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- Stability of morphine, codeine, and 6-acetylmorphine in blood at different sampling and storage conditions. [Journal Article]
- J Forensic Sci 2014 Mar; 59(2):550-4.
The stability of drugs in biological specimens is a major concern during the evaluation of the toxicological results. The stability of morphine, codeine, and 6-acetyl-morphine in blood was studied after different sampling conditions: (i) in glass, polypropylene or polystyrene tubes, (ii) with addition of dipotassium ethylene diamine tetraacetic acid (K2EDTA) or sodium oxalate (Na2C2O4), and (iii) with or without the addition of sodium fluoride (NaF). Spiked blood samples were stored at two different temperatures (4 and -20°C), analyzed after different storage times and after three freeze–thaw cycles. Opiate concentrations were decreased in all conditions, but the most unstable was 6-acetyl-morphine. The addition of NaF as preservative improved the stability of opiates at all conditions studied, whereas the type of anticoagulant did not affect the stability of opiates. It was concluded that blood samples should be stored at -20°C in glass tubes containing oxalate and NaF for maximum stability.
- Comparison of Continuous Femoral Nerve Block, Caudal Epidural Block, and Intravenous Patient-controlled Analgesia in Pain Control After Total Hip Arthroplasty: A Prospective Randomized Study. [Journal Article]
- Orthop Rev (Pavia) 2014 Jan 20; 6(1):5138.
Thirty-six patients who underwent primary unilateral total hip arthroplasty (THA) were randomly allocated to 4 groups with different pain control protocols; continuous femoral nerve block (FNB group), single-shot caudal epidural block with morphine (EB group), intravenous patient-controlled analgesia with fentanyl (IV-PCA group), and systemic administration of nonsteroidal anti-inflammatory drugs (NSAIDs group). Postoperative pain was assessed using the numerical rating scale (NRS) scores and the analgesic effect was compared among the groups. The NRS upon arrival at the recovery room and 6 hours after surgery in the FNB, EB, and IV-PCA groups were significantly lower than that in the NSAIDs group. The amount of additional analgesics requested by the patient was smaller in the FNB, EB, and IV-PCA groups as compared to the NSAIDs group. Regarding the complications related to the analgesia, 5 of the 9 patients in the IV-PCA group complained nausea and vomiting and received antiemetic drugs. Delay in the rehabilitation process due to drowsiness was encountered in 3 patients in this group, while no patient in the FNB and EB groups suffered from delayed rehabilitation. Considering both the analgesic effect and the potential risk of complications, continuous femoral nerve blocks and caudal epidural blocks for are recommended for postoperative pain control after THA procedure.
- Evaluation of Dexmedetomidine and Postoperative Pain Management in Patients With Adolescent Idiopathic Scoliosis: Conclusions Based on a Retrospective Study at a Tertiary Pediatric Hospital. [JOURNAL ARTICLE]
- Pediatr Crit Care Med 2014 Apr 16.
This study evaluated the effectiveness of dexmedetomidine in decreasing opioid use in children with adolescent idiopathic scoliosis following posterior spinal fusion surgery at a pediatric tertiary care hospital over the past 10 years.This was a retrospective chart review. Patients were separated into two groups: those that received opioid via patient-controlled analgesia pain therapy alone and those that received opioid via patient-controlled analgesia pain therapy with dexmedetomidine.A tertiary pediatric free-standing hospital. The study focused on care administered in the perioperative period, including the operating room, ICU, and general hospital floor.One hundred sixty-three children with adolescent idiopathic scoliosis.None.Measurements included patient demographics, American Society of Anesthesiologists Physical Status Classification System, levels of spinal fusion, length of hospital stay, complications, numeric pain scores, opioid requirement, elastomeric pain pump use, length of time until ambulation, adverse effects, and naloxone use. Data were collected through the first 72 hours of the perioperative period. One hundred six patients received opioids via patient-controlled analgesia therapy with dexmedetomidine and 57 received opioids via patient-controlled analgesia alone. Within the groups, there were 46 patients who received local anesthetic infusions via elastomeric pumps in the patient-controlled analgesia with dexmedetomidine group and 16 patients had pumps in the patient-controlled analgesia-alone group. There was no overall difference in postoperative use of morphine (or equivalents) between the two groups. However, the use of elastomeric pain pumps demonstrated a statistically significant decrease in mean overall opioid consumption (42.6 mg vs 63.1 mg, p < 0.001).There was no difference in opioid use related to dexmedetomidine on any postoperative day. The only variable showing a significant opioid sparing effect was the use of local anesthetic infusions via elastomeric pumps. Using continuous local anesthetic infusions instead of dexmedetomidine could eliminate the need for ICU admission, require shorter hospital stays, and reduce costs while still providing safe and effective pain control.
