Karimialavijeh, Ehsan

2016-01-01

Tolerance to opioids among opium-dependent patients creates obstacles for proper pain management of these patients in the emergency department (ED). The aim of the present study was to investigate the efficacy of intramuscular (IM) haloperidol plus midazolam on morphine analgesia among opium-dependent patients. Opium-dependent adults who were admitted to the ED for new-onset severe pain in the limbs or abdomen (within 24 hours of admission and a pain score of over six, using a numerical rating scale [NRS]) were recruited. Participants were randomly assigned into two groups. Group A received morphine 0.05 mg/kg intravenously (IV) and a mixture of midazolam 2.5 mg and haloperidol 2.5 mg (diluted in 5 cc of distilled water, IM); group B received morphine 0.05 mg/kg IV and distilled water 5 cc, IM. Measured outcomes were related to: 1) pain intensity; 2) total doses of morphine; 3) changes in hemodynamic status and level of consciousness of patients. NRS scores (zero to 10) before and one, three and six hours following intervention, as well as total doses of morphine, were recorded. We recruited 68 males (78.16%) and 19 females (21.83%). The mean age was 38.28±6.59 years. The pain score in group A declined more rapidly over six hours than that in group B. Moreover, as compared to group B, the amount of morphine use decreased significantly in group A. Based on the present data, adding haloperidol plus midazolam to morphine for pain management improved pain scores and lowered morphine consumption among opium-dependent patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison between the analgesic effects of morphine and tramadol delivered epidurally in cats receiving a standardized noxious stimulation.

PubMed

Castro, Douglas S; Silva, Marta F A; Shih, Andre C; Motta, Pedro P A; Pires, Marcos V M; Scherer, Paulo O

2009-12-01

This study compared the analgesic effects of epidural tramadol versus morphine in six healthy cats. Under general anesthesia, each cat received an epidural injection of saline 0.22 ml/kg (control treatment, CT), tramadol 1mg/kg (tramadol treatment, TT), or morphine 0.1mg/kg (morphine treatment, MT). After cats had recovered from anesthesia a simple descriptive scale (SDS), visual analog scale (VAS) and physiological parameters (respiratory and heart rate) were used to assess analgesia level to a noxious stimulus (base of the tail skin fold clamping) at 1, 2, 3, 4, 6, 8, 10, and 12h post-epidural. Group TT had a higher SDS and VAS score when compared to MT at 8, 10 and 12h post-epidural. CT had higher SDS and VAS score at all time points when compared to TT and MT. In conclusion both morphine and tramadol provided analgesia in this model for the first 6h; with epidural morphine resulting in longer lasting analgesia when compared to tramadol.

Epidural analgesia versus intravenous patient-controlled analgesia following minimally invasive pectus excavatum repair: a systematic review and meta-analysis

PubMed Central

Stroud, Andrea M.; Tulanont, Darena D.; Coates, Thomasena E.; Goodney, Philip P.; Croitoru, Daniel P.

2017-01-01

Background/Purpose The minimally invasive pectus excavatum repair (MIPER) is a painful procedure. The ideal approach to postoperative analgesia is debated. We performed a systematic review and meta-analysis to assess the efficacy and safety of epidural analgesia compared to intravenous Patient Controlled Analgesia (PCA) following MIPER. Methods We searched MEDLINE (1946–2012) and the Cochrane Library (inception–2012) for randomized controlled trials (RCT) and cohort studies comparing epidural analgesia to PCA for postoperative pain management in children following MIPER. We calculated weighted mean differences (WMD) for numeric pain scores and summarized secondary outcomes qualitatively. Results Of 699 studies, 3 RCTs and 3 retrospective cohorts met inclusion criteria. Compared to PCA, mean pain scores were modestly lower with epidural immediately (WMD −1.04, 95% CI −2.11 to 0.03, p = 0.06), 12 hours (WMD −1.12; 95% CI −1.61 to −0.62, p < 0.001), 24 hours (WMD −0.51, 95%CI −1.05 to 0.02, p = 0.06), and 48 hours (WMD −0.85, 95% CI −1.62 to −0.07, p = 0.03) after surgery. We found no statistically significant differences between secondary outcomes. Conclusions Epidural analgesia may provide superior pain control but was comparable with PCA for secondary outcomes. Better designed studies are needed. Currently the analgesic technique should be based on patient preference and institutional resources. PMID:24851774

Comparison of Adductor Canal Block Versus Local Infiltration Analgesia on Postoperative Pain and Functional Outcome after Total Knee Arthroplasty: A Randomized Controlled Trial

PubMed Central

Tanavalee, A; Ngarmukos, S; Amarase, C; Songthamwat, B; Boonshua, A

2018-01-01

Introduction: Total knee arthroplasty (TKA) is associated with intense postoperative pain for which effective analgesia is essential to facilitate early postoperative recovery. Adductor canal block (ACB) and local infiltration analgesia (LIA) have become increasingly involved in postoperative pain management after TKA. We aimed to compare their efficacy and outcomes in patients undergoing TKA. Materials and Methods: Sixty patients undergoing unilateral TKA were randomized to receive either postoperative single-injection ACB (Group A) or LIA (Group L) during the operation. All patients received spinal anaesthesia. Primary outcome was total morphine consumption over postoperative 24 hours. Visual analog pain scale, time to first and total dosage of rescue analgesia, performance-based evaluations [timed-up and go (TUG) test, quadriceps strength], side-effects, length of hospital stay and patient satisfaction were measured. Results: Fifty-seven patients were available for analysis. Median total morphine consumption over 24 and 48 postoperative hours of Group A were significantly less than Group L (6/10 mg vs 13/25 mg, p, 0.008 and 0.001, respectively). Similarly, Group A had significantly lower VAS at postoperative 6, 12 and 18 hours, VAS at ambulation on postoperative (POD) 1-3, better TUG tests on POD 2 and during POD 3 than those of Group L. However, quadriceps strength and patient satisfaction were not different between both groups. Conclusion: Patients undergoing TKA with single-injection ACB required less postoperative opioids than those with LIA. Furthermore, multimodal analgesia using ACB provided better postoperative analgesia, as well as performance-based activities, than those with LIA. PMID:29725506

A Comparison of Nonopioid and Opioid Oral Analgesia Following Pediatric Palatoplasty.

PubMed

Pierson, Brandon W; Cardon, Brandon S; Anderson, Michael P; Glade, Robert S

2017-03-01

  This article evaluates postoperative analgesia in pediatric palatoplasty patients using nonopioid oral medications.   This study was a retrospective chart review.   The setting for this study was a tertiary-care children's hospital.   Study participants were pediatric patients who underwent palatoplasty procedures performed by a single surgeon.   Interventions included nonopioid and opioid oral medications for postoperative analgesia.   The adequacy of nonopioid versus opioid oral analgesia was assessed by (1) time to discontinue IV fluid, (2) total IV morphine doses for breakthrough pain, (3) daily IV morphine doses for breakthrough pain, (4) time to discharge from the hospital, and (5) perioperative weight change. Group comparisons of outcome measures were performed using a two one-sided test.   A total of 61 patients were identified who received three standard pain regimens: acetaminophen + ibuprofen (12), hydrocodone/acetaminophen (23), and hydrocodone/acetaminophen + ibuprofen (26). There was sufficient evidence to suggest equivalence in outcome measures for acetaminophen + ibuprofen versus hydrocodone/acetaminophen and hydrocodone/acetaminophen + ibuprofen for the following: time to discontinue IV fluid (P = .02, 90% confidence interval [CI] = -0.42 to 0.17; P = .007, 90% CI = -0.28 to 0.34), daily IV morphine doses (P = .023, 90% CI = -0.83 to 0.65; P = .032, 90% CI = -0.92 to 0.28), time to discharge from the hospital (P = .017, 90% CI = -0.40 to 0.27; P = .015, 90% CI = -0.24 to 0.39), and perioperative weight change (P = .002; 90% CI = -0.25 to 0.46; P < .0001; 90% CI = -0.34 to 0.18). There was no sufficient evidence to suggest equivalence for total IV morphine doses (P = .189, 90% CI = -1.51 to 1.78; P = .169, 90% CI = -1.51 to 0.88).   Oral acetaminophen and ibuprofen alone may provide similar analgesia to traditional regimens with reduced risks following pediatric palatoplasty.

STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance

PubMed Central

Kim, Yoon-Jung; Kang, Young; Park, Hye-Yeon; Lee, Jae-Ran; Yu, Dae-Yeul; Murata, Takuya; Gondo, Yoichi; Hwang, Jung Hwan; Kim, Yong-Hoon; Lee, Chul-Ho; Rhee, Myungchull; Han, Pyung-Lim; Chung, Bong-Hyun; Lee, Hyun-Jun; Kim, Kyoung-Shim

2016-01-01

Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEPC230X−/− mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEPC230X−/− mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine. PMID:26915673

Proinflammatory cytokines oppose opioid induced acute and chronic analgesia

PubMed Central

Hutchinson, Mark R.; Coats, Benjamen D.; Lewis, Susannah S.; Zhang, Yingning; Sprunger, David B.; Rezvani, Niloofar; Baker, Eric M.; Jekich, Brian M.; Wieseler, Julie L.; Somogyi, Andrew A.; Martin, David; Poole, Stephen; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.

2008-01-01

Spinal proinflammatory cytokines are powerful pain-enhancing signals that contribute to pain following peripheral nerve injury (neuropathic pain). Recently, one proinflammatory cytokine, interleukin-1, was also implicated in the loss of analgesia upon repeated morphine exposure (tolerance). In contrast to prior literature, we demonstrate that the action of several spinal proinflammatory cytokines oppose systemic and intrathecal opioid analgesia, causing reduced pain suppression. In vitro morphine exposure of lumbar dorsal spinal cord caused significant increases in proinflammatory cytokine and chemokine release. Opposition of analgesia by proinflammatory cytokines is rapid, occurring ≤5 minutes after intrathecal (perispinal) opioid administration. We document that opposition of analgesia by proinflammatory cytokines cannot be accounted for by an alteration in spinal morphine concentrations. The acute anti-analgesic effects of proinflammatory cytokines occur in a p38 mitogen-activated protein kinase and nitric oxide dependent fashion. Chronic intrathecal morphine or methadone significantly increased spinal glial activation (toll-like receptor 4 mRNA and protein) and the expression of multiple chemokines and cytokines, combined with development of analgesic tolerance and pain enhancement (hyperalgesia, allodynia). Statistical analysis demonstrated that a cluster of cytokines and chemokines was linked with pain-related behavioral changes. Moreover, blockade of spinal proinflammatory cytokines during a stringent morphine regimen previously associated with altered neuronal function also attenuated enhanced pain, supportive that proinflammatory cytokines are importantly involved in tolerance induced by such regimens. These data implicate multiple opioid-induced spinal proinflammatory cytokines in opposing both acute and chronic opioid analgesia, and provide a novel mechanism for the opposition of acute opioid analgesia. PMID:18599265

Subcutaneous morphine infusion by syringe driver for terminally ill patients.

PubMed

Cools, H J; Berkhout, A M; De Bock, G H

1996-05-01

The study aimed to find whether subcutaneous morphine administration by syringe driver for terminally ill patients in a Dutch nursing home led to higher morphine doses and earlier death than routine morphine administration. The data comprised the files of all patients dying over a 2 year period in a 355-bed nursing home in Delft in the Netherlands. Thirty-eight per cent of the patients had been given morphine, 29% by continuous subcutaneous syringe driver. In comparing the patients given morphine with and without a syringe driver no differences emerged in mean age, sex, length of admission, type of ward, diagnosis, duration of morphine administration and mean dose. The data indicate that subcutaneous morphine administration by syringe driver decreases dose frequency problems and improves the control of pain and other symptoms in the last week before death. There was no evidence that administration of morphine in this way shortens survival.

Opiate and non-opiate aspects of morphine induced seizures.

PubMed

Frenk, H; Liban, A; Balamuth, R; Urca, G

1982-12-16

The intraperitoneal administration of morphine hydrochloride at doses of 300 mg/kg produced analgesia, catalepsy, and electrographic spiking in rats that developed into electrographic seizure patterns after approximately 2.5 h. Whereas naltrexone (12 mg/kg) reversed analgesia and catalepsy, and diminished electrographic spiking, it precipitated electrographic seizure activity similar to that observed following intraperitoneal morphine alone. These seizures were accompanied by behavioral convulsions. No tolerance to these seizures developed with repeated paired administration of morphine and naltrexone or in morphine tolerant rats, but rather potentiation was observed. The epileptogenic effects were found to be potentiated in amygdaloid kindled rats, as well. It was concluded that morphine at these doses activates two different epileptogenic mechanisms, one mediated by opiate receptors, the other not. The possibility of the simultaneous activation of a morphine sensitive anticonvulsant mechanism is discussed.

[Effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase and S-100β and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head].

PubMed

Li, Jing-zhu; Li, Xiao-zheng; Wang, Xiao-min; Wang, Ming-shan; Yu, Hai-fang; Shi, Fei; Miao, Dan; Bi, Yan-lin

2013-07-16

To explore the effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase (NSE) and S-100β and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head. After the approval of institutional review board and the provision of informed consent, 80 patients over 70 years old, undergoing acute replacement of femoral head under combined spinal and epidural anesthesia and midazolam sedation at Qingdao Municipal Hospital and Qingdao Hiser Medical Center from January 2011 to May 2012, were randomly assigned into control group (group C, n = 40) and parecoxib group (group P, n = 40). In group P, parecoxib sodium 20/40 mg (based on weight 50 kg) was administered via an intravenous injection after admission with 12 hours intervals for six times. In group C, morphine 2/4 mg was given initially. Additional morphine 2 mg was given to maintain the pain visual analog scale (VAS) of 3 points or less in both groups. Primary observation indices: (1) postoperative time and additional amount of morphine; (2) rate of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) at 3 days, 1 week, 3 months and 6 months postoperation (T1-T4); (3) se rum levels of NSE and S-100β were measured at the timepoints of before analgesia (t0), before anesthesia (t1), end of surgery (t2) and 6 hours, 24 hours, 48 hours postoperation (t3-t5); (4) other serious complications. Compared with group C, the additional amount of morphine, postoperative time, rate of POD and POCD at T1-T4, the level of NSE at t2-t5 and S-100β at t1-t5 were lower in group P (P < 0.05). No other serious complications were observed. Parecoxib sodium analgesia reduces the rate of POD and POCD in elderly patients with neuroprotective effects.

A Leptin-Mediated Central Mechanism in Analgesia-Enhanced Opioid Reward in Rats

PubMed Central

Lim, Grewo; Kim, Hyangin; McCabe, Michael F.; Chou, Chiu-Wen; Wang, Shuxing; Chen, Lucy L.; Marota, John J.A.; Blood, Anne; Breiter, Hans C.

2014-01-01

Opioid analgesics are commonly used in chronic pain management despite a potential risk of rewarding. However, it remains unclear whether opioid analgesia would enhance the opioid rewarding effect thereby contributing to opioid rewarding. Utilizing a rat paradigm of conditioned place preference (CPP) combined with ankle monoarthritis as a condition of persistent nociception, we showed that analgesia induced by either morphine or the nonsteroid anti-inflammatory drug ibuprofen increased CPP scores in arthritic rats, suggesting that analgesia itself had a rewarding effect. However, arthritic rats exhibited a significantly higher CPP score in response to morphine than ibuprofen. Thus, the rewarding effect of morphine was enhanced in the presence of persistent nociception, producing a phenomenon of analgesia-enhanced opioid reward. At the cellular level, administration of morphine activated a cascade of leptin expression, glial activation, and dopamine receptor upregulation in the nucleus accumbens (NAc), while administration of ibuprofen decreased glial activation with no effect on leptin expression in the NAc. Furthermore, the morphine rewarding effect was blocked in leptin deficient ob/ob mice or by neutralizing leptin or interleukin-1β in the NAc without diminishing morphine analgesia. The data indicate that systemic opioid can activate a leptin-mediated central mechanism in the NAc that led to the enhanced opioid rewarding effect. These findings provide evidence for an interaction between opioid analgesia and opioid rewarding, which may have implications in clinical opioid dose escalation in chronic pain management. PMID:25031415

Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone.

PubMed

Maddocks, I; Somogyi, A; Abbott, F; Hayball, P; Parker, D

1996-09-01

We have observed among patients of the Southern Community Hospice Programme that up to 25% experience acute delirium when treated with morphine and improve when the opioid is changed to oxycodone or fentanyl. This study aimed to confirm by a prospective trial that oxycodone produces less delirium than morphine in such patients. Oxycodone was administered by a continuous subcutaneous infusion, as this allowed more flexible and reliable dosing, and patients were monitored for any adverse reactions to the drug. Thirteen patients completed the study. Statistically significant improvements in mental state and nausea and vomiting occurred following a change from morphine to oxycodone. Pain scores improved but did not reach a level of statistical significance. The phenotype status of the patients was tested to establish their capacity to metabolize oxycodone. One patient who did not achieve adequate pain control proved to be a poor metabolizer. These results show that oxycodone administered by the subcutaneous route can provide effective analgesia without significant side effects in patients with morphine-induced delirium. This treatment allows patients to remain more comfortable and lucid in their final days. A small proportion of patients who do not metabolize oxycodone effectively may not receive this benefit.

[Critical infusion incident caused by incorrect use of a patient-controlled analgesia pump].

PubMed

Steffen, M; von Hintzenstern, U; Obermayer, A

2002-01-01

We report on the case of a 17-year-old male patient who received a PCA pump after nephrectomy for postoperative analgesia. The syringe of the PCA pump was filled with 50 mg morphine and positioned about 25 cm above the heart. Since the piston of the syringe was not bolted while the pump was switched off, an unnoticed accidental evacuation of the whole content of the syringe into the intravenous line of the patient occurred because of gravity. This problem exists not only with PCA pumps, but can happen with syringe pumps in general. The incident, which can only be explained by strongly reduced venous pressure, was detected by chance. No harm resulted for the patient, but under different conditions it could have been lethal. This critical incident was caused by various factors: incorrect application in combination with insufficient experience or training, stress, inadequate handing-over of the patient and a lack of arrangements and instructions for procedures in routine situations. Suggestions for preventing such dangerous critical incidents are made and discussed. In particular, an algorithm for the correct procedure when inserting or changing the syringe of a syringe pump is presented.

[Perioperative managements of the patients with cancer-pain receiving morphine].

PubMed

Matsuda, M; Murakawa, K; Noma, K; Uemura, Y; Maeda, S; Tashiro, C

1998-09-01

In the patients receiving morphine preoperatively, it is preoperatively important to avoid withdrawal symptoms postoperatively and to suppress postoperative pain and to maintain an appropriate anesthetic depth during the operation. We experienced six patients who had been under preoperative pain control with oral and/or epidural morphine and undergone palliative operation for their cancer pain. Four of the patients were preoperatively administered with oral morphine ranging from 30 to 270 mg.day-1. One patient was given epidural morphine 10 mg.day-1. Another was with morphine 1800 mg.day-1 orally and 50 mg.day-1 epiduraly. In all cases, general anesthesia was maintained with inhalation anesthetics. Anesthetic supplementation and postoperative pain management were performed with continuous i.v. infusion of morphine (half dosage of daily oral dosage), or subcutaneous injection (one sixth dosage of daily oral morphine) while preoperative epidural morphine was continued throughout the perioperative period. We were able to manage these patients well and none of them developed withdrawal symptom or increased postoperative pain.

Comparison of continuous femoral nerve block (CFNB/SA) and continuous femoral nerve block with mini-dose spinal morphine (CFNB/SAMO) for postoperative analgesia after total knee arthroplasty (TKA): a randomized controlled study.

PubMed

Sundarathiti, Petchara; Thammasakulsiri, Jadesadha; Supboon, Supawadee; Sakdanuwatwong, Supalak; Piangjai, Molruedee

2016-07-16

Unsatisfactory analgesia for major knee surgery with femoral nerve block (FNB) alone was reported and the additional benefit of sciatic block to continuous femoral nerve block (CFNB) was not conclusive. The aim of the present study was to find the benefit of the additional mini-dose spinal morphine (0.035 mg) to CFNB for postoperative pain control and to compare their associated side effects after total knee arthroplasty (TKA). After written informed consent and with Institutional Ethics Committee approval, 68 American Society of Anesthesiologists (ASA) Physical Status I-III patients scheduled for elective unilateral TKA under spinal anesthesia (SA) were included in the present prospective, randomized controlled study. The patients were allocated into two groups. CFNB was placed in all patients by the inguinal paravascular approach with 20 ml of 0.25 % levobupivacaine. Group I (named CFNB/SA group), SA was administered with 2.8 ml levobupivacaine and Group II (named CFNB/SAMO group), SA with 2.8 ml levobupivacaine plus morphine 0.035 mg. At Post Anesthesia Care Unit (PACU), pain and other adverse effects were recorded. Pain was assessed by visual analog scale (VAS) 0-10. Tramadol 50 mg intravenous (IV) was given if the VAS > 4. In the ward, all patients were maintained by continuous femoral infusion of 0.125 % levobupivacaine rate 7 ml/hr and then reduced to 5 ml/hr if VAS ≤3. Patient's demographics data in each group were not different. At post-operative (PO) 12-24 h, the VAS scores were significantly lesser in the CFNB/SAMO group. Cumulative tramadol IV requirement for PO48h were also significantly lesser in the CFNB/SAMO group. Nausea, vomiting and numbness were significantly greater in the CFNB/SAMO group during early postoperative period (PO1-6 h). Though in some patients CFNB was inadequate, a mini-dose of intrathecal morphine (0.035 mg) in addition to CFNB was found to be effective with minimal side effects. Thai Clinical Trial Registry

Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomised controlled trial

PubMed Central

Rainer, Timothy H; Jacobs, Philip; Ng, Y C; Cheung, N K; Tam, Michael; Lam, Peggo K W; Wong, Robert; Cocks, Robert A

2000-01-01

Objectives To investigate the cost effectiveness of intravenous ketorolac compared with intravenous morphine in relieving pain after blunt limb injury in an accident and emergency department. Design Double blind, randomised, controlled study and cost consequences analysis. Setting Emergency department of a university hospital in the New Territories of Hong Kong. Participants 148 adult patients with painful isolated limb injuries (limb injuries without other injuries). Main outcome measures Primary outcome measure was a cost consequences analysis comparing the use of ketorolac with morphine; secondary outcome measures were pain relief at rest and with limb movement, adverse events, patients' satisfaction, and time spent in the emergency department. Results No difference was found in the median time taken to achieve pain relief at rest between the group receiving ketorolac and the group receiving morphine, but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour (95% confidence interval 1.05 to 2.02) compared with 0.87 (0.84 to 1.06) in the morphine group (P=0.003). The odds of experiencing adverse events was 144.2 (41.5 to 501.6) times more likely with morphine than with ketorolac. The median time from the initial delivery of analgesia to the participant leaving the department was 20 (4.0 to 39.0) minutes shorter in the ketorolac group than in the morphine group (P=0.02). The mean cost per person was $HK44 (£4; $5.6) in the ketorolac group and $HK229 in the morphine group (P<0.0001). The median score for patients' satisfaction was 6.0 for ketorolac and 5.0 for morphine (P<0.0001). Conclusion Intravenous ketorolac is a more cost effective analgesic than intravenous morphine in the management of isolated limb injury in an emergency department in Hong Kong, and its use may be considered as the dominant strategy. PMID:11082083

Impact of Preemptive Analgesia on inflammatory responses and Rehabilitation after Primary Total Knee Arthroplasty: A Controlled Clinical Study.

PubMed

Jianda, Xu; Yuxing, Qu; Yi, Gao; Hong, Zhao; Libo, Peng; Jianning, Zhao

2016-08-31

The aim of this study was to investigate the effects of preemptive analgesia on the inflammatory response and rehabilitation in TKA. 75 patients with unilateral primary knee osteoarthritis were conducted in this prospective study. All patients were randomly divided into two groups (MMA with/without preemptive analgesia group). The following parameters were used to evaluate analgesic efficacy: knee flexion, pain at rest and walking, functional walking capacity (2 MWT and 6 MWT), WOMAC score, and hs-CRP level. Patients in MMA with preemptive analgesia group had lower hs-CRP level and less pain at rest and walking during the first week postoperatively (P < 0.05). The 2 MWT was significantly better in MMA with preemptive analgesia group (17.13 ± 3.82 VS 14.19 ± 3.56, P = 0.001). The 6 MWT scores and WOMAC scores increased significantly within Groups (P = 0.020, 0.000), but no difference between groups postoperatively (P > 0.05). Less cumulative consumption of morphine was found in MMA with preemptive analgesia group at 48 h (P = 0.017, 0.023), but no difference at total requirement (P = 0.113). Preemptive analgesia added to a multimodal analgesic regime improved analgesia, reduced inflammatory reaction and accelerated functional recovery at the first week postoperatively, but not improved long-term function.

Impact of Preemptive Analgesia on inflammatory responses and Rehabilitation after Primary Total Knee Arthroplasty: A Controlled Clinical Study

PubMed Central

Jianda, Xu; Yuxing, Qu; Yi, Gao; Hong, Zhao; Libo, Peng; Jianning, Zhao

2016-01-01

The aim of this study was to investigate the effects of preemptive analgesia on the inflammatory response and rehabilitation in TKA. 75 patients with unilateral primary knee osteoarthritis were conducted in this prospective study. All patients were randomly divided into two groups (MMA with/without preemptive analgesia group). The following parameters were used to evaluate analgesic efficacy: knee flexion, pain at rest and walking, functional walking capacity (2 MWT and 6 MWT), WOMAC score, and hs-CRP level. Patients in MMA with preemptive analgesia group had lower hs-CRP level and less pain at rest and walking during the first week postoperatively (P < 0.05). The 2 MWT was significantly better in MMA with preemptive analgesia group (17.13 ± 3.82 VS 14.19 ± 3.56, P = 0.001). The 6 MWT scores and WOMAC scores increased significantly within Groups (P = 0.020, 0.000), but no difference between groups postoperatively (P > 0.05). Less cumulative consumption of morphine was found in MMA with preemptive analgesia group at 48 h (P = 0.017, 0.023), but no difference at total requirement (P = 0.113). Preemptive analgesia added to a multimodal analgesic regime improved analgesia, reduced inflammatory reaction and accelerated functional recovery at the first week postoperatively, but not improved long-term function. PMID:27578313

Analgesia or addiction?: implications for morphine use after spinal cord injury.

PubMed

Woller, Sarah A; Moreno, Georgina L; Hart, Nigel; Wellman, Paul J; Grau, James W; Hook, Michelle A

2012-05-20

Opioid analgesics are among the most effective agents for treatment of moderate to severe pain. However, the use of morphine after a spinal cord injury (SCI) can potentiate the development of paradoxical pain symptoms, and continuous administration can lead to dependence, tolerance, and addiction. Although some studies suggest that the addictive potential of morphine decreases when it is used to treat neuropathic pain, this has not been studied in a SCI model. Accordingly, the present studies investigated the addictive potential of morphine in a rodent model of SCI using conditioned place preference (CPP) and intravenous self-administration paradigms. A contusion injury significantly increased the expression of a CPP relative to sham and intact controls in the acute phase of injury. However, contused animals self-administered significantly less morphine than sham and intact controls, but this was dose-dependent; at a high concentration, injured rats exhibited an increase in drug-reinforced responses over time. Exposure to a high concentration of morphine impeded weight gain and locomotor recovery. We suggest that the increased preference observed in injured rats reflects a motivational effect linked in part to the drug's anti-nociceptive effect. Further, although injured rats exhibited a suppression of opiate self-administration, when given access to a high concentration, addictive-like behavior emerged and was associated with poor recovery.

Modest increase in risk of acute coronary syndrome associated with morphine use in cancer patients: a population-based nested case-control study.

PubMed

Lee, Cynthia Wei-Sheng; Muo, Chih-Hsin; Liang, Ji-An; Sung, Fung-Chang; Kao, Chia-Hung

2014-06-01

Morphine is widely used for pain management in cancer patients. Use of heroin, a morphine derivative, is a risk factor for acute coronary syndrome (ACS). This study investigates the risk of ACS associated with morphine use by comparing the incidence of ACS in cancer patients treated with and without morphine. This is a population-based nested case-control study using the Longitudinal Health Insurance Database 2000 in Taiwan. In total, 31,384 patients on the database were diagnosed with cancer without prior history of ACS during 1998-2010. In this cohort, 499 patients subsequently developed ACS and 30,885 patients did not. The 499 patients were designated as the ACS group; controls were selected from the remaining 30,885 patients and matched 3:1 to each case for age, sex, year of cancer diagnosis, and index year. Logistic regression was used to estimate the odds ratios and 95% confidence intervals, and the multivariable model was applied to control for age, sex, and Charlson comorbidity score. Cancer patients who received morphine had a 32% higher risk of developing ACS than non-morphine users. This increase in risk was significant when evaluating the overall cancer patients, but non-significant when evaluating any specific cancer type. The risk of ACS increased significantly with increasing morphine dosage (to ≥65 mg/y). Morphine treatment is associated with a modest increase in risk of ACS in patients with malignancy, but this association displays low significance in specific cancer types. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analgesic tolerance to morphine is regulated by PPARγ

PubMed Central

de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Stopponi, Serena; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

2014-01-01

Background and Purpose Opioid drugs are potent analgesics. However, their chronic use leads to the rapid development of tolerance to their analgesic effects and subsequent increase of significant side effects, including drug dependence and addiction. Here, we investigated the role of PPARγ in the development of analgesic tolerance to morphine in mice. Experimental Approach We monitored analgesia on alternate days using the tail immersion test. Key Results Daily administration of morphine (30 mg·kg−1, bid) resulted in the rapid development of tolerance to thermal analgesia. Co-administration of pioglitazone (10 and 30 mg·kg−1, bid) significantly attenuated the development and expression of tolerance. However, pretreatment with GW-9662 (5 mg·kg−1, bid), a selective PPARγ antagonist, completely abolished this effect. Injection of GW-9662 and a lower dose of morphine (15 mg·kg−1, bid) accelerated the development of tolerance to its antinociceptive effect. Subsequently, we found that conditional neuronal PPARγ knockout (KO) mice develop a more rapid and pronounced tolerance to morphine antinociception compared with wild-type (WT) controls. Moreover, in PPARγ KO mice, pioglitazone was no longer able to prevent the development of morphine tolerance. Conclusions and Implications Overall, our results demonstrate that PPARγ plays a tonic role in the modulation of morphine tolerance, and its pharmacological activation may help to reduce its development. These findings provide new information about the role of neuronal PPARγ and suggest that combining PPARγ agonists with opioid analgesics may reduce the development of tolerance and possibly attenuate the potential for opioid abuse. PMID:25048682

A randomized, double-blind, placebo-controlled pilot study of IV morphine-6-glucuronide for postoperative pain relief after knee replacement surgery.

PubMed

Romberg, Raymonda; van Dorp, Eveline; Hollander, Justus; Kruit, Michel; Binning, Alexander; Smith, Terry; Dahan, Albert

2007-01-01

To determine the dose-response effect of intravenous morphine-6-glucuronide (M6G) on acute postoperative pain. Patients undergoing knee replacement surgery under spinal anesthesia were randomly assigned to 1 of 4 single intravenous M6G doses, 0 (placebo), 10, 20, or 30 mg/70 kg, administered 150 minutes after the spinal anesthetic was given. Analgesic effects were evaluated by determining the cumulative patient controlled analgesia (PCA) morphine dose, consumed over a 12 and 24 hours period, after the initial dose of M6G. For pain assessments, a 10 cm visual analog scale was used. Data from 41 patients were evaluated (n=10, 10, 10, and 11 in the 0, 10, 20, and 30 mg M6G groups). Only at the highest M6G dose (30 mg/70 kg), morphine PCA consumption was significantly less compared with placebo: over the first 12 postoperative hours mean PCA morphine consumption was 3.0+/-2.0 mg/h after placebo and 1.4+/-0.5 mg/h after 30 mg M6G (P=0.03); over the first 24 h mean PCA morphine consumption was 2.5+/-2.1 mg after placebo and 1.0+/-0.4 mg after 30 mg M6G (P=0.04) (mean+/-SD). Visual analog scale values were similar across all groups during these time periods. The analgesic effect of M6G in postoperative pain was demonstrated with 30 mg/70 kg M6G superior to placebo. At this dose, M6G has a long duration of action as determined by a reduction in the use of morphine PCA over 12 and 24 hours.

Patient-controlled analgesia in patients with sickle cell vaso-occlusive crisis.

PubMed

McPherson, E; Perlin, E; Finke, H; Castro, O; Pittman, J

1990-01-01

Pain control using intramuscular analgesia is often unsatisfactory in sickle cell patients. In a pilot study, 15 patients with sickle cell anemia (SS) and one patient with SB thalassemia in vaso-occlusive crisis were treated with the Patient-Controlled Analgesia (PCA) technique using a Pharmacia Deltec Programmable pump (CADD PCA). Age range was 19-50 years (median = 27); there were nine females and seven males. The protocol consisted of 3 days of therapy using a background of continuous infusion meperidine. The starting dose was 20 mg/hr and was escalated to 30 mg/hr. The average amount given was 25.8 mg/hr. One to two boluses of 2.5-5.0 mg/dose (mode = 5.0) were also allowed each hour. In addition, patients number 8 through 16 were given hydroxyzine (Vistaril) 50 mg PO q6h. The number of days in pain prior to study entry (mean +/- SD) was 3.3 +/- 1.6. The number of pain sites per patient was 3.6 +/- 1.2. Using categorical and analog pain scales, patients' pain scores decreased only about 30%. However, most patients were fairly satisfied with the treatment and rated it overall as follows: 1 poor, 1 fair, 3 good, 6 very good, 4 excellent, 1 no comment. Patients number 8 through 16 gave higher ratings probably because a more idealized dosage regimen was being used by that time in the study. There were no adverse effects or major problems noted. It is our impression that PCA, when optimized, will be a safe and effective alternative method for providing patients with sickle cell vaso-occlusive crisis pain relief.

Comparative study of fentanyl and morphine in addition to hyperbaric or isobaric bupivacaine in combined spinal anaesthesia for caesarean section

PubMed Central

Saracoglu, Ayten; Saracoglu, Kemal T.; Eti, Zeynep

2011-01-01

Introduction The aim of our study was to compare the effects of isobaric and hyperbaric bupivacaine combined with morphine or fentanyl in patients undergoing caesarean section. We assessed quality and spread of analgesia and anaesthesia, postoperative analgesic requirement and side effects. Material and methods Hundred patients with American Society of Anesthesiologists physical status (ASA) I-II, age 18 to 40 years, were randomized to 4 groups. The intrathecal solutions were isobaric bupivacaine + morphine (group A), isobaric bupivacaine + fentanyl (group B), heavy bupivacaine + + morphine (group C) and heavy bupivacaine + fentanyl (group D). Mean arterial pressure, heart rate, oxygen saturation, ephedrine consumption, analgesic requirement time and additional analgesic needs were recorded. Results The 1st min value of mean arterial pressure was the lowest one in all groups. Heart rate decreased significantly in group A at the 10th min but not in the other groups. The decrease of visual analogue scale (VAS) pain scores began in the groups after the 4th postoperative h (p < 0.05) and the VAS value of group B at the 8th h was significantly higher than the other groups. The first analgesic requirement time in the postoperative period was longer in patients who had intrathecal morphine than those who had fentanyl. The duration of analgesia with isobaric bupivacaine and morphine was the longest one. Conclusions We concluded that intrathecal morphine provides a long duration of postoperative analgesia but the duration gets longer when it is combined with plain bupivacaine instead of heavy bupivacaine. PMID:22291807

Analgesic plasma concentrations of morphine in children with terminal malignancy receiving a continuous subcutaneous infusion of morphine sulfate to control severe pain.

PubMed

Nahata, M C; Miser, A W; Miser, J S; Reuning, R H

1984-02-01

Three children with terminal malignancy received a continuous subcutaneous infusion of morphine sulfate for the control of severe pain, the morphine dose being adjusted until the patient and/or parent reported complete freedom from pain. Analgesic plasma morphine concentrations at the steady state in these patients ranged from 12.9 to 57 ng/ml (median 19.6 ng/ml) while receiving morphine doses of 0.45-2.0 mg/h (0.034-0.06 mg/kg/h). One patient, who received 2 mg morphine per hour for 12 days demonstrated a 2-fold variation in steady-state plasma concentration during this period.

