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- Impact of Intravenous Acetaminophen on Reducing Opioid Use After Hysterectomy. [JOURNAL ARTICLE]
- Pharmacotherapy 2014 Dec; 34(S1):27S-33S.
To examine the impact of intravenous acetaminophen on the total quantity of opioids (in morphine equivalents) administered within the first 48 hours postoperatively and perioperatively, while still affording patients adequate analgesia, in women who underwent total abdominal hysterectomies.Retrospective chart review.Tertiary care community hospital.One hundred women underwent total abdominal hysterectomies performed by a single surgeon: 50 patients received opioids only (fentanyl, morphine, hydromorphone, meperidine, or oxycodone), without the addition of any acetaminophen, between January 1 and March 28, 2011, and 50 patients received intravenous acetaminophen 1000 mg every 6 hours in addition to opioids (multimodal group) between May 1 and July 16, 2012 (time period coincided with the addition of intravenous acetaminophen to the hospital formulary). Patients in both groups were also given nonopioids (celecoxib, dexmedetomidine, aspirin, or tizanidine) perioperatively.Patients in both groups had a mean age of 55 years (mean ± SD 55 ± 13 yrs in the multimodal group, 55 ± 15 yrs in the opioids-only group), surgery time of ~2 hours (116 ± 51 min in the multimodal group, 118 ± 40 min in the opioids-only group), and an anesthesia time of ~3.5 hours (209 ± 79 min in the multimodal group, 207 ± 79 min in the opioids-only group). During postoperative days 1-2, intravenous acetaminophen reduced opioid use by 31% (mean ± SD 47 ± 24 mg in the multimodal group vs 68 ± 37 mg in the opioids-only group, p=0.003) and by 26% during the total perioperative period, defined as preoperative, intraoperative, recovery room, and postoperative days 1-2 (73 ± 24 mg in the multimodal group vs 99 ± 39 mg in the opioids-only group, p=0.001).The multimodal approach to perioperative analgesic management, which includes concurrent administration of intravenous acetaminophen and opioids, is effective in reducing the total average amount of opioids administered on postoperative days 1-2 and perioperatively. Limitations of this study include its short duration, retrospective design, and single-site setting. These results may not be generalized to patients undergoing other types of obstetric-gynecologic surgeries.
- Opioid Use in Knee Arthroplasty After Receiving Intravenous Acetaminophen. [JOURNAL ARTICLE]
- Pharmacotherapy 2014 Dec; 34(S1):22S-26S.
Intravenous (IV) acetaminophen may be an effective component of multimodal postoperative pain management. The primary objective of this study was to evaluate the impact of IV acetaminophen on total opioid use in postoperative patients. The secondary objective was to evaluate the effect of IV acetaminophen on hospital length of stay.This retrospective, case-control study evaluated the impact of IV acetaminophen on total opioid use in surgical patients. Patients were included if they received at least one perioperative dose of IV acetaminophen and underwent a surgical knee procedure. Controls were matched and randomly selected based on procedure type, age, and severity of illness. Postoperative opioids were converted into oral morphine equivalents, and overall use was compared between groups.One hundred patients were enrolled, with 25 patients receiving IV acetaminophen and 75 matched controls. A total of 135 mg versus 112.5 mg oral morphine equivalents were used in the IV acetaminophen group and control group, respectively (p=0.987). There were 45 mg/day oral morphine equivalents used in the IV acetaminophen group versus 37.5 mg in the control group (p=0.845). The median hospital length of stay in both groups was 3 days (p=0.799).IV acetaminophen did not significantly decrease postoperative opioid use in patients who underwent surgical knee procedures. In addition, there was a nonsignificant trend toward increased opioid use in the IV acetaminophen group. There was no significant difference in hospital length of stay between the IV acetaminophen group and the control group. These findings require further study in larger patient populations and in other orthopedic procedures that typically require longer hospital stays.
- Optimizing Multimodal Analgesia with Intravenous Acetaminophen and Opioids in Postoperative Bariatric Patients. [JOURNAL ARTICLE]
- Pharmacotherapy 2014 Dec; 34(S1):14S-21S.