- Evaluation the effects of adding ketamine to morphine in intravenous patient-controlled analgesia after orthopedic surgery. [Journal Article]
- Perspect Clin Res 2014 Apr; 5(2):85-7.
Intravenous patient-controlled analgesia (PCA) with morphine is commonly used for post-operative pain after major surgery. Ketamine has analgesic property at lower doses, and in combination with opioids it could have synergistic effect. The aim of this study is to determine effects of the addition of ketamine to morphine for PCA after orthopedic surgery.In this double-blind randomized clinical trial, 60 patients were randomly allocated to receive PCA consisting: Group 1 (morphine 0.2 mg/ml), Group 2 (morphine 0.2 mg/ml + ketamine 1 mg/ml), and Group 3 (morphine 0.1 mg/ml + ketamine 2 mg/ml). In this, anesthesiologists managed study, patients had orthopedic surgery. Assessments were made at 24 h and 48 h post-operatively. Visual analog scale (VAS) was used for recording pain score. PCA morphine use was recorded at 24 h and 48 h. VAS scores over 48 h were analyzed with analysis of variance for repeated measures. Significance level was taken as 0.05.There is no significant difference between demographic information of the three groups (P > 0.05). Control of pain in Group 2 and Group 3 was better than in Group 1 (only morphine) (P = 0.001) but there was no significant difference between Group 2 and Group 3 (P > 0.05). Rate of narcotic consumption in groups 2 and 3 was significantly lower than Group 1 (P < 0.05).After orthopedic surgery, the addition of ketamine to morphine for intravenous PCA was superior to Intravenous PCA opioid alone. The combination induces a significant reduction in pain score and cumulative morphine consumption.
- Evaluation of anxiety-like behaviour in a rat model of acute postoperative pain. [JOURNAL ARTICLE]
- Eur J Anaesthesiol 2014 Apr 15.
Unrelieved acute postoperative pain can lead to a wide range of adverse effects, such as anxiety, depression, restlessness and sleep deprivation.Although clinical studies frequently report anxiety, immobility and feelings of helplessness as a result of untreated or inadequately treated acute pain, anxiety-like behaviour in animal models of acute postoperative pain has not been evaluated.The present study investigates anxiety-like behaviour in the postoperative pain model. Mechanical hypersensitivity was assessed with an electronic von Frey device, whereas anxiety-like behaviour was measured with light/dark testing and elevated plus maze testing.Rats developed significant mechanical hyperalgesia on 1, 3 and 8 days postsurgery compared with sham-operated rats. There was no reduction in motility between preincision and postincision when animals were allowed to move freely in an open field locomotion test. In light-dark tests, incised animals spent significantly less time than sham rats in the light compartment on the 1st and 3rd postoperative days. However, in an elevated plus maze test, differences between sham and incised rats were only observed on the 8th postoperative day as they spent significantly more time in the open arms. Pretreatment with morphine significantly increased withdrawal thresholds compared with treatment with saline (0.9% NaCl), but had no effect on light or open arm avoidance behaviour.We report that a rat model of acute postoperative pain is associated with anxiety-like increased light and open arm avoidance behaviour.
- PKC-Mediated Potentiation of Morphine Analgesia by St. John's Wort in Rodents and Humans. [Journal Article]
- J Pharmacol Sci 2014; 124(4):409-17.