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast)

PubMed Central

Hutchinson, Mark R.; Lewis, Susannah S.; Coats, Benjamen D.; Skyba, David A.; Crysdale, Nicole Y.; Berkelhammer, Debra L.; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M.; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.; Johnson, Kirk W.

2009-01-01

Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused 3-to-5-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, whilst improving analgesia. PMID:18938237

Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury

PubMed Central

Moreno, Georgina; Woller, Sarah; Puga, Denise; Hoy, Kevin; Balden, Robyn; Grau, James W.

2009-01-01

Abstract Prior work has shown that a high dose (20 mg/kg) of systemic morphine, required to produce significant analgesia in the acute phase of a contusion injury, undermines the long-term health of treated subjects and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24 h post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic phase. The present study examines the locus of the effects using intrathecal morphine administration. Subjects were treated with one of three doses (0, 30, or 90 μg) of intrathecal morphine 24 h after a moderate contusion injury. The 90-μg dose produced significant analgesia when subjects were exposed to noxious stimuli (thermal and incremented shock) below the level of injury. Yet, despite analgesic efficacy, intrathecal morphine significantly attenuated the recovery of locomotor function and increased lesion size rostral to the injury site. A single dose of 30 or 90 μg of intrathecal morphine also decreased weight gain, and more than doubled the incidence of mortality and autophagia when compared to vehicle-treated controls. Morphine is one of the most effective pharmacological agents for the treatment of neuropathic pain and, therefore, is indispensable for the spinally injured. Treatment can, however, adversely affect the recovery process. A morphine-induced attenuation of recovery may result from increases in immune cell activation and, subsequently, pro-inflammatory cytokine concentrations in the contused spinal cord. PMID:19388818

Comparison of intra-articular bupivacaine-morphine with bupivacaine-tenoxicam combinations on post-operative analgesia in patients with arthroscopic meniscectomy: a prospective, randomised study.

PubMed

Sanel, Selim; Arpaz, Osman; Unay, Koray; Turkmen, Ismail; Simsek, Selcuk; Ugutmen, Ender

2016-03-01

There are many alternatives for post-operative pain relief in patients who have had general anaesthesia. The aim of this study was to evaluate the efficacy of intra-articular bupivacaine + morphine and bupivacaine + tenoxicam applications in post-operative pain control in patients undergoing knee arthroscopy with general anaesthesia. This was a prospective study. Standard anaesthesia procedures were applied to each patient, and the 240 patients chosen at random were then divided into two groups. Each group received a different combination of drugs for this double-blind study. The first group (group A: 120 patients) received 0.5% bupivacaine 100 mg + tenoxicam 20 mg (22 ml); the second group (group B) received 0.5% bupivacaine 100 mg + morphine 2 mg (22 ml); both groups received their drugs at the end of the intra-articular operation before tourniquet deflation. Before the operation, patients were asked about their post-operative pain at particular periods over the following 24 hours using the visual analogue scale (VAS) and the numeric rating scale (NRS). An additional analgaesic requirement and possible side effects were also recorded. Group A patients needed analgaesics sooner after operation than patients in group B. In Group B, VAS and NRS values were statistically higher compared with group A at the 12th hour. There were also fewer side effects seen in group A versus group B. Effective and reliable results were obtained in post-operative pain control in bupivacaine added to the morphine or tenoxicam groups following arthroscopic meniscectomy. In the tenoxicam group, patients reported less pain, fewer side effects and less need for analgesics at 12 hours after the operation. level 1, therapeutic, randomised, multicentric study.

Local anaesthetic wound infiltration for postcaesarean section analgesia: A systematic review and meta-analysis.

PubMed

Adesope, Oluwaseyi; Ituk, Unyime; Habib, Ashraf S

2016-10-01

Wound infiltration with local anaesthetics has been investigated as a potentially useful method for providing analgesia after caesarean delivery, but the literature is inconclusive. The objective is to assess the efficacy of local anaesthetic wound infiltration in reducing pain scores and opioid consumption in women undergoing caesarean delivery. Systematic review of randomised controlled trials with meta-analyses. MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled trials (CENTRAL) until December 2015. Randomised controlled trials that assessed the efficacy of local anaesthetic wound infiltration using an infusion or single injection technique for postcaesarean section analgesia. A total of 21 studies were included in the final analysis (11 studies using an infusion technique and 10 studies using single infiltration). Local anaesthetic wound infiltration significantly decreased opioid consumption at 24 h [mean difference -9.69 mg morphine equivalents, 95% confidence interval (CI), -14.85 to -4.52] and pain scores after 24 h at rest (mean difference -0.36, 95% CI, -0.58 to -0.14) and on movement (mean difference -0.61, 95% CI, -1.19 to -0.03). Subgroup analysis did not suggest a difference in primary outcomes between infusions and single infiltration. Opioid consumption was reduced in patients who did not receive intrathecal morphine but not in those who received intrathecal morphine, although there were very little data in patients receiving intrathecal morphine. Pain scores at rest and on movement at 24 h were reduced with catheter placement below the fascia but not above the fascia. There were no statistically significant reductions in nausea, vomiting or pruritus with local anaesthetic infiltration. Local anaesthetic wound infiltration reduces postoperative opioid consumption but had minimal effect on pain scores and did not reduce opioid-related side-effects in women who had undergone delivery by caesarean section. The review is

Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia.

PubMed

Ryu, J-H; Kang, M-H; Park, K-S; Do, S-H

2008-03-01

This randomized, double-blind, prospective study was undertaken to evaluate the effects of magnesium sulphate on anaesthetic requirements and postoperative analgesia in patients undergoing total i.v. anaesthesia (TIVA). Fifty patients who underwent gynaecological surgery were randomly divided into two groups. Before induction of anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and then 15 mg kg(-1) h(-1) i.v. by continuous infusion. The control group (Group S) received the same amount of isotonic saline. TIVA (propofol+remifentanil) was administered under bispectral index monitoring during anaesthesia induction and maintenance. Rocuronium was administered before orotracheal intubation and during surgery when the train-of-four count was 2 or more. After operation, patient-controlled analgesia with a solution of ketorolac and morphine was used and the consumption of this solution was recorded. Pain scores at rest and upon movement were evaluated 30 min, 4, 24, and 48 h after surgery. Patients in Group M required less rocuronium than those in Group S [mean (SD) 0.44 (0.09) vs 0.35 (0.07) microg kg(-1) min(-1), P<0.05]. The total amounts of propofol and remifentanil administered were similar in the two groups. Postoperative pain scores, cumulative analgesic consumption, and shivering incidents were significantly lower in Group M (P<0.05). Mean arterial pressure just after intubation and during the immediate postoperative period was also significantly lower in Group M (P<0.05). I.v. magnesium sulphate during TIVA reduced rocuronium requirement and improved the quality of postoperative analgesia.

Morphine clearance in children: does race or genetics matter?

PubMed

Sadhasivam, Senthilkumar; Krekels, Elke H J; Chidambaran, Vidya; Esslinger, Hope R; Ngamprasertwong, Pornswan; Zhang, Kejian; Fukuda, Tsuyoshi; Vinks, Alexander A

2012-01-01

Interindividual variability in analgesic response and adverse effects of opioids because of narrow therapeutic indices are major clinical problems. Morphine is an opioid commonly used in children to manage perioperative pain. Al-though size and age often are considered primary covariates for morphine pharmacokinetic models, the impact of other factors important in personalizing care such as race and genetic variations on morphine disposition is not well documented. Genotype blinded clinical observational pharmacokinetic study. One hundred forty-six African American and Caucasian children scheduled for elective outpatient adenotonsillectomy were enrolled in our prospective genotype blinded observational study with standard perioperative clinical care. Tertiary care pediatric institution. Morphine bolus for intraoperative analgesia in children and pharmacokinetic analyses in different races. Pharmacokinetics and pharmacogenetics of intravenous morphine in a homogeneous pediatric outpatient surgical pain population were evaluated. The authors observed that African American children have higher morphine clearance than Caucasian children. The increased clearance is directed toward the formation of morphine-3-glucuronide formation, rather than the formation of morphine-6-glucuronide. Common uridine diphosphate glucuronosyl transferase (UGT) 2B7 genetic variations (2161C>T and 802C>T) were not associated with observed racial differences in morphine's clearance although the wild type of the UGT2B7 isozyme is more prevalent in the African Americans. Race of the child is an important factor in perioperative intravenous morphine's clearance and its potential role in personalizing analgesia with morphine needs further investigation.

Fatty acid amide hydrolase–morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children

PubMed Central

Chidambaran, Vidya; Pilipenko, Valentina; Spruance, Kristie; Venkatasubramanian, Raja; Niu, Jing; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Zhang, Kejian; Kaufman, Kenneth; Vinks, Alexander A; Martin, Lisa J; Sadhasivam, Senthilkumar

2017-01-01

Aim: Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid–endocannabinoid interactions. Patients & methods: In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics. Results: We found significant FAAH–morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH–HCVR association predicts risk of impending RD from morphine use. Conclusion: FAAH genotypes predict risk for morphine-related adverse outcomes. PMID:27977335

Single-dose intra-articular bupivacaine versus morphine after arthroscopic knee surgery: a meta-analysis of randomized-controlled studies.

PubMed

Wei, Jie; Lei, Guang-hua; Gao, Shu-Guang; Zeng, Chao; Qin, Jia-bi; Kong, Fan-jing; Yang, Tu-bao

2014-07-01

This meta-analysis compared the earliest clinical effects of intra-articular bupivacaine and morphine for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted using MEDLINE (1966 to 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Google Scholar databases for identification of randomized-controlled trials that compared IA bupivacaine and morphine for postoperative pain. The relative risk, weighted mean difference (WMD), and their corresponding 95% confidence intervals (CI) were calculated using RevMan statistical software. Bupivacaine and morphine group had similar acute postoperative pain scores (WMD: 0.07; 95% CI, -0.18 to 0.32; P=0.60); number of patients requiring supplementary analgesia (relative risk: 0.74; 95% CI, 0.42 to 1.31; P=0.30) for the trials in this meta-analysis (n=13); and side effects (relative risk: 0.63; 95% CI, 0.39 to 1.02, P=0.06). Even though, the time to first analgesic request resulted in a significant difference (WMD: 66.59; 95% CI, 11.75 to 122.14, P=0.02), this result was not supported by the sensitivity analysis. On the basis of the currently available literature, this study failed to demonstrate a significant difference between single-dose intra-articular bupivacaine and morphine at the end of the arthroscopic knee surgery in terms of pain relief, need for supplementary analgesics, times interval before the first request for additional analgesic, and short-term side effects. Level II-meta-analysis of Level I and II studies.

The interaction of tetrahydroisoquinoline derivatives with antinociceptive action of morphine and oxotremorine in mice.

PubMed

Vetulani, J; Pavone, F; Przewłocka, B; Borghi, V; Nalepa, I

2003-11-01

To extend our earlier data on synergistic action of tetrahydroisoquinolines and morphine, we have investigated the analgesic effects of 1,2,3,4-tetrahydroisoquinoline (TIQ) and its 1-methyl-(1-MeTIQ) and N-methyl (N-MeTIQ) analogs on analgesia induced by morphine and oxotremorine. 1-MeTIQ and N-MeTIQ induced a moderate, delayed and prolonged analgesic action measured in the tail-flick test in CD-1 mice; 1-MeTIQ and TIQ prolonged the opiate (morphine, 2.5 mg/kg i.p.) analgesia while TIQ and N-TIQ potentiated cholinergic (oxotremorine, 0.02 mg/kg i.p.) analgesia. The involvement of the opioid and noradrenergic systems in this effect is discussed.

Single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery: a meta-analysis of randomised placebo-controlled studies

PubMed Central

Wang, Yi-lun; Zeng, Chao; Xie, Dong-xing; Yang, Ye; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-hua

2015-01-01

Objectives To evaluate the efficacy and safety of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery. Design Meta-analysis. Data sources and study eligibility criteria A comprehensive literature search, using Medline (1966–2014), the Cochrane Central Register of Controlled Trials and Embase databases, was conducted to identify randomised placebo-controlled trials that used a combination of single-dose intra-articular bupivacaine and morphine for postoperative pain relief. Results 12 articles were included in this meta-analysis. The mean visual analogue scale (VAS) scores of the bupivacaine plus morphine group were significantly lower than those of the placebo group (weighted mean difference (WMD) −1.75; 95% CI −2.16 to −1.33; p<0.001). The VAS scores at the last follow-up time point (last VAS scores) of the bupivacaine plus morphine group were also significantly lower than those of the placebo group (WMD −1.46; 95% CI −1.63 to −1.29; p<0.001). The number of patients requiring supplementary analgesia was also significantly reduced (RR 0.60; 95% CI 0.39 to 0.93; p=0.02), while there was no significant difference in the time to first analgesic request (WMD 3.46; 95% CI −1.81 to 8.72; p=0.20) or short-term side effects (RR 1.67; 95% CI 0.65 to 4.26; p=0.29). Conclusions The administration of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery is effective for pain relief, and its short-term side effects remain similar to saline placebo. PMID:26078306

The surgical rectus sheath block for post-operative analgesia: a modern approach to an established technique.

PubMed

Crosbie, Emma J; Massiah, Nadine S; Achiampong, Josephine Y; Dolling, Stuart; Slade, Richard J

2012-02-01

To describe the surgical rectus sheath block for post-operative pain relief following major gynaecological surgery. Local anaesthetic (20 ml 0.25% bupivacaine bilaterally) is administered under direct vision to the rectus sheath space at the time of closure of the anterior abdominal wall. We conducted a retrospective case note review of 98 consecutive patients undergoing major gynaecological surgery for benign or malignant disease who received either standard subcutaneous infiltration of the wound with local anaesthetic (LA, n=51) or the surgical rectus sheath block (n=47) for post-operative pain relief. (1) Pain scores on waking, (2) duration of morphine-based patient controlled analgesia (PCA), (3) quantity of morphine used during the first 48 post-operative hours and (4) length of post-operative stay. The groups were similar in age, the range of procedures performed and the type of pathology observed. Patients who received the surgical rectus sheath block had lower pain scores on waking [0 (0-1) vs. 2 (1-3), p<0.001], required less morphine post-operatively [12 mg (9-26) vs. 36 mg (30-48), p<0.001], had their PCAs discontinued earlier [24h (18-34) vs. 37 h (28-48), p<0.001] and went home earlier [4 days (3-4) vs. 5 days post-op (4-8), p<0.001] [median (interquartile range)] than patients receiving standard subcutaneous local anaesthetic into the wound. The surgical rectus sheath block appears to provide effective post-operative analgesia for patients undergoing major gynaecological surgery. A randomised controlled clinical trial is required to assess its efficacy further. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Local anaesthetic infiltration at the end of carotid endarterectomy improves post-operative analgesia.

PubMed

Cherprenet, A-L; Rambourdin-Perraud, M; Laforêt, S; Faure, M; Guesmi, N; Baud, C; Rosset, E; Schoeffler, P; Dualé, C

2015-01-01

Wound infiltration at the end of carotid endarterectomy under general anaesthesia is a simple technique that can be delegated to the surgeon. It was hypothesised that this technique could improve early post-operative analgesia by reducing the need for post-operative opioids. Forty patients underwent carotid endarterectomy under general anaesthesia with desflurane and remifentanil supplemented with morphine for post-operative analgesia. In a prospective double-blinded randomised study, patients were allocated pre-operatively to receive either subcutaneous infiltration of both wound edges with 20 ml of 0.75% ropivacaine or infiltration with isotonic saline. The primary outcome was morphine consumption while in the post-anaesthesia care unit (PACU). Pain scores at rest and movement, sedation, and patient satisfaction were the other main outcomes used to assess post-operative analgesia. The median dose of morphine administered in the PACU was 2 mg [0-3] in the ropivacaine vs. 4 mg [3-6] in the placebo group (P = 0.0004, Mann-Whitney's test). Pain at rest and at movement was lower in the ropivacaine group throughout observation in the PACU. No difference was found for both pain and opioid consumption after discharge from the PACU or for patient satisfaction. Sedative events in the early post-operative period were less frequent in the ropivacaine group. Local anaesthetic wound infiltration performed before closure reduces the need for additional opioids, lowers the immediate post-operative pain and improves alertness. These results argue for the use of local infiltration anaesthesia for carotid endarterectomy. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Efficacy of the Bilateral Ilioinguinal-Iliohypogastric Block with Intrathecal Morphine for Postoperative Cesarean Delivery Analgesia

PubMed Central

Vallejo, Manuel C.; Steen, Talora L.; Cobb, Benjamin T.; Phelps, Amy L.; Pomerantz, Joel M.; Orebaugh, Steven L.; Chelly, Jacques E.

2012-01-01

The ilioinguinal-iliohypogastric (IIIH) block is frequently used as multimodal analgesia for lower abdominal surgeries. The aim of this study is to compare the efficacy of IIIH block using ultrasound visualization for reducing postoperative pain after caesarean delivery (CD) in patients receiving intrathecal morphine (ITM) under spinal anesthesia. Participants were randomly assigned to 1 of 3 treatment groups for the bilateral IIIH block: Group A = 10 mL of 0.5% bupivacaine, Group B = 10 mL of 0.5% bupivacaine on one side and 10 mL of a normal saline (NSS) placebo block on the opposite side, and Group C = 10 mL of NSS placebo per side. Pain and nausea scores, treatment for pain and nausea, and patient satisfaction were recorded for 48 hours after CD. No differences were noted with respect to pain scores or treatment for pain over the 48 hours. There were no differences to the presence of nausea (P = 0.64), treatment for nausea (P = 0.21), pruritus (P = 0.39), emesis (P = 0.35), or patient satisfaction (P = 0.29). There were no differences in pain and nausea scores over the measured time periods (MANOVA, P > 0.05). In parturients receiving ITM for elective CD, IIIH block offers no additional postoperative benefit for up to 48 hours. PMID:23304075

Effect-site concentration of remifentanil during patient-controlled analgesia in labour.

PubMed

Jost, A; Blagus, R; Ban, B; Kamenik, M

2015-08-01

Intravenous remifentanil has been described for patient-controlled analgesia in labour. Recently, the application of target-controlled infusion pumps with Minto's pharmacokinetic/pharmacodynamic model has been reported. Hypothetical effect-site remifentanil concentration during patient-controlled analgesia for labour has yet to be examined. The aim of this concept study was to explore characteristics of this parameter. We performed a historical cohort study based on our previous randomised cross-over clinical trial and analysed hypothetical effect-site remifentanil concentration. Values at spontaneous vaginal delivery and Apgar scores were tested for correlation. The association between pain score and the corresponding effect-site remifentanil concentration before and after bolus administration, and their relative difference, was examined with a linear mixed-effects model, adjusted for other variables. A series of 23 parturients with uncomplicated singleton pregnancies were included. On average, effect-site remifentanil concentration was highest during the third quarter throughout our recordings (5.5ng/mL; maximum 15.8ng/mL). The mean (median) {IQR} [range] at spontaneous vaginal delivery (n=14) was 2.52 (1.32) {0.95-4.28} [0.65-6.88] ng/mL, all Apgar scores were >7, and no correlation was confirmed. A negative association between effect-site remifentanil concentration before bolus administration and pain score (scale 0-100) was observed (-3.9, 95% CI -5.16 to -2.61, P <0.01). The residual value of hypothetical effect-site remifentanil concentration before uterine contraction, at the beginning of bolus administration, predicted lower pain scores. Monitoring effect-site remifentanil concentration may be potentially useful when remifentanil is administered for labour analgesia. However, our results need to be confirmed with a pharmacokinetic model optimized for pregnant patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Blood pressure and heart rate during orthostatic stress and walking with continuous postoperative thoracic epidural bupivacaine/morphine.

PubMed

Møiniche, S; Hjortsø, N C; Blemmer, T; Dahl, J B; Kehlet, H

1993-01-01

Thirty-one patients scheduled for elective cholecystectomy performed through a mini-laparotomy, were randomized to received either combined thoracic epidural anaesthesia/light general anaesthesia and postoperative balanced analgesia with continuous epidural bupivacaine 10 mg.h-1 and morphine 0.2 mg.h-1 for 38 h after surgery plus systemic ibuprofen 600 mg x 8 h-1 (N = 15) or general anaesthesia and postoperative analgesia with systemic morphine and ibuprofen 600 mg x 8 h-1 (N = 16). During postoperative epidural infusion sensory blockade to pinprick was Th4 to L1, and analgesia at rest and during mobilisation was superior compared to systemic morphine and NSAID. There were no significant differences between groups in haemodynamic responses (BP and heart rate) during rest, orthostatic stress and after walking assessed before, 24 and 48 h after operation except for a clinically unimportant lower heart rate (approximately 10 bpm) 48 h after surgery at rest and during orthostatic stress in the epidural group. There was no significant difference between groups in number of patients with a reduction > 20 mmHg (2.7 kPa) in systolic blood pressure during orthostatic stress (two in each group at 24 h) or in number of episodes of dizziness, nausea or vomiting during rest or mobilisation. These results do not support the common belief that low-dose thoracic epidural bupivacaine/morphine may prevent ambulation due to sympathetic blockade or to impaired cardiovascular adaptation to the upright position.

Soft tissue and intra-articular injection of bupivacaine, epinephrine, and morphine has a beneficial effect after total knee arthroplasty.

PubMed

Lombardi, Adolph V; Berend, Keith R; Mallory, Thomas H; Dodds, Kathleen L; Adams, Joanne B

2004-11-01

The purpose of this study was to determine if an intraoperative intraarticular and soft-tissue injection of local anaesthetic, epinephrine, and morphine has a beneficial effect for total knee arthroplasty. A control group of 138 patients (181 knees) received no intraoperative injection. The study group of 171 patients (197 knees) received intraoperative injection of 0.25% bupivacaine with epinephrine and morphine with 2/3 injected into the soft tissues and 1/3 injected into the joint. Patients having bilateral simultaneous procedures received a divided dose. The pain treatment protocol otherwise was identical. Pain, sedation, rescue narcotic usage, narcotic reversal and blood loss were examined. Pain levels during the immediate postoperative period, blood loss, and bleeding indices were reduced with injection. Considerably more control patients required rescue doses of narcotics. Preemptive analgesia with soft tissue and intra-articular injection of long-acting local anesthetic with epinephrine and morphine provides better pain control in the immediate postoperative period, decreases blood loss, and decreases the need for rescue narcotics and reversal agents. This simple, inexpensive method provides an effective adjunct to a multimodal approach in improving the postoperative course of primary total knee arthroplasty.

Bacterial infection in deep paraspinal muscles in a parturient following epidural analgesia.

PubMed

Yang, Ying-Wei; Chen, Wei-Ting; Chen, Jui-Yuan; Lee, She-Chin; Chang, Yi; Wen, Yeong-Ray

2011-06-01

We report a case of paraspinal muscle infection shortly after epidural analgesia for labor pain in a nulliparous parturient who was subjected to emergent Cesarean section because of fetal distress. Epidural morphine was administered for 3 days for postoperative pain control. She began to have constant lower back pain on postpartum Day 4. Magnetic resonance image study revealed a broad area of subcutaneous edema with a continuum along the catheter trajectory deep to the paraspinal muscles. An injection-related bacterial infection was suspected; the patient was treated with intravenous antibiotics and was soon cured uncomplicatedly. Epidural analgesia is effective to control labor pain and, in general, it is safe. However, the sequelae of complicated infection may be underestimated. We herein report a case complicated by iatrogenic infection, discuss the causes, and give suggestions for prevention. Copyright © 2011. Published by Elsevier B.V.

Lubiprostone for Opioid-Induced Constipation Does Not Interfere with Opioid Analgesia in Patients with Chronic Noncancer Pain.

PubMed

Spierings, Egilius L H; Brewer, Randall P; Rauck, Richard L; Losch-Beridon, Taryn; Mareya, Shadreck M

2017-03-01

To determine whether lubiprostone 24 μg twice daily (BID), administered to relieve opioid-induced constipation (OIC), affects opioid analgesia in patients with chronic noncancer pain. Data were pooled from 3 randomized, double-blind, placebo-controlled trials of lubiprostone in adults with chronic noncancer pain receiving stable opioid analgesia and who had documented OIC. In each study, lubiprostone 24 μg BID or placebo was administered for 12 weeks for relief of OIC using a common protocol. The Brief Pain Inventory short form (BPI-SF) was administered, and opioid use (expressed as morphine-equivalent daily dose [MEDD]) was recorded at baseline and months 1, 2, and 3. The BPI-SF provided patient scores for pain severity, the worst pain experienced in the past 24 hours, and pain interference with daily life. The pooled patient population (N = 1300) was predominately female (62.5%) and white (82.1%), with a mean age of 50.5 years. The MEDD was 97.5 mg (range, 5 to 3656 mg) in patients receiving placebo and 112.5 mg (range, 4 to 7605 mg) in patients treated with lubiprostone. Lubiprostone 24 μg BID treatment did not appear to affect opioid use or pain scores; changes from baseline were not significantly different with placebo vs. lubiprostone 24 μg BID at months 1, 2, and 3 for MEDD (P ≥ 0.435) and for BPI-SF scores for pain interference, pain severity, and worst pain (P ≥ 0.402). Lubiprostone 24 μg BID administered for relief of OIC in patients with chronic noncancer pain does not interfere with opioid analgesia. © 2016 World Institute of Pain.

Fatty acid amide hydrolase-morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children.

PubMed

Chidambaran, Vidya; Pilipenko, Valentina; Spruance, Kristie; Venkatasubramanian, Raja; Niu, Jing; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Zhang, Kejian; Kaufman, Kenneth; Vinks, Alexander A; Martin, Lisa J; Sadhasivam, Senthilkumar

2017-01-01

Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid-endocannabinoid interactions. In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO 2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics. We found significant FAAH-morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH-HCVR association predicts risk of impending RD from morphine use. FAAH genotypes predict risk for morphine-related adverse outcomes.

Nose and vein, speed and pain: comparing the use of intranasal diamorphine and intravenous morphine in a Scottish paediatric emergency department.

PubMed

Regan, Luke; Chapman, Andrew R; Celnik, Anna; Lumsden, Lesley; Al-Soufi, Reem; McCullough, Nicola P

2013-01-01

Urgent analgesia is essential for all children who present in severe pain, but difficulties in obtaining venous access can delay the use of adequate opiate analgesia. Intranasal diamorphine (IND) is now in use in around 60% of emergency departments and is the preferred choice of analgesia as reported by both parents and healthcare professionals. While IND has similar efficacy to intramuscular morphine in children, no study has compared its use against the current gold standard, intravenous morphine (IVM). IND was introduced to the Royal Aberdeen Children's Hospital on 24 December 2009. A retrospective case series was constructed to compare its clinical performance with its predecessor IVM. Three unexplored factors were investigated: time to opiate analgesia, the requirement for further analgesia when still in the emergency department and the effect of simple coanalgesia (eg, paracetamol/ibuprofen) on these requirements. 297 patients were eligible for the study (147 IND, 150 IVM) over a 28-month period. There was a non-significant trend to a longer median time to administration of analgesia in patients receiving IND (p=0.170). Patients who received IND were less likely to require further analgesia (p<0.001). Both groups were less likely to require further analgesia when simple coanalgesia was given (p=0.049). The authors found no significant difference in time to administration of analgesia between agents, but a learning curve has been identified. Sustained effort should be placed on the use of simple coanalgesia. The clinical performance of IND compares favourably with IVM in children with severe pain, and it remains an appropriate preferred agent.

Preemptive multimodal pain regimen reduces opioid analgesia for patients undergoing robotic-assisted laparoscopic radical prostatectomy.

PubMed

Trabulsi, Edouard J; Patel, Jitesh; Viscusi, Eugene R; Gomella, Leonard G; Lallas, Costas D

2010-11-01

Minimally invasive surgical techniques have many benefits, including reduced postoperative pain. Despite this, most patients require opioid analgesia, which can have significant side effects and toxicity. We report the first urologic study using multimodal analgesia with pregabalin, a gabapentinoid. The present retrospective study included 60 patients who underwent robotic-assisted laparoscopic radical prostatectomy. Of the 60 patients, 30 received multimodal treatment with pregabalin 150 mg, acetaminophen 975 mg, and celecoxib 400 mg orally 2 hours before the start of the procedure and continued postoperatively. These patients were compared with 30 consecutive previous patients, who had received a standard postoperative analgesic regimen with intravenous ketorolac 15 mg every 6 hours with oxycodone 5 mg and acetaminophen 325 mg, 1 to 2 tablets, every 4 hours as needed for pain. The patients in the multimodal treatment group had a significantly reduced intraoperative opioid requirement, as measured by the mean morphine equivalent dose administered (38.4 ± 2.73 mg vs 49.1 ± 2.65 mg; P < .01). The mean postoperative opioid use was also significantly reduced (10.7 ± 2.82 mg vs 26.2 ± 6.56 mg; P = .034), as was the mean total morphine equivalent dose administered (49.1 ± 2.7 mg vs 75.3 ± 4.6 mg; P < .001). The operative time, estimated operative blood loss, antiemetic use, postoperative creatinine and hemoglobin levels, and length of stay were similar in the 2 groups. No operative or treatment complications occurred in either group. The present retrospective review has indicated that a multimodal analgesic approach with pregabalin and celecoxib administered preoperatively decreases intraoperative and postoperative opioid use in patients undergoing robotic-assisted laparoscopic radical prostatectomy. Copyright © 2010 Elsevier Inc. All rights reserved.

Continuous wound infiltration versus epidural analgesia after hepato-pancreato-biliary surgery (POP-UP): a randomised controlled, open-label, non-inferiority trial.

PubMed

Mungroop, Timothy H; Veelo, Denise P; Busch, Olivier R; van Dieren, Susan; van Gulik, Thomas M; Karsten, Tom M; de Castro, Steve M; Godfried, Marc B; Thiel, Bram; Hollmann, Markus W; Lirk, Philipp; Besselink, Marc G

2016-10-01

Epidural analgesia is the international standard for pain treatment in abdominal surgery. Although some studies have advocated continuous wound infiltration with local anaesthetics, robust evidence is lacking, especially on patient-reported outcome measures. We aimed to determine the effectiveness of continuous wound infiltration in hepato-pancreato-biliary surgery. In this randomised controlled, open label, non-inferiority trial (POP-UP), we enrolled adult patients undergoing hepato-pancreato-biliary surgery by subcostal or midline laparotomy in two Dutch hospitals. Patients were centrally randomised (1:1) to receive either pain treatment with continuous wound infiltration using bupivacaine plus patient-controlled analgesia with morphine or to receive (patient-controlled) epidural analgesia with bupivacaine and sufentanil. All patients were treated within an enhanced recovery setting. Randomisation was stratified by centre and type of incision. The primary outcome was the mean Overall Benefit of Analgesic Score (OBAS) from day 1-5, a validated composite endpoint of pain scores, opioid side-effects, and patient satisfaction (range 0 [best] to 28 [worst]). Analysis was per-protocol. The non-inferiority limit of the mean difference was + 3·0. This trial is registered with the Netherlands Trial Registry, number NTR4948. Between Jan 20, 2015, and Sept 16, 2015, we randomly assigned 105 eligible patients: 53 to receive continuous wound infiltration and 52 to receive epidural analgesia. One patient in the continuous wound infiltration group discontinued treatment, as did five in the epidural analgesia group; of these five patients, preoperative placement failed in three (these patients were treated with continuous wound infiltration instead), one patient refused an epidural, and data for the primary endpoint was lost for one. Thus, 55 patients were included in the continuous wound infiltration group and 47 in the epidural analgesia group for the per-protocol analyses

A randomised controlled trial investigating the analgesic efficacy of transversus abdominis plane block for adult laparoscopic appendicectomy.

PubMed

Tupper-Carey, Darell Alexander; Fathil, Shahridan Mohd; Tan, Yin Kiat Glenn; Kan, Yuk Man; Cheong, Chern Yuen; Siddiqui, Fahad Javaid; Assam, Pryseley Nkouibert

2017-08-01

We conducted a single-centre, prospective randomised clinical trial to investigate the analgesic efficacy of transversus abdominis plane (TAP) block in adult patients undergoing laparoscopic appendicectomy. Patients undergoing urgent laparoscopic appendicectomy under general anaesthesia alone (control group) and general anaesthesia supplemented by TAP block (TAP intervention group) were compared. All patients received a multimodal analgesia regime, which included postoperative morphine via a patient-controlled analgesia device. The primary endpoints were morphine consumption at 12 hours and 24 hours postoperatively. Secondary endpoints included pain scores, incidence of nausea and vomiting, and time to hospital discharge. A total of 58 patients were recruited, with 29 patients in each group. Mean postoperative morphine consumption at 12 hours (control group: 11.45 ± 7.64 mg, TAP intervention group: 9.79 ± 8.09 mg; p = 0.4264) and 24 hours (control group: 13.38 ± 8.72 mg, TAP intervention group: 11.31 ± 8.66 mg; p = 0.3686) for the control and TAP intervention groups were not statistically different. Secondary outcomes were also not different between the two groups. Length of stay in the post-anaesthesia care unit was significantly shorter for the TAP intervention group, with a trend toward faster hospital discharge being observed. TAP block, a regional anaesthetic procedure performed immediately prior to skin incision for laparoscopic appendicectomy, did not significantly improve postoperative analgesia outcomes. Copyright: © Singapore Medical Association

Postoperative pain control in cats: clinical trials with pre-emptive lidocaine epidural co-administered with morphine or methadone.

PubMed

DeRossi, Rafael; Hermeto, Larissa Correa; Jardim, Paulo Henrique Affonseca; de Andrade Bicudo, Natalia; de Assis, Klebs Tavares

2016-11-01

Objectives The aim of the study was to evaluate the effectiveness of epidural lidocaine in combination with either methadone or morphine for postoperative analgesia in cats undergoing ovariohysterectomy. Methods Under general anesthesia, 24 cats that underwent ovariohysterectomy were randomly allocated into three treatment groups of eight each. Treatment 1 included 2% lidocaine (4.0 mg/kg); treatment 2 included lidocaine and methadone (4.0 mg/kg and 0.3 mg/kg, respectively); and treatment 3 included lidocaine and morphine (4.0 mg/kg and 0.1 mg/kg, respectively). All drugs were injected in a total volume of 0.25 ml/kg via the lumbosacral route in all cats. During the anesthetic and surgical periods, the physiologic variables (respiratory and heart rate, arterial blood pressure and rectal temperature) were measured at intervals of time zero, 10 mins, 20 mins, 30 mins, 60 mins and 120 mins. After cats had recovered from anesthesia, a multidimensional composite pain scale was used to assess postoperative analgesia 2, 4, 8, 12, 18 and 24 h after epidural. Results The time to first rescue analgesic was significantly ( P <0.05) prolonged in cats that received both lidocaine and methadone or lidocaine and morphine treatments compared with those that received lidocaine treatment alone. All cats that received lidocaine treatment alone required rescue analgesic within 2 h of epidural injections. All treatments produced significant cardiovascular and respiratory changes but they were within an acceptable range for healthy animals during the surgical period. Conclusions and relevance The two combinations administered via epidural allowed ovariohysterectomy with sufficient analgesia in cats, and both induced prolonged postoperative analgesia.

The effect of caudal vs intravenous morphine on early extubation and postoperative analgesic requirements for stage 2 and 3 single-ventricle palliation: a double blind randomized trial.