To evaluate the effect of therapeutic doses of intravenous acetaminophen (IV APAP) on postoperative opioid use following bariatric surgery.Retrospective review of medical records.A 654-bed academic hospital.Records for 104 patients who underwent laparoscopic sleeve gastrectomy (LSG; 44 patients) or laparoscopic Roux-en-Y gastric bypass (LRYGB; 60 patients) were reviewed. Patients received IV APAP 1 g every 6 hours postoperatively (22 LSG patients and 30 LRYGB patients) or no IV APAP (22 LSG patients and 30 LRYGB patients).Baseline demographic features were similar for both groups. Patients receiving IV APAP required fewer intravenous morphine equivalents than patients treated with opioids alone. Reductions in morphine equivalents with IV APAP were 21 mg (LSG), 33 mg (LRYGB), and 28 mg (all patients) (p<0.001 for all comparisons). IV APAP was associated with a shorter hospital length of stay (LOS) for the LRYGB (mean difference 1.47 days; p=0.039) and combined groups (mean difference 0.95 days; p=0.025). Patients who received IV APAP had earlier return of bowel sounds and flatus. IV APAP did not reduce mean pain scores in any group.Patients undergoing bariatric surgery who received IV APAP during the 24-hour postoperative period consumed fewer intravenous morphine equivalents and had similar pain scores as patients who were treated with opioids alone. Use of IV APAP reduced the hospital LOS and resulted in earlier return of bowel sounds and passage of flatus.
- Opioid Receptors and Cardioprotection - 'Opioidergic Conditioning' of the Heart. [JOURNAL ARTICLE]
- Br J Pharmacol 2014 Dec 17.
Ischaemic heart disease (IHD) remains a lead cause of morbidity/mortality globally, firmly established in Westernised or 'developed' countries and rising in prevalence in developing nations. Cardioprotective therapies to limit myocardial damage with associated ischaemia-reperfusion (I-R), during infarction or surgical ischaemia, are thus a very important though still elusive clinical goal. The opioid receptor (OPR) system, encompassing the δ (vas deferens), κ (ketocyclazocine) and μ (morphine) OPRs and their endogenous opioid ligands (endorphins, dynorphins, enkephalins), appears a logical candidate for such exploitation. This regulatory system may orchestrate organism and organ responses to stress, induces mammalian hibernation and associated metabolic protection, triggers powerful adaptive stress-resistance in response to ischaemia/hypoxia (preconditioning), and mediates cardiac benefit stemming from physical activity. In addition to direct myocardial actions, central OPR signalling may also enhance the ability of the heart to withstand I-R injury. The δ- and κ-OPR sub-types are strongly implicated in cardioprotection across models and species (including anti-infarct and anti-arrhythmic actions), with mixed evidence for μ-OPR dependent protection in animal and human tissues. A small number of clinical trials evidence cardiac benefit via morphine or remifentanil in cardiopulmonary by-pass or coronary angioplasty patients, though further trials of sub-type specific OPR agonists are needed. The precise roles and utility of this G-protein coupled receptor (GPCR) family in healthy and diseased human myocardium, and in mediating central and peripheral survival responses, warrant further investigation, as do the putative negative influences of ageing, IHD co-morbidities, and relevant drugs on OPR signalling and protective responses.
- Opioid-Related Adverse Effects in Children Undergoing Surgery: Unequal Burden on Younger Girls with Higher Doses of Opioids. [JOURNAL ARTICLE]
- Pain Med 2014 Dec 17.