Our purpose was to combine the use of morphine with clinically available inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic morphine combined or not with increasing doses of the PKC-blocker St. John's Wort (SJW) or its main component hypericin. Phosphorylation of the γ subunit of PKC enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin co-administration with morphine, inducing a potentiation of morphine analgesia in thermal pain. The score of pain assessment in healthy volunteers were decreased by 40% when morphine was co-administered with SJW at a dose largely below those used to obtain an antidepressant or analgesic effect in both rodents and humans. The SJW/hypericin potentiating effect lasted in time and preserved morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of morphine obtaining the same analgesic effect. Therefore, SJW and one of its main components, hypericin, appear ideal to potentiate morphine-induced analgesia.
- Postoperative comparison of four perioperative analgesia protocols in dogs undergoing stifle joint surgery. [Journal Article]
- J Am Vet Med Assoc 2014 May 1; 244(9):1041-6.
Objective-To compare 4 analgesic protocols in dogs undergoing stifle joint surgery. Design-Randomized, blinded, prospective clinical trial. Animals-48 client-owned dogs that underwent stifle joint surgery. Procedures-Dogs undergoing tibial plateau leveling osteotomy were randomly assigned to receive a constant rate infusion of a combination of morphine, lidocaine, and ketamine; a lumbosacral epidural with morphine and ropivacaine; both treatments (ie, constant rate infusion and lumbosacral epidural); or only IM premedication with morphine. Indices of cardiorespiratory function and isoflurane requirement were recorded at 5-minute intervals during anesthesia. A validated sedation scoring system and the modified Glasgow composite measure pain score were used to assess comfort and sedation after surgery and anesthesia once the swallowing reflex returned and a body temperature of ≥ 36.7°C (98.1°F) was attained. Pain and sedation scores were acquired at 60-minute intervals for 4 hours, then at 4-hour intervals for 24 hours. Dogs with a postoperative pain score > 5 of 24 were given morphine as rescue analgesia. Results-No differences in heart rate, respiratory rate, systolic arterial blood pressure, end-tidal Pco2, end-tidal isoflurane concentration, and vaporizer setting were detected among groups. No differences in pain score, sedation score, rescue analgesia requirement, or time to first rescue analgesia after surgery were detected. Conclusions and Clinical Relevance-Pain scores were similar among groups, and all 4 groups had similar rescue analgesia requirements and similar times to first administration of rescue analgesia. All 4 analgesic protocols provided acceptable analgesia for 24 hours after stifle joint surgery.
- Incidence of delayed hair re-growth, pruritus, and urinary retention after epidural anaesthesia in dogs. [Journal Article]
- Tierarztl Prax Ausg K Kleintiere Heimtiere 2014 Apr 16; 42(2):94-100.
Objective:Delayed hair re-growth, pruritus and urinary retention are known complications after epidural anaesthesia in dogs. The aim of this study was to prospectively evaluate the effect of epidurally administered drugs on the occurrence of these complications in dogs. Material and methods: Ninety dogs were included in this study. Eighty client-owned dogs undergoing surgery were randomly assigned to one of three epidural treatment groups: either morphine and bupivacaine (MB), bupivacaine (B), or saline solution 0.9% (S) was administered epidurally to these patients. Ten dogs were only clipped in the lumbosacral area (C). Follow-up started 4 weeks after clipping and was performed every 4-5 weeks in cases of delayed hair re-growth or pruritus. Hair re-growth in the lumbosacral area was observed and compared to hair re-growth in the surgical field and the fentanyl patch area. Cytological analysis and a trichogram were performed if hair re-growth was delayed after 6 months. Time interval to first urination postoperatively was recorded (n = 80).
Results:Hair re-growth was delayed in 11 dogs (12.2%; B: n = 7, S: n = 2, MB: n = 1, C: n = 1) with no differences between groups. Pruritus was evident in two dogs (2.2%; MB: n = 1, S: n = 1). After 6 months, hair had started to re-grow in all but one dog (B). After 10 months the coat of this dog had re-grown. Time to first urination did not differ between groups. Conclusion and clinical relevance: No direct correlation between the particular drugs injected epidurally and delayed hair re-growth, pruritus and urinary retention could be shown. Dog owners should be informed that hair re-growth after epidural anaesthesia could be markedly delayed.