PubMed

Stuth, Eckehard A E; Berens, Richard J; Staudt, Susan R; Robertson, Frederick A; Scott, John P; Stucke, Astrid G; Hoffman, George M; Troshynski, Todd J; Tweddell, James S T; Zuperku, Edward J

2011-04-01

High-dose single-shot caudal morphine has been postulated to facilitate early extubation and to lower initial analgesic requirements after staged single-ventricle (SV) palliation. With Institutional Review Board approval and written informed parental consent, 64 SV children aged 75-1667 days were randomized to pre-incisional caudal morphine-bupivacaine (100 μg·kg(-1) morphine (concentration 0.1%), mixed with 0.25% bupivacaine with 1 : 200,000 epinephrine, total 1 ml·kg(-1)) and postcardiopulmonary bypass (CPB) intravenous (IV) droperidol (75 μg·kg(-1)) ('active caudal group') or pre-incisional caudal saline (1 ml·kg(-1)) and post-CPB IV morphine (150 μg·kg(-1)) with droperidol (75 μg·kg(-1)) ('active IV group'). Assignment remained concealed from families and the care teams throughout the trial. Early extubation failure rates (primary or reintubation within 24 h), time to first postoperative rescue morphine analgesia, and 12-h postoperative morphine requirements were assessed for extubated patients. Thirty-one (12 stage 2) SV patients received caudal morphine and 32 (15 stage 2) received IV morphine. Extubation failure rates were 6/31 (19%) for caudal and 5/32 (16%) for IV morphine. For successfully extubated patients (n = 54), active caudal treatment significantly delayed the need for postoperative rescue morphine in stage 3 patients (P = 0.02) but not in stage 2 patients (P = 0.189) (Kaplan-Meier survival analysis with LogRank test). The reduction in 12-h postoperative morphine requirements with active caudal treatment did not reach significance (P = 0.085) but morphine requirements were significantly higher for stage 2 compared with stage 3 patients (P < 0.001) (two-way anova in n = 50 extubated patients). High-dose caudal morphine with bupivacaine delayed the need for rescue morphine analgesia in stage 3 patients. All stage 2 patients required early rescue morphine and had significantly higher postoperative 12-h morphine requirements than stage 3

Increased glutamate synaptic transmission in the nucleus raphe magnus neurons from morphine-tolerant rats.

PubMed

Bie, Bihua; Pan, Zhizhong Z

2005-02-09

Currently, opioid-based drugs are the most effective pain relievers that are widely used in the treatment of pain. However, the analgesic efficacy of opioids is significantly limited by the development of tolerance after repeated opioid administration. Glutamate receptors have been reported to critically participate in the development and maintenance of opioid tolerance, but the underlying mechanisms remain unclear. Using whole-cell voltage-clamp recordings in brainstem slices, the present study investigated chronic morphine-induced adaptations in glutamatergic synaptic transmission in neurons of the nucleus raphe magnus (NRM), a key supraspinal relay for pain modulation and opioid analgesia. Chronic morphine significantly increased glutamate synaptic transmission exclusively in one class of NRM cells that contains mu-opioid receptors in a morphine-tolerant state. The adenylyl cyclase activator forskolin and the cAMP analog 8-bromo-cAMP mimicked the chronic morphine effect in control neurons and their potency in enhancing the glutamate synaptic current was significantly increased in neurons from morphine-tolerant rats. MDL12330a, an adenylyl cyclase inhibitor, and H89, a protein kinase A (PKA) inhibitor, reversed the increase in glutamate synaptic transmission induced by chronic morphine. In addition, PMA, a phorbol ester activator of protein kinase C (PKC), also showed an increased potency in enhancing the glutamate synaptic current in these morphine-tolerant cells. The PKC inhibitor GF109203X attenuated the chronic morphine effect. Taken together, these results suggest that chronic morphine increases presynaptic glutamate release in mu receptor-containing NRM neurons in a morphine-tolerant state, and that the increased glutamate synaptic transmission appears to involve an upregulation of both the cAMP/PKA pathway and the PKC pathway. This glutamate-mediated activation of these NRM neurons that are thought to facilitate spinal pain transmission may contribute to

Physician attitudes and beliefs about use of morphine for cancer pain.

PubMed

Elliott, T E; Elliott, B A

1992-04-01

The recent literature asserts that mistaken physician beliefs and attitudes are critical barriers to adequate cancer pain relief. To determine the prevalence of 12 proposed myths or misconceptions about morphine use in cancer pain management (CPM), we surveyed all physicians engaged in direct patient care in Duluth, Minnesota (N = 243). A 62% response was obtained. Many physicians misunderstood concepts of morphine tolerance, both to analgesia (51%) and to side effects (39%). Many were unaware of the use of adjuvant analgesics (29%), efficacy of oral morphine (27%), and nonexistent risk of addiction in CPM (20%). Analysis of result by physician age and specialy groups confirmed significant levels of misunderstanding in all subsets. Strategies to change physician attitudes and beliefs regarding morphine in CPM should focus on tolerance concepts, dosing schemes, safety, efficacy, lack of addictive risk, use of drug combinations, and the fact that cancer pain can be relieved.

The analgesic efficacy of ultrasound-guided transversus abdominis plane block on postoperative pain and morphine consumption in varicocelectomy.

PubMed

Ömür, Dilek; Oğuzalp, Hüseyin; Kiraz, Hasan A; Ekin, Serpil; Alan, Cabir; Ersay, Ahmet R; Hancı, Volkan

2016-06-01

To evaluate the analgesic effect of transversus abdominis plane (TAP) block administered before varicocele surgery. This study was completed at the Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, between January 2011 and April 2013. In a prospective, double blind, randomized, placebo controlled clinical study, 40 male patients scheduled for elective varicocele operations were randomized to group T (treatment group) or group C (controls). After receiving general anesthesia, group T received a TAP block using 20 mL 0.25% bupivacaine on the operation side, whereas group C received a control block using 20 mL 0.9% Sodium chloride. During the first 24 hours after surgery, the patient pain was evaluated using the visual analogue scale (VAS) at rest and while coughing. Postoperative patient controlled analgesia morphine consumption, VAS scores, and side effects were recorded. Of 34 patients, Group T (n=18) had significantly lower VAS pain scores than Group C (n=16) both at rest and while coughing. The total morphine consumed was  lower (7.7 ± 4.0) versus 21.6 ± 12.4 mg, p less than 0.001) in the 24 hours after surgery. As part of a multimodal analgesic regime after varicocelectomy surgery, morphine consumption and VAS pain scores were significantly lower among those receiving 20 mL 0.25% bupivacaine administered for a TAP block than among controls.

Effect of local wound infiltration and transversus abdominis plane block on morphine use after laparoscopic colectomy: a nonrandomized, single-blind prospective study.

PubMed

Park, Jun-Seok; Choi, Gyu-Seog; Kwak, Kyung-Hwa; Jung, Hoon; Jeon, Younghoon; Park, Sungsik; Yeo, Jinseok

2015-05-01

Recently, nonopioid-based treatment modalities have been used to improve analgesia and decrease opioid-related side effects after surgery. Transversus abdominis plane (TAP) block and local infiltration of the surgical wound are commonly used multimodal analgesia techniques after abdominal surgery; however, few studies have compared the effectiveness of a TAP block with that of local infiltration of surgical wounds in patients who have undergone laparoscopic colorectal surgery. Sixty patients undergoing laparoscopic colorectal surgery participated in this prospective comparative study. All patients were allocated to 1 of 2 groups as follows: the TAP group or the infiltration group. Patients in the TAP group received bilateral TAP blocks at the end of the surgery. Patients in the infiltration group received local infiltration of anesthetics in the surgical wounds after closure of the peritoneum. All patients received postoperative analgesia with morphine as a patient-controlled analgesia. Opioid consumption and pain scores were recorded at 2, 6, 24, and 48 h after the operation. The characteristics of patients in the TAP group (n = 30) and local infiltration group (n = 29) were comparable. Pain scores while coughing and at rest were not different between the two groups. Postoperative morphine use was significantly reduced in the TAP group compared with that in the local infiltration group at 2-6 h (2.9 ± 1.9 mg versus 4.5 ± 3.2 mg, P = 0.02), 6-24 h (5.5 ± 3.3 mg versus 10.2 ± 8.4 mg, P = 0.00), the first 24 h (16.6 ± 6.6 mg versus 24.0 ± 9.7 mg), and 48 h (23.6 ± 8.2 mg versus 31.8 ± 12.5 mg, P = 0.00). No differences in rescue analgesic use or side effects were noted between the groups. Compared with local anesthetic infiltration, bilateral TAP blocks decreased the cumulative morphine use at 24 h and 48 h postoperatively in patients who had undergone laparoscopic colorectal surgery. Copyright © 2015 Elsevier Inc

Preincisional and postoperative epidural morphine, ropivacaine, ketamine, and naloxone treatment for postoperative pain management in upper abdominal surgery.

PubMed

Lai, Hou-Chuan; Hsieh, Chung-Bao; Wong, Chih-Shung; Yeh, Chun-Chang; Wu, Zhi-Fu

2016-09-01

Previous studies have shown that preincisional epidural morphine, bupivacaine, and ketamine combined with epidural anesthesia (EA) and general anesthesia (GA) provided pre-emptive analgesia for upper abdominal surgery. Recent studies reported that ultralow-dose naloxone enhanced the antinociceptive effect of morphine in rats. This study investigated the benefits of preincisional and postoperative epidural morphine + ropivacaine + ketamine + naloxone (M + R + K + N) treatment for achieving postoperative pain relief in upper abdominal surgery. Eighty American Society of Anesthesiology I-II patients scheduled for major upper abdominal surgery were allocated to four groups in a randomized, single-blinded study. All patients received combined GA and EA with a continuous epidural infusion of 2% lidocaine (6-8 mL/h) 30 minutes after pain regimen. After GA induction, in Group I, an epidural pain control regimen (total 10 mL) was administered using 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg; M + R); in Group II, 1% lidocaine 8 (mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg; M + R + K); in Group III, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + naloxone (2 μg; M + R + N); and in Group IV, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg) + naloxone (2 μg; M + R + K + N), respectively. All patients received patient-controlled epidural analgesia (PCEA) with different pain regimens to control subsequent postoperative pain for 3 days following surgery. During the 3-day period following surgery, PCEA consumption (mL), numerical rating scale (NRS) score while cough/moving, and analgesic-related adverse effects were recorded. Total PCEA consumption for the 3-day observation period was 161.5±17.8 mL, 103.2±21.7 mL, 152.4±25.6 mL, and 74.1±16.9 mL for Groups I, II, III, and IV, respectively. (p < 0.05). The cough/moving NRS

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial.

PubMed

Cosgrave, David; Galligan, Marie; Soukhin, Era; McMullan, Victoria; McGuinness, Siobhan; Puttappa, Anand; Conlon, Niamh; Boylan, John; Hussain, Rabia; Doran, Peter; Nichol, Alistair

2017-12-29

Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety

Patient-Controlled Epidural Analgesia or Multimodal Pain Regimen with Periarticular Injection After Total Hip Arthroplasty

PubMed Central

Jules-Elysee, Kethy M.; Goon, Amanda K.; Westrich, Geoffrey H.; Padgett, Douglas E.; Mayman, David J.; Ranawat, Amar S.; Ranawat, Chitranjan S.; Lin, Yi; Kahn, Richard L.; Bhagat, Devan D.; Goytizolo, Enrique A.; Ma, Yan; Reid, Shane C.; Curren, Jodie; YaDeau, Jacques T.

2015-01-01

Background: The optimal postoperative analgesia after primary total hip arthroplasty remains in question. This randomized, double-blind, placebo-controlled study compared the use of patient-controlled epidural analgesia (PCEA) with use of a multimodal pain regimen including periarticular injection (PAI). We hypothesized that PAI would lead to earlier readiness for discharge, decreased opioid consumption, and lower pain scores. Methods: Forty-one patients received PAI, and forty-three patients received PCEA. Preoperatively, both groups were administered dexamethasone (6 mg, orally). The PAI group received a clonidine patch and sustained-release oxycodone (10 mg), while the PCEA group had placebo. Both groups received combined spinal-epidural anesthesia and used an epidural pain pump postoperatively; the PAI group had normal saline solution, while the PCEA group had bupivacaine and hydromorphone. The primary outcome, readiness for discharge, required the discontinuation of the epidural, a pain score of <4 (numeric rating scale) without parenteral narcotics, normal eating, minimal nausea, urination without a catheter, a dry surgical wound, no acute medical problems, and the ability to independently transfer and walk 12.2 m (40 ft). Results: The mean time to readiness for discharge (and standard deviation) was 2.4 ± 0.7 days (PAI) compared with 2.3 ± 0.8 days (PCEA) (p = 0.86). The mean length of stay was 3.0 ± 0.8 days (PAI) compared with 3.1 ± 0.7 days (PCEA) (p = 0.46). A significant mean difference in pain score of 0.74 with ambulation (p = 0.01; 95% confidence interval [CI], 0.18 to 1.31) and 0.80 during physical therapy (p = 0.03; 95% CI, 0.09 to 1.51) favored the PCEA group. The mean opioid consumption (oral morphine equivalents in milligrams) was significantly higher in the PAI group on postoperative day 0 (43 ± 21 compared with 28 ± 23; p = 0.002) and postoperative days 0 through 2 (136 ± 59 compared with 90 ± 79; p = 0.004). Opioid-Related Symptom

Nursing knowledge and beliefs regarding patient-controlled oral analgesia (PCOA).

PubMed

Sawhney, Monakshi; Maeda, Eri

2013-12-01

Patient-controlled oral analgesia (PCOA) allows patients to self-administer oral opioids for pain management. Advantages of PCOA include improved pain control with lower doses of opioids, decreased length of stay, increased patient satisfaction, and better functional outcomes than conventional nurse-administered oral analgesia. Sucessful PCOA programs are well described in the literature. However, nurses have concerns about allowing patients to self-administer opioids. The purpose of this study was to identify nurses' knowledge and beliefs regarding PCOA. Nurses who work at the Holland Orthopaedic and Arthritic Centre were asked to complete a survey exploring their beliefs regarding PCOA. The nurses were asked to complete the same survey twice: before an education program in February 2010, and 3 months after implementation of PCOA in June 2010. In February 2010, 74 nurses and in June 2010, 32 nurses participated in the survey. Some nurses (18%) had previous experience with PCOA. At both the pre-education and the postimplementation times, nurses thought that the PCOA program reduced wait times for analgesics and improved patient satisfaction with pain management. Before program implementation, negative beliefs included that patients on the PCOA program would lose their analgesics, would give their analgesics to visitors or other patients, and were at risk for having their analgesics stolen and that the nurse was liable if the patient's analgesics were lost or stolen. After program implementation, no nurse believed that patients would lose their analgesics or give their analgesics to visitors or other patients or that they were liable for lost or stolen analgesics. However, nurses continued to think that patients were at risk for having their analgesics stolen. We found that nurses were concerned that analgesics could be lost, misused, or stolen and that they would be liable for lost analgesics. These findings were consistent with literature discussing patients

Neonatal morphine exposure in very preterm infants-cerebral development and outcomes.

PubMed

Steinhorn, Rachel; McPherson, Christopher; Anderson, Peter J; Neil, Jeffrey; Doyle, Lex W; Inder, Terrie

2015-05-01

To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood. Observational study of very preterm infants in the Victorian Infant Brain Study cohort. A total of 230 infants born <30 weeks' gestational age or <1250 g were recruited from all admissions to the neonatal intensive care unit of the Royal Women's Hospital. Fifty-seven (25%) infants received morphine analgesia during their neonatal intensive care unit stay at the attending physician's discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine. At term, preterm infants who received morphine had similar rates of gray matter injury to no-morphine infants, but a trend toward smaller cortical volumes in the orbitofrontal (Pleft=.002, Pright=.01) and subgenual (Pleft=.01) regions. At 7 years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (P=.007) than no-morphine children, but at 7 years no detrimental impacts of morphine on neurobehavioral outcome were observed. Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined adductor canal block with periarticular infiltration versus periarticular infiltration for analgesia after total knee arthroplasty.

PubMed

Ma, Jinhui; Gao, Fuqiang; Sun, Wei; Guo, Wanshou; Li, Zirong; Wang, Weiguo

2016-12-01

Both adductor canal block (ACB) and periarticular infiltration (PI) have been shown to reduce pain after total knee arthroplasty (TKA) without the motor blockade. However, the efficacy and safety of combined ACB with PI (ACB + PI) as compared to PI alone for analgesia after TKA remains controversial. We therefore performed a meta-analysis to compare the effects of ACB + PI with PI alone on pain controll after TKA. PubMed, Medline, Embase, Web of Science, and the Cochrane Library were searched to identify studies comparing ACB + PI with PI alone for TKA patients. The primary outcomes included pain score with rest or activity and morphine consumption. Secondary outcomes were distance walked, length of hospital stay, and postoperative complications. Relevant data were analyzed using RevMan v5.3. Three studies involving 337 patients were included. Combined ACB with PI was associated with longer distances walked than PI alone (MD = 7.27, 95% CI: 0.43-14.12, P = 0.04) on postoperative day 1. The outcomes of pain, morphine consumption, length of hospital stay, and postoperative complications were not statistically different between the 2 groups (P > 0.05). Our meta-analysis suggests that combined ACB with PI may achieve earlier ambulation for patients after TKA without a reduction in analgesia when compared to PI alone in the early postoperative period. There were no significant differences in morphine consumption, length of hospital stay, and postoperative complications between the 2 groups. However, owing to the variation of included studies, no firm conclusions can be drawn.

Opioid needs of patients with advanced cancer and the morphine dose-limiting law in Egypt.

PubMed

Alsirafy, Samy A; El-Mesidi, Salah M; El-Sherief, Wesam A; Galal, Khaled M; Abou-Elela, Enas N; Aklan, Nahla A

2011-01-01

Morphine is the drug of choice for moderate to severe cancer pain management. The Egyptian Narcotics Control Law limits the amount of morphine prescribed in a single prescription to a maximum of 420 mg for tablets and 60 mg for ampoules. The usual practice in Egypt is to provide that limited amount of morphine on a weekly basis. The aim of this study is to estimate the extent to which Egyptian patients may be undertreated because of this law. We reviewed the medical records of advanced cancer patients referred to the first palliative care unit in Egypt over a seven-month period. Cancer pain was managed following the WHO guidelines. After modifying the internal institutional policy, patients received adequate amounts of the available opioids without any violations of the law. From 117 eligible advanced cancer patients, 58 (50%) patients required strong opioids, 32 (27%) required weak opioids, and 27 (23%) required no regular opioids. The mean last prescribed opioid dose for those who required strong opioids was 194 mg of oral morphine equivalent/24 h (± 180). For this group of patients, a single weekly prescription would supply enough oral morphine for only 26% of them. In the case of parenteral morphine, none of these patients would receive an adequate supply. In view of the current morphine dose-limiting law and practices in Egypt, the majority of patients suffering severe cancer pain would not have access to adequate morphine doses. That dose-limiting law and other restrictive regulations represent an obstacle to cancer pain control in Egypt and should be revised urgently.

Opioid analgesia on the battlefield: a retrospective review of data from Operation HERRICK.

PubMed

Lewis, Pip; Wright, C; Hooper, C

2018-04-06

Acute pain secondary to trauma is commonly encountered on the battlefield. The use of morphine to manage pain during combat has been well established since the 19th century. Despite this, there is relatively little research on analgesia use in this environment. This study aims to review the use and complications of morphine and other opioids during Operation HERRICK. A database search of the Joint Theatre Trauma Registry was completed looking for all incidences of morphine, fentanyl or naloxone use from February 2007 to September 2014. Microsoft Excel was used to analyse the results. Opioid analgesia was administered to 5801 casualties. Morphine was administered 6742 times to 3808 patients. Fentanyl was administered 9672 times to 4318 patients. Naloxone was used 18 times on 14 patients, giving a complication rate of 0.24%. Opioid doses prior to naloxone administration range from 0 to 72 mg of morphine and from 0 to 100 mcg of fentanyl. Four casualties (two local civilians and two coalition forces) received naloxone despite no recorded opioids being administered. Opium abuse was prevalent among the local population in Afghanistan, and this could explain the rationale behind two local national casualties receiving naloxone without any documented opioids being given. The use of opioids in a battlefield environment is extremely safe. Complication rates are similar to previously published data which is reassuring. The efficacy of different opioids was not covered by this study, and further analysis is required, particularly following the introduction of oral transmucosal fentanyl citrate and the availability of novel non-opioid analgesics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of Intraabdominal and Trocar Site Local Anaesthetic Infiltration on Postoperative Analgesia After Laparoscopic Cholecystectomy.

PubMed

Altuntaş, Gülsüm; Akkaya, Ömer Taylan; Özkan, Derya; Sayın, Mehmet Murat; Balas, Şener; Özlü, Elif

2016-12-01

This study aimed to compare the efficacy of local anaesthetic infiltration to trocar wounds and intraperitoneally on postoperative pain as a part of a multimodal analgesia method after laparoscopic cholecystectomies. The study was performed on 90 ASA I-III patients aged between 20 and 70 years who underwent elective laparoscopic cholecystectomy. All patients had the same general anaesthesia drug regimen. Patients were randomized into three groups by a closed envelope method: group I (n=30), trocar site local anaesthetic infiltration (20 mL of 0.5% bupivacaine); group II (n=30), intraperitoneal local anaesthetic instillation (20 mL of 0.5%) and group III (n=30), saline infiltration both trocar sites and intraperitoneally. Postoperative i.v. patient controlled analgesia was initiated for 24 h. In total, 4 mg of i.v. ondansetron was administered to all patients. Visual analogue scale (VAS), nausea and vomiting and shoulder pain were evaluated at 1., 2., 4., 8., 12., 24. hours. An i.v. nonsteroidal anti-inflammatory drug (NSAID) (50 mg of dexketoprofen) as a rescue analgesic was given if the VAS was ≥5. There were no statistical significant differences between the clinical and demographic properties among the three groups (p≥0.005). During all periods, VAS in group I was significantly lower than that in groups II and III (p<0.001). Among the groups, although there was no significant difference in nausea and vomiting (p=0.058), there was a significant difference in shoulder pain. Group III (p<0.05) had more frequent shoulder pain than groups I and II. The total morphine consumption was higher in groups II and III (p<0.001 vs p<0.001) than in group I. The requirement for a rescue analgesic was significantly higher in group III (p<0.05). Trocar site local anaesthetic infiltration is more effective for postoperative analgesia, easier to apply and safer than other analgesia methods. Morphine consumption is lesser and side effects are fewer; therefore, this method can be

Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment

PubMed Central

Posa, Luca; Accarie, Alison; Marie, Nicolas

2016-01-01

Background: Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin reduces tolerance to morphine. So far, no studies have been conducted to evaluate the ability of methadone to reduce morphine tolerance in morphine-pretreated animals, a treatment sequence that could be encountered in opiate rotation protocol. We investigated the ability of methadone (a mu opioid receptor internalizing agonist used in therapy) to reverse morphine tolerance and the associated cellular mechanisms in the periaqueductal gray matter, a region involved in pain control. Methods: We measured analgesic response following a challenge dose of morphine in the hot plate test and investigated regulation of mu opioid receptor (coupling and endocytosis) and some cellular mechanisms involved in tolerance such as adenylate cyclase superactivation and changes in N-methyl-d-aspartate receptor subunits expression and phosphorylation state. Results: A chronic treatment with morphine promoted tolerance to its analgesic effects and was associated with a lack of mu opioid receptor endocytosis, adenylate cyclase overshoot, NR2A and NR2B downregulation, and phosphorylation of NR1. We reported that a methadone treatment in morphine-treated mice reversed morphine tolerance to analgesia by promoting mu opioid receptor endocytosis and blocking cellular mechanisms of tolerance. Conclusions: Our data might lead to rational strategies to tackle opiate tolerance in the frame of opiate rotation. PMID:26390873

Effect of epidural analgesia in patients with traumatic rib fractures: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Carrier, François M; Turgeon, Alexis F; Nicole, Pierre C; Trépanier, Claude A; Fergusson, Dean A; Thauvette, Daniel; Lessard, Martin R

2009-03-01

A consensus group recently proposed epidural analgesia as the optimal analgesic modality for patients with multiple traumatic rib fractures. However, its beneficial effects are not consistently recognized in the literature. We performed a systematic review and a meta-analysis of randomized controlled trials (RCT) of epidural analgesia in adult patients with traumatic rib fractures. A systematic search strategy was applied to MEDLINE, EMBASE, the Cochrane Library and to the annual meeting of relevant societies (up to July 2008). All randomized controlled trials comparing epidural analgesia with other analgesic modalities in adult patients with traumatic rib fractures were included. Primary outcomes were mortality, ICU length of stay (LOS), hospital LOS and duration of mechanical ventilation. Eight studies (232 patients) met eligibility criteria. Epidural analgesia did not significantly affect mortality (odds ratio [OR] 1.6, 95% CI, 0.3, 9.3, 3 studies, n = 89), ICU LOS (weighted mean difference [WMD] -3.7 days, 95% CI, -11.4, 4.0, 4 studies, n = 135), hospital LOS (WMD -6.7, 95% CI, -19.8, 6.4, 4 studies, n = 140) or duration of mechanical ventilation (WMD -7.5, 95% CI, -16.3, 1.2, 3 studies, n = 101). Duration of mechanical ventilation was decreased when only studies using thoracic epidural analgesia with local anesthetics were evaluated (WMD -4.2, 95% CI, -5.5, -2.9, 2 studies, n = 73). However, hypotension was significantly associated with the use of thoracic epidural analgesia with local anesthetics (OR 13.76, 95% CI, 2.89, 65.51, 3 studies, n = 99). No significant benefit of epidural analgesia on mortality, ICU and hospital LOS was observed compared to other analgesic modalities in adult patients with traumatic rib fractures. However, there may be a benefit on the duration of mechanical ventilation with the use of thoracic epidural analgesia with local anesthetics. Further research is required to evaluate the benefits and harms of epidural analgesia in this

Effects of Intravenous Patient-Controlled Sufentanil Analgesia and Music Therapy on Pain and Hemodynamics After Surgery for Lung Cancer: A Randomized Parallel Study.

PubMed

Wang, Yichun; Tang, Haoke; Guo, Qulian; Liu, Jingshi; Liu, Xiaohong; Luo, Junming; Yang, Wenqian

2015-11-01

Postoperative pain is caused by surgical injury and trauma; is stressful to patients; and includes a series of physiologic, psychological, and behavioral reactions. Effective postoperative analgesia helps improve postoperative pain, perioperative safety, and hospital discharge rates. This study aimed to observe the influence of postoperative intravenous sufentanil patient-controlled analgesia combined with music therapy versus sufentanil alone on hemodynamics and analgesia in patients with lung cancer. This was a randomized parallel study performed in 60 patients in American Society of Anesthesiologists class I or II undergoing lung cancer resection at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University. Patients were randomly assigned to a music therapy (MT) group and a control (C) group. The MT group underwent preoperative and postoperative music intervention while the C group did not. Both groups received intravenous patient-controlled sufentanil analgesia. The primary outcome was the visual analogue scale (VAS) score at 24 hours after surgery. The secondary outcomes included hemodynamic changes (systolic blood pressure, diastolic blood pressure, heart rate), changes on the Self-Rating Anxiety Scale (SAS), total consumption of sufentanil, number of uses, sedation, and adverse effects. The postoperative sufentanil dose and analgesia frequency were recorded. Compared with the C group, the MT group had significantly lower VAS score, systolic and diastolic blood pressure, heart rate, and SAS score within 24 hours after surgery (p < 0.01). In addition, postoperative analgesia frequency and sufentanil dose were reduced in the MT group (p < 0.01). Combined music therapy and sufentanil improves intravenous patient-controlled analgesia effects compared with sufentanil alone after lung cancer surgery. Lower doses of sufentanil could be administered to more effectively improve patients' cardiovascular parameters.

Comparison of caudal ropivacaine-morphine and paravertebral catheter for major upper abdominal surgery in infants.

PubMed

Sato, Makoto; Iida, Takafumi; Kikuchi, Chika; Sasakawa, Tomoki; Kunisawa, Takayuki

2017-05-01

The caudal epidural block is one of the most commonly used regional anesthetic techniques in children. Administration of morphine via caudal injection enables analgesia, even for upper abdominal surgery. The thoracic paravertebral block has also been successfully used to treat perioperative pain during upper abdominal procedures in pediatric patients. In the current study, we compared the two regional techniques for upper abdominal surgery in infants to determine whether one of them was preferable to the other. Consecutive patients under 12 months of age who underwent upper abdominal surgery were retrospectively divided according to the chosen postoperative analgesia: Group C, caudal ropivacaine-morphine; Group P, paravertebral catheter. We analyzed the following outcomes: requirement for additional analgesics, pain scores, need for mechanical ventilation and oxygen dosage, postoperative blood pressure and heart rate, time to pass first stool, time until first full meal, and complications. Twenty-one consecutive patients were included: 10 in Group C and 11 in Group P. Median age at surgery was 80 (47.5-270.0) and 84.5 (34.3-287.5) days, respectively. No difference was found between the two groups in requirement for additional analgesics at 24 h after surgery (median 1 in Group C vs 1 in Group P, P = 0.288, 95% CI: -2 to 1). BOPS pain scores were only lower in Group P when compared to Group C at 24 h after surgery (median 1 vs 2, P = 0.041, 95% CI: -2 to 0). None of the patients had perioperative complications. In this small series, there was no significant difference between caudal ropivacaine-morphine and paravertebral catheter for postoperative care in infants undergoing upper abdominal surgery. Further prospective studies are needed to compare the efficacy and incidence of complications of caudal block and paravertebral catheter for postoperative analgesia. © 2017 John Wiley & Sons Ltd.

Comparison of the Effects of Ketamine and Morphine on the Performance of Representative Military Tasks

DTIC Science & Technology

2010-08-01

skill (autonomous phase) remains somewhat resilient to the drugged state at this dosage. ketamine, morphine, analgesia, pain control, Warrior Skill...3  Pain ...are important points to mind when first considering why the military might be interested in the possibility of treating the pain of battlefield

Intra-operative periarticular multimodal injection in total knee arthroplasty: a local hospital experience in Hong Kong.

PubMed

Fan, J Ch

2018-04-01

Data from a local report revealed the superior outcome of regional anaesthesia and analgesia compared with general anaesthesia and intravenous patient-controlled analgesia in total knee arthroplasty. This retrospective study aimed to assess the efficacy of intra-operative periarticular multimodal injection in improving postoperative pain and reducing morphine consumption with patient-controlled analgesia after total knee arthroplasty in patients with knee osteoarthritis. From July 2005 to May 2009, 213 total knee arthroplasties without intra-operative periarticular multimodal injection (control group) were performed at a local hospital. From June 2009 to December 2012, 185 total knee arthroplasties were performed with intra-operative periarticular multimodal injection (cocktail group). The inclusion criteria were osteoarthritis of the knee, single method of anaesthesia (general or neuraxial), simple total knee arthroplasty without any metal augmentation or constraint, and postoperative patient-controlled analgesia. Postoperative patient-controlled morphine doses were compared. A total of 152 total knee arthroplasties were recruited to the cocktail group, and 89 to the control group. Duration of tourniquet application and preoperative knee score did not significantly correlate with morphine consumption by patient-controlled analgesia. Multimodal injection significantly decreased such consumption for 36 h. When injection was separately analysed for general and neuraxial anaesthesia, the effect lasted for 42 h and 24 h, respectively. Intra-operative periarticular multimodal injection decreased morphine consumption for up to 42 h postoperatively.

Low-Dose Cannabinoid Type 2 Receptor Agonist Attenuates Tolerance to Repeated Morphine Administration via Regulating μ-Opioid Receptor Expression in Walker 256 Tumor-Bearing Rats.

PubMed

Zhang, Mingyue; Wang, Kun; Ma, Min; Tian, Songyu; Wei, Na; Wang, Guonian

2016-04-01

Morphine is widely used in patients with moderate and severe cancer pain, whereas the development of drug tolerance remains a major problem associated with opioid use. Previous studies have shown that cannabinoid type 2 (CB2) receptor agonists induce morphine analgesia, attenuate morphine tolerance in normal and neuropathic pain animals, induce transcription of the μ-opioid receptor (MOR) gene in Jurkat T cells, and increase morphine analgesia in cancer pain animals. However, no studies of the effects of CB2 receptor agonists on morphine tolerance in cancer pain have been performed. Therefore, we investigated the effect of repeated intrathecal (IT) injection of the low-dose CB2 receptor agonist AM1241 on the development of morphine tolerance in walker 256 tumor-bearing rats. We also tested the influence of the CB2 receptor agonist AM1241 on MOR protein and messenger ribonucleic acid (mRNA) expression in the rat spinal cord and dorsal root ganglia (DRG). Walker 256 cells were implanted into the plantar region of each rat's right hindpaw. Tumor-bearing rats received IT injection of the CB2 receptor agonist AM1241 or antagonist AM630 with or without morphine subcutaneously twice daily for 8 days. Rats receiving drug vehicle only served as the control group. Mechanical paw withdrawal threshold and thermal paw withdrawal latency were assessed by a von Frey test and hot plate test 30 minutes after drug administration every day. MOR protein and mRNA expression in the spinal cord and DRG were detected after the last day (day 8) of drug administration via Western blot and real-time reverse transcription polymerase chain reaction. The data were analyzed via analysis of variance followed by Student t test with Bonferroni correction for multiple comparisons. Repeated morphine treatments reduced the mechanical withdrawal threshold and thermal latency. Coadministration of a nonanalgetic dose of the CB2 receptor agonist AM1241 with morphine significantly inhibited the

Caudal bupivacaine supplemented with morphine or clonidine, or supplemented with morphine plus clonidine in children undergoing infra-umbilical urological and genital procedures: a prospective, randomized and double-blind study.

PubMed

Fernandes, Magda L; Pires, Kleber C C; Tibúrcio, Moacir A; Gomez, Renato S

2012-04-01

We aimed to evaluate postoperative analgesia of morphine, or clonidine, or morphine plus clonidine, added to caudal bupivacaine in children undergoing infra-umbilical urological and genital procedures. Eighty patients aged 1-10 years were prospectively enrolled. After the induction of general anesthesia, the patients were randomized to four caudal anesthesia groups: Group B (1.0 mL/kg of bupivacaine 0.166% with epinephrine 1:600,000); Group BM (1.0 mL/kg of bupivacaine 0.166% with epinephrine 1:600,000 plus morphine 20 μg/kg); Group BC (bupivacaine 0.166% with epinephrine 1:600,000 plus clonidine 1.0 μg/kg), and Group BMC (bupivacaine 0.166% with epinephrine 1:600,000 plus morphine 20 μg/kg and clonidine 1.0 μg/kg). Duration of surgery, emergence time, postoperative pain score measured by the face, legs, activity, cry, consolability (FLACC) scale, postoperative analgesia time, and overall use of rescue analgesics were recorded. The FLACC pain score (6, 12, and 24 h after the surgery) and the number of patients requiring analgesics during the first 24 h of the postoperative period were higher in Groups B and BC than in Groups BM and BMC (p < 0.05). The incidence of pruritus and urinary retention was comparable between the groups (p > 0.05). However, the incidence of postoperative nausea and vomiting (PONV) was higher in Groups BM (35%) and BMC (25%) than in Groups B (5%) and BC (5%) (p < 0.05). To conclude, we showed that 20 μg/kg of morphine added to caudal bupivacaine 0.166% plus epinephrine 1:600,000 decreased the use of analgesics in the postoperative period, although it was associated with an increased incidence of PONV. However, the addition of clonidine (1.0 μg/kg) to caudal bupivacaine provided no additional clinical benefit over bupivacaine alone.

Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

PubMed

Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

2015-09-14

Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of 12-monoketocholic acid on modulation of analgesic action of morphine and tramadol.

PubMed

Kuhajda, Ivan; Posa, Mihalj; Jakovljević, Vida; Ivetić, Vesna; Mikov, Momir

2009-01-01

This work is concerned with the potential promotive action of 12-monoketocholic acid (12-MKC) on the analgesic effect of morphine and tramadol. The investigation was carried out on laboratory Wistar rats divided into five test groups, each treated with either morphine (2 mg/kg), tramadol (9.6 mg/kg), 12-MKC (2 mg/kg), morphine + 12-MKC, or tramadol + 12-MKC, the control group receiving physiological solution (2 mg/kg). The effect of 12-MKC on the analgesic action of morphine and tramadol was determined by radiation heat method. Morphine and tramadol, given in equimolar doses, did not show significant difference in the degree of analgesia. In combination with morphine, 12-MKC increased significantly the analgesic effect compared with the group treated with morphine alone. However, 12-MKC caused no change in the action of tramadol. The 5-day intravenous application of 12-MKC in combination with the two analgesics caused no changes in the biochemical parameters nor pathohistological changes in the liver parenchyma of tested animals.

The Neuroanatomy of Sexual Dimorphism in Opioid Analgesia

DTIC Science & Technology

2014-04-13

2012 for review). Studies utilizing orofacial , somatosensory or visceral pain assays typically report that morphine produces a significantly greater...Review The neuroanatomy of sexual dimorphism in opioid analgesia Dayna R. Loyd a, Anne Z. Murphy b,⁎ a Pain Management Research Area, United States...online 13 April 2014 Keywords: Pain Periaqueductal gray Morphine Mu opioid receptor The influence of sex has been neglected in clinical studies on pain

Single-shot intraoperative local anaesthetic infiltration does not reduce morphine consumption after total hip arthroplasty: a double-blinded placebo-controlled randomized study.

PubMed

Zoric, L; Cuvillon, P; Alonso, S; Demattei, C; Vialles, N; Asencio, G; Ripart, J; Nouvellon, E

2014-04-01

The infiltration of local anaesthetic (LA), ketorolac, and epinephrine has been suggested to be effective for analgesia after total hip arthroplasty (THA). The part of action of each component of the mixture remains unclear. We investigated the contribution of infiltration of ropivacaine alone on the morphine consumption during the first 24 h after surgery. Sixty patients undergoing primary THA were included in this prospective randomized double-blinded placebo-controlled trial, after IRB approval and informed consent. Surgical and general anaesthetic management were standardized. At the end of surgery, 80 ml of ropivacaine 0.2% (160 mg) or saline was infiltrated. The primary endpoint was morphine consumption 24 h after surgery. The secondary endpoints were: visual analogue scale scores and opioid side-effects at H2, H4, H8, H12, H24, D1, D2, D3, D4, D5, rehabilitation programme progress, chronic pain level, analgesic consumption, and surgical result at 3 months and 1 yr after surgery. The observation period was 1 yr. Groups were similar for patient characteristic and perioperative characteristics. The ropivacaine wound infiltration did not reduce morphine consumption at 24 h [median (25th and 75th inter-quartile) 27 (17-37) mg in the ropivacaine group vs 24 (18-34) mg in the placebo group, P=0.51] or its side-effects. No effect was found on rehabilitation progress or chronic pain after 3 months or 1 yr, but these were not the main endpoints of the study. Ropivacaine infiltration alone did not reduce morphine consumption at 24 h after operation nor did it improve postoperative rehabilitation.

Intravenous parecoxib and continuous femoral block for postoperative analgesia after total knee arthroplasty. A randomized, double-blind, prospective trial.

PubMed

Sarridou, Despoina G; Chalmouki, Georgia; Braoudaki, Maria; Koutsoupaki, Anna; Mela, Argiro; Vadalouka, Athina

2015-01-01

Up until now, the optimal strategy for postoperative pain management after total knee arthroplasty (TKA) remains to be elucidated. The current investigation aimed to examine the analgesic efficacy and the opioid sparing effects of intravenous parecoxib in combination with continuous femoral blockade. Randomized, double-blind, prospective trial. University hospital in the United Kingdom. In total, 90 patients underwent TKA under subarachnoid anesthesia and received continuous femoral block initially as a bolus with 20 mL of ropivacaine 0.75%. Infusion of 0.2% on 10 mL/h followed. Patients were randomized into 2 groups. Group D and Group P received parecoxib and placebo, respectively at 12 hour time intervals. Visual analog scale (VAS) pain scores were obtained at different time intervals including 4, 8, 12, 24 and 36 hours. The pain scores were measured with patients in a resting position. Morphine could also be administered with a patient controlled analgesia (PCA) pump if the specified analgesia was deemed inadequate (VAS > 5). None of the patients were withdrawn from the study. Parecoxib provided greater relief than placebo following TKA. The VAS pain scores measured at rest were statistically significantly lower in parecoxib-treated patients compared to the placebo group (P = 0.007) at 4 (P = 0.044), 12 (P = 0.001), and 24 hours (P = 0.012), postoperatively. Patients receiving parecoxib consumed less morphine at all time intervals than patients receiving placebo, with borderline statistical significance (P = 0.054). In each time period, all patients receiving continuous femoral block irrespectively of the treatment group, required low morphine doses. Current protocol did not answer question as to functional recovery. According to our findings intravenous parecoxib in combination with continuous femoral block provided superior analgesic efficacy and opioid sparing effects in patients undergoing TKA.

Epidural Neostigmine versus Fentanyl to Decrease Bupivacaine Use in Patient-controlled Epidural Analgesia during Labor: A Randomized, Double-blind, Controlled Study.

PubMed

Booth, Jessica L; Ross, Vernon H; Nelson, Kenneth E; Harris, Lynnette; Eisenach, James C; Pan, Peter H

2017-07-01

The addition of opioids to epidural local anesthetic reduces local anesthetic consumption by 20% but at the expense of side effects and time spent for regulatory compliance paperwork. Epidural neostigmine also reduces local anesthetic use. The authors hypothesized that epidural bupivacaine with neostigmine would decrease total hourly bupivacaine use compared with epidural bupivacaine with fentanyl for patient-controlled epidural analgesia. A total of 215 American Society of Anesthesiologists physical status II, laboring parturients requesting labor epidural analgesia consented to the study and were randomized to receive 0.125% bupivacaine with the addition of either fentanyl (2 μg/ml) or neostigmine (2, 4, or 8 μg/ml). The primary outcome was total hourly local anesthetic consumption, defined as total patient-controlled epidural analgesia use and top-ups (expressed as milliliters of 0.125% bupivacaine) divided by the infusion duration. A priori analysis determined a group size of 35 was needed to have 80% power at α = 0.05 to detect a 20% difference in the primary outcome. Of 215 subjects consented, 151 patients were evaluable. Demographics, maternal and fetal outcomes, and labor characteristics were similar among groups. Total hourly local anesthetic consumption did not differ among groups (P = 0.55). The total median hourly bupivacaine consumption in the fentanyl group was 16.0 ml/h compared with 15.3, 14.6, and 16.2 ml/h in the 2, 4, and 8 μg/ml neostigmine groups, respectively (P = 0.55). The data do not support any difference in bupivacaine requirements for labor patient-controlled epidural analgesia whether patients receive epidural bupivacaine with 2 to 8 μg/ml neostigmine or epidural bupivacaine with 2 μg/ml fentanyl.

Midazolam Exacerbates Morphine Tolerance and Morphine-induced Hyperactive Behaviors in Young Rats with Burn Injury

PubMed Central

Song, Li; Wang, Shuxing; Zuo, Yunxia; Chen, Lucy; Martyn, Jeevendra A.; Mao, Jianren

2014-01-01

Midazolam and morphine are often used in pediatric intensive care unit (ICU) for analgesia and sedation. However, how these two drugs interact behaviorally remains unclear. Here, we examined whether 1) co-administration of midazolam with morphine would exacerbate morphine tolerance and morphine-induced hyperactive behaviors, and 2) protein kinase C (PKC) would contribute to these behavioral changes. Male rats of 3 to 4 weeks old were exposed to a hindpaw burn injury. In Experiment 1, burn-injured young rats received once daily saline or morphine (10 mg/kg, subcutaneous, s.c.), followed 30 min later by either saline or midazolam (2 mg/kg, intraperitoneal, i.p.), for 14 days beginning 3 days after burn injury. In Experiment 2, young rats with burn injury were administered with morphine (10 mg/kg, s.c.), midazolam (2 mg/kg, i.p.), and chelerythrine chloride (a non-specific PKC inhibitor 10 nmol, intrathecal) for 14 days. For both experiments, cumulative morphine anti-nociceptive dose-response (ED50) was tested and hyperactive behaviors such as jumping and scratching were recorded. Following 2 weeks of each treatment, ED50 dose was significantly increased in rats receiving morphine alone as compared with rats receiving saline or midazolam alone. The ED50 dose was further increased in rats receiving both morphine and midazolam. Co-administration of morphine and midazolam also exacerbated morphine-induced hyperactive behaviors. Expression of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and PKCγ in the spinal cord dorsal horn (immunohistochemistry; Western blot) was upregulated in burn-injured young rats receiving morphine alone or in combination with midazolam, and chelerythrine prevented the development of morphine tolerance. These results indicate that midazolam exacerbated morphine tolerance through a spinal NMDA/PKC-mediated mechanism. PMID:24713351

Time-dependent analysis of dosage delivery information for patient-controlled analgesia services.

PubMed

Kuo, I-Ting; Chang, Kuang-Yi; Juan, De-Fong; Hsu, Steen J; Chan, Chia-Tai; Tsou, Mei-Yung

2018-01-01

Pain relief always plays the essential part of perioperative care and an important role of medical quality improvement. Patient-controlled analgesia (PCA) is a method that allows a patient to self-administer small boluses of analgesic to relieve the subjective pain. PCA logs from the infusion pump consisted of a lot of text messages which record all events during the therapies. The dosage information can be extracted from PCA logs to provide easily understanding features. The analysis of dosage information with time has great help to figure out the variance of a patient's pain relief condition. To explore the trend of pain relief requirement, we developed a PCA dosage information generator (PCA DIG) to extract meaningful messages from PCA logs during the first 48 hours of therapies. PCA dosage information including consumption, delivery, infusion rate, and the ratio between demand and delivery is presented with corresponding values in 4 successive time frames. Time-dependent statistical analysis demonstrated the trends of analgesia requirements decreased gradually along with time. These findings are compatible with clinical observations and further provide valuable information about the strategy to customize postoperative pain management.

A comparison of intraoperative morphine sulfate and methadone hydrochloride on postoperative visual analogue scale pain scores and narcotic requirements.

PubMed

Laur, D F; Sinkovich, J; Betley, K

1995-02-01

Morphine sulfate and methadone hydrochloride exhibit very different half-lives but are described as having an analgesic potency of one. The use of a drug like methadone may provide prolonged and constant analgesia in the perioperative setting. This double-blinded investigation used methadone and morphine intraoperatively and measured pain scores and narcotic requirements in the first 24 hours postoperatively. Thirty American Society of Anesthesiology (ASA) patients, physical status I through III, between the ages of 18 to 65 years were scheduled for orthopedic surgery and randomly assigned to receive morphine or methadone at 0.30 mg/kg. Fifteen patients received morphine and fifteen patients received methadone. There was no significant difference between the two groups in terms of age, height, weight, and ASA status. No statistically significant difference was observed among the two groups between the amount of analgesic requirements postoperatively or in the visual analogue scale pain score.

Effect of Bacopasides on acquisition and expression of morphine tolerance.

PubMed

Rauf, Khalid; Subhan, Fazal; Abbas, Muzaffar; Badshah, Amir; Ullah, Ihsan; Ullah, Sami

2011-07-15

Opioids are extensively used for the management of both chronic malignant and non malignant pains. One major serious limitation associated with chronic use of opioids is the development of tolerance to its analgesic effect. The effect of Bacopa monnieri, a renowned ayurvedic medicine for acquisition and expression of morphine tolerance in mice, was investigated. Bacopa monnieri, n-Butanol fraction was analyzed on High performance liquid chromatography (HPLC), for Bacopaside A major components i.e. Bacoside A(3), Bacopaside ll and Bacosaponin C. Antinociceptive effect of n-Butanol extract of Bacopa monnieri (n Bt-ext BM) (5, 10 and 15 mg/kg) was assessed on hot plate. Effect of different doses of n Bt-ext BM on morphine antinociception was also assessed. n Bt-ext BM was also screened for development of tolerance to antinociceptive effect of Bacopa monnieri by administering 15 mg/kg n Bt-ext BM for seven days. Tolerance to morphine analgesia was induced in mice by administering intraperitoneally (I.P.) 20 mg/kg morphine twice daily for five days. Acute and Chronic administration of 5, 10 and 15 mg/kg n Bt-ext BM significantly reduced both expression and development of tolerance to morphine analgesia in mice. Additionally, Bacopa monnieri was found to enhance antinociceptive effect of morphine in intolerant animals. However, no tolerance to Bacopa monnieri antinociceptive effect was observed in seven days treatment schedule. These findings indicate effectiveness of Bacopa monnieri for management of morphine tolerance. Copyright © 2011 Elsevier GmbH. All rights reserved.

Dexmedetomidine in a surgically inserted catheter for transversus abdominis plane block in donor hepatectomy: A prospective randomized controlled study.

PubMed

Aboelela, Mohamed Adel; Kandeel, Al-Refaey; Elsayed, Usama; Elmorshedi, Mohamed; Elsarraf, Waleed; Elsayed, Eman; Elgawalby, Ahmed; Sultan, Ahmed Mohamed; Wahab, Mohamed Abdel; Yassen, Amr

2018-01-01

Transversus abdominis plane (TAP) block is a promising technique for analgesia after abdominal surgery. This prospective, randomized controlled trial assessed the effect of adding dexmedetomidine to bupivacaine in TAP block for donor hepatectomy. We hypothesized that this would improve postoperative morphine consumption and reduce analgesia related complication and inflammation. A total of 50 donor hepatectomy were enrolled in this study. Patients divided into two equal groups according to drugs used for TAP block. Group (B) received 20 ml of bupivacaine hydrochloride 0.25%, Group (BD) received 20 ml of bupivacaine hydrochloride 0.25% and 0.3 μg/kg dexmedetomidine, on both sides at the end of surgery and every 8 h for 48 h at right side only through inserted catheter. Primary outcome objective was morphine consumption at first 72 h. Secondary outcome objectives were morphine requirement, numbers of intake, time to first intake, pain score numerical analog scale (NAS), postoperative analgesia related complications, recovery of intestinal motility, and inflammatory markers. Data were analyzed, rescue morphine analgesia was significantly lower in (BD) group compared with (B) groups as considering total morphine consumption (B 4 ± 1.9, BD 1.5 ± 0.5, P = 0.03), numbers of morphine intake ( P = 0.04), morphine requirement ( P = 0.03), and first time of analgesia intake ( P = 0.04). NAS was significantly lower in group (BD) compared with group (B) group in the first 12 h (NAS 0 - P = 0.001, NAS 1 - P = 0.03). Adding dexmedetomidine improved gut motility, first oral intake without detectable anti-inflammatory effect. Adding dexmedetomidine to bupivacine in a surgically inserted catheter for TAP block in donor hepatectomy reduced morphine consumption without detectable anti-inflammatory effect.

Respiratory failure following delayed intrathecal morphine pump refill: a valuable, but costly lesson.

PubMed

Ruan, Xiulu; Couch, J Patrick; Liu, HaiNan; Shah, Rinoo V; Wang, Frank; Chiravuri, Srinivas

2010-01-01

Spinal analgesia, mediated by opioid receptors, requires only a fraction of the opioid dose that is needed systemically. By infusing a small amount of opioid into the cerebrospinal fluid in close proximity to the receptor sites in the spinal cord, profound analgesia may be achieved while sparing some of the side effects due to systemic opioids. Intraspinal drug delivery (IDD) has been increasingly used in patients with intractable chronic pain, when these patients have developed untoward side effects with systemic opioid usage. The introduction of intrathecal opioids has been considered one of the most important breakthroughs in pain management in the past three decades. A variety of side effects associated with the long-term usage of IDD have been recognized. Among them, respiratory depression is the most feared. To describe a severe adverse event, i.e., respiratory failure, following delayed intrathecal morphine pump refill. A 65-year-old woman with intractable chronic low back pain, due to degenerative disc disease, and was referred to our clinic for an intraspinal drug delivery evaluation, after failing to respond to multidisciplinary pain treatment. Following a psychological evaluation confirming her candidacy, she underwent an outpatient patient-controlled continuous epidural morphine infusion trial. The infusion trial lasted 12 days and was beneficial in controlling her pain. The patient reported more than 90% pain reduction with improved distance for ambulation. She subsequently consented and was scheduled for permanent intrathecal morphine pump implantation. The intrathecal catheter was inserted at right paramedian L3-L4, with catheter tip advanced to L1, confirmed under fluoroscopy. Intrathecal catheter placement was confirmed by positive CSF flow and by myelogram. A non-programmable Codman 3000 constant-flow rate infusion pump was placed in the right mid quandrant between right rib cage and right iliac crest. The intrathecal infusion consisted of

Ultrasound-guided transversus abdominis plane block for postoperative analgesia in living liver donors: A prospective, randomized, double-blinded clinical trial.

PubMed

Kıtlık, Arzu; Erdogan, Mehmet Ali; Ozgul, Ulku; Aydogan, Mustafa Said; Ucar, Muharrem; Toprak, Huseyin Ilksen; Colak, Cemil; Durmus, Mahmut

2017-02-01

Transversus abdominis plane (TAP) block is a peripheral nerve block that reduces postoperative pain, nausea, vomiting and the need for postoperative opioids following various types of abdominal surgery. The primary aim of the present study was to evaluate the effects of TAP block on postoperative analgesia and opioid consumption in living liver donors in whom a right "J" abdominal incision was used. This prospective, double-blinded, randomized controlled study was conducted with 50 living liver donors, aged 18-65years, who were scheduled to undergo right hepatectomy. Patients who received ultrasonography-guided subcostal TAP block were allocated into Group 1, and patients who did not receive TAP block were allocated into Group 2. The TAP blocks were performed bilaterally at the conclusion of surgery using 1.5mg∗kg -1 bupivacaine diluted with saline to reach a total volume of 40mL. For each patient, morphine consumption, pain scores at rest and movement, sedation scores, nausea, vomiting and the need for antiemetic medication were assessed at 0, 2, 4, 6, 12 and 24h postoperatively by researchers who were blinded to the study groups. Morphine consumption was significantly lower in Group 1 than in Group 2 at the 2nd, 6th and 24th hours (P<0.05). The mean total morphine consumption values after 24h were 40mg and 65mg in Groups 1 and 2, respectively. The TAP block significantly reduced postoperative visual analog scale pain scores both at rest and during movement at 0, 2, 4, 6, and 24h postoperatively (P<0.05). The TAP block reduced 24-h postoperative morphine consumption and contributed to analgesia in living liver donors who underwent upper abdominal wall incisions. Copyright © 2016 Elsevier Inc. All rights reserved.

The fentanyl HCl patient-controlled transdermal system (PCTS): an alternative to intravenous patient-controlled analgesia in the postoperative setting.

PubMed

Sinatra, Raymond

2005-01-01

Inadequate pain control in the postoperative period not only contributes to patient discomfort, but also causes physiological changes that may result in increased risk of myocardial ischaemia, deep vein thrombosis and pulmonary embolism. These events complicate postoperative recovery and may lead to longer hospital stays as well as increased healthcare costs. Patient-controlled analgesia (PCA) has emerged as an effective way for patients to manage their pain, allowing self-administration of small doses of analgesics to maintain a certain level of pain control. PCA is most commonly delivered via an intravenous (IV) or epidural route, and while patient satisfaction is higher with PCA than with conventional methods of analgesic administration, the invasiveness, costs and risk of errors associated with currently available modalities may limit their utility. These systems also require significant healthcare resources, as nurses must manually program the pumps to deliver the correct amount of medication. Several new PCA modalities are being developed to address these limitations. These systems deliver drug through a variety of routes, including nasal transmucosal and transdermal. Most notably, a self-contained, credit card-sized, transdermal PCA system is currently in the final stages of development. The fentanyl HCl patient-controlled transdermal system (PCTS; IONSYS, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) uses an imperceptible, low-intensity direct current to transfer fentanyl on demand across the skin into the systemic circulation. This compact system is patient-activated, can be applied to the patient's upper arm or chest, and is designed to manage moderate-to-severe pain requiring opioid analgesia. The system delivers a preprogrammed amount of fentanyl HCI over 10 minutes, for a total of 80 doses, or for 24 hours, whichever occurs first. The on-demand dosing and pharmacokinetics of this system differentiate it from the passive transdermal formulation of

Thoracic paravertebral block versus intravenous patient-controlled analgesia for pain treatment in patients with multiple rib fractures.

PubMed

Yeying, Ge; Liyong, Yuan; Yuebo, Chen; Yu, Zhang; Guangao, Ye; Weihu, Ma; Liujun, Zhao

2017-12-01

Objectives To assess the effect of thoracic paravertebral block (PVB) on pain management and preservation of pulmonary function compared with intravenous, patient-controlled analgesia (IVPCA) in patients with multiple rib fractures (MRFs). Methods Ninety patients with unilateral MRFs were included in this prospective study and randomly assigned to the TPVB or IVPCA group. The visual analogue scale (VAS) pain score, blood gas analysis, and bedside spirometry were measured and recorded at different time points after analgesia. Results TPVB and IVPCA provided good pain relief. VAS scores were significantly lower in the TPVB group than in the IVPCA group at rest and during coughing ( P < 0.05). Patients in the TPVB group had a higher PaO 2 and PaO 2 /FiO 2 and lower P (A-a) O 2 compared with the IVPCA group ( P < 0.05). Moreover, patients in the TPVB group showed higher FVC, FEV1/FVC, and PEFR, and fewer complications than did the IVPCA group ( P < 0.05). Conclusion TPVB is superior to IVPCA in pain relief and preservation of pulmonary function in patients with MRFs.

Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

PubMed

Yang, Ye; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Deng, Zhen-Han; Li, Yu-Sheng; Yang, Tu-Bao; Lei, Guang-Hua

2017-03-01

The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p < 0.0001). As far as safety, there was no significant difference in side effects between the two groups (RR 1.10, 95 % CI 0.59-2.04, n.s.). Sensitivity analyses suggested that the results of these two primary outcomes were stable and reliable. However, the current evidence did not suggest a superior effect with respect to the time to first analgesic request (WMD 51.33, 95 % CI -110.99 to 213.65, n.s.) and the number of patients requiring supplementary analgesia (RR 1.13, 95 % CI 0.92-1.39, n.s.). On the basis of the currently available literature, this study is the first to suggest that single-dose intra-articular bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. II.

Comparison of Morphine and Tramadol in Transforaminal Epidural Injections for Lumbar Radicular Pain

PubMed Central

2013-01-01

Background Transforaminal epidural steroid injections are known to reduce inflammation by inhibiting synthesis of various proinflammatory mediators and have been used increasingly. The anti-inflammatory properties of opioids are not as fully understood but apparently involve antagonism sensory neuron excitability and pro-inflammatory neuropeptide release. To date, no studies have addressed the efficacy of transforaminal epidural morphine in patients with radicular pain, and none have directly compared morphine with a tramadol for this indication. The aim of this study was to compare morphine and tramadol analgesia when administered via epidural injection to patients with lumbar radicular pain. Methods A total of 59 patients were randomly allocated to 1 of 2 treatment groups and followed for 3 months after procedure. Each patient was subjected to C-arm guided transforaminal epidural injection (TFEI) of an affected nerve root. As assigned, patients received either morphine sulfate (2.5 mg/2.5 ml) or tramadol (25 mg/0.5 ml) in combination with 0.2% ropivacaine (1 ml). Using numeric rating scale was subsequently rates at 2 weeks and 3 months following injection for comparison with baseline. Results Both groups had significantly lower mean pain scores at 2 weeks and at 3 months after treatment, but outcomes did not differ significantly between groups. Conclusions TFEI of an opioid plus local anesthetic proved effective in treating radicular pain. Although morphine surpassed tramadol in pain relief scores, the difference was not statistically significant. PMID:23862000

Effects of parecoxib on analgesia benefit and blood loss following open prostatectomy: a multicentre randomized trial.

PubMed

Dirkmann, Daniel; Groeben, Harald; Farhan, Hassan; Stahl, David L; Eikermann, Matthias

2015-01-01

This multi-centre, prospective, randomized, double-blind, placebo-controlled study was designed to test the hypotheses that parecoxib improves patients' postoperative analgesia without increasing surgical blood loss following radical open prostatectomy. 105 patients (64 ± 7 years old) were randomized to receive either parecoxib or placebo with concurrent morphine patient controlled analgesia. Cumulative opioid consumption (primary objective) and the overall benefit of analgesia score (OBAS), the modified brief pain inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR-SDS), and perioperative blood loss (secondary objectives) were assessed. In each group 48 patients received the study medication for 48 hours postoperatively. Parecoxib significantly reduced cumulative opioid consumption by 24% (43 ± 24.1 mg versus 57 ± 28 mg, mean ± SD, p=0.02), translating into improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI-sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss was significantly higher at 24 hours following surgery in the parecoxib group (4.3 g⋅dL(-1) (3.6/4.9) versus (3.2 g⋅dL(-1) (2.4/4.95), p=0.02). Following major abdominal surgery, parecoxib significantly improves patients' perceived analgesia. Parecoxib may however increase perioperative blood loss. Further trials are needed to evaluate the effects of selective cyclooxygenase-2 inhibitors on blood loss. ClinicalTrials.gov Identifier: NCT00346268.

Comparison of clinical effects of epidural levobupivacaine morphine versus bupivacaine morphine in dogs undergoing elective pelvic limb surgery.

PubMed

Cerasoli, Ilaria; Tutunaru, Alexandru; Cenani, Alessia; Ramirez, Juan; Detilleux, Johann; Balligand, Marc; Sandersen, Charlotte

2017-03-01

To evaluate the efficacy, in terms of the amount of rescue analgesia required, and the clinical usefulness of epidural injection of morphine with bupivacaine or levobupivacaine for elective pelvic limb surgery in dogs during a 24-hour perioperative period. Prospective, blinded, randomized clinical study. A group of 26 dogs weighing 31.7 ± 14.2 (mean ± standard deviation) kg and aged 54 ± 36 months. All dogs were premedicated with methadone intravenously (0.2 mg kg -1 ) and anaesthesia induced with diazepam (0.2 mg kg -1 ) and propofol intravenously to effect. After induction of anaesthesia, dogs randomly received a lumbosacral epidural injection of morphine 0.1 mg kg -1 with either levobupivacaine 0.5% (1 mg kg -1 ; group LevoBM) or bupivacaine 0.5% (1 mg kg -1 ; group BM). Cardiovascular, respiratory and temperature values were recorded during the intra- and postoperative period. A visual analogue scale, subjective pain scale, sedation scale and the short form of the Glasgow pain scale were assessed every 6 hours after epidural injection during 24 hours. The ability to stand and walk, neurological deficits and other side effects were assessed at the same time points. The amount of rescue analgesia (sufentanil intraoperatively and methadone postoperatively) was recorded. No statistically significant differences were found between groups for any of the recorded data, with the exception of the incidence of spontaneous urination and postoperative rescue analgesia requirement. In group LevoBM four dogs spontaneously urinated at recovery while none of the dogs in group BM did (p = 0.03) and seven dogs of group LevoBM required postoperative rescue analgesia versus none of the dogs in the BM group (p = 0.005). and clinical relevance Epidural LevoBM is a suitable alternative to BM in healthy dogs during elective pelvic limb surgery. Epidural BM produced more urinary retention but better pain control compared to the same concentration and dose of LevoBM in dogs

Intrathecal hypobaric versus hyperbaric bupivacaine with morphine for cesarean section.

PubMed

Richardson, M G; Collins, H V; Wissler, R N

1998-08-01

Both hyper- and hypobaric solutions of bupivacaine are often combined with morphine to provide subarachnoid anesthesia for cesarean section. Differences in the baricity of subarachnoid solutions influence the intrathecal distribution of anesthetic drugs and would be expected to influence measurable clinical variables. We compared the effects of hyper- and hypobaric subarachnoid bupivacaine with morphine to determine whether one has significant advantages with regard to intraoperative anesthesia and postoperative analgesia in term parturients undergoing elective cesarean section. Thirty parturients were randomized to receive either hyper- or hypobaric bupivacaine (15 mg) with morphine sulfate (0.2 mg). Intraoperative outcomes compared included extent of sensory block, quality of anesthesia, and side effects. Postoperative outcomes, including pain visual analog scale scores, systemic analgesic requirements, and side effects, were monitored for 48 h. Sedation effects were quantified and compared using Trieger and digit-symbol substitution tests. We detected no differences in sensory or motor block, quality of anesthesia, quality of postoperative analgesia, incidence of side effects, or psychometric scores. Both preparations provide highly satisfactory anesthesia for cesarean section and effective postoperative analgesia. Dextrose alters the density of intrathecal bupivacaine solutions and is thought to influence subarachnoid distribution of the drug. We randomized parturients undergoing cesarean section to one of two often used spinal bupivacaine preparations, hypobaric and hyperbaric. We detected no differences in clinical outcomes between groups.

Ethanol-induced analgesia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pohorecky, L.A.; Shah, P.

1987-09-07

The effect of ethanol (ET) on nociceptive sensitivity was evaluated using a new tail deflection response (TDR) method. The IP injection of ET (0.5 - 1.5 g/kg) produced raid dose-dependent analgesia. Near maximal effect (97% decrease in TDR) was produced with the 1.5 g/kg dose of ET ten minutes after injection. At ninety minutes post-injection there was still significant analgesia. Depression of ET-induced nociceptive sensitivity was partially reversed by a 1 mg/kg dose of naloxone. On the other hand, morphine (0.5 or 5.0 mg/kg IP) did not modify ET-induced analgesia, while 3.0 minutes of cold water swim (known to producemore » non-opioid mediated analgesia) potentiated ET-induced analgesic effect. The 0.5 g/kg dose of ET by itself did not depress motor activity in an open field test, but prevented partially the depression in motor activity produced by cold water swim (CWS). Thus, the potentiation by ET of the depression of the TDR produced by CWS cannot be ascribed to the depressant effects of ET on motor activity. 21 references, 4 figures, 1 table.« less

Intraarticular vs. extraarticular ropivacaine infusion following high-dose local infiltration analgesia after total knee arthroplasty

PubMed Central

2011-01-01

Background and purpose Ropivacaine infusion following high-volume local infiltration analgesia has been shown to be effective after total knee arthroplasty, but the optimum site of administration of ropivacaine has not been evaluated. We compared the effects of intraarticular and extraarticular adminstration of the local anesthetic for postoperative supplementation of high-volume local infiltration analgesia. Patients and methods In this double-blind study, 36 rheumatic patients aged 51–78 years with physical status ASA 2–3 who were scheduled for total knee arthroplasty were randomized into 2 groups. All patients received wound infiltration at the end of surgery with 300 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 156 mL). A tunneled catheter was randomly placed either extraarticularly or intraarticularly. Continuous infusion of ropivacain (0.5%, 2 mL/h) was started immediately and was maintained during the next 48 h. Pain intensity at rest, on movement, and with mobilization was estimated by the patients and the physiotherapist; rescue morphine consumption was recorded. Results As estimated by the patients, ropivacaine administered intraarticularly did not improve analgesia relative to extraarticular infusion, but improved the first mobilization. The incidence of high intensity of pain (VAS 7–10) was less in the group with intraarticular infusion. Analgesic requirements were similar in the 2 groups (47 mg and 49 mg morphine). No complications of postoperative wound healing were seen and there were no toxic side effects. Interpretation Continuous infusion of ropivacaine intraarticulary did not improve postoperative analgesia at rest relative to extraarticular administration, but it appeared to reduce the incidence of high pain intensity during first exercises, and could therefore be expected to improve mobilization up to 24 h after total knee arthroplasty. PMID:22026413

Transversus abdominal plane block for postoperative analgesia: a systematic review and meta-analysis of randomized-controlled trials.

PubMed

Brogi, Etrusca; Kazan, Roy; Cyr, Shantale; Giunta, Francesco; Hemmerling, Thomas M

2016-10-01

The transversus abdominal plane (TAP) block has been described as an effective pain control technique after abdominal surgery. We performed a systematic review and meta-analysis of randomized-controlled trials (RCTs) to account for the increasing number of TAP block studies appearing in the literature. The primary outcome we examined was the effect of TAP block on the postoperative pain score at six, 12, and 24 hr. The secondary outcome was 24-hr morphine consumption. We searched the United States National Library of Medicine database, the Excerpta Medica database, and the Cochrane Central Register of Controlled Clinical Studies and identified RCTs focusing on the analgesic efficacy of TAP block compared with a control group [i.e., placebo, epidural analgesia, intrathecal morphine (ITM), and ilioinguinal nerve block after abdominal surgery]. Meta-analyses were performed on postoperative pain scores at rest at six, 12, and 24 hr (visual analogue scale, 0-10) and on 24-hr opioid consumption. In the 51 trials identified, compared with placebo, TAP block reduced the VAS for pain at six hours by 1.4 (95% confidence interval [CI], -1.9 to -0.8; P < 0.001), at 12 hr by 2.0 (95% CI, -2.7 to -1.4; P < 0.001), and at 24 hr by 1.2 (95% CI, -1.6 to -0.8; P < 0.001). Similarly, compared with placebo, TAP block reduced morphine consumption at 24 hr after surgery (mean difference, -14.7 mg; 95% CI, -18.4 to -11.0; P < 0.001). We observed this reduction in pain scores and morphine consumption in the TAP block group after gynecological surgery, appendectomy, inguinal surgery, bariatric surgery, and urological surgery. Nevertheless, separate analysis of the studies comparing ITM with TAP block revealed that ITM seemed to have a greater analgesic efficacy. The TAP block can play an important role in the management of pain after abdominal surgery by reducing both pain scores and 24-hr morphine consumption. It may have particular utility when neuraxial techniques or opioids are

Long-term effects of routine morphine infusion in mechanically ventilated neonates on children's functioning: five-year follow-up of a randomized controlled trial.

PubMed

de Graaf, Joke; van Lingen, Richard A; Simons, Sinno H P; Anand, Kanwaljeet J S; Duivenvoorden, Hugo J; Weisglas-Kuperus, Nynke; Roofthooft, Daniella W E; Groot Jebbink, Liesbeth J M; Veenstra, Ravian R; Tibboel, Dick; van Dijk, Monique

2011-06-01

Newborns on ventilatory support often receive morphine to induce analgesia. Animal experiments suggest that this may impair subsequent cognitive and behavioral development. There are sparse human data on long-term effects of neonatal morphine. We aimed to investigate the effects of continuous morphine administered in the neonatal period on the child's functioning. We conducted a follow-up study among 5-year-olds who, as mechanically ventilated neonates, had participated in a placebo-controlled trial on effects of morphine administration on pain and neurologic outcome. They were now tested on intelligence, visual motor integration, behavior, chronic pain, and health-related quality of life. Univariate analyses showed significantly lower overall intelligence quotient (IQ) scores for children who earlier had received morphine, that is, mean 94 (SD 14.5) versus 100 (SD 12.9) for those who received placebo (P = 0.049). Other between-group differences in outcomes were not found. The statistical difference disappeared after correction for treatment condition, open-label morphine consumption over the first 28 days, and a propensity score for clinically relevant co-variables in multiple regression analyses. However, scores on one IQ subtest, "visual analysis," were significantly negatively related to having received morphine and to open-label morphine consumption the first 28 days. The finding of a significant effect of morphine on the "visual analysis" IQ subtest calls for follow-up at a later age focusing on the higher-order neurocognitive functions. Morphine received in the neonatal period has negative effects on the child's cognitive functioning at the age of 5 years which warrants follow-up at a later age. Copyright © 2011 International Association for the Study of Pain. All rights reserved.

Differential startle magnitude in mice selected for high and low swim analgesia is not related to difference in nociception.

PubMed

Blaszczyk, Janusz W; Lapo, Iwona B; Werka, Tomasz; Sadowski, Bogdan

2010-01-01

The acoustic startle response (ASR) elicited by 110 dB 10-ms pulses was studied in relation to pain sensitivity in mouse lines selectively bred for high (HA) and for low (LA) swim analgesia. The magnitudes of ASR, similarly as hot-plate latencies, differed between the lines in the rank order HA is greater than unselected controls (C) greater than LA. The animals' nociception did not change after the ASR session consisting of a sequence of 20 acoustic stimuli. Morphine hydrochloride (5 and 10 mg per kg i.p.) increased hot-plate latencies in the order of HA greater than C greater than LA, and was not effective on ASR magnitude in HA as well as in C mice. In the LA line, 10 mg per kg of morphine slightly attenuated ASR, but caused only a little analgesia. We conclude that (1) the difference in ASR between the selected lines is inversely correlated with the difference in pain sensitivity; (2) the magnitude of ASR is not altered by morphine analgesia; (3) the procedure of ASR using brief acoustic pulses is not stressful enough to elicit a form of stress analgesia. The lack of a direct relationship between the readiness to startle and pain sensation may be beneficial for an animal's survival in dangerous situations. It is beneficial when the startle to a warning signal precedes defensive behaviors and it often must be effectuated in a state of decreased nociception.

Analgesic effect of the electromagnetic resonant frequencies derived from the NMR spectrum of morphine.