- Characterization of drug-related problems identified by clinical pharmacy staff at Danish hospitals. [JOURNAL ARTICLE]
- Int J Clin Pharm 2014 Apr 16.
Background In 2010, a database of drug related problems (DRPs) was implemented to assist clinical pharmacy staff in documenting clinical pharmacy activities locally. A study of quality, reliability and generalisability showed that national analyses of the data could be conducted. Analyses at the national level may help identify and prevent DRPs by performing national interventions. Objective The aim of the study was to explore the DRP characteristics as documented by clinical pharmacy staff at hospital pharmacies in the Danish DRP-database during a 3-year period. Setting Danish hospital pharmacies. Method Data documented in the DRP-database during the initial 3 years after implementation were analyzed retrospectively. The DRP-database contains DRPs reported at hospitals by clinical pharmacy staff. The analyses focused on DRP categories, implementation rates and drugs associated with the DRPs. Main outcome measure Characteristics of DRPs. Results In total, 72,044 DRPs were documented in the DRP-database during the first 3 years of implementation, and the number of documented DRPs increased every year. An overall stable implementation rate of approximately 58 % was identified. The DRPs identified were multi-facetted, however evenly distributed for each of the 3 years. The most frequently identified DRP categories were: "Dose", followed by "Nonadherence to guidelines" and "Supplement to treatment". The highest implementation rates were found for the following DRP categories: "Non-adherence to guidelines" (79 %) followed by "Therapeutic duplication" (73 %) and "Dosing time and interval" (70 %). Even though the top 25 drugs were involved in 58 % of all DRPs, multiple drugs were associated with DRPs. The drugs most frequently involved in DRPs were paracetamol (4.6 % of all DRPs), simvastatin (3.0 %), lansoprazole (2.7 %), morphine (2.6 %) and alendronic acid (2.4 %). Conclusions The study found that a national database on DRPs contained multi-facetted DRPs, however evenly distributed for each of the 3 years. Even though the top 25 drugs were involved in 58 % of all DRPs, multiple drugs were associated with DRPs. The study emphasizes the importance of detecting and intervening for DRPs.
- Effect of sitting position on equal-dose spinal anaesthetic for caesarean section and post-partum tubal ligation. [JOURNAL ARTICLE]
- Acta Anaesthesiol Scand 2014 Apr 16.
We studied the hypothesis that an equal spinal anaesthetic dose administered in the sitting position to patients undergoing post-partum tubal ligation (PPTL) and caesarean section (CS) would yield similar sensory block characteristics and analgesic efficacy.This prospective, non-randomised trial recruited 20 women undergoing PPTL within 48 h of vaginal delivery and 20 undergoing CS. Spinal anaesthesia comprising intrathecal hyperbaric bupivacaine 12 mg and morphine 100 μg was administered at L3/4 with patients sitting. Our primary end point was the maximal dermatomal sensory block (to cold).Baseline demographics were comparable, but PPTL patients had greater parity, with mean ± standard deviation 17.54 ± 11.2 h from delivery to spinal anaesthesia, and shorter duration of surgery, 17.54 ± 11.2 vs. 40.3 ± 15.5 min. Similar maximal sensory blocks (to cold) were achieved in group PPTL vs. CS, T4 (T1-T5) vs. T3 (T1-T5), P = 0.104, in comparable times, 8.6 ± 2.6 vs. 7.6 ± 3.0 min, P = 0.267. PPTL patients had significantly faster two-segment block regression (70.7 ± 23.5 vs. 97.6 ± 23.9 min, P = 0.001) and to T10 (120.8 ± 35.6 vs. 145.1 ± 24.3 min, P = 0.016), with less hypotension (25% vs. 65%, P = 0.025) and phenylephrine (20.0 ± 60.6 μg vs. 120.0 ± 119.6 μg, P = 0.005).The same dose of hyperbaric bupivacaine 12 mg and morphine 100 μg administered in the sitting position to both PPTL and CS parturients yielded similar maximal sensory blocks, but PPTL exhibited faster block regression and less hypotension/vasopressor requirement.