PubMed

Verginadis, Ioannis I; Simos, Yannis V; Velalopoulou, Anastasia P; Vadalouca, Athina N; Kalfakakou, Vicky P; Karkabounas, Spyridon Ch; Evangelou, Angelos M

2012-12-01

Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p < 0.05), while exposure to the non resonant random EMFs exerted no effects. Additionally, naloxone administration inhibited the analgesic effects of the NMR spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

Epidural analgesia is infrequently used in patients with acute pancreatitis : a retrospective cohort study.

PubMed

Sasabuchi, Y; Yasunaga, H; Matsui, H; Lefor, A K; Fushimi, K; Sanui, M

2017-01-01

Epidural analgesia is an option for pain control in patients with acute pancreatitis. The aim of this study is to describe characteristics, morbidity and mortality of patients with acute pancreatitis treated with epidural analgesia. Data was extracted from a national inpatient database in Japan on patients hospitalized with acute pancreatitis between July 2010 and March 2013. A total of 44,146 patients discharged from acute care hospitals were included in this retrospective cohort study. The patient background, timing and duration of epidural analgesia, complications (epidural hematoma or abscess), surgery (for cholelithiasis / cholecystitis or complications) and mortality were verified. Epidural analgesia was used in 307 patients (0.70 %). The mean age was 64.0 years (standard deviation, 15.4 years) and 116 (37.8%) of the patients were female. The median duration of epidural analgesia was four days (interquartile range, 3-5 days). No patient underwent surgery for epidural hematoma or abscess. Six (2.0%) patients died during hospitalization. Most likely causes of death were pulmonary embolism, multiple organ failure, sepsis, and methicillin-resistant staphylococcus aureus enterocolitis. The responsible physician for 250 of the patients (81.4%) was a gastroenterological surgeon. Epidural analgesia was started on the day of surgery in 278 (90.6%) patients. Epidural analgesia is rarely used in patients with acute pancreatitis. None of the patients included in the study required surgery for epidural hematoma or abscess. Further research to evaluate the efficacy and safety of epidural analgesia in patients with acute pancreatitis is warranted. © Acta Gastro-Enterologica Belgica.

Electrolytic lesion of the nucleus raphe magnus reduced the antinociceptive effects of bilateral morphine microinjected into the nucleus cuneiformis in rats.

PubMed

Haghparast, Abbas; Ordikhani-Seyedlar, Mehdi; Ziaei, Maryam

2008-06-27

Several lines of investigation show that the rostral ventromedial medulla is a critical relay for midbrain regions, including the nucleus cuneiformis (CnF), which control nociception at the spinal cord. There is some evidence that local stimulation or morphine administration into the CnF produces the effective analgesia through the nucleus raphe magnus (NRM). The present study tries to determine the effect of morphine-induced analgesia following microinjection into the CnF in the absence of NRM. Seven days after the cannulae implantation, morphine was microinjected bilaterally into the CnF at the doses of 0.25, 1, 2.5, 5, 7.5 and 10 microg/0.3 microl saline per side. The morphine-induced antinociceptive effect measured by tail-flick test at 30, 60, 90 and 120 min after microinjection. The results showed that bilateral microinjection of morphine into the CnF dose-dependently causes increase in tail-flick latency (TFL). The 50% effective dose of morphine was determined and microinjected into the CnF (2.5 microg/0.3 microl saline per side) in rats after NRM electrolytic lesion (1 mA, 30 s). Lesion of the NRM significantly decreased TFLs, 30 (P<0.01) and 60 (P<0.05) but not 90-120 min after morphine microinjection into the CnF, compared with sham-lesion group. We concluded that morphine induces the analgesic effects through the opioid receptors in the CnF. It is also appeared that morphine-induced antinociception decreases following the NRM lesion but it seems that there are some other descending pain modulatory pathways that activate in the absence of NRM.

Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin.

PubMed

Mansouri, Mohammad Taghi; Khodayar, Mohammad Javad; Tabatabaee, Amirhossein; Ghorbanzadeh, Behnam; Naghizadeh, Bahareh

2015-10-01

Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, are widely used in the management of different diseases beyond their primary indication for lowering cholesterol. Previous studies have demonstrated the neuroprotective effects of simvastatin in different animal models. In the present study, we examined the effects of simvastatin (30, 60, 100 and 300mg/kg, p.o.) on the development and expression of morphine-induced tolerance and dependence in mice. For the induction of morphine tolerance and dependence, mice were twice daily treated with morphine (10mg/kg, s.c.) for 5 consecutive days. Tolerance was evaluated by the hot-plate test and physical dependence by naloxone challenge, on the sixth day. The results showed that oral administration of simvastatin produced antinociceptive activity in a dose-dependent way. Co-administration of simvastatin with morphine did not affect the acute morphine-induced analgesia (10mg/kg, s.c.). However, repeated co-administration of simvastatin with morphine significantly attenuated the development of tolerance to the analgesic effect of morphine and inhibited the naloxone (5mg/kg, s.c.)-precipitated withdrawal signs (jumping and body weight loss). Also, simvastatin at doses of 100 and 300mg/kg attenuated the expression of morphine-induced tolerance and dependence. These data indicated that, while simvastatin can alleviate both development and expression of morphine-induced tolerance, it cannot enhance morphine-induced antinociception. Taken together, simvastatin may be used as an adjutant therapeutic agent in combination with morphine and or other opioids in patients with severe chronic pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of Electroacupuncture and Morphine-Mediated Analgesic Patterns in a Plantar Incision-Induced Pain Model

PubMed Central

Tsai, Shih-Ying; Chen, Kuen-Bao; Hsu, Sheng-Feng; Chen, Julia Yi-Ru

2014-01-01

Electroacupuncture (EA) is a complementary therapy to improve morphine analgesia for postoperative pain, but underlying mechanism is not well-known. Herein, we investigated EA-induced analgesic effect in a plantar incision (PI) model in male Sprague-Dawley rats. PI was performed at the left hind paw. EA of 4 Hz and high intensity or sham needling was conducted at right ST36 prior to PI and repeated for another 2 days. Behavioral responses to mechanical and thermal stimuli, spinal phospho-ERK, and Fos expression were all analyzed. In additional groups, naloxone and morphine were administered to elucidate involvement of opioid receptors and for comparison with EA. EA pretreatment significantly reduced post-PI tactile allodynia for over 1 day; repeated treatments maintained analgesic effect. Intraperitoneal naloxone could reverse EA analgesia. Low-dose subcutaneous morphine (1 mg/kg) had stronger inhibitory effect on PI-induced allodynia than EA for 1 h. However, analgesic tolerance appeared after repeated morphine injections. Both EA and morphine could equally inhibit PI-induced p-ERK and Fos inductions. We conclude that though EA and morphine attenuate postincision pain through opioid receptor activations, daily EA treatments result in analgesic accumulation whereas daily morphine injections develop analgesic tolerance. Discrepant pathways and mechanisms underlying two analgesic means may account for the results. PMID:25530786

Effect of agmatine on long-term potentiation in morphine-treated rats.

PubMed

Lu, Wei; Dong, Hua-Jin; Bi, Guo-Hua; Zhao, Yong-Qi; Yang, Zheng; Su, Rui-Bin; Li, Jin

2010-08-01

Agmatine is an endogenous amine derived from l-arginine that potentiates morphine analgesia and inhibits naloxone precipitated abstinent symptoms in morphine dependent rats. In this study, the effects of agmatine on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of the rat dentate gyrus (DG) on saline or morphine-treated rats were investigated. Population spikes (PS), evoked by stimulation of the LPP, was recorded from DG region. Acute agmatine (2.5-10mg/kg, s.c.) treatment facilitated hippocampal LTP. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and agmatine (10mg/kg, s.c.) restored the amplitude of PS that was attenuated by morphine. Chronic morphine treatment resulted in the enhancement of hippocampal LTP, agmatine co-administered with morphine significantly attenuated the enhancement of morphine on hippocampal LTP. Imidazoline receptor antagonist idazoxan (5mg/kg, i.p.) reversed the effect of agmatine. These results suggest that agmatine attenuated the effect of morphine on hippocampal LTP, possibly through activation of imidazoline receptor. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.

Comparative Analysis of Inpatient Costs for Obstetrics and Gynecology Surgery Patients Treated With IV Acetaminophen and IV Opioids Versus IV Opioid-only Analgesia for Postoperative Pain.

PubMed

Hansen, Ryan N; Pham, An T; Lovelace, Belinda; Balaban, Stela; Wan, George J

2017-10-01

Recovery from obstetrics and gynecology (OB/GYN) surgery, including hysterectomy and cesarean section delivery, aims to restore function while minimizing hospital length of stay (LOS) and medical expenditures. Our analyses compare OB/GYN surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia with those who received IV opioid-only analgesia and estimate differences in LOS, hospitalization costs, and opioid consumption. We performed a retrospective analysis of the Premier Database between January 2009 and June 2015, comparing OB/GYN surgery patients who received postoperative pain management with combination IV acetaminophen and IV opioids with those who received only IV opioids starting on the day of surgery and continuing up to the second postoperative day. We performed instrumental variable 2-stage least-squares regressions controlling for patient and hospital covariates to compare the LOS, hospitalization costs, and daily opioid doses (morphine equivalent dose) of IV acetaminophen recipients with that of opioid-only analgesia patients. We identified 225 142 OB/GYN surgery patients who were eligible for our study of whom 89 568 (40%) had been managed with IV acetaminophen and opioids. Participants averaged 36 years of age and were predominantly non-Hispanic Caucasians (60%). Multivariable regression models estimated statistically significant differences in hospitalization cost and opioid use with IV acetaminophen associated with $484.4 lower total hospitalization costs (95% CI = -$760.4 to -$208.4; P = 0.0006) and 8.2 mg lower daily opioid use (95% CI = -10.0 to -6.4), whereas the difference in LOS was not significant, at -0.09 days (95% CI = -0.19 to 0.01; P = 0.07). Compared with IV opioid-only analgesia, managing post-OB/GYN surgery pain with the addition of IV acetaminophen is associated with decreased hospitalization costs and reduced opioid use.

Local infiltration analgesia in TKA patients reduces length of stay and postoperative pain scores.

PubMed

Tripuraneni, Krishna R; Woolson, Steven T; Giori, Nicholas J

2011-03-11

Numerous postoperative pain protocols exist for patients undergoing total knee arthroplasty (TKA). We compared the length of stay, early range of motion (ROM), and pain scores of a control group with a femoral nerve block to those of a group with femoral nerve block and local infiltration analgesia following TKA. In a consecutive series of patients undergoing primary TKA at a Veteran's Administration hospital, 40 patients (40 TKAs) who had local infiltration analgesia were compared to a historical group of 43 patients (43 TKAs) who had a long-acting femoral nerve block without local infiltration analgesia. Local infiltration analgesia consisted of intraoperative injection of 150 mL of 300 mg ropivacaine, 30 mg ketorolac, and 500 μg epinephrine using 50 mL into each of 3 areas: (1) posterior capsule, (2) medial and lateral capsule, and (3) anterior capsule and subcutaneous tissues. A 17-gauge intra-articular catheter was used to inject an additional 100 mg of ropivacaine on postoperative day 1. The control group had a single-shot femoral nerve block using 150 mg of ropivacaine with epinephrine. Mean length of stay for the local infiltration analgesia group compared to controls was 3.2±1.4 days vs 3.8±1.6 days, respectively (P=.03). No significant differences existed in average ROM (6 weeks), discharge hematocrit, transfusions, and temperature. Mean pain scores were lower in the local infiltration analgesia group on postoperative day 1 (P=.04), but not on postoperative day 2 or 3. Maximum visual analog scale scores (P<.01) were reduced in the local infiltration analgesia group. Our early experience with local infiltration analgesia demonstrated a significantly reduced length of stay due to decreased postoperative pain. Copyright 2011, SLACK Incorporated.

Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

PubMed

Wilkes, Denise M; Orillosa, Susan J; Hustak, Erik C; Williams, Courtney G; Doulatram, Gulshan R; Solanki, Daneshvari R; Garcia, Eduardo A; Huang, Li-Yen M

2017-06-13

The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Retrospective review of medical records. Private and academic pain clinic practices. Chronic noncancer pain patients. We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (<3 mg/d) of morphine. Furthermore, microdose therapy was feasible, safe, and cost-effective in the outpatient setting. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

Reducing Postoperative Opioid Consumption by Adding an Ultrasound-Guided Rectus Sheath Block to Multimodal Analgesia for Abdominal Cancer Surgery With Midline Incision

PubMed Central

Bashandy, Ghada Mohammad Nabih; Elkholy, Abeer Hassan Hamed

2014-01-01

Background: Many multimodal analgesia techniques have been tried to provide adequate analgesia for midline incisions extending above and below the umbilicus aiming at limiting the perioperative use of morphine thus limiting side effects. Ultrasound (US) guidance made the anesthesiologist reconsider old techniques for wider clinical use. The rectus sheath block (RSB) is a useful technique under-utilized in the adult population. Objectives: Our study examined the efficacy of a preemptive single-injection rectus sheath block in providing better early postoperative pain scores compared to general anesthesia alone. Patients and Methods: Sixty patients were recruited in this randomized controlled trial. These patients were divided into two groups: RSB group had an RSB after induction of anesthesia and before surgical incision, and GA (general anesthesia) group had general anesthesia alone. Both groups were compared for verbal analogue scale (VAS) score, opioid consumption and hemodynamic variables in the post-anesthesia care unit (PACU). Analgesic requirements in surgical wards were recorded in postoperative days (POD) 0, 1 and 2. Results: The median VAS score was significantly lower in RSB group compared with GA group in all 5 time points in the PACU (P ˂ 0.05). Also PACU morphine consumption was lower in RSB group than GA group patients (95% confidence interval [CI] of the difference in means between groups, −4.59 to −2.23 mg). Morphine consumption was also less in the first 2 postoperative days (POD0 and POD1). Conclusions: Ultrasound-guided rectus sheath block is an easy technique to learn. This technique, when it is used with general anesthesia, will be more effective in reducing pain scores and opioid consumption compared with general anesthesia alone. PMID:25289373

Morphine Spinal Block Anesthesia in Patients Who Undergo an Open Hemorrhoidectomy: A Prospective Analysis of Pain Control and Postoperative Complications

PubMed Central

Moreira, José PT; Isaac, Raniere R; Alves-Neto, Onofre; Moreira, Thiago AC; Vieira, Tiago HM; Brasil, Andressa MS

2014-01-01

Purpose This study evaluated the use of adding morphine to bupivacaine in spinal anesthesia for pain control in patients who underwent an open hemorrhoidectomy. Methods Forty patients were prospectively selected for an open hemorrhoidectomy at the same institution and were randomized into two groups of 20 patients each: group 1 had a spinal with 7 mg of heavy bupivacaine associated with 80 µg of morphine (0.2 mg/mL). Group 2 had a spinal with 7 mg of heavy bupivacaine associated with distilled water, achieving the same volume of spinal infusion as that of group 1. Both groups were prescribed the same pain control medicine during the postoperative period. Pain scores were evaluated at the anesthetic recovery room and at 3, 6, 12, and 24 hours after surgery. Postoperative complications, including pruritus, nausea, headaches, and urinary retention, were also recorded. Results There were no anthropometric statistical differences between the two groups. Pain in the anesthetic recovery room and 3 hours after surgery was similar for both groups. However, pain was better controlled in group 1 at 6 and 12 hours after surgery. Although pain was better controlled for group 1 after 24 hours of surgery, the difference between the groups didn't achieved statistical significance. Complications were more common in group 1. Six patients (6/20) presented coetaneous pruritus and 3 with (3/20) urinary retention. Conclusion A hemorrhoidectomy under a spinal with morphine provides better pain control between 6 and 12 hours after surgery. However, postoperative complications, including cutaneous pruritus (30%) and urinary retention (15%), should be considered as a negative side of this procedure. PMID:24999465

Ethnicity-dependent influence of innate immune genetic markers on morphine PCA requirements and adverse effects in postoperative pain.

PubMed

Somogyi, Andrew A; Sia, Alex T; Tan, Ene-Choo; Coller, Janet K; Hutchinson, Mark R; Barratt, Daniel T

2016-11-01

Although several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2, TLR4, MYD88, MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA, TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition to OPRM1, COMT, and ABCB1 genetic variability identified previously. Postsurgical patient-controlled analgesia morphine use (mg/24 hours) was binned into 6 normally distributed groups and scored 0 to 5 to facilitate step-down multiple linear regression analysis of genetic predictors, controlling for ethnicity and nongenetic variables. Ethnicity, OPRM1 rs1799971 (increased), TLR2 rs3804100 (decreased), and an interaction between ethnicity and IL1B rs1143634 (increased), predicted 9.8% of variability in morphine use scores in the entire cohort. In the Indian cohort, 14.5% of the variance in morphine use score was explained by IL1B rs1143634 (increased) and TGFB1 rs1800469 (decreased). In Chinese patients, the incidence of postsurgical pain was significantly higher in variant COMT rs4680 genotypes (P = 0.0007) but not in the Malay or Indian cohorts. Innate immune genetics may contribute to variability in postsurgical opioid requirements in an ethnicity-dependent manner.

[Comparison of clinical effectiveness of thoracic epidural and intravenous patient-controlled analgesia for the treatment of rib fractures pain in intensive care unit].

PubMed

Topçu, Ismet; Ekici, Zeynep; Sakarya, Melek

2007-07-01

The results of thoracic epidural and systemic patient controlled analgesia practice were evaluated retrospectively in patients with thoracic trauma. Patients who were admitted to the intensive care unit between 1997 and 2003, with a diagnosis of multiple rib fractures related to thoracic trauma were evaluated retrospectively. Data were recorded from 49 patients who met the following criteria; three or more rib fractures, initiation of PCA with I.V. phentanyl or thoracic epidural analgesia with phentanyl and bupivacaine. There were no significant differences between the groups concerning injury severity score. APACHE II score (8.1+/-1.6 and 9.2+/-1.7) and the number of rib fractures (4+/-1.1 and 6.8+/-2.7) were higher in thoracic epidural analgesia group (p<0.05). Pain scores of patients who received thoracic epidural analgesia were significantly lower as from 6th hour during whole therapy (p<0.05). Length of intensive care unit stay (15.6+/-5.9 and 12.1+/-4.4 day) was found to be shorter in thoracic epidural analgesia group (p<0.05). There were no differences between the groups regarding mechanical ventilation requirement, pulmonary and cardiac complications. We suggest that the use of thoracic epidural analgesia with infusion of local anesthetics and opioids are more appropriate as they provide more effective analgesia and shorten length of intensive care unit stay in chest trauma patients with more than three rib fractures who require intensive care.

Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis.

PubMed

Rubinstein, M; Mogil, J S; Japón, M; Chan, E C; Allen, R G; Low, M J

1996-04-30

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms.

Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis.

PubMed Central

Rubinstein, M; Mogil, J S; Japón, M; Chan, E C; Allen, R G; Low, M J

1996-01-01

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms. Images Fig. 1 Fig. 2 PMID:8633004

A history of intraspinal analgesia, a small and personal journey.

PubMed

Krames, Elliot S

2012-01-01

There is a large and robust literature on the spinal use of opioids and non-opioids alike, but unless one is my age and older, very few persons know how we got here. This small history offering tells us how we got to where we are today regarding the science, clinical uses, and management of intraspinal analgesia. I have reviewed the literature bases of Google Scholar and the National Library of Medicine using the key words: history, opium, spinal analgesia, spinal morphine, intrathecal (IT), opioid receptors, endogenous opioids, IT delivery of opioids, and IT side-effects/complications. In this personal review of the history of intraspinal analgesia, I relate my own early and later experiences of the science and clinical uses of intraspinal morphine, other opioids, and non-opioids alike to a historical context. This review outlines a rather small history of opium, the historical use of opium and its various compounds, and the search for and answer to the question, "why was the poppy created for wondrous medicinal uses for mankind?" This search led to the discovery of endogenous opioid like chemicals, the discovery of opiate receptors for these endogenous opioids, the first uses of intraspinal opioids in animal models and man, and, finally, our understanding of the appropriate and inappropriate clinical uses of intraspinal analgesia. Within this paper, I acknowledge the works of my colleagues and the "heroes" who have laid the foundation for our understanding of intraspinal analgesia. The history of the use of intraspinal analgesia is rich and guides us to advance the science and clinical use of intraspinal analgesia without reinventing the wheel. © 2012 International Neuromodulation Society.

[Patient-controlled Analgesia (PCA): an Overview About Methods, Handling and New Modalities].

PubMed

Abrolat, Marie; Eberhart, Leopold H J; Kalmus, Gerald; Koch, Tilo; Nardi-Hiebl, Stefan

2018-04-01

Patient-controlled analgesia (PCA) is one of the well established methods for the treatment of postoperative pain. A cochrane-review concluded that PCA is associated with better postoperative pain ratings and improved patient-satifaction compared to traditional way of administering opioids. Some prerequisites concerning patient selection, education of the patient and the medical staff, and supervision during PCA therapy are mandatory for a safe use of PCA. Current PCA modalities (intravenous and epidural routes of application) are expanded by newer, less invasive routes of drug administration, e.g. by the iontophoretic transdermal and the sublingual route. Their role in improving safety and the quality of pain therapy on the one hand side, and costs on the other hand side are discussion. Georg Thieme Verlag KG Stuttgart · New York.

Analgesic efficacy of ultrasound guided transversus abdominis plane block versus local anesthetic infiltration in adult patients undergoing single incision laparoscopic cholecystectomy: A randomized controlled trial.

PubMed

Bava, Ejas P; Ramachandran, Rashmi; Rewari, Vimi; Chandralekha; Bansal, Virinder Kumar; Trikha, Anjan

2016-01-01

Transversus abdominis plane (TAP) block has been used to provide intra- and post-operative analgesia with single incision laparoscopic (SIL) bariatric and gynecological surgery with mixed results. Its efficacy in providing analgesia for SIL cholecystectomy (SILC) via the same approach remains unexplored. The primary objective of our study was to compare the efficacy of bilateral TAP block with local anesthetic infiltration for perioperative analgesia in patients undergoing SILC. This was a prospective, randomized, controlled, double-blinded trial performed in a tertiary care hospital. Forty-two patients undergoing SILC were randomized to receive either ultrasound-guided (USG) bilateral mid-axillary TAP blocks with 0.375% ropivacaine or local anesthetic infiltration of the port site. The primary outcome measure was the requirement of morphine in the first 24 h postoperatively. The data were analyzed using t -test, Mann-Whitney test or Chi-square test. The 24 h morphine requirement (mean ± standard deviation) was 34.57 ± 14.64 mg in TAP group and 32.76 ± 14.34 mg in local infiltration group ( P = 0.688). The number of patients requiring intraoperative supplemental fentanyl in TAP group was 8 and in local infiltration group was 16 ( P = 0.028). The visual analog scale scores at rest and on coughing were significantly higher in the local infiltration group in the immediate postoperative period ( P = 0.034 and P = 0.007, respectively). USG bilateral TAP blocks were not effective in decreasing 24 h morphine requirement as compared to local anesthetic infiltration in patients undergoing SILC although it provided some analgesic benefit intraoperatively and in the initial 4 h postoperatively. Hence, the benefits of TAP blocks are not worth the effort and time spent for administering them for this surgery.

Analgesic efficacy of ultrasound guided transversus abdominis plane block versus local anesthetic infiltration in adult patients undergoing single incision laparoscopic cholecystectomy: A randomized controlled trial

PubMed Central

Bava, Ejas P.; Ramachandran, Rashmi; Rewari, Vimi; Chandralekha; Bansal, Virinder Kumar; Trikha, Anjan

2016-01-01

Background: Transversus abdominis plane (TAP) block has been used to provide intra- and post-operative analgesia with single incision laparoscopic (SIL) bariatric and gynecological surgery with mixed results. Its efficacy in providing analgesia for SIL cholecystectomy (SILC) via the same approach remains unexplored. Aims: The primary objective of our study was to compare the efficacy of bilateral TAP block with local anesthetic infiltration for perioperative analgesia in patients undergoing SILC. Settings and Design: This was a prospective, randomized, controlled, double-blinded trial performed in a tertiary care hospital. Materials and Methods: Forty-two patients undergoing SILC were randomized to receive either ultrasound-guided (USG) bilateral mid-axillary TAP blocks with 0.375% ropivacaine or local anesthetic infiltration of the port site. The primary outcome measure was the requirement of morphine in the first 24 h postoperatively. Statistical Analysis: The data were analyzed using t-test, Mann–Whitney test or Chi-square test. Results: The 24 h morphine requirement (mean ± standard deviation) was 34.57 ± 14.64 mg in TAP group and 32.76 ± 14.34 mg in local infiltration group (P = 0.688). The number of patients requiring intraoperative supplemental fentanyl in TAP group was 8 and in local infiltration group was 16 (P = 0.028). The visual analog scale scores at rest and on coughing were significantly higher in the local infiltration group in the immediate postoperative period (P = 0.034 and P = 0.007, respectively). Conclusion: USG bilateral TAP blocks were not effective in decreasing 24 h morphine requirement as compared to local anesthetic infiltration in patients undergoing SILC although it provided some analgesic benefit intraoperatively and in the initial 4 h postoperatively. Hence, the benefits of TAP blocks are not worth the effort and time spent for administering them for this surgery. PMID:27746552

Suprascapular block associated with supraclavicular block: An alternative to isolated interscalene block for analgesia in shoulder instability surgery?

PubMed

Trabelsi, W; Ben Gabsia, A; Lebbi, A; Sammoud, W; Labbène, I; Ferjani, M

2017-02-01

Interscalene brachial plexus block (ISB) is the gold standard for postoperative pain management in shoulder surgery. However, this technique has side effects and potentially serious complications. The aim of this study was to compare the combinations of ultrasound-guided suprascapular (SSB) associated with supraclavicular nerve block (SCB) and ultrasound-guided ISB for postoperative analgesia after shoulder instability surgery. Sixty ASA physical status I-II patients scheduled to undergo shoulder instability surgery were included. Two groups: (i) the SSB+SCB group (n=30) in which the patients received a combination of US-guided SSB (15mL of bupivacaine 0.25%) and US-guided SCB (15mL of bupivacaine 0.25%) and (ii) the ISB group (n=30) in which the patients received US-guided ISB with 30mL of bupivacaine 0.25%. General anesthesia was administered to all patients. During the first 24h, the variables assessed were time to administer the anesthesia, duration of the analgesia, onset and duration of motor and sensory blockade, opioid consumption, cardiovascular stability, complications, and patient satisfaction. Anesthesia induction took more time for the SSB+SCB group than for the ISB group. However, the onset time of motor and sensory blockade was similar in the two groups. Statistical analysis of the visual analog postoperative pain scoring at H0, H6, H12, and H24 showed nonsignificant differences between the groups. Analgesia, the first request for morphine, and total morphine consumption during the first 24h was similar in both groups. No complication was recorded in the SSB+SCB group. However, phrenic nerve block occurred in all patients in the ISB group. US-guided SCB combined with US-guided SSB was as effective as ISB for postoperative analgesia after shoulder instability surgery without decreasing potential side effects. NCT identifier: NCT02397330. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Is Local Infiltration Analgesia Superior to Peripheral Nerve Blockade for Pain Management After THA: A Network Meta-analysis.

PubMed

Jiménez-Almonte, José H; Wyles, Cody C; Wyles, Saranya P; Norambuena-Morales, German A; Báez, Pedro J; Murad, Mohammad H; Sierra, Rafael J

2016-02-01

Local infiltration analgesia and peripheral nerve blocks are common methods for pain management in patients after THA but direct head-to-head, randomized controlled trials (RCTs) have not been performed. A network meta-analysis allows indirect comparison of individual treatments relative to a common comparator; in this case placebo (or no intervention), epidural analgesia, and intrathecal morphine, yielding an estimate of comparative efficacy. We asked, when compared with a placebo, (1) does use of local infiltration analgesia reduce patient pain scores and opioid consumption, (2) does use of peripheral nerve blocks reduce patient pain scores and opioid consumption, and (3) is local infiltration analgesia favored over peripheral nerve blocks for postoperative pain management after THA? We searched six databases, from inception through June 30, 2014, to identify RCTs comparing local infiltration analgesia or peripheral nerve block use in patients after THA. A total of 35 RCTs at low risk of bias based on the recommended Cochrane Collaboration risk assessment tool were included in the network meta-analysis (2296 patients). Primary outcomes for this review were patient pain scores at rest and cumulative opioid consumption, both assessed at 24 hours after THA. Because of substantial heterogeneity (variation of outcomes between studies) across included trials, a random effect model for meta-analysis was used to estimate the weighted mean difference (WMD) and 95% CI. The gray literature was searched with the same inclusion criteria as published trials. Only one unpublished trial (published abstract) fulfilled our criteria and was included in this review. All other studies included in this systematic review were full published articles. Bayesian network meta-analysis included all RCTs that compared local infiltration analgesia or peripheral nerve blocks with placebo (or no intervention), epidural analgesia, and intrathecal morphine. Compared with placebo, local

Differential analgesic effects of a mu-opioid peptide, [Dmt(1)]DALDA, and morphine.

PubMed

Shimoyama, Megumi; Szeto, Hazel H; Schiller, Peter W; Tagaito, Yugo; Tokairin, Hideyuki; Eun, Chong moon; Shimoyama, Naohito

2009-01-01

H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA. We compared the effects of [Dmt(1)]DALDA and morphine after systemic administration in two different acute pain tests, the tail flick test and the paw withdrawal test, and examined how antagonizing the spinal opioid actions would affect their analgesic effects. [Dmt(1)]DALDA was markedly more potent in the tail flick test than in the hot plate test, while the potencies of morphine were similar in the two tests. Intrathecal naloxone completely blocked the effect of systemic [Dmt(1)]DALDA in the tail flick test, while it only partially blocked the effect of morphine. At higher doses that produced analgesia in the hot plate test, the effect of [Dmt(1)]DALDA in this test was only partially blocked by naloxone. Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.

Effect of morphine and methadone acute treatment on immunological activity in mice: pharmacokinetic and pharmacodynamic correlates.

PubMed

Pacifici, R; Patrini, G; Venier, I; Parolaro, D; Zuccaro, P; Gori, E

1994-06-01

This report describes the 24-hr time course of the immunomodulatory effects of an acute s.c. injection of morphine in C57BL6 mice, and correlates these effects with the drug's analgesic properties and serum levels. Acute morphine treatment had a biphasic effect on various immune parameters: there was an increase in in vitro phagocytosis and the killing of Candida Albican cells by peritoneal polymorphonuclear leukocytes 20 and 40 min after the injection of morphine, 20 mg/kg, when analgesia and serum morphine concentrations were at their peak. Interestingly, 24 hr after morphine administration (when antinociception and morphine blood levels were no longer detectable) these parameters underwent a marked reduction. Similarly, macrophage-mediated inhibition of tumor cells proliferation was first stimulated (at 20 and 40 min) and then depressed (at 24 hr). Splenic natural killer cell cytotoxicity, determined by standard 51Cr release from YAC-1 target cells, also was evaluated. No differences in natural killer activity was observed at any of the monitored time points. In addition, we evaluated the immunomodulatory effects of an acute injection of methadone (a synthetic narcotic compound) at a dose inducing the same degree of analgesia as morphine. None of the tested immunoparameters were affected by the administration of methadone, which indicates the different drug-sensitivity of immunological correlates in vivo.

Morphine Glucuronidation and Elimination in Intensive Care Patients: A Comparison with Healthy Volunteers.

PubMed

Ahlers, Sabine J G M; Välitalo, Pyry A J; Peeters, Mariska Y M; Gulik, Laura van; van Dongen, Eric P A; Dahan, Albert; Tibboel, Dick; Knibbe, Catherijne A J

2015-11-01

Although morphine is used frequently to treat pain in the intensive care unit, its pharmacokinetics has not been adequately quantified in critically ill patients. We evaluated the glucuronidation and elimination clearance of morphine in intensive care patients compared with healthy volunteers based on the morphine and morphine-3-glucuronide (M3G) concentrations. A population pharmacokinetic model with covariate analysis was developed with the nonlinear mixed-effects modeling software (NONMEM 7.3). The analysis included 3012 morphine and M3G concentrations from 135 intensive care patients (117 cardiothoracic surgery patients and 18 critically ill patients), who received continuous morphine infusions adapted to individual pain levels, and 622 morphine and M3G concentrations from a previously published study of 20 healthy volunteers, who received an IV bolus of morphine followed by a 1-hour infusion. For morphine, a 3-compartment model best described the data, whereas for M3G, a 1-compartment model fits best. In intensive care patients with a normal creatinine concentration, a decrease of 76% was estimated in M3G clearance compared with healthy subjects, conditional on the M3G volume of distribution being the same in intensive care patients and healthy volunteers. Furthermore, serum creatinine concentration was identified as a covariate for both elimination clearance of M3G in intensive care patients and unchanged morphine clearance in all patients and healthy volunteers. Under the assumptions in the model, M3G elimination was significantly decreased in intensive care patients when compared with healthy volunteers, which resulted in substantially increased M3G concentrations. Increased M3G levels were even more pronounced in patients with increased serum creatinine levels. Model-based simulations show that, because of the reduction in morphine clearance in intensive care patients with renal failure, a 33% reduction in the maintenance dose would result in morphine

Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling

PubMed Central

Lee, Pin-Tse; Chao, Po-Kuan; Ou, Li-Chin; Chuang, Jian-Ying; Lin, Yen-Chang; Chen, Shu-Chun; Chang, Hsiao-Fu; Law, Ping-Yee; Loh, Horace H.; Chao, Yu-Sheng; Su, Tsung-Ping; Yeh, Shiu-Hwa

2014-01-01

Heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds to the promoter region of mu-opioid receptor (MOR) to regulate its transcriptional activity. How hnRNP K contributes to the analgesic effects of morphine, however, is largely unknown. We provide evidence that morphine increases hnRNP K protein expression via MOR activation in rat primary cortical neurons and HEK-293 cells expressing MORs, without increasing mRNA levels. Using the bicistronic reporter assay, we examined whether morphine-mediated accumulation of hnRNP K resulted from translational control. We identified potential internal ribosome entry site elements located in the 5′ untranslated regions of hnRNP K transcripts that were regulated by morphine. This finding suggests that internal translation contributes to the morphine-induced accumulation of hnRNP K protein in regions of the central nervous system correlated with nociceptive and antinociceptive modulatory systems in mice. Finally, we found that down-regulation of hnRNP K mediated by siRNA attenuated morphine-induced hyperpolarization of membrane potential in AtT20 cells. Silencing hnRNP K expression in the spinal cord increased nociceptive sensitivity in wild-type mice, but not in MOR-knockout mice. Thus, our findings identify the role of translational control of hnRNP K in morphine-induced analgesia through activation of MOR. PMID:25361975

Analgesic efficacy of butorphanol and morphine in bearded dragons and corn snakes.

PubMed

Sladky, Kurt K; Kinney, Matthew E; Johnson, Stephen M

2008-07-15

To test the hypothesis that administration of butorphanol or morphine induces antinociception in bearded dragons and corn snakes. Prospective crossover study. 12 juvenile and adult bearded dragons and 13 corn snakes. Infrared heat stimuli were applied to the plantar surface of bearded dragon hind limbs or the ventral surface of corn snake tails. Thermal withdrawal latencies (TWDLs) were measured before (baseline) and after SC administration of physiologic saline (0.9% NaCl) solution (equivalent volume to opioid volumes), butorphanol tartrate (2 or 20 mg/kg [0.91 or 9.1 mg/lb]), or morphine sulfate (1, 5, 10, 20, or 40 mg/kg [0.45, 2.27, 4.5, 9.1, or 18.2 mg/lb]). For bearded dragons, butorphanol (2 or 20 mg/kg) did not alter hind limb TWDLs at 2 to 24 hours after administration. However, at 8 hours after administration, morphine (10 and 20 mg/kg) significantly increased hind limb TWDLs from baseline values (mean +/- SEM maximum increase, 2.7+/-0.4 seconds and 2.8+/-0.9 seconds, respectively). For corn snakes, butorphanol (20 mg/kg) significantly increased tail TWDLs at 8 hours after administration (maximum increase from baseline value, 3.0+/-0.8 seconds); the low dose had no effect. Morphine injections did not increase tail TWDLs at 2 to 24 hours after administration. Compared with doses used in most mammalian species, high doses of morphine (but not butorphanol) induced analgesia in bearded dragons, whereas high doses of butorphanol (but not morphine) induced analgesia in corn snakes.

Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial.

PubMed

Jennings, Paul A; Cameron, Peter; Bernard, Stephen; Walker, Tony; Jolley, Damien; Fitzgerald, Mark; Masci, Kevin

2014-10-01

Improved early pain control may affect the longer-term prevalence of persistent pain. In a previous randomised, controlled trial, we found that the administration of ketamine on hospital arrival decreased pain scores to a greater extent than morphine alone in patients with prehospital traumatic pain. In this follow-up study, we sought to determine the prevalence of persistent pain and whether there were differences in patients who received ketamine or morphine. This study was a long-term follow-up study of the prehospital, prospective, randomised, controlled, open-label study comparing ketamine with morphine in patients with trauma and a verbal pain score of >5 after 5 mg intravenous morphine. Patients were followed-up by telephone 6-12 months after enrollment, and a questionnaire including the SF-36 (V.2) health-related quality of life survey and the Verbal Numerical Rating Scale for pain was administered. A total of 97/135 (72%) patients were able to be followed-up 6-12 months after enrollment between July 2008 and July 2010. Overall, 44/97 (45%) participants reported persistent pain related to their injury, with 3/97 (3%) reporting persistent severe pain. The prevalence of persistent pain was the same between study groups (22/50 (44%) for the ketamine group vs 22/47 (46%) for the morphine group). There was no difference in the SF-36 scores between study arms. There is a high incidence of persistent pain after traumatic injury, even in patients with relatively minor severity of injury. Although decreased pain scores at hospital arrival are achieved with ketamine compared with morphine, this difference does not affect the prevalence of persistent pain or health-related quality of life 6 months after injury. Further larger studies are required to confirm this finding. Australian and New Zealand Clinical Trials Registry (ACTRN12607000441415). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

Initial experience with ketamine-based analgesia in patients undergoing robotic radical cystectomy and diversion.

PubMed

Jacobsohn, Kenneth; Davis, Tanya D; El-Arabi, Ahmad M; Tlachac, Jonathan; Langenstroer, Peter; O'Connor, R Corey; Guralnick, Michael L; See, William A; Schlosser, Robert

2015-01-01

We instituted a ketamine-predominant analgesic regimen in the peri- and postoperative periods to limit the effects of narcotic analgesia on bowel function in patients undergoing radical cystectomy. The primary end points of interest were time to return of bowel function, time to discharge, and efficacy of the analgesic regimen. We performed a retrospective chart review of patients undergoing robotic-assisted laparoscopic cystectomy (RARC) with urinary diversion by a single surgeon at our institution from January 1, 2011 to June 30, 2012. Patients receiving the opioid-minimizing ketamine protocol were compared to a cohort of patients undergoing RARC with an opioid-predominant analgesic regimen. In total, 15 patients (Group A) were included in the ketamine-predominant regimen and 25 patients (Group B) in the opioid-predominant control group. Three patients (19%) in Group A discontinued the protocol due to ketamine side effects. The mean time to bowel movement and length of stay in Group A versus Group B was 3 versus 6 days (p < 0.001), and 4 versus 8 days, respectively (p < 0.001). Group A patients received an average of 13.0 mg of morphine versus 97.5 mg in Group B (p < 0.001). Patients who received our ketamine pain control regimen had a shorter time to return of bowel function and length of hospitalization after RARC. Our study has its limitations as a retrospective, single surgeon, single institution study and the non-randomization of patients. Notwithstanding these limitations, this study was not designed to show inferiority of one approach, but instead to show that our protocol is safe and efficacious, warranting further study in a prospective fashion.

Suppression of transmission of nociceptive impulses by morphine

PubMed Central

Duggan, A.W.; Hall, J.G.; Headley, P.M.

1977-01-01

1 In spinal cats anaesthetized with α-chloralose, a study was made of the effects of morphine and naloxone, administered electrophoretically from micropipettes, on the responses of dorsal horn neurones to noxious (raising of skin temperature above 45°C) and innocuous (deflection of hairs) peripheral stimuli. 2 Administered near cell bodies, morphine reduced the nociceptive responses of only 2 of 37 cells. Excitation occurred more commonly than depression and abnormalities in action potentials were commonly observed following ejection of morphine. None of these effects of morphine was antagonized by electrophoretically applied naloxone. 3 Administered in the substantia gelatinosa from one micropipette while recording responses of deeper neurones with a second micropipette, morphine reduced the nociceptive responses of 15 of 19 neurones. Firing in response to deflection of hairs was not reduced by morphine. Depression of nociceptive responses by morphine was long lasting (>20 minutes). Naloxone ejected into the substantia gelatinosa or given intravenously in doses as low as 0.1 mg/kg antagonized the effects of morphine. The effectiveness of this dose of intravenous naloxone suggests that the concentrations of morphine in the substantia gelatinosa which reduced nociceptive responses were not unlike those present after analgesic doses of systemic morphine. Naloxone alone, and excitant and depressant amino acids ejected into the substantia gelatinosa had little effect on cell firing. 4 Both the selective action of morphine on nociceptive responses and the reversal of this action by intravenous naloxone suggest that the opiate receptor present in the substantia gelatinosa is relevant to analgesia produced by opiates given systemically. PMID:199311

Epidural Analgesia Versus Patient-Controlled Analgesia for Pain Relief in Uterine Artery Embolization for Uterine Fibroids: A Decision Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kooij, Sanne M. van der, E-mail: s.m.vanderkooij@amc.uva.nl; Moolenaar, Lobke M.; Ankum, Willem M.

Purpose: This study was designed to compare the costs and effects of epidural analgesia (EDA) to those of patient-controlled intravenous analgesia (PCA) for postintervention pain relief in women having uterine artery embolization (UAE) for systematic uterine fibroids. Methods: Cost-effectiveness analysis (CEA) based on data from the literature by constructing a decision tree to model the clinical pathways for estimating the effects and costs of treatment with EDA and PCA. Literature on EDA for pain-relief after UAE was missing, and therefore, data on EDA for abdominal surgery were used. Outcome measures were compared costs to reduce one point in visual analoguemore » score (VAS) or numeric rating scale (NRS) for pain 6 and 24 h after UAE and risk for complications. Results: Six hours after the intervention, the VAS was 3.56 when using PCA and 2.0 when using EDA. The costs for pain relief in women undergoing UAE with PCA and EDA were Euro-Sign 191 and Euro-Sign 355, respectively. The costs for EDA to reduce the VAS score 6 h after the intervention with one point compared with PCA were Euro-Sign 105 and Euro-Sign 179 after 24 h. The risk of having a complication was 2.45 times higher when using EDA. Conclusions: The results of this indirect comparison of EDA for abdominal surgery with PCA for UAE show that EDA would provide superior analgesia for post UAE pain at 6 and 24 h but with higher costs and an increased risk of complications.« less

Reducing postoperative opioid consumption by adding an ultrasound-guided rectus sheath block to multimodal analgesia for abdominal cancer surgery with midline incision.

PubMed

Bashandy, Ghada Mohammad Nabih; Elkholy, Abeer Hassan Hamed

2014-08-01

Many multimodal analgesia techniques have been tried to provide adequate analgesia for midline incisions extending above and below the umbilicus aiming at limiting the perioperative use of morphine thus limiting side effects. Ultrasound (US) guidance made the anesthesiologist reconsider old techniques for wider clinical use. The rectus sheath block (RSB) is a useful technique under-utilized in the adult population. Our study examined the efficacy of a preemptive single-injection rectus sheath block in providing better early postoperative pain scores compared to general anesthesia alone. Sixty patients were recruited in this randomized controlled trial. These patients were divided into two groups: RSB group had an RSB after induction of anesthesia and before surgical incision, and GA (general anesthesia) group had general anesthesia alone. Both groups were compared for verbal analogue scale (VAS) score, opioid consumption and hemodynamic variables in the post-anesthesia care unit (PACU). Analgesic requirements in surgical wards were recorded in postoperative days (POD) 0, 1 and 2. The median VAS score was significantly lower in RSB group compared with GA group in all 5 time points in the PACU (P ˂ 0.05). Also PACU morphine consumption was lower in RSB group than GA group patients (95% confidence interval [CI] of the difference in means between groups, -4.59 to -2.23 mg). Morphine consumption was also less in the first 2 postoperative days (POD0 and POD1). Ultrasound-guided rectus sheath block is an easy technique to learn. This technique, when it is used with general anesthesia, will be more effective in reducing pain scores and opioid consumption compared with general anesthesia alone.

Effects of Flurbiprofen Axetil on Postoperative Analgesia and Cytokines in Peripheral Blood of Thoracotomy Patients.

PubMed

Zhou, Mi; Li, Beiping; Kong, Ming

2015-06-01

The objective is to study the effects of flurbiprofen axetil (FA) with fentanyl together in postoperative controlled intravenous analgesia (PCIA) on pain intensity, cytokine levels in peripheral blood and adverse reactions of thoracotomy patients. Fifty thoracotomy patients were divided into a FA and a control group, each with 25 cases. Postoperative analgesia was administered in the two groups using PCIA. The pressing times of analgesia pump, the visual analog scale (VAS) scores during resting and coughing at 2, 6, 24, 48, 72 h after surgery and the incidence of adverse drug reactions were recorded. Levels of IL-1β, IL-6, IL-8, IL-2, and TNF-α in peripheral blood were determined before the administration of FA (T0), and at 24 h (T1), 48 h (T2), 72 h (T3) after surgery. The analgesia pump pressing times in the FA group was less than that of the control group. The VAS scores during resting and coughing at 2, 6, 24, 48, 72 h after surgery, were statistically less than those of control group. The incidence rate of nausea and vomiting was insignificantly different between the two groups. Administration of FA together with PCIA in thoracotomy patients can improve postoperative analgesia.

Polyglycerol-opioid conjugate produces analgesia devoid of side effects.

PubMed

González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph

2017-07-04

Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

Brain cholinergic involvement during the rapid development of tolerance to morphine

NASA Technical Reports Server (NTRS)

Wahba, Z. Z.; Oriaku, E. T.; Soliman, S. F. A.

1987-01-01

The effect of repeated administration of morphine on the activities of the cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in specific brain regions were studied in rats treated with 10 mg/kg morphine for one or two days. Repeated administration of morphine was associated with a decline in the degree of analgesia produced and with a significant increase of AChE activity of the medulla oblongata. A single injection of morphine resulted in a significant decline in ChAT activity in the hypothalamus, cerebellum, and medulla oblongata regions. After two consecutive injections, no decline in ChAT was observed in these regions, while in the cerebral cortex the second administration elicited a significant decline. The results suggest that the development of tolerance to morphine may be mediated through changes in ChAT activity and lend support to the involvement of the central cholinergic system in narcotic tolerance.

Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

PubMed

Dampier, Carlton D; Smith, Wally R; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C; Minniti, Caterina P; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A Kyle; McClish, Donna; McKinlay, Sonja M; Miller, Scott T; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J; Weiner, Debra L

2011-12-01

Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.

Mu opioid receptors on primary afferent nav1.8 neurons contribute to opiate-induced analgesia: insight from conditional knockout mice.

PubMed

Weibel, Raphaël; Reiss, David; Karchewski, Laurie; Gardon, Olivier; Matifas, Audrey; Filliol, Dominique; Becker, Jérôme A J; Wood, John N; Kieffer, Brigitte L; Gaveriaux-Ruff, Claire

2013-01-01

Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. We generated conditional knockout (cKO) mice in which mu opioid receptors are deleted specifically in primary afferent Nav1.8-positive neurons. Mutant animals were compared to controls for acute nociception, inflammatory pain, opiate-induced analgesia and constipation. There was a 76% decrease of mu receptor-positive neurons and a 60% reduction of mu-receptor mRNA in dorsal root ganglia of cKO mice. Mutant mice showed normal responses to heat, mechanical, visceral and chemical stimuli, as well as unchanged morphine antinociception and tolerance to antinociception in models of acute pain. Inflammatory pain developed similarly in cKO and controls mice after Complete Freund's Adjuvant. In the inflammation model, however, opiate-induced (morphine, fentanyl and loperamide) analgesia was reduced in mutant mice as compared to controls, and abolished at low doses. Morphine-induced constipation remained intact in cKO mice. We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain.

Mu Opioid Receptors on Primary Afferent Nav1.8 Neurons Contribute to Opiate-Induced Analgesia: Insight from Conditional Knockout Mice

PubMed Central

Karchewski, Laurie; Gardon, Olivier; Matifas, Audrey; Filliol, Dominique; Becker, Jérôme A. J.; Wood, John N.; Kieffer, Brigitte L.; Gaveriaux-Ruff, Claire

2013-01-01

Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. We generated conditional knockout (cKO) mice in which mu opioid receptors are deleted specifically in primary afferent Nav1.8-positive neurons. Mutant animals were compared to controls for acute nociception, inflammatory pain, opiate-induced analgesia and constipation. There was a 76% decrease of mu receptor-positive neurons and a 60% reduction of mu-receptor mRNA in dorsal root ganglia of cKO mice. Mutant mice showed normal responses to heat, mechanical, visceral and chemical stimuli, as well as unchanged morphine antinociception and tolerance to antinociception in models of acute pain. Inflammatory pain developed similarly in cKO and controls mice after Complete Freund’s Adjuvant. In the inflammation model, however, opiate-induced (morphine, fentanyl and loperamide) analgesia was reduced in mutant mice as compared to controls, and abolished at low doses. Morphine-induced constipation remained intact in cKO mice. We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain. PMID:24069332

Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: Study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Children with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain. Methods/design This study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05. Discussion This clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in

The Effect of the Time of Injection of Intrathecal Analgesia on the Length of Early and Advanced Labor

DTIC Science & Technology

2000-01-03

drug combinations. Intrathecal Analgesia 36 Future Studies Recommendations for future studies include a prospective randomized clinical trial to examine...second stages of labor because of the variations in client population and in clinical practice. Friedman (1978) Intrathecal Analgesia 7 however, does...that the administration of morphine into the subarchnoid space of rats produced potent analgesia (Wang, 1977). These effects were then clinically applied

Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a randomised controlled trial

PubMed Central

Pak, Linda Ma; Haroutounian, Simon; Hawkins, William G; Worley, Lori; Kurtz, Monika; Frey, Karen; Karanikolas, Menelaos; Swarm, Robert A; Bottros, Michael M

2018-01-01

Introduction Epidural analgesia provides an important synergistic method of pain control. In addition to reducing perioperative opioid consumption, the deliverance of analgesia into the epidural space, effectively creating a sympathetic blockade, has a multitude of additional potential benefits, from decreasing the incidence of postoperative delirium to reducing the development of persistent postsurgical pain (PPSP). Prior studies have also identified a correlation between the use of epidural analgesia and improved oncological outcomes and survival. The aim of this study is to evaluate the effect of epidural analgesia in pancreatic operations on immediate postoperative outcomes, the development of PPSP and oncological outcomes in a prospective, single-blind, randomised controlled trial. Methods The Epidurals in Pancreatic Resection Outcomes (E-PRO) study is a prospective, single-centre, randomised controlled trial. 150 patients undergoing either pancreaticoduodenectomy or distal pancreatectomy will be randomised to receive an epidural bupivacaine infusion following anaesthetic induction followed by continued epidural bupivacaine infusion postoperatively in addition to the institutional standardised pain regimen of hydromorphone patient-controlled analgesia (PCA), acetaminophen and ketorolac (intervention group) or no epidural infusion and only the standardised postoperative pain regimen (control group). The primary outcome was the postoperative opioid consumption, measured in morphine or morphine-equivalents. Secondary outcomes include patient-reported postoperative pain numerical rating scores, trend and relative ratios of serum inflammatory markers (interleukin (IL)-1β, IL-6, tumour necrosis factor-α, IL-10), occurrence of postoperative delirium, development of PPSP as determined by quantitative sensory testing, and disease-free and overall survival. Ethics and dissemination The E-PRO trial has been approved by the institutional review board. Recruitment began

Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2.

PubMed

Zhai, Mei-Li; Chen, Yi; Liu, Chong; Wang, Jian-Bo; Yu, Yong-Hao

2018-05-23

Opioid use has been limited in the treatment of chronic pain due to their side effects, including analgesic tolerance. Previous studies demonstrated that glucocorticoid receptors (GRs) may be involved in the development of chronic morphine tolerance; however, the mechanism remains unknown. It was hypothesized that the expression of spinal phosphorylated mitogen‑activated protein kinase [MAPK; phosphorylated extracellular signal‑regulated kinase (ERK)] is regulated through the spinal GRs, following chronic treatment with morphine. In the first experiment, the experimental rats were randomly divided into four groups: Control, morphine, morphine+GR antagonist mifepristone (RU38486) and morphine+GR agonist dexamethasone (Dex). Each group was treated with continuous intrathecal (IT) injection of the drugs for 6 days. The expression of GRs and MAPK 3/1 (p‑ERK 1/2) in the spinal dorsal horn was detected by western blot analysis and immunofluorescence staining. In the second experiment, the MAPK inhibitor PD98059 was added and the rats were randomly divided into four groups: Control, morphine, PD98059+morphine and PD98059+morphine+Dex. The continuous IT injection lasted for 7 days in each group. For all experiments, the tail flick test was conducted 30 min following administration every day to assess the thermal hyperalgesia of the rats. The experimental results demonstrated that there was a co‑existence of GRs and p‑ERK 1/2 in the spinal cord dorsal horn by double immunofluorescence staining. The GR antagonist RU38486 attenuated the morphine analgesia tolerance by inhibiting the expression of GR and increasing the expression of p‑ERK. The MAPK inhibitor PD98059 increased the effect of morphine tolerance and prolonged the duration of morphine tolerance. The present results suggest that spinal GRs may serve an important role in the development of morphine tolerance through the ERK signaling pathway.

Efficacy and Safety of Morphine and Low Dose Ketamine for Pain Control of Patients with Long Bone Fractures: A Randomized, Double-Blind, Clinical Trial

PubMed Central

Jahanian, Fatemeh; Hosseininejad, Seyed Mohammad; Amini Ahidashti, Hamed; Bozorgi, Farzad; Goli Khatir, Iraj; Montazar, Seyyed Hosein; Azarfar, Vahideh

2018-01-01

Objective: To compare the effects of intravenous morphine and a low dose of ketamine on pain intensity of patients with traumatic fractures of the long bones. Methods: This randomized, controlled, double-blinded, clinical trial was conducted in the adult emergency department (ED) of Emam Khomeini hospital, a tertiary general hospital affiliated with Mazandaran University of Medical Sciences, in Northern Iran, during a 6-month period. Patients were randomly assigned to receive intravenous morphine (0.1 mg/kg) or low dose ketamine (0.5 mg/kg) for control of the pain in the emergency room. The pain intensity was checked by a nurse using the visual analogue scale (VAS) at 30, 60, 90, 120, 180 and 240, minutes after the intervention. Results: Overall we included a total number of 156 patients with mean age of 35.87±3.38 years. There were 111 (71.2%) men and 4 (28.8%) women among the patients. Patients were randomly assigned to receive intravenous morphine (n=78) or low dose ketamine (n=78). The pain intensity decreased significantly in both study groups after 240 minutes of intervention. However, there was no significant difference between the two study groups regarding the pain intensity at 30 (p=0.378), 60 (p=0.927), 90 (p=0.434), 120 (p=0.557), 180 (p=0.991) and 240 (p=0.829) minutes. The side effects were comparable while low dose ketamine was associated with higher need for rescue analgesic (p=0.036).    Conclusion: The results of the current study demonstrates that the intravenous low dose ketamine leads to successful pain control in patients with long bone fractures and the effects are comparable with intravenous morphine. PMID:29379807

Analgesia after total knee replacement: local infiltration versus epidural combined with a femoral nerve blockade: a prospective, randomised pragmatic trial.

PubMed

Yadeau, J T; Goytizolo, E A; Padgett, D E; Liu, S S; Mayman, D J; Ranawat, A S; Rade, M C; Westrich, G H

2013-05-01

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR.

Analgesia after total knee replacement: local infiltration versus epidural combined with a femoral nerve blockade. A prospective, randomised pragmatic trial

PubMed Central

Goytizolo, Enrique A.; Padgett, Douglas E.; Liu, Spencer S.; Mayman, David J.; Ranawat, Amar S.; Rade, Matthew C.; Westrich, Geoffrey H.

2014-01-01

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine, and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR. PMID:23632672

Inhibition of Morphine Tolerance and Dependence by the NMDA Receptor Antagonist MK-801

NASA Astrophysics Data System (ADS)

Trujillo, Keith A.; Akil, Huda

1991-01-01

The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.

I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia.

PubMed

Hwang, J-Y; Na, H-S; Jeon, Y-T; Ro, Y-J; Kim, C-S; Do, S-H

2010-01-01

In a randomized, double-blind, prospective study, we have evaluated the effect of i.v. infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements. Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included. After the induction of spinal anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) for 15 min and then 15 mg kg(-1) h(-1) by continuous i.v. infusion until the end of surgery. The saline group (Group S) received the same volume of isotonic saline over the same period. After surgery, a patient-controlled analgesia (PCA) device containing morphine and ketorolac was provided for the patients. Postoperative pain scores, PCA consumption, and the incidences of shivering, postoperative nausea, and vomiting were evaluated immediately after surgery, and at 30 min, 4, 24, and 48 h after surgery. Serum magnesium concentrations were checked before the induction of anaesthesia, immediately after surgery, and at 1 and 24 h after surgery. Postoperative pain scores were significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Postoperative magnesium concentrations were higher in Group M (P<0.05 at 4, 24, and 48 h after surgery), but no side-effects associated with hypermagnesemia were observed. Haemodynamic variables and the incidences of shivering, nausea, and vomiting were similar in the two groups. I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia.

Delay discounting of oral morphine and sweetened juice rewards in dependent and non-dependent rats.

PubMed

Harvey-Lewis, Colin; Perdrizet, Johnna; Franklin, Keith B J

2014-07-01

Opioid-dependent humans are reported to show accelerated delay discounting of opioid rewards when compared to monetary rewards. It has been suggested that this may reflect a difference in discounting of consumable and non-consumable goods not specific to dependent individuals. Here, we evaluate the discounting of similar morphine and non-morphine oral rewards in dependent and non-dependent rats We first tested the analgesic and rewarding effects of our morphine solution. In a second experiment, we assigned rats randomly to either dependent or non-dependent groups that, 30 min after daily testing, received 30 mg/kg subcutaneous dose of morphine, or saline, respectively. Delay discounting of drug-free reward was examined prior to initiation of the dosing regimen. We tested discounting of the morphine reward in half the rats and retested the discounting of the drug-free reward in the other half. All tests were run 22.5 h after the daily maintenance dose. Rats preferred the morphine cocktail to the drug-free solution and consumed enough to induce significant analgesia. The control quinine solution did not produce these effects. Dependent rats discounted morphine rewards more rapidly than before dependence and when compared to discounting drug-free rewards. In non-dependent rats both reward types were discounted similarly. These results show that morphine dependence increases impulsiveness specifically towards a drug reward while morphine experience without dependence does not.

Paramedic attitudes regarding prehospital analgesia.

PubMed

Walsh, Brooks; Cone, David C; Meyer, Emily M; Larkin, Gregory L

2013-01-01

Although pain is a major reason why patients summon emergency medical services (EMS), prehospital medical providers administer analgesic agents at inappropriately low rates. One possible reason is the role of EMS provider attitudes. This study was conducted to elicit attitudes that may act as impediments or deterrents to administering analgesia in the prehospital environment. A qualitative methodology was employed. We recruited experienced paramedics, with at least one year of full-time fieldwork, from a variety of agencies in New England. We sought to include a balance of rural and urban as well as both private and hospital-based agencies. Participants at each site were selected through purposive sampling. A semistructured discussion guide was designed to elicit the paramedics' past experiences with administering analgesia, as well as reflections on their role in the care of patients in pain. Both interviews and focus groups were conducted. These sessions were recorded and transcribed verbatim. The transcripts were topic-analyzed and iteratively coded by two independent investigators utilizing the constant comparative method of Glaser and Strauss' Grounded Theory; coding ambiguities were resolved by consensus. Through a series of conceptual mapping and iterative code refinement, themes and domains were generated. Fifteen paramedics from five EMS agencies in three New England states were recruited. Major themes were: 1) a reluctance to administer opioids to patients without significant objective signs (e.g., deformity, hypertension); 2) a preoccupation with potential malingering; 3) ambivalence about the degree of pain control to target or to expect (e.g., aiming to "take the edge off"); 4) a fear of masking diagnostic symptoms; and 5) an aversion to aggressive dosing of opioids (e.g., initial doses of morphine did not exceed 5 mg). A number of potentially modifiable attitudinal barriers to appropriate pain management were revealed.

A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain.

PubMed

Nelson, K A; Glare, P A; Walsh, D; Groh, E S

1997-05-01

withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

Comparison of Intravenous Morphine Versus Paracetamol in Sciatica: A Randomized Placebo Controlled Trial.

PubMed

Serinken, Mustafa; Eken, Cenker; Gungor, Faruk; Emet, Mucahit; Al, Behcet

2016-06-01

The objective was to compare intravenous morphine and intravenous acetaminophen (paracetamol) for pain treatment in patients presenting to the emergency department with sciatica. Patients, between the ages of 21 and 65 years, suffering from pain in the sciatic nerve distribution and a positive straight leg-raise test composed the study population. Study patients were assigned to one of three intravenous interventions: morphine (0.1 mg/kg), acetaminophen (1 g), or placebo. Physicians, nurses, and patients were blinded to the study drug. Changes in pain intensity were measured at 15 and 30 minutes using a visual analog scale. Rescue drug (fentanyl) use and adverse effects were also recorded. Three-hundred patients were randomized. The median change in pain intensity between treatment arms at 30 minutes were as follows: morphine versus acetaminophen 25 mm (95% confidence interval [CI] = 20 to 29 mm), morphine versus placebo 41 mm (95% CI = 37 to 45 mm), and acetaminophen versus placebo 16 mm (95% CI = 12 to 20 mm). Eighty percent of the patients in the placebo group (95% CI = 63.0% to 99%), 18% of the patients in the acetaminophen group (95% CI = 10.7% to 28.5%), and 6% of those in the morphine group (95% CI = 2.0% to 13.2%) required a rescue drug. Adverse effects were similar between the morphine and acetaminophen groups. Morphine and acetaminophen are both effective for treating sciatica at 30 minutes. However, morphine is superior to acetaminophen. © 2016 by the Society for Academic Emergency Medicine.

Comparison of Local Infiltration Analgesia With Femoral Nerve Block for Total Knee Arthroplasty: A Prospective, Randomized Clinical Trial.

PubMed

Fan, Lin; Yu, Xiao; Zan, Pengfei; Liu, Jin; Ji, Tongxiang; Li, Guodong

2016-06-01

Total knee arthroplasty (TKA) is usually associated with severe postoperative pain, which can prevent rehabilitation of patients' knee function and influence the satisfaction of surgery. Local infiltration analgesia (LIA) as a new method to managing postoperative pain has been applied in clinical practice recently. However, the safety and efficacy of LIA compared with femoral nerve block (FNB) in postoperative pain management of TKA still remains controversial. Thus, we conducted an original clinical trial to compare LIA and FNB. One hundred fifty-seven patients undergoing TKA were enrolled in a randomized, double-blind, single-center study. The patients received either FNB (group A) or periarticular infiltration of local anesthetic (group B). The morphine consumption used in patient-controlled analgesia after surgery, postoperative Visual Analogue Scale (VAS), Knee Society Score, and range of motion before and after surgery in both groups were analyzed, as well as the adverse effects. Group A consisted 78 patients, and group B contained 79 patients. The patients' characteristics including age and body mass index had no significant difference (P > .05). Morphine consumption, VAS at rest, range of motion, and Knee Society Score were similar between the 2 groups. Our study showed group B, the local anesthetic group had less VAS with movement on postoperative day 1 (P = .01) than that of group A, which means a better pain control. Because of the study design, the surgery time showed no significant difference. Eighteen patients in group A and 21 patients in group B experienced mild-to-medium nausea or vomiting. One patient in group B had dizziness and one patient in group A suffered a neuropraxic injury to the femoral nerve. No urinary retention case was seen during inpatient days. There were no significant differences between the 2 groups about side effects. Our research showed that no significant differences were observed between the 2 treatment groups. LIA could

The Analgesic Effects of Morphine and Tramadol Added to Intra-articular Levobupivacaine-Tenoxicam Combination for Arthroscopic Knee Surgery on Postoperative Pain; a Randomized Clinical Trial

PubMed Central

Oral, Ebru Gelici; Hanci, Ayse; Ulufer Sivrikaya, Gulcihan; Dobrucali, Hale; Turkoglu Kilinc, Leyla

2015-01-01

Background: Arthroscopic knee surgery is commonly performed as an outpatient procedure and is often associated with postoperative pain. Objectives: We aimed to compare the effects of intra-articular levobupivacaine-tenoxicam-tramadol and levobupivacaine-tenoxicam-morphine combinations on postoperative pain in patients undergoing elective arthroscopic knee surgery. Materials and Methods: A total of 90 ASA I-II patients undergoing elective arthroscopic meniscectomy under general anesthesia were enrolled. The participants were randomly allocated to three groups to receive the following intra-articular medications after completion of the surgery and before deflation of the tourniquet: Group S, 20 mL of saline; Group T, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 100 mg of tramadol in 20 mL saline; and Group M, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 4 mg of morphine in 20 mL saline. Visual analogue scale values at rest (VASr) and at active flexion of knee (VASa) at postoperation hours 1, 2, 4, 8, 12, and 24, duration of analgesia, total analgesic consumption, and number of rescue analgesia at 24 hours were evaluated. Results: VASr and VASa were significantly higher in group S in comparison to other groups (P < 0.05). Duration of analgesia was significantly longer in Group T and Group M than in Group S (P < 0.05). The difference between group T and group M was also significant (P < 0.05). Number of rescue analgesia and total analgesic consumption at postoperative hour 24 was significantly fewer in group M compared with other groups (P < 0.05). Conclusions: Intra-articular levobupivacaine-tenoxicam-morphine combination provides effective pain relief, longer analgesic duration, and less analgesic requirement when compared with intra-articular levobupivacaine-tenoxicam-tramadol combination and saline after knee arthroscopic surgery. PMID:26161321

Comparison of 2 Analgesia Modalities in Total Knee Replacement Surgery: Is There an Effect on Knee Function Rehabilitation?

PubMed

Zinkus, Janis; Mockutė, Lina; Gelmanas, Arūnas; Tamošiūnas, Ramūnas; Vertelis, Arūnas; Macas, Andrius

2017-06-20

BACKGROUND We compared the effects of continuous femoral nerve block (CFNB) and continuous intraarticular block (CIAB) on pain, functional recovery and adverse effects after total knee arthroplasty (TKA). MATERIAL AND METHODS We prospectively randomized 54 patients undergoing TKA into 2 groups: CFNB (Group F) and CIAB (Group I). Surgery was performed under spinal anesthesia. All patients received patient-controlled analgesia (PCA) with morphine, diclofenac, and acetaminophen for the first 72 h postoperatively. Pain was assessed with a visual analog scale (VAS), 48-h morphine consumption and 72-h local anesthetic dosage were recorded, motor blockade was assessed, maximum range of motion (ROM) was measured, and adverse effect profiles were recorded. RESULTS There was no significant difference in postoperative pain at rest, in passive motion, active motion, or active movement (2-min walk test (2MWT)) between study groups. Group I had less opioid usage in the first 24 h postoperatively (p<0.05). No significant difference was found between the groups in the postoperative local anesthetic dosage (p>0.05). Significantly lower scores of Bromage scale in Group I in 72 h after surgery (p<0.05) were found. Group I had superior passive maximum ROM in 1 month after surgery and superior active maximum ROM on day 7 and at 1 month after surgery (p<0.05). CONCLUSIONS Both CFNB and CIAB are effective postoperative analgesia methods after TKA. CIAB leads to lower postoperative opioid usage in the first 24 h, lower motor blockade in the first 72 h, and better knee function on day 7 and at 1 month after surgery.

Ultrasound-guided continuous interscalene block: the influence of local anesthetic background delivery method on postoperative analgesia after shoulder surgery: a randomized trial.

PubMed

Hamdani, Mehdi; Chassot, Olivier; Fournier, Roxane

2014-01-01

Automated bolus delivery has recently been shown to reduce local anesthetic consumption and improve analgesia, compared with continuous infusion, in continuous sciatic and epidural block. However, there are few data on the influence of local anesthetic delivery method on local anesthetic consumption following interscalene blockade. This randomized, double-blind trial was designed to determine whether hourly automated perineural boluses (4 mL) of local anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses would result in a reduction in total local anesthesia consumption during continuous interscalene blockade after shoulder surgery compared with continuous perineural infusion (4 mL/h) plus patient-controlled PRN boluses. One hundred one patients undergoing major shoulder surgery under general anesthesia with ultrasound-guided continuous interscalene block were randomly assigned to receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse events were recorded. There were no significant differences in either the number of PRN ropivacaine boluses or total 48 hour local anesthetic consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group). Postoperative pain was similar in both groups; on day 2, the median average pain score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the automated bolus group (P = 0.54). Nor were any statistically significant intergroup differences observed with respect to morphine rescue, incidence of adverse events, or patient satisfaction. In continuous interscalene blockade under

Opioid Patient Controlled Analgesia (PCA) use during the Initial Experience with the IMPROVE PCA Trial: A Phase III Analgesic Trial for Hospitalized Sickle Cell Patients with Painful Episodes

PubMed Central

Dampier, Carlton D.; Smith, Wally R.; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C.; Minniti, Caterina P.; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A. Kyle; McClish, Donna; McKinlay, Sonja M.; Miller, Scott T.; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J.; Weiner, Debra L.

2015-01-01

Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents, mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI and in the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI 0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage. PMID:21953763

Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial.

PubMed

Beaudoin, Francesca L; Lin, Charlie; Guan, Wentao; Merchant, Roland C

2014-11-01

Low-dose ketamine has been used perioperatively for pain control and may be a useful adjunct to intravenous (IV) opioids in the control of acute pain in the emergency department (ED). The aim of this study was to determine the effectiveness of low-dose ketamine as an adjunct to morphine versus standard care with morphine alone for the treatment of acute moderate to severe pain among ED patients. A double-blind, randomized, placebo-controlled trial with three study groups was conducted at a large, urban academic ED over a 10-month period. Eligible patients were 18 to 65 years old with acute moderate to severe pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and pain duration < 7 days) who were deemed by their treating physician to require IV opioids. The three study groups were: 1) morphine and normal saline placebo (standard care group), 2) morphine and 0.15 mg/kg ketamine (group 1), or 3) morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60, and 120 minutes after study medication administration and received rescue analgesia as needed to target a 50% reduction in pain. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the NRS and calculated as the summed pain-intensity (SPID) difference over 2 hours. The amount and timing of rescue opioid analgesia was evaluated as a secondary outcome. The occurrence of adverse events was also measured. Sixty patients were enrolled (n = 20 in each group). There were no differences between study groups with respect to age, sex, race/ethnicity, preenrollment analgesia, or baseline NRS. Over the 2-hour poststudy medication administration period, the SPIDs were higher (greater pain relief) for the ketamine study groups than the control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1 7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p < 0.02). The SPIDs for the ketamine groups were similar (p < 0.46). When

Effect of gabapentin on morphine consumption and pain after surgical debridement of burn wounds: a double-blind randomized clinical trial study.

PubMed

Rimaz, Siamak; Alavi, Cyrus Emir; Sedighinejad, Abbas; Tolouie, Mohammad; Kavoosi, Sharareh; Koochakinejad, Leila

2012-01-01

Burn pain is recognized as being maximal during therapeutic procedures, and wound debridement can be more painful than the burn injury itself. Uncontrolled acute burn pain increases the stress response and the incidence of chronic pain and associated depression. Although opiates are excellent analgesics, they do not effectively prevent central sensitization to pain. The anticonvulsant gabapentin has been proven effective for treating neuropathic pain in large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models with central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of this study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in burn patients undergoing resection of burn wounds. In a randomized, double-blind, placebo-controlled study, 50 burn patients received a single oral dose of gabapentin (1200mg) or placebo 2h before surgery. Anesthesia was induced with propofol and fentanyl and maintained by infusingpropofol, remifentanil, and 50% N2O in O2. All patients received patient-controlled analgesia with morphine at doses of 2.5 mg bolus and a lock-out time of 10 min for 24h before the operation. Pain was assessed on a visual analog scale (VAS) at rest and during movement at 1,4,8,12,16,20, and 24 h before the operation. Heart rate, oxygen saturation, mean arterial blood pressure, respiratory rate, sedation score, and morphine consumption were studied. All the enrolled patients were able to complete the study; therefore, data from 50 patients wereanalyzed. The VAS scores at rest andduring movement at 1,4,8,12,16,20, and 24 h after the operation were significantly lower in the gabapentin group than in the placebo group (P < 0.05). Morphine consumption was significantly lessr in the gabapentin group than in the placebo group (P < 0.05). Sedation scores were

Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system

PubMed Central

Aricioglu, Feyza; Means, Andrea; Regunathan, Soundar

2010-01-01

Agmatine is an endogenous amine derived from arginine that potentiates morphine analgesia and blocks symptoms of naloxone-precipitated morphine withdrawal in rats. In this study, we sought to determine whether treatment with agmatine during the development of morphine dependence inhibits the withdrawal symptoms and that the effect is mediated by cAMP system. Exposure of rats to morphine for 7 days resulted in marked naloxone-induced withdrawal symptoms and agmatine treatment along with morphine significantly decreasing the withdrawal symptoms. The levels of cAMP were markedly increased in morphine-treated rat brain slices when incubated with naloxone and this increase was significantly reduced in rats treated with morphine and agmatine. The induction of tyrosine hydroxylase after morphine exposure was also reduced in locus coeruleus when agmatine was administered along with morphine. We conclude that agmatine reduces the development of dependence to morphine and that this effect is probably mediated by the inhibition of cAMP signaling pathway during chronic morphine exposure. PMID:15541421

Comparing adductor canal block with local infiltration analgesia in total knee arthroplasty: A prospective, blinded and randomized clinical trial.

PubMed

Tong, Qian Jun; Lim, Yean Chin; Tham, Huae Min

2018-05-01

Total knee arthroplasty (TKA) is associated with significant pain post-operatively. Our hypothesis is that adductor canal block (ACB) would be superior to local infiltration analgesia (LIA) in terms of providing analgesia, while still preserving quadriceps strength and enabling early postoperative rehabilitation. A prospective, blinded and randomized clinical trial between LIA and ACB was conducted. Tertiary care urban hospital. 40 patients (ASA I to III) undergoing primary TKA under single-dose spinal anesthesia were prospectively randomized from January 2014 to October 2015. The LIA group received local infiltration of Ropivacaine 150 mg, Ketorolac 30 mg, Morphine 10 mg, and Adrenaline 200 mcg in a total volume of 75 mls, administered intraoperatively by the surgeon. The ACB group was given an ACB postoperatively by one of the study investigators at the end of surgery with 30 mls of 0.5% Ropivacaine. The primary outcome was total Morphine consumption in the first 24 h. Secondary outcomes included total Morphine consumption in the first 48 h, pain scores, quadriceps strength, the Timed Up and Go test (TUG), the 30 s Chair Stand Test (30s-CST) and length of hospital stay. The median (interquartile range) 24 h Morphine consumption was 6 mg (2.3-18.3) in the ACB group and 17.5 mg (12-24.3) in the LIA group, p = 0.004. The 48 h Morphine consumption was 14.5 mg (7.5-28.5) in the ACB group as compared to 24 mg (14-33.8) in the LIA group, p = 0.03. There were no statistically significant differences in the other secondary outcomes. ACB group had statistically significant reduced total Morphine consumption in the first 24 and 48 hours as compared to LIA group, with no statistically significant differences in functional outcomes of TKA patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of opioid-mediated analgesia in Phase III studies of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain

PubMed Central

Webster, Lynn R; Brenner, Darren M; Barrett, Andrew C; Paterson, Craig; Bortey, Enoch; Forbes, William P

2015-01-01

Background Subcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC) but may theoretically disrupt opioid-mediated analgesia. Methods Opioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores) were reported in a randomized, double-blind trial with an open-label extension (RCT) and an open-label trial (OLT) evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methyl naltrexone 12 mg once daily (n=150), every other day (n=148), or placebo (n=162) for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364) for 8 weeks. In the OLT, patients (n=1,034) on stable opioid doses with OIC received methylnaltrexone 12 mg prn for up to 48 weeks. Results Minimal fluctuations of median morphine equivalent dose from baseline (BL) were observed in the RCT double-blind period (BL, 154.8–161.0 mg/d; range, 137.1–168.0 mg/d), RCT open-label period (BL, 156.3–174.6; range, 144.0–180.0) and OLT (BL, 120 mg/d; range, 117.3–121.1 mg/d). No significant change from BL in pain intensity score occurred in any group at weeks 2 or 4 (both P≥0.1) of the RCT double-blind period, and scores remained stable during the open-label period and in the OLT (mean change, −0.2 to 0.1). Changes from BL in OOWS and SOWS scores during the double-blind period were not significantly impacted by methylnaltrexone exposure at weeks 2 or 4 (P>0.05 for all). Conclusion Methylnaltrexone did not affect opioid-mediated analgesia in patients with chronic noncancer pain and OIC. PMID:26586963

Melanocortin-1 receptor gene variants affect pain and µ-opioid analgesia in mice and humans

PubMed Central

Mogil, J; Ritchie, J; Smith, S; Strasburg, K; Kaplan, L; Wallace, M; Romberg, R; Bijl, H; Sarton, E; Fillingim, R; Dahan, A

2005-01-01

Background: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on κ-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant µ-opioid receptor. Objective: To characterise sensitivity to pain and µ-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. Methods: Comparisons of spontaneous mutant C57BL/6-Mc1re/e mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants. Results: C57BL/6-Mc1re/e mutant mice and human redheads—both with non-functional MC1Rs—display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the µ-opioid selective morphine metabolite, M6G. In both species the differential analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are similar across genotype. Conclusions: Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics. PMID:15994880

Polymorphism of μ-Opioid Receptor Gene (OPRM1:c.118A>G) Might Not Protect against or Enhance Morphine-Induced Nausea or Vomiting

PubMed Central

Chen, Li-Kuei; Chen, Shiou-Sheng; Huang, Chi-Hsiang; Yang, Hong-Jyh; Lin, Chen-Jung; Chien, Kuo-Liong; Fan, Shou-Zen

2013-01-01

A cohort, double blind, and randomized study was conducted to investigate the effect of a single nucleotide polymorphism of the μ-opioid receptor at nucleotide position 118 (OPRM1:c.118A>G) on the association with the most common side effects (nausea or vomiting) induced by intravenous patient control analgesia (IVPCA) with morphine, including incidence and severity analysis. A total of 129 Taiwanese women undergoing gynecology surgery received IVPCA with pure morphine for postoperative pain relief. Blood samples were collected and sequenced with high resolution melting analysis to detect three different genotypes of OPRM1 (AA, AG, and GG). All candidates 24 h postoperatively will be interviewed to record the clinical phenotype with subjective complaints and objective observations. The genotyping after laboratory analysis showed that 56 women (43.4%) were AA, 57 (44.2%) were AG, and 16 (12.4%) were GG. The distribution of genotype did not violate Hardy-Weinberg equilibrium test. There was no significant difference neither between the severity and incidence of IVPCA morphine-induced side effects and genotype nor between the association between morphine consumption versus genotype. However, there was significant difference of the relation between morphine consumption and the severity and incidence of IVPCA morphine-induced nausea and vomiting. The genetic analysis for the severity and incidence of IVPCA morphine-induced nausea or vomiting showed no association between phenotype and genotype. It might imply that OPRM1:c.118A>G does not protect against IVPCA morphine-induced nausea or vomiting. PMID:23431434

Epidural Dexamethasone for Postoperative Analgesia in Patients Undergoing Unilateral Inguinal Herniorrhaphy: A Comparative Study

PubMed Central

Razavizadeh, M. R.; Heydarian, N.; Atoof, F.

2017-01-01

Background. This study was designed to evaluate the effect of adding dexamethasone to epidural bupivacaine on postoperative analgesia in unilateral inguinal herniorrhaphy. Methods. Forty-four patients were enrolled in this double-blind, clinical trial study. Patients were randomly allocated into dexamethasone or control group. In the dexamethasone group, patients received 18 ml of bupivacaine 0.5% and 2 ml (8 mg) of dexamethasone; in the control group, patients received 18 ml of bupivacaine 0.5% and 2 ml of normal saline. The onset of sensory block and its duration and incidence of nausea and vomiting were recorded. Results. The onset of epidural anesthesia was significantly more rapid in the dexamethasone group than in the control group (P < 0.001). Duration of analgesia was markedly prolonged in the dexamethasone group than in the control group (P < 0.001). Five patients (22.7%) in the control group had nausea in the first hour after the procedure (P = 0.048). None of the patients in the dexamethasone group had nausea. None of our patients had vomiting in the two groups. Conclusions. This study showed that adding dexamethasone to bupivacaine significantly prolongs the duration of postoperative analgesia. This trial is registered with Iranian Registry of Clinical Trials (IRCT) number IRCT2012062910137N1. PMID:28348504

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents.

PubMed

Burma, Nicole E; Bonin, Robert P; Leduc-Pessah, Heather; Baimel, Corey; Cairncross, Zoe F; Mousseau, Michael; Shankara, Jhenkruthi Vijaya; Stemkowski, Patrick L; Baimoukhametova, Dinara; Bains, Jaideep S; Antle, Michael C; Zamponi, Gerald W; Cahill, Catherine M; Borgland, Stephanie L; De Koninck, Yves; Trang, Tuan

2017-03-01

Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. We show that withdrawal from morphine induces long-term synaptic facilitation in lamina I and II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia. Genetic ablation of Panx1 in microglia abolished the spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal. Panx1 is unique in its permeability to molecules up to 1 kDa in size and its release of ATP. We show that Panx1 activation drives ATP release from microglia during morphine withdrawal and that degrading endogenous spinal ATP by administering apyrase produces a reduction in withdrawal behaviors. Conversely, we found that pharmacological inhibition of ATP breakdown exacerbates withdrawal. Treatment with a Panx1-blocking peptide ( 10 panx) or the clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid, suppressed ATP release and reduced withdrawal severity. Our results demonstrate that Panx1-mediated ATP release from microglia is required for morphine withdrawal in rodents and that blocking Panx1 alleviates the severity of withdrawal without affecting opiate analgesia.

Quadratus Lumborum Block Versus Transversus Abdominis Plane Block for Postoperative Pain After Cesarean Delivery: A Randomized Controlled Trial.

PubMed

Blanco, Rafael; Ansari, Tarek; Riad, Waleed; Shetty, Nanda

Effective postoperative analgesia after cesarean delivery enhances early recovery, ambulation, and breastfeeding. In a previous study, we established the effectiveness of the quadratus lumborum block in providing pain relief after cesarean delivery compared with patient-controlled analgesia (morphine). In the current study, we hypothesized that this method would be equal to or better than the transversus abdominis plane block with regard to pain relief and its duration of action after cesarean delivery. Between April 2015 and August 2015, we randomized 76 patients scheduled for elective cesarean delivery under spinal anesthesia to receive the quadratus lumborum block or the transversus abdominis plane block for postoperative pain relief. This trial was registered prospectively (NCT 02489851) [corrected]. Patients in the quadratus lumborum block group used significantly less morphine than the transversus abdominis plane block group (P < 0.05) at 12, 24, and 48 hours but not at 4 and 6 hours after cesarean delivery. This group also had significantly fewer morphine demands than the control group (P < 0.05) at 6, 12, 24, and 48 hours after cesarean delivery. No significant differences in visual analog scale results were shown between the 2 groups at rest or with movement. Calculated total pain relief at rest and with movement were similar (P < 0.001) in both groups. The quadratus lumborum block was more effective in reducing morphine consumption and demands than transversus abdominis plane blocks after cesarean section. This effect was observed up to 48 hours postoperatively.

Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial.

PubMed

Kubica, Jacek; Adamski, Piotr; Ostrowska, Małgorzata; Sikora, Joanna; Kubica, Julia Maria; Sroka, Wiktor Dariusz; Stankowska, Katarzyna; Buszko, Katarzyna; Navarese, Eliano Pio; Jilma, Bernd; Siller-Matula, Jolanta Maria; Marszałł, Michał Piotr; Rość, Danuta; Koziński, Marek

2016-01-14

The currently available data indicate a drug-drug interaction between morphine and oral P2Y12 receptor inhibitors, when administered together. The aim of this trial was to assess the influence of infused morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with acute myocardial infarction. In a single-centre, randomized, double-blind trial, patients were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry and ticagrelor antiplatelet effects were measured with up to three different platelet function tests: vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry and VerifyNow. The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine lowered the total exposure to ticagrelor and its active metabolite by 36% (AUC(0-12): 6307 vs. 9791 ng h/mL; P = 0.003), and 37% (AUC(0-12): 1503 vs. 2388 ng h/mL; P = 0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; P = 0.004). Multiple regression analysis showed that lower AUC(0-12) values for ticagrelor were independently associated with the administration of morphine (P = 0.004) and the presence of ST-segment elevation myocardial infarction (P = 0.014). All three methods of platelet reactivity assessment showed a stronger antiplatelet effect in the placebo group and a greater prevalence of high platelet reactivity in patients receiving morphine. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction. ClinicalTrials.gov Identifier: NCT02217878. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study.

PubMed

Verberkt, C A; van den Beuken-van Everdingen, M H J; Franssen, F M E; Dirksen, C D; Schols, J M G A; Wouters, E F M; Janssen, D J A

2016-03-01

Dyspnea is one of the most reported symptoms of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is often undertreated. Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain. This study primarily evaluates the impact of oral sustained release morphine (morphine SR) on health-related quality of life and respiratory adverse effects in patients with COPD. Secondary objectives include the impact on exercise capacity, the relationship between description and severity of dyspnea and the presence of a clinically relevant response to morphine, and cost-effectiveness. A single-center, randomized, double blind, placebo controlled intervention study will be performed in 124 patients with COPD who recently completed a comprehensive pulmonary rehabilitation program. Participants will receive 20-30 mg/24h morphine SR or placebo for four weeks. After the intervention, participants will be followed for twelve weeks. Outcomes include: the COPD Assessment Test, six minute walking test, Multidimensional Dyspnea Scale and a cost diary. Furthermore, lung function and arterial blood gasses will be measured. These measures will be assessed during a baseline and outcome assessment, two home visits, two phone calls, and three follow-up assessments. The intervention and control group will be compared using uni- and multivariate regression analysis and logistic regression analysis. Finally, an economic evaluation will be performed from a societal and healthcare perspective. The current manuscript describes the rationale and methods of this study and provides an outline of the possible strengths, weaknesses and clinical consequences. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrating Patient-Controlled Analgesia Using Implanted Intrathecal Pumps for Postoperative Pain Management: A Case Report.

PubMed

Peniche, Alec; Poree, Lawrence; Schumacher, Mark; Yu, Xiaobing

2018-06-01

Intrathecal patient-controlled analgesia (IT-PCA) through implanted intrathecal infusion pumps has been increasingly utilized for severe cancer and chronic noncancer pain management. However, its application for acute postoperative pain management has not been reported to date. We present a case of a patient with an implanted intrathecal pump for chronic nonmalignant back pain who underwent an extensive spinal fusion surgery. The IT-PCA functionality of her intrathecal pump was successfully integrated into her postoperative multimodal pain regimen. Hence, IT-PCA can be safely incorporated into acute postoperative pain management with vigilant monitoring and close multidisciplinary collaboration.

Effects of Patient-Controlled Epidural Analgesia on Uterine Electromyography During Spontaneous Onset of Labor in Term Nulliparous Women.

PubMed

Ye, Yuanjuan; Song, Xingrong; Liu, Lei; Shi, Shao-Qing; Garfield, Robert E; Zhang, Guozheng; Liu, Huishu

2015-11-01

To investigate the effect of patient-controlled epidural analgesia (PCEA) on uterine electromyography (EMG) activity in term pregnant women during labor. Nulliparous pregnant women in spontaneous term labor (N = 30) were enrolled (PCEA group, n = 20 and control group, n = 10). Five time periods (30 minutes each) were defined for noninvasive abdominal recordings and analysis of uterine EMG activity, that is, period I: before PCEA treatment with 2-cm cervical dilation; periods II to IV: each period successively at 30, 60, and 120 minutes after PCEA; and period V: second stage of labor with cervix at 10 cm dilation. Control patients without PCEA were monitored during the same times. The number of bursts/30 min, power density spectrum peak frequency, mean amplitude, and duration of uterine EMG bursts were measured to assess uterine EMG activity. Maternal, fetal, and labor characteristics were also recorded. Data were analyzed by analysis of variance followed by other tests. Electromyography parameters are significantly lower (P < .001) after PCEA (periods II to IV) compared to controls but similar between groups by period V (P > .05). Also, patients with PCEA have a slower rate of cervical dilation (P < .003, period IV only) and longer labor in both stage 1 and stage 2 (P < .05). All patients have similar (P > .05) positive labor outcomes. Patient-controlled epidural analgesia initially suppresses uterine EMG and slows cervical dilation thereby prolonging labor. However, the EMG activity recovers with labor progress with no effects on delivery outcomes. © The Author(s) 2015.

Multimodal infiltration of local anaesthetic in total knee arthroplasty; is posterior capsular infiltration worth the risk? a prospective, double-blind, randomised controlled trial.

PubMed

Pinsornsak, P; Nangnual, S; Boontanapibul, K

2017-04-01

Multimodal infiltration of local anaesthetic provides effective control of pain in patients undergoing total knee arthroplasty (TKA). There is little information about the added benefits of posterior capsular infiltration (PCI) using different combinations of local anaesthetic agents. Our aim was to investigate the effectiveness of the control of pain using multimodal infiltration with and without infiltration of the posterior capsule of the knee. In a double-blind, randomised controlled trial of patients scheduled for unilateral primary TKA, 86 were assigned to be treated with multimodal infiltration with (Group I) or without (Group II) PCI. Routine associated analgesia included the use of bupivacaine, morphine, ketorolac and epinephrine. All patients had spinal anaesthesia and patient-controlled analgesia (PCA) post-operatively. A visual analogue scale (VAS) for pain and the use of morphine were recorded 24 hours post-operatively. Side effects of the infiltration, blood loss, and length of stay in hospital were recorded. There were no statistically significant differences between the groups in relation to: VAS pain scores in the first 24 hours post-operatively (p = 0.693), the use of morphine in the PCA (p = 0.647), blood loss (p = 0.625), and length of stay (p = 0.17). There were no neurovascular complications in either group. The multimodal infiltration of local anaesthetic with infiltration of the posterior capsule did not provide significant added analgesic benefits or reduce the use of morphine after TKA. Multimodal infiltration is a satisfactory technique for the management of pain in these patients without the attendant risks of PCI. Cite this article: Bone Joint J 2017; 99-B:483-8. ©2017 The British Editorial Society of Bone & Joint Surgery.

The willingness of patients to pay for intravenous patient-controlled analgesia in Korea.

PubMed

Lim, Hyungsun; Lee, Duck-Hyoung; Lee, Jeongwoo; Han, Young Jin; Choe, Huhn; Son, Ji-Seon

2012-06-01

The use of intravenous patient-controlled analgesia (IV-PCA) has been increasing because it has advantages such as improved pain relief, greater patient satisfaction, and fewer postoperative complications. However, current research has not considered the patients' thoughts about IV-PCA's cost-effectiveness. The purpose of this study was to investigate the willingness to pay (WTP) for IV-PCA and the relationship between patients' characteristics and WTP in Korea. We enrolled 400 adult patients who were scheduled for elective surgery. The patient was requested to indicate a series of predefined amounts of money (Korean won; 30,000/50,000/100,000/150,000/200,000/300,000/500,000). We also recorded patient characteristics, such as age, sex, type of surgery, IV-PCA history, education level, the person responsible for medical expenses, type of insurance, net annual income, and residential area. Three days after surgery, we asked about the degree of satisfaction and the WTP for IV-PCA. For IV-PCA, the median WTP was 100,000 won (25-75%; 50,000-200,000 won: US$1 = W1078.04; July 19, 2011) before surgery. All patients' characteristics were not related to preoperative WTP for IV-PCA, whereas the increase in WTP after surgery showed a tendency correlated to higher IV-PCA satisfaction. The median WTP was 100,000 won. The satisfaction of IV-PCA increased patients' WTP after surgery, but the WTP may be independent of patient characteristics in Korea.

Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery.

PubMed

Goot, Benjamin H; Kaufman, Jon; Pan, Zhaoxing; Bourne, David W A; Hickey, Francis; Twite, Mark; Galinkin, Jeffrey; Christians, Uwe; Zuk, Jeannie; da Cruz, Eduardo M

2018-05-01

To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome. Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics. A 16-bed cardiac ICU at an university-affiliated hospital. Forty-two patients (20 Down syndrome, 22 controls) were enrolled. None. The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant. This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.

Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study.

PubMed

Arıkan, Müge; Aslan, Bilge; Arıkan, Osman; Horasanlı, Eyüp; But, Abdulkadir

2016-01-01

To compare the effects of magnesium sulfate and ketamine on postoperative pain and total morphine consumption in a placebo-controlled design. One hundred and twenty women scheduled for total abdominal hysterectomy were included in this prospective, randomized, double-blind study. Postoperatively, when the Numeric Pain Rating Scale (NPRS) was four or more, IV-PCA morphine was applied to all patients. The patients were randomized into three groups: Group K ketamine, Group M magnesium, and Group C saline received as infusion. Total morphine consumption for 48h, pain scores, adverse effects, and patients' satisfaction were evaluated. Total morphine consumption was significantly lower in Group K (32.6±9.2 mg) than in Group M (58.9±6.5 mg) and in Group C (65.7±8.2 mg). The satisfaction level of patients in Group K was higher than the other two groups (p<0.05). Pruritus and nausea were observed more frequently in Group C. CONCLUSİON: The addition of ketamine to IV-PCA morphine reduces the total consumption of morphine without psychotic effects; however, magnesium did not influence morphine consumption.

A double-blind, randomized comparative study to investigate the morphine to hydromorphone conversion ratio in Japanese cancer patients

PubMed Central

Inoue, Satoshi; Saito, Yoji; Tsuneto, Satoru; Aruga, Etsuko; Ogata, Takeshi; Uemori, Mitsutoshi

2018-01-01

Abstract Objective To confirm the morphine to hydromorphone conversion ratio for hydromorphone (DS-7113b) immediate-release tablets in cancer patients who achieved pain control with oral morphine. Methods This was a multicenter, active-controlled, randomized, double-blind, parallel-group, comparative study (July 2013 to December 2014) at 39 Japanese sites. Seventy-one patients (aged >20 years) who had achieved pain control with morphine 60 mg/day and 90 mg/day were randomly allocated 1:1 to hydromorphone immediate-release tablets at a dose converted at a hydromorphone:morphine ratio of 1:5 or 1:8, respectively, and treated for up to 5 days. The efficacy was evaluated as the pain control ratio. Results The pain control ratio in the full analysis set was 83.3% (25/30) in the conversion ratio 1:5 group and 95.0% (38/40) in the conversion ratio 1:8 group, and both groups demonstrated highly successful pain control. The incidence of adverse events was 46.7% (14/30) in the conversion ratio 1:5 group and 58.5% (24/41) in the 1:8 group; the difference was not clinically relevant. Frequently observed adverse events (incidence ≥5%) were nausea, vomiting, diarrhea, somnolence and dyspnea. Conclusions A high pain control ratio was maintained by a switch at either conversion ratio, and no notable difference was observed in the incidence of adverse events. A switch from morphine to hydromorphone is effective at a dose converted at ratios of 1:5 and 1:8. PMID:29635632

Effect of intravenous parecoxib on post-craniotomy pain.

PubMed

Williams, D L; Pemberton, E; Leslie, K

2011-09-01

Pain management in craniotomy patients is challenging, with mild-to-moderate pain intensity, moderate-to-high risk of postoperative nausea and vomiting (PONV), and potentially catastrophic consequences of analgesic-related side-effects. The aim of this study was to determine whether i.v. parecoxib administered at dural closure during craniotomy decreased total morphine consumption and morphine-related side-effects compared with placebo. One hundred adult patients presenting for supratentorial craniotomy under propofol/remifentanil anaesthesia were randomized to receive parecoxib, 40 mg i.v., or placebo in a double-blind manner. All patients received local anaesthetic scalp infiltration, regular i.v. paracetamol, nurse-administered morphine in the post-anaesthesia care unit (PACU) until verbal analogue pain scores were ≤4/10 and patient-controlled morphine thereafter. Morphine consumption, pain intensity, and analgesia-related side-effects were recorded during the first 24 h after operation. Ninety-six patients (49 control and 47 parecoxib) were included in the analyses. Fifty-nine (61%) patients received morphine in the PACU and only one patient (control) did not receive any morphine in the postoperative period. There were no significant differences between the two groups in morphine consumption [20 (range: 0-102) vs 16 (range: 1-92) mg; P=0.38], pain intensity [excellent/very good pain relief in 78% of parecoxib patients; 74% of control patients (P=0.72)] or analgesia-related side-effects (PONV in 51% of parecoxib patients; 56% of control patients; P=0.55) in the first 24 h after operation. No major morbidity was recorded. Our study demonstrated no clinical benefit to adding i.v. parecoxib to local anaesthetic scalp infiltration, i.v. paracetamol, and patient-controlled i.v. morphine after supratentorial craniotomy.

Effects of preemptive analgesia with flurbiprofen ester on lymphocytes and natural killer cells in patients undergoing esophagectomy: A randomized controlled pilot study

PubMed Central

Zhou, Yi; Huang, Jinxi; Bai, Yu; Li, Changsheng

2017-01-01

Background Tumors may induce systemic immune dysfunction, which can be aggravated by surgery and anesthesia/analgesia. Data on the effect of flurbiprofen preemptive analgesia on immune dysfunction is limited. The aim of this study was to investigate the effect of flurbiprofen preemptive analgesia on lymphocytes and natural killer (NK) cells in patients undergoing thoracotomy and thoracoscopy radical esophagectomy, and to explore the analgesic methods suitable for tumor patients. Methods This was a randomized controlled pilot study of 89 patients with esophageal cancer treated with surgery at the Henan Cancer Hospital between January 1, 2015 and December 31, 2016. The patients were divided into three groups: group 1, thoracotomy; group 2, thoracoscopy and laparoscopic surgery; and group 3, flurbiprofen, thoracoscopy, and laparoscopic surgery. CD3+, CD19+, NK, CD4+, and CD8+ cells in whole blood were measured by flow cytometry 30 minutes before surgery (T0), at the end of the thoracic section of the procedure (T1), and at the end of the operation (T2). Results There were no significant differences in CD3+, CD19+, CD8+, NK, and CD4+ cells between the three groups or regarding the time points during the procedure (all P > 0.05). Thoracotomy and thoracoscopy surgery resulted in similar immunological outcomes. Conclusion Flurbiprofen ester preemptive analgesia did not suppress the immune function in patients and could be a safe analgesic method for patients with esophageal cancer undergoing surgery. PMID:28892265

Morphine, but not Trauma, Sensitizes to Systemic Acinetobacter baumannii Infection

PubMed Central

Breslow, Jessica M.; Monroy, M. Alexandra; Daly, John M.; Meissler, Joseph J.; Gaughan, John; Adler, Martin W.; Eisenstein, Toby K.

2014-01-01

Acinetobacter baumannii is an important nosocomial pathogen in civilian intensive care units. Recently the incidence has increased in wounded military personnel. Morphine is documented in numerous animal studies to be immunosuppressive and to sensitize to infection. The hypotheses were tested that morphine, administered for analgesia in the battlefield, predisposes to Acinetobacter infection, and that the opioid may have an additive or synergistic effect with trauma. To test these hypotheses, an intraperitoneal infection model was established in mice using several Acinetobacter strains. Morphine administered for 48 hr by implantation of a slow-release morphine pellet increased mortality compared to animals receiving a placebo pellet, an effect that was blocked by the mu-opioid receptor antagonist, naltrexone. Acinetobacter burdens in the blood, spleens, livers, and lungs of morphine-treated mice, were significantly higher than those in placebo-treated animals, confirming that mortality was due to potentiated growth of the bacteria. There were also elevated levels of pro-inflammatory cytokines in morphine-treated versus placebo-treated mice. Morphine caused a reduction in the total number of cells in the peritoneal cavity, a decrease in the percentage and total numbers of neutrophils, and a decrease in the total number of macrophages. Morphine treatment also suppressed levels of the neutrophil-inducing molecules, IL-17A and KC/CXCL1. However, IL-17A−/− mice given morphine were not sensitized to Acintobacter infection to a greater degree than similarly treated wild-type mice. Trauma alone did not sensitize to Acinetobacter infection, and there was no additive effect between morphine and trauma. These results support the hypothesis that morphine potentiates Acinetobacter infection. PMID:21826405

Morphine, but not trauma, sensitizes to systemic Acinetobacter baumannii infection.

PubMed

Breslow, Jessica M; Monroy, M Alexandra; Daly, John M; Meissler, Joseph J; Gaughan, John; Adler, Martin W; Eisenstein, Toby K

2011-12-01

Acinetobacter baumannii is an important nosocomial pathogen in civilian intensive care units. Recently the incidence has increased in wounded military personnel. Morphine is documented in numerous animal studies to be immunosuppressive and to sensitize to infection. The hypotheses were tested that morphine, administered for analgesia in the battlefield, predisposes to Acinetobacter infection, and that the opioid may have an additive or synergistic effect with trauma. To test these hypotheses, an intraperitoneal infection model was established in mice using several Acinetobacter strains. Morphine administered for 48 h by implantation of a slow-release morphine pellet increased mortality compared to animals receiving a placebo pellet, an effect that was blocked by the mu-opioid receptor antagonist, naltrexone. Acinetobacter burdens in the blood, spleens, livers, and lungs of morphine-treated mice, were significantly higher than those in placebo-treated animals, confirming that mortality was due to potentiated growth of the bacteria. There were also elevated levels of pro-inflammatory cytokines in morphine-treated versus placebo-treated mice. Morphine caused a reduction in the total number of cells in the peritoneal cavity, a decrease in the percentage and total numbers of neutrophils, and a decrease in the total number of macrophages. Morphine treatment also suppressed levels of the neutrophil-inducing molecules, IL-17A and KC/CXCL1. However, IL-17A(-/-) mice given morphine were not sensitized to Acintobacter infection to a greater degree than similarly treated wild-type mice. Trauma alone did not sensitize to Acinetobacter infection, and there was no additive effect between morphine and trauma. These results support the hypothesis that morphine potentiates Acinetobacter infection.

Action of Phα1β, a peptide from the venom of the spider Phoneutria nigriventer, on the analgesic and adverse effects caused by morphine in mice.

PubMed

Tonello, Raquel; Rigo, Flávia; Gewehr, Camila; Trevisan, Gabriela; Pereira, Elizete Maria Rita; Gomez, Marcus Vinicius; Ferreira, Juliano

2014-06-01

Opioids are standard therapy for the treatment of pain; however, adverse effects limit their use. Voltage-gated calcium channel blockers may be used to increase opioid analgesia, but their effect on opioid-induced side effects is little known. Thus, the goal of this study was to evaluate the action of the peptide Phα1β, a voltage-gated calcium channel blocker, on the antinociceptive and adverse effects produced by morphine in mice. A single administration of morphine (3-10 mg/kg) was able to reduce heat nociception as well as decrease gastrointestinal transit. The antinociception caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β (30 pmol/site). Repeated treatment with morphine caused tolerance, hyperalgesia, withdrawal syndrome, and constipation, and the Phα1β (.1-30 pmol/site, intrathecal) was able to reverse these effects. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide. Taken together, these data show that Phα1β was effective in potentiating the analgesia caused by a single dose of morphine as well as in reducing tolerance and the adverse effects induced by repeated administration of morphine, indicating its potential use as an adjuvant drug in combination with opioids. This article presents preclinical evidence for a useful adjuvant drug in opioid treatment. Phα1β, a peptide calcium channel blocker, could be used not only to potentiate morphine analgesia but also to reduce the adverse effects caused by repeated administration of morphine. Copyright © 2014. Published by Elsevier Inc.

[Local infiltration analgesia in total joint replacement].

PubMed

de Jonge, Tamás; Görgényi, Szabolcs; Szabó, Gabriella; Torkos, Miklós Bulcsú

2017-03-01

Total hip and knee replacment surgeries are characterized by severe postoperative pain. Local infiltration analgesia is proved to be very effective. However this method has not been widely used in Hungary. To evaluate the efficacy of the local infiltration analgesia with modified components in patients underwent total hip or knee replacement surgery. Data of 99 consecutive patients underwent primary total hip or knee replacement surgery were evaluated prospectively. In all the 99 surgeries modified local infiltration analgesia was applied. Postoperative pain reported on a visual analog scale was recorded as well as the need for further analgetics during the first 18 hours after surgery. The cost of the analgetic drugs was calculated. The control group comprised 97 consecutive patients underwent total hip or knee replacement, where local infiltration analgesia was not applied. Statistical analysis was done. Patients received local infiltration analgesia reported significantly less pain (p<0.001). The need for postoperatively given analgetics was almost 50% less, and the cost of all postoperative analgetics was 47% less than in the control group. In total hip and knee replacement surgeries the modified local infiltration analgesia decreases postoperative pain effectively and contribute to the early mobilization of the patients. Orv. Hetil., 2017, 158(9), 352-357.

Rational use and effectiveness of morphine in the palliative care of cancer patients at the Ocean Road Cancer Institute in Dar es Salaam, Tanzania.

PubMed

Kamuhabwa, A; Ezekiel, D

2009-10-01

Morphine and other opioids is the mainstay of cancer pain management. However, considerable fears surrounding their use present barriers to pain control. The aim of this study was to assess the rational use and effectiveness of morphine for management of pain in the palliative care of cancer patients at Ocean Road Cancer Institute (ORCI) in Tanzania. A total of 100 cancer patients who were receiving morphine therapy at the ORCI were interviewed to get information on morphine use. In addition, information on the prescribed doses of morphine was obtained from medical records of 200 patients who have used morphine from September 2005 to April 2006. Both outpatients and inpatients with advanced cancer who were receiving morphine for palliative care were involved. Seven (7) palliative caregivers, including two doctors, two nurses, a pharmacist, a pharmaceutical technician and a social worker were also interviewed. Of the 100 interviewees, 37% were aware of morphine. The level of education and duration of therapy had an impact on the awareness. The results also showed that oral morphine solution was the most common route (96%) of administration. Fifty-seven percent of the patients described the doses of morphine given to be effective in relieving their pain. Although most patients (79%) experienced morphine-induced side effects, the majority (93%) were continuing with the therapy. There were no indication of irrational use of morphine and morphine-induced side effects were well managed. The majority of patients and caregivers had positive attitude towards the use of morphine. In conclusion, the study revealed that the use of morphine is acceptable among a large proportion of patients receiving palliative care and that the majority of them find the doses given effective to relieve their pain.

Comparing parecoxib and ketorolac as preemptive analgesia in patients undergoing posterior lumbar spinal fusion: a prospective randomized double-blinded placebo-controlled trial.

PubMed

Siribumrungwong, Koopong; Cheewakidakarn, Julin; Tangtrakulwanich, Boonsin; Nimmaanrat, Sasikaan

2015-03-18

Poor postoperative pain control is frequently associated with complications and delayed discharge from a hospital. Preemptive analgesia is one of the methods suggested for reducing postoperative pain. Opioids are effective for pain control, but there known addictive properties make physicians cautious about using them. Parecoxib and ketorolac are potent non-opioid NSAIDs that are attractive alternative drugs to opioids to avoid opioid-related side effects. However, there are no good head-to-head comparisons between these two drugs in the aspect of preemptive analgesic effects in lumbar spinal fusion surgery. This study aimed to compare the efficacy in terms of postoperative pain control and safety of parecoxib with ketorolac as preemptive analgesia in posterior lumbar spinal fusion patients. A prospective, double-blinded randomized controlled trial was carried out in patients undergoing posterior lumbar spinal fusion, who were randomized into 3 groups (n = 32). Parecoxib, ketorolac or a placebo was given to each patient via injection around 30 minutes prior to incision. The efficacy of postoperative pain control was assessed by a verbal numerical rating score (0-10). And various postoperative things were monitored for analysis, such as total opioid consumption, complications, and estimated blood loss. Both the ketorolac and parecoxib groups showed significantly better early postoperative pain reduction at the postanesthesia care unit (PACU) than the control group (p < 0.05). There were no differences between the pain scores of ketorolac and parecoxib at any time points. Complications and bleeding were not significantly different between all three groups. Preemptive analgesia using both ketorolac and parecoxib showed a significantly better early postoperative pain control in the PACU than the control group in patients undergoing lumbar spinal fusion. ClinicalTrials.gov NCT01859585. Registered 15 May 2013.

The pharmacokinetics of morphine and lidocaine in nine severe trauma patients.

PubMed

Berkenstadt, H; Mayan, H; Segal, E; Rotenberg, M; Almog, S; Perel, A; Ezra, D

1999-12-01

To study the pharmacokinetic parameters of morphine and lidocaine after a single intravenous (i.v.) bolus in severe trauma patients. Clinical case study. Department of Anesthesiology and Intensive Care of a university hospital. Nine patients, ages 24 to 91 years (mean 54.4 yrs), admitted to the hospital with severe trauma (Injury Severity Score > 20) were included in the study. After initial evaluation and stabilization, a single i.v. dose of morphine 0.025 mg/kg and lidocaine 1.5 mg/kg was given separately, and blood samples were drawn for each drug serum concentration. Morphine pharmacokinetics was studied in eight patients, lidocaine pharmacokinetics in seven patients, and both drugs were studied in six patients. Morphine clearance 2.5 to 10 ml/kg/min (6 +/- 2.6, mean +/- SD) and volume of distribution 0.28 to 3.30 L/kg (1.4 +/- 1.0) were found to be lower than values described previously for healthy volunteers (33.5 +/- 9 ml/kg/min and 5.16 +/- 1.40 L/kg, respectively), and are similar to those described in trauma patients (5 +/- 2.9 ml/kg/min and 0.9 +/- 0.2 L/kg, respectively). In contrast, lidocaine clearance 4.5 to 9.4 ml/kg/min (6.7 +/- 1.7) and volume of distribution 0.39 to 1.20 L/kg (0.72 +/- 0.28) were similar to the value described in healthy volunteers (10 ml/kg/min and 1.32 L/kg, respectively). Changes in pharmacokinetics of drugs eliminated by the liver may occur in patients with severe trauma. The preserved lidocaine clearance indicates an almost normal hepatic blood flow and suggests that other mechanisms may be involved in the lower morphine clearance. The findings may have applications for the treatment of severe trauma patients and suggest that drug monitoring might be needed in some instances so as to avoid toxicity.

Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial.

PubMed

Nielsen, Rikke Vibeke; Fomsgaard, Jonna Storm; Siegel, Hanna; Martusevicius, Robertas; Nikolajsen, Lone; Dahl, Jørgen Berg; Mathiesen, Ole

2017-03-01

Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0 to 24 hours postoperatively. Secondary outcomes were acute pain at rest and during mobilization 2 to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg·h or placebo. Postoperatively, patients received their usual opioids, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean difference 42 mg (95% confidence interval -59 to -25), P < 0.001. Sedation was significantly reduced in the ketamine group 6 and 24 hours postoperatively. There were no significant differences regarding acute pain, nausea, vomiting, hallucinations, or nightmares. Back pain at 6 months postoperatively compared with preoperative pain was significantly more improved in the ketamine group compared with the placebo group, P = 0.005. In conclusion, intraoperative ketamine significantly reduced morphine consumption 0 to 24 hours after lumbar fusion surgery in opioid-dependent patients. The trend regarding less persistent pain 6 months postoperatively needs further investigation.

Evaluation of the antiemetic efficacy of maropitant in dogs medicated with morphine and acepromazine.

PubMed

Lorenzutti, A Matías; Martín-Flores, Manuel; Litterio, Nicolás J; Himelfarb, Martín A; Zarazaga, M Pilar

2016-03-01

To evaluate whether maropitant (1 mg kg(-1)) injected subcutaneously (SC), administered simultaneously or 30 minutes prior to intramuscular (IM) administration of morphine (0.5 mg kg(-1)) and acepromazine (0.05 mg kg(-1)), reduces the incidence of salivation, retching and emesis in dogs. Randomized, controlled, prospective clinical trial. Sixty dogs scheduled for an ovariohysterectomy as part of a population control program. Dogs were randomly allocated to be administered maropitant (1 mg kg(-1)) SC simultaneously (group M0) or 30 minutes prior to (group M30) administration of morphine (0.5 mg kg(-1)) and acepromazine (0.05 mg kg(-1)) IM. A control group was administered normal saline (C) at T-30 and T0. Dogs were observed for 30 minutes after morphine-acepromazine administration. The occurrence of vomiting, retching and salivation were recorded, as well as the time to first emesis and the number of emetic events per dog. The occurrence of salivation was not different between the groups. Retching and vomiting occurred significantly less frequently in M30 than in the other two groups (p < 0.02). The number of emetic events was also significantly less for M30 than for the other two groups (p = 0.01). When emesis occurred, the time to the first emetic event was similar among the groups. Maropitant (1 mg kg(-1)) SC reduced the frequency of morphine-induced emesis by as much as 70% when administered 30 minutes in advance. Simultaneous administration of maropitant and morphine-acepromazine produced no measurable effect on the frequency of retching or vomiting. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Agmatine reduces only peripheral-related behavioral signs, not the central signs, of morphine withdrawal in nNOS deficient transgenic mice.

PubMed

Aricioglu, Feyza; Paul, Ian A; Regunathan, Soundar

2004-01-09

Agmatine inhibits morphine tolerance/dependence and potentiates morphine analgesia. This study was designed to investigate whether neuronal nitric oxide mediates the actions of agmatine in morphine dependence by using mice lacking a functional form of this enzyme. Mice received agmatine just after the morphine pellet implantation for 3 days twice daily or single injection 30 min before naloxone. In both genotypes treated for 3 days with morphine pellets, naloxone administration precipitated clear signs of withdrawal. Both acute and chronic administration of agmatine reduced withdrawal signs in wild type mice and reduced only peripheral signs of morphine dependence in neuronal nitric oxide synthase knockout mice. Withdrawal signs, that are related to central nervous system activity were not affected. These findings indicate that neuronal nitric oxide synthase partly mediates the effects of agmatine in morphine physical dependence.

Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine

PubMed Central

Hill, Rob; Lyndon, Abi; Withey, Sarah; Roberts, Joanne; Kershaw, Yvonne; MacLachlan, John; Lingford-Hughes, Anne; Kelly, Eamonn; Bailey, Chris; Hickman, Matthew; Henderson, Graeme

2016-01-01

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths. PMID:26171718

Excessive daytime sleepiness in patients on intrathecal analgesia for chronic pain.

PubMed

Demartini, Laura; Fanfulla, Francesco; Bonezzi, Cesare; Armiento, Luciana; Buonocore, Michelangelo

2015-01-01

Intrathecal (IT) drug administration is an advanced technique in pain treatment algorithm for patients poorly responsive to systemic pharmacological treatment or less invasive techniques. The aim is to improve analgesia lowering side effects; despite this premise, many side effects of long-term IT therapy have been described, mainly related to opioid administration. We observed, in some of the patients regularly followed for pump refills in our Pain Unit, the appearance of excessive daytime sleepiness (EDS) interfering with daily life and work activity; this study aims to investigate the incidence of EDS in patients on IT analgesia with opioid or non-opioid drugs and its possible relationship with respiratory problems during sleep. 21 patients on IT therapy for chronic pain answered the Epworth Sleepiness Scale (ESS). The incidence of EDS in patients receiving IT opioids was compared to a control group not receiving opioids. In 10 patients, who performed polysomnography (PSG) and maintenance of wakefulness test (MWT) for sleep complaints, we studied the relationship between PSG data and ESS scores and we verified the concordance of ESS and MWT results. 38% of the patients reported EDS, according to ESS data; all the patients with EDS were receiving an IT opioid. Even if some patients presented sleep apneas, we failed to correlate this data with daytime sleepiness. Subjective sleepiness is confirmed by the results of MWT. Our data demonstrate that EDS is a frequent and important side effect of IT analgesia and it seems related to opioids administration.

Effects of preemptive analgesia with flurbiprofen ester on lymphocytes and natural killer cells in patients undergoing esophagectomy: A randomized controlled pilot study.

PubMed

Zhou, Yi; Huang, Jinxi; Bai, Yu; Li, Changsheng; Lu, Xihua

2017-11-01

Tumors may induce systemic immune dysfunction, which can be aggravated by surgery and anesthesia/analgesia. Data on the effect of flurbiprofen preemptive analgesia on immune dysfunction is limited. The aim of this study was to investigate the effect of flurbiprofen preemptive analgesia on lymphocytes and natural killer (NK) cells in patients undergoing thoracotomy and thoracoscopy radical esophagectomy, and to explore the analgesic methods suitable for tumor patients. This was a randomized controlled pilot study of 89 patients with esophageal cancer treated with surgery at the Henan Cancer Hospital between January 1, 2015 and December 31, 2016. The patients were divided into three groups: group 1, thoracotomy; group 2, thoracoscopy and laparoscopic surgery; and group 3, flurbiprofen, thoracoscopy, and laparoscopic surgery. CD3+, CD19+, NK, CD4+, and CD8+ cells in whole blood were measured by flow cytometry 30 minutes before surgery (T0), at the end of the thoracic section of the procedure (T1), and at the end of the operation (T2). There were no significant differences in CD3+, CD19+, CD8+, NK, and CD4+ cells between the three groups or regarding the time points during the procedure (all P > 0.05). Thoracotomy and thoracoscopy surgery resulted in similar immunological outcomes. Flurbiprofen ester preemptive analgesia did not suppress the immune function in patients and could be a safe analgesic method for patients with esophageal cancer undergoing surgery. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Cardioprotective Effects of Intracoronary Morphine in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: A Prospective, Randomized Trial.

PubMed

Gwag, Hye Bin; Kim, Eun Kyoung; Park, Taek Kyu; Lee, Joo Myung; Yang, Jeong Hoon; Song, Young Bin; Choi, Jin-Ho; Choi, Seung-Hyuk; Lee, Sang Hoon; Chang, Sung-A; Park, Sung-Ji; Lee, Sang-Chol; Park, Seung Woo; Jang, Woo Jin; Lee, Mirae; Chun, Woo Jung; Oh, Ju Hyeon; Park, Yong Hwan; Choe, Yeon Hyeon; Gwon, Hyeon-Cheol; Hahn, Joo-Yong

2017-04-03

A cardioprotective role of morphine acting via opioid receptors has been demonstrated, and previous preclinical studies have reported that morphine could reduce reperfusion injury and myocardial infarct size in a way similar to that of ischemic periconditioning. This study aimed to evaluate the effect of intracoronary morphine on myocardial infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. This study was designed as a 2-center, prospective, randomized, open-label, blinded end point trial. A total of 91 ST-elevation myocardial infarction patients with thrombolysis in myocardial infarction flow grade of 0 to 1 undergoing primary percutaneous coronary intervention were randomly assigned to a morphine or control group at a 1:1 ratio. The morphine group received 3 mg of morphine sulfate diluted with 3 mL of normal saline, and the control group received 3 mL of normal saline into a coronary artery immediately after restoration of coronary flow. The primary end point was myocardial infarct size assessed by cardiac magnetic resonance imaging The cardiac magnetic resonance images were evaluated for 42 and 38 patients in the morphine and control groups, respectively. Myocardial infarct size was not different between the 2 groups (25.6±11.2% versus 24.6±10.5%, P =0.77), nor was the extent of microvascular obstruction or myocardial salvage index (6.0±6.3% versus 5.1±4.6%, P =0.91; 31.1±15.2% versus 30.3±10.9%, P =0.75, respectively). There was no difference in peak creatine kinase-MB level, final thrombolysis in myocardial infarction flow, myocardial brush grade, or complete resolution of ST-segment. Intracoronary morphine administration could not reduce myocardial infarct size in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01738100. © 2017 The Authors. Published on behalf of the

Improved Outcomes Associated with the Liberal Use of Thoracic Epidural Analgesia in Patients with Rib Fractures.

PubMed

Jensen, Courtney D; Stark, Jamie T; Jacobson, Lewis L; Powers, Jan M; Joseph, Michael F; Kinsella-Shaw, Jeffrey M; Denegar, Craig R

2017-09-01

Each year, more than 150,000 patients with rib fractures are admitted to US trauma centers; as many as 10% die. Effective pain control is critical to survival. One way to manage pain is thoracic epidural analgesia. If this treatment reduces mortality, more frequent use may be indicated. We analyzed the patient registry of a level II trauma center. All patients admitted with one or more rib fractures (N = 1,347) were considered. Patients who were not candidates for epidural analgesia (N = 382) were eliminated. Mortality was assessed with binary logistic regressions. Across the total population, mortality was 6.7%; incidence of pneumonia was 11.1%; mechanical ventilation was required in 23.8% of patients, for an average duration of 10.0 days; average stay in the hospital was 7.7 nights; and 49.7% of patients were admitted to the ICU for an average of 7.2 nights. Epidural analgesia was administered to 18.4% of patients. After matching samples for candidacy, patients who received epidurals were 3.7 years older, fractured 2.6 more ribs, had higher injury severity scores, and were more likely to present with bilateral fractures, flail segments, pulmonary contusions, hemothoraces, and pneumothoraces. Despite greater injury severity, mortality among these patients was lower (0.5%) than those who received alternative care (1.9%). Controlling for age, injury severity, and use of mechanical ventilation, epidural analgesia predicted a 97% reduction in mortality. Thoracic epidural analgesia associates with reduced mortality in rib fracture patients. Better care of this population is likely to be facilitated by more frequent reliance on this treatment. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

[Clinical significance of ropivacaine local infiltration for postoperative analgesia after total laparoscopic radical gastrectomy in elderly patients].

PubMed

Huang, Zhengjie; Xie, Yongjin; You, Jun; Xu, Lin; Chen, Yueda; Chen, Baisheng; Wei, Bin; Luo, Qi

2014-07-22

To explore the analgesic effects and postoperative recovery of ropivacaine incision infiltration in elderly patients after total laparoscopic radical gastrectomy. The clinical data were obtained prospectively from 61 elderly patients ( ≥ 65y) undergoing traditional total laparoscopic radical gastrectomy under standard general anesthesia at our department during January 2012 and September 2013. After surgery, they were randomly double-blindly divided into 3 groups: local infiltration of ropivacaine group (0.5% ropivacaine incision infiltration, 40 ml, n = 22), local infiltration of sodium chloride group (0.9% sodium chloride injection incision infiltration, 40 ml, n = 20) and control group (no analgesic, n = 19). The intensity of postoperative pain was evaluated by numeric rating scale (NRS). And 10 mg of morphine was administered intramuscularly as rescue medication when NRS exceeded 4.NRS, cases on remedy analgesia and associated side effects were observed and recorded after 6 h postoperatively. A comparative study was made for postoperative first ambulation time, intestinal function recovery time, complication incidence, postoperative hospital stay and medical expenses among three groups. Significant postoperative difference existed in NRS at 6, 12, 24, 48 h among ropivacaine, sodium and control groups respectively (6 h: 2.65 ± 0.25 vs 5.47 ± 0.12 vs 5.63 ± 0.27, 12 h: 2.42 ± 0.34 vs 5.82 ± 0.63 vs 5.67 ± 0.49, 24 h: 2.27 ± 0.83 vs 3.95 ± 0.51 vs 3.84 ± 0.60, 48 h: 2.05 ± 0.90 vs 3.75 ± 0.72 vs 3.74 ± 0.56, P < 0.05) . The patients with ropivacaine local infiltration had a lower rate of remedy analgesia than those with sodium chloride injection incision infiltration or without analgesic (both P < 0.05). There was no obvious adverse effect of ropivacaine infiltration at 48 h postoperatively. Both postoperative first ambulation and peristalsis recovery time were shorter (P < 0.05) in ropivacaine group ((53 ± 9) and (80 ± 6) h) than sodium group ((91

Which one is more effective for analgesia in infratentorial craniotomy? The scalp block or local anesthetic infiltration.

PubMed

Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Vehid, Hayriye; Ibısoglu, Lutfiye Serap; Tunali, Yusuf

2017-03-01

The most painful stages of craniotomy are the placement of the pin head holder and the skin incision. The primary aim of the present study is to compare the effects of the scalp block and the local anesthetic infiltration with bupivacaine 0.5% on the hemodynamic response during the pin head holder application and the skin incision in infratentorial craniotomies. The secondary aims are the effects on pain scores and morphine consumption during the postoperative 24h. This prospective, randomized and placebo controlled study included forty seven patients (ASA I, II and III). The scalp block was performed in the Group S, the local anesthetic infiltration was performed in the Group I and the control group (Group C) only received remifentanil as an analgesic during the intraoperative period. The hemodynamic response to the pin head holder application and the skin incision, as well as postoperative pain intensity, cumulative morphine consumption and opioid related side effects were compared. The scalp block reduced the hemodynamic response to the pin head holder application and the skin incision in infratentorial craniotomies. The local anesthetic infiltration reduced the hemodynamic response to the skin incision. As well as both scalp block and local anesthetic infiltration reduced the cumulative morphine consumption in postoperative 24h. Moreover, the pain intensity was lower after scalp block in the early postoperative period. The scalp block may provide better analgesia in infratentorial craniotomies than local anesthetic infiltration. Copyright © 2017 Elsevier B.V. All rights reserved.

Does adding low doses of oral naltrexone to morphine alter the subsequent opioid requirements and side effects in trauma patients?

PubMed

Farahmand, Shervin; Ahmadi, Omid; Dehpour, Ahmadreza; Khashayar, Patricia

2012-01-01

The present study aims to assess the influence of ultra-low doses of opioid antagonists on the analgesic properties of opioids and their side effects. In the present randomized, double-blind controlled trial, the influence of the combination of ultra-low-dose naltrexone and morphine on the total opioid requirement and the frequency of the subsequent side effects was compared with that of morphine alone (added with placebo) in patients with trauma in the upper or lower extremities. Although the morphine and naltrexone group required 0.04 mg more opioids during the study period, there was no significant difference between the opioid requirements of the 2 groups. Nausea was less frequently reported in patients receiving morphine and naltrexone. The combination of ultra-low-dose naltrexone and morphine in extremity trauma does not affect the opioid requirements; it, however, lowers the risk of nausea. Copyright © 2012 Elsevier Inc. All rights reserved.

Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine

PubMed Central

Garzón, Javier; de la Torre-Madrid, Elena; Rodríguez-Muñoz, María; Vicente-Sánchez, Ana; Sánchez-Blázquez, Pilar

2009-01-01

Background Although the systemic administration of cannabinoids produces antinociception, their chronic use leads to analgesic tolerance as well as cross-tolerance to morphine. These effects are mediated by cannabinoids binding to peripheral, spinal and supraspinal CB1 and CB2 receptors, making it difficult to determine the relevance of each receptor type to these phenomena. However, in the brain, the CB1 receptors (CB1Rs) are expressed at high levels in neurons, whereas the expression of CB2Rs is marginal. Thus, CB1Rs mediate the effects of smoked cannabis and are also implicated in emotional behaviors. We have analyzed the production of supraspinal analgesia and the development of tolerance at CB1Rs by the direct injection of a series of cannabinoids into the brain. The influence of the activation of CB1Rs on supraspinal analgesia evoked by morphine was also evaluated. Results Intracerebroventricular (icv) administration of cannabinoid receptor agonists, WIN55,212-2, ACEA or methanandamide, generated a dose-dependent analgesia. Notably, a single administration of these compounds brought about profound analgesic tolerance that lasted for more than 14 days. This decrease in the effect of cannabinoid receptor agonists was not mediated by depletion of CB1Rs or the loss of regulated G proteins, but, nevertheless, it was accompanied by reduced morphine analgesia. On the other hand, acute morphine administration produced tolerance that lasted only 3 days and did not affect the CB1R. We found that both neural mu-opioid receptors (MORs) and CB1Rs interact with the HINT1-RGSZ module, thereby regulating pertussis toxin-insensitive Gz proteins. In mice with reduced levels of these Gz proteins, the CB1R agonists produced no such desensitization or morphine cross-tolerance. On the other hand, experimental enhancement of Gz signaling enabled an acute icv administration of morphine to produce a long-lasting tolerance at MORs that persisted for more than 2 weeks, and it also

The Effect of the Time of Injection of Intrathecal Analgesia on the Length of Early and Advanced Labor

DTIC Science & Technology

1999-10-01

Recommendations for future studies include a prospective randomized clinical trial to examine the effect of the timing of intrathecal narcotic...population and in clinical practice. Friedman (1978) Intrathecal Analgesia 7 however, does provide averages and upper statistical limits for the first and...morphine into the subarchnoid space of rats produced potent analgesia (Wang, 1977). These effects were then clinically applied in man for the relief of

[Continuous subcutaneous morphine--treatment of pain in patients with terminal cancer].

PubMed

Nielsen, F B; Clemensen, S E; Olesen, A S; Hole, P

1990-06-11

Nine patients with terminal cancer were treated for pain with continuous subcutaneous injection of morphine via a portable battery-driven injection pump. Treatment was instituted on account of failure of other forms of treatment with oral or epidural morphine derivatives or on account of severe nausea and vomiting which necessitated parenteral administration. Treatment proved reasonably effective and no side effects of significance occurred. Two of the patients could be treated in their homes. The method is thus considered as suitable for treatment of pain in patients with terminal cancer.

Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats.

PubMed

Pypendop, Bruno H; Shilo-Benjamini, Yael; Ilkiw, Jan E

2016-11-01

To determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. Randomized crossover study. Six healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. Morphine sulfate (0.2 mg kg -1 IV or 0.5 mg kg -1 buccal), methadone hydrochloride (0.3 mg kg -1 IV or 0.75 mg kg -1 buccal), hydromorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) or oxymorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. Administration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. At the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Local infiltration analgesia: a 2-year follow-up of patients undergoing total hip arthroplasty.

PubMed

Kuchálik, Ján; Magnuson, Anders; Lundin, Anders; Gupta, Anil

2017-12-01

Local infiltration analgesia (LIA) is commonly used for postoperative pain management following total hip arthroplasty (THA). However, the long-term effects of the component drugs are unclear. The aim of our study was to investigate functional outcome, quality of life, chronic post-surgical pain, and adverse events in patients within 2 years of undergoing THA. The study was a secondary analysis of data from a previous larger study. Eighty patients were randomized to receive either intrathecal morphine (Group ITM) or local infiltration analgesia (Group LIA) for pain management in a double-blind study. The parameters measured were patient-assessed functional outcome [using the Hip dysfunction and Osteo-arthritis Outcome Score (HOOS) questionnaire], health-related quality of life [using the European Quality of Life-5 dimensions (EQ-5D) questionnaire and the 36-Item Short Form Health Survey (SF-36) score], and pain using the numeric rating score (NRS), with persistent post-surgical pain having a NRS of > 3 or a HOOS pain sub-score of > 30. All complications and adverse events were investigated during the first 2 years after primary surgery. Pain intensity and rescue analgesic consumption were similar between the groups after hospital discharge. No differences were found in HOOS or SF-36 score between the groups up to 6 months after surgery. A significant group × time interaction was seen in the EQ 5D form in favor of the LIA group. No between-group difference in persistent post-surgical pain was found at 3 or 6 months, or in adverse events up to 2 years after surgery. Analysis of functional outcome, quality of life, and post-discharge surgical pain did not reveal significant differences between patients receiving LIA and those receiving ITM. LIA was found to be a safe technique for THA during the long-term follow-up. However, it should be noted that these conclusions are based on a limited number of patients.

Treatment of severe cancer pain by low-dose continuous subcutaneous morphine.

PubMed

Drexel, H; Dzien, A; Spiegel, R W; Lang, A H; Breier, C; Abbrederis, K; Patsch, J R; Braunsteiner, H

1989-02-01

In a prospective and intraindividually controlled trial, we have compared the efficacy and safety of a continuous subcutaneous morphine infusion with conventional intermittent oral or subcutaneous morphine application. Twenty-eight in-patients with cancer pain received a short-term infusion lasting 2-42 days, and 8 out-patients underwent long-term infusion from 49 to 197 days during the terminal stage of their disease. Continuous subcutaneous morphine infusion significantly (P less than 0.001) improved both pain and quality of life when compared to conventional morphine application. With continuous infusion, 5-48 mg (median 19 mg) of morphine was required daily, significantly (P less than 0.001) less than the 10-90 mg (median 50 mg) necessary with conventional use. As a result of lower dosage, side effects under continuous infusion were infrequent and mild. Constipation occurred in 3 of the 36 patients and was always controlled by the addition of laxatives; no nausea, sedation or respiratory depression were observed. Signs of tolerance developed in 2 patients on long-term infusion, but the use of continuous subcutaneous methadone for 2 weeks reversed the tolerance. The study presented indicates that low-dose continuous subcutaneous morphine provides a valuable treatment modality for severe terminal cancer pain exhibiting a high degree of both efficacy and safety.

Labour analgesia: Recent advances

PubMed Central

Pandya, Sunil T

2010-01-01

Advances in the field of labour analgesia have tread a long journey from the days of ether and chloroform in 1847 to the present day practice of comprehensive programme of labour pain management using evidence-based medicine. Newer advances include introduction of newer techniques like combined spinal epidurals, low-dose epidurals facilitating ambulation, pharmacological advances like introduction of remifentanil for patient-controlled intravenous analgesia, introduction of newer local anaesthetics and adjuvants like ropivacaine, levobupivacaine, sufentanil, clonidine and neostigmine, use of inhalational agents like sevoflourane for patient-controlled inhalational analgesia using special vaporizers, all have revolutionized the practice of pain management in labouring parturients. Technological advances like use of ultrasound to localize epidural space in difficult cases minimizes failed epidurals and introduction of novel drug delivery modalities like patient-controlled epidural analgesia (PCEA) pumps and computer-integrated drug delivery pumps have improved the overall maternal satisfaction rate and have enabled us to customize a suitable analgesic regimen for each parturient. Recent randomized controlled trials and Cochrane studies have concluded that the association of epidurals with increased caesarean section and long-term backache remains only a myth. Studies have also shown that the newer, low-dose regimes do not have a statistically significant impact on the duration of labour and breast feeding and also that these reduce the instrumental delivery rates thus improving maternal and foetal safety. Advances in medical technology like use of ultrasound for localizing epidural space have helped the clinicians to minimize the failure rates, and many novel drug delivery modalities like PCEA and computer-integrated PCEA have contributed to the overall maternal satisfaction and safety. PMID:21189877

Post-operative analgesic effect of dexmedetomidine administration in wound infiltration for abdominal hysterectomy: A randomised control study

PubMed Central

Singh, Swati; Prasad, Chandrakant

2017-01-01

Background and Aims: Local infiltration of the surgical wound is one of the important components of multimodal analgesia for post-operative pain relief. This study determines the post-operative analgesic effect of addition of dexmedetomidine to bupivacaine for local infiltration of the surgical wound. Methods: Sixty women belonging to American Society of Anesthesiologists’ Grade 1 or 2 posted for abdominal hysterectomy were randomly allocated to Group I (control group) where patients received wound infiltration with 30 mL 0.25% bupivacaine at the end of surgery, or Group II, where patients received wound infiltration with 1.0 μg/kg dexmedetomidine diluted in 30 mL 0.25% bupivacaine. The primary objective of the study was to assess post-operative pain scores. Number of patients requiring rescue analgesia and total morphine consumption during 24 h after surgery were also recorded. Statistical significance for analgesic requirement was determined by one-way analysis of variance. Results: Pain scores were lower at rest for 12 h and on cough for 6 h in Group II (<0.01). All patients in Group I required supplemental morphine compared to only 3 patients in Group II (P < 0.003). Post-operative analgesia requirement was significantly less in patients receiving dexmedetomidine in wound infiltration compared to patients receiving bupivacaine alone (P < 0.001). Conclusions: Wound infiltration of dexmedetomidine with bupivacaine provides superior pain relief compared to bupivacaine alone. PMID:28655956

A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting.

PubMed

Sanchez-Ledesma, M J; López-Olaondo, L; Pueyo, F J; Carrascosa, F; Ortega, A

2002-12-01

In this study we compared the efficacy and safety of three antiemetic combinations in the prevention of postoperative nausea and vomiting (PONV). Ninety ASA status I-II women, aged 18-65 yr, undergoing general anesthesia for major gynecological surgery, were included in a prospective, randomized, double-blinded study. A standardized anesthetic technique and postoperative analgesia (intrathecal morphine plus IV patient-controlled analgesia (PCA) with morphine) were used in all patients. Patients were randomly assigned to receive ondansetron 4 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 1, n = 30), dexamethasone 8 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 2, n = 30), or ondansetron 4 mg plus dexamethasone 8 mg after the induction of anesthesia and placebo 12 h later (Group 3, n = 30). A complete response, defined as no PONV in 48 h, occurred in 80% of patients in Group 1, 70% in Group 3, and 40% in Group 2 (P = 0.004 versus Groups 1 and 3). The incidences of side effects and other variables that could modify the incidence of PONV were similar among groups. In conclusion, ondansetron, in combination with droperidol or dexamethasone, is more effective than dexamethasone in combination with droperidol in women undergoing general anesthesia for major gynecological surgery with intrathecal morphine plus IV PCA with morphine for postoperative analgesia. The combination of ondansetron plus dexamethasone or droperidol was significantly better than the combination of dexamethasone plus droperidol in the prophylaxis of postoperative nausea and vomiting in women undergoing general anesthesia for major gynecological surgery, with intrathecal and IV morphine (patient-controlled analgesia) for management of postoperative pain.

A Costly Lesson: Fatal Respiratory Depression Induced by Clindamycin during Postoperative Patient Controlled Analgesia.

PubMed

Wu, Gao; Wu, Guo; Wu, Hanbin

2015-01-01

Many drugs can cause neuromuscular blockade. Clindamycin-related neuromuscular blockade is commonly reported, but fatal clindamycin-induced neuromuscular blockade is rarely reported. We describe a 47-year-old woman who initially presented with endometrial carcinoma. She underwent a laparoscopic-assisted vaginal hysterectomy (LAVH) and bilateral adnexectomy under general anesthesia, secondary to antibiotic treatment with clindamycin 1.2g in 250 mL for about 30 minutes through the peripheral intravenous route during postoperative patient controlled analgesia (PCA). She became unconscious near the end of the infusion, then, despite resuscitation attempts, she died. Clindamycin appeared to have triggered delayed respiratory depression during PCA. A combination of clindamycin and fentanyl led to her respiratory depression in the fatal case.

Postoperative analgesic efficiency of transversus abdominis plane block after ventral hernia repair: a prospective, randomized, controlled clinical trial.

PubMed

Chesov, Ion; Belîi, Adrian

2017-10-01

Effective postoperative analgesia is a key element in reducing postoperative morbidity, accelerating recovery and avoiding chronic postoperative pain. The aim of this study was to evaluate the effectiveness of ultrasound-guided Transversus Abdominis Plane (TAP) block, performed before surgical incision, in providing postoperative analgesia for patients undergoing open ventral hernia repair under general anaesthesia. Seventy elective patients scheduled for open ventral hernia repair surgery under general anaesthesia were divided randomly into two equal groups: Group I received bilateral TAP block performed before surgical incision (n = 35); Group II received systemic postoperative analgesia with parenteral opioid (morphine) alone (n = 35). Postoperatively pain scores at rest and with movement, total morphine consumption and opioid related side effects were recorded. Postoperative pain scores at rest and mobilization/cough were significantly higher in patients without TAP block (p < 0.05). Mean intraoperative fentanyl consumption was comparable between the two groups: 0.75 ± 0.31 mg in group I (TAP) and 0.86 ± 0.29 mg in group II (MO), p = 0.1299. Patients undergoing preincisional TAP block had reduced morphine requirements during the first 24 hours after surgery, compared to patients from group II, without TAP block (p = 0.0001). There was no difference in the incidence of opioid related side effects (nausea, vomiting) in the both groups during the first 24 postoperative hours. The use of preincisional ultrasound guided TAP block reduced the pain scores at rest and with movement/cough, opioid consumption and opioid-related side effects after ventral hernia repair when compared with opioid-only analgesia.

Antiemetic effects of midazolam added to fentanyl-ropivacaine patient-controlled epidural analgesia after subtotal gastrectomy: A prospective, randomized, double-blind, controlled trial

PubMed Central

Kim, Sioh; Seo, Jeongwon; Jeon, Younghoon

2010-01-01

Background: Nausea and vomiting are frequent adverse effects of patient-controlled epidural analgesia (PCEA) with opioids. Objective: This study was designed to assess the antiemetic effect of midazolam added to fentanyl—ropivacaine PCEA. Methods: In a prospective, randomized, double-blind, controlled trial, smoking patients with gastric cancer undergoing elective subtotal gastrectomy were evenly allocated to 1 of 2 treatment groups to manage postoperative pain: 0.2% ropivacaine mixed with fentanyl 4 μg/mL and midazolam 0.2 mg/mL (test group) or 0.2% ropivacaine mixed with fentanyl 4 μg/mL (control group). The PCEA infusion was set to deliver 4 μL/h of the study solution, with a bolus of 2 mL per demand and a 15-minute lockout time. The incidence of postoperative nausea and vomiting (PONV), pain intensity, sedation score, usage of rescue analgesia and rescue antiemetic, respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, 48, and 72 hours after surgery. Total infused volume of PCEA at 72 hours after surgery was measured. Results: A total of 60 patients were approached and randomized to treatment. No patients were excluded by exclusion criteria and all enrolled patients completed this study. Incidence of nausea (7% vs 33%; P = 0.02) in the test group was significantly lower than in the control group. The overall frequency of PONV in the test group was significantly less than that of the control group (7% vs 40%; P = 0.006). In addition, the mean (SD) infused volume of PCEA in the test group was significantly lower than that in the control group (392.3 [68.9] vs 351.2 [49.8] mL; P = 0.01). However, there were no significant differences in pain intensity, usage of rescue antiemetics and rescue analgesics, and mild pruritus between groups. No patient reported moderate or severe sedation, respiratory depression, or hypoxemia. In addition, there were no severe adverse events. Conclusions: Midazolam added to fentanyl-ropivacaine PCEA

Improving postoperative tonsillectomy pain management in children--a double blinded randomised control trial of a patient analgesia information sheet.

PubMed

Bailey, Lucas; Sun, Jing; Courtney, Mark; Murphy, Paul

2015-05-01

To evaluate paediatric post-tonsillectomy pain management using oxycodone when a specific analgesia information sheet is included with standard postoperative information. Oxycodone information sheets were randomly allocated to half the study children's post-tonsillectomy information pack. The trial was double-blinded to the surgeon, anaesthetist, nursing and administrative staff. Parents and children completed the pain assessment on day 3, 5 and 7. On day 10 the parents completed a questionnaire. A postoperative analgesia information sheet provides for higher satisfaction and knowledge for parents using oxycodone (p<0.001) and children have improved postoperative pain control, most significantly at day 5 (p<0.05). Parent assessment of the child's analgesia was superior with the oxycodone information sheet, most significantly at day 3 and 7 post operatively (p<0.05). There is also a positive correlation between the parents' observed pain score and children's self reported pain score, with a low correlation efficient level observed (p<0.001). Information sheets are useful in education and use of postoperative analgesia. The primary objective to explore the efficacy of the information sheet has proved to be successful in this setting. Given risks of opioid analgesia, it is recommended that postoperative information sheets be given to all parents, to provide for improved analgesia control and safe management of children in the postoperative period. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Safety and Efficacy of Oral Transmucosal Fentanyl Citrate for Prehospital Pain Control on the Battlefield

DTIC Science & Technology

2012-01-01

Butler FK, Blackbourne LH. We don’t know what we don’t know: combat casualty care pre-hospital data. US Army Med Dep J. 2011;11 14. 50. Kotwal RS... used for prehospital analgesia on the battlefield during the past century has been morphine. Intramuscular morphine has a delayed onset of pain relief...to March 31, 2010, were analyzed. Patients were US Army Special Operations Command casualties. Patients receiving OTFC for acute pain were evaluated