Unpredictable interindividual variability in response to opioids results in inadequate analgesia and opioid-related adverse effects. The effects of the child's sex on opioid response have not been well studied. The aim of this study is to determine the effects of sex on opioid-related adverse effects in children undergoing tonsillectomy.Prospective observational clinical study.Outpatient pediatric surgery.Two hundred and seventy five children between 6 and 15 years of age undergoing outpatient tonsillectomy.All children received standard perioperative care with a standard intraoperative dose of morphine. Opioid-related analgesia and safety outcomes included incidences of respiratory depression (RD), postoperative nausea and vomiting (PONV) and incidence of prolonged stay in the, post-anesthesia recovery unit (PACU) due to opioid related adverse effects.Given the small sample of minority population, we focused our study on 219 white children. Significant morphine effect was observed in girls but not boys for PONV (P = 0.001) and prolonged PACU stay due to PONV (P = 0.010). Although the overall incidence of RD is not statistically different between boys and girls, the incidence of RD (52% vs 32%) and PONV (43% vs 4%) tended to be more in white girls than boys as the total perioperative morphine dose increased to 0.3 mg/kg or more.This study demonstrates that child's sex influences morphine's dose response and adverse effects. White girls have an unequal burden with higher incidences of PONV, RD, and prolonged PACU stays following tonsillectomy from PONV and RD as total morphine doses are increased.
- Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model. [JOURNAL ARTICLE]
- Br J Pharmacol 2014 Dec 17.
We have demonstrated previously that oxycodone had potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal grey (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer-related pain.We characterised the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model. Based on the disinhibition mechanism underlying supraspinal opioid antinociception, the effects of oxycodone and morphine on GABAA receptor-mediated inhibitory post-synaptic currents (IPSCs) in VLPAG neurons were evaluated in slices from the FBC model.Supraspinal antinociceptive effects of oxycodone, but not morphine, were abolished by blocking G protein-gated inwardly rectifying potassium1 (KIR 3.1) channels. In slices from the FBC model, GABAergic synaptic transmission at VLPAG neurons was enhanced, as indicated by a leftward shift of the input-output relationship curve of evoked IPSCs, the increased paired pulse facilitation and the enhancement of miniature IPSC frequency. Following treatment with oxycodone and morphine, IPSCs were reduced in the FBC model, and the inhibition of pre-synaptic GABA release by oxycodone but not morphine was enhanced and dependent on KIR 3.1 channels.Our results demonstrate that KIR 3.1 channels are important for supraspinal antinociception and pre-synaptic GABA release inhibition by oxycodone in the FBC model. Enhanced GABAergic synaptic transmission at VLPAG neurons in the FBC model is an important site of supraspinal antinociception by oxycodone via KIR 3.1 channel activation.
- Urinary Retention After Hysterectomy and Postoperative Analgesic Use. [JOURNAL ARTICLE]
- Female Pelvic Med Reconstr Surg 2014 Dec 17.
This study aimed to determine risk factors, including postoperative analgesic use, for the development of postoperative urinary retention (PUR) after hysterectomy for routine gynecologic indications using a case-control study design.Cases of PUR after hysterectomy were identified from billing data. Cases were those patients requiring recatheterization for inability to void. Controls were similarly identified and matched by age and date of surgery in a 3:1 control-to-case ratio. Chart review was performed to obtain demographic, medical, surgical, anesthetic, and medication data. Cumulative and interval doses of postoperative narcotic were recorded and converted into morphine equivalents. Crude odds ratios (ORs) were determined for potential risk factors for PUR using standard statistical analysis. Conditional logistic regression was used on multivariate models, including cumulative postoperative narcotic use, to determine adjusted ORs for risk factors.Twenty-six cases of PUR were matched with 78 controls. The cases had a higher body mass index (32 vs 28 kg/m, P = 0.02), had a higher preoperative use of tricyclic antidepressants (TCA; 19.2% vs 1.3%, P = 0.004), were more likely to present preoperative urinary retention associated with fibroids (19.2% vs 0%, P < 0.01), and received a higher cumulative narcotic dose in the postoperative period (109 vs 73.6 mg, P < 0.001). In a multivariate model, preoperative TCA use (OR, 30.1; 95% confidence interval, 1.99-456; P = 0.01) and cumulative narcotic dose (OR, 2.54; 95% confidence interval, 1.44-4.56; P < 0.01) were significantly associated with PUR.Postoperative urinary retention after hysterectomy is associated with higher postoperative narcotic dose, preoperative TCA use, and preoperative urinary retention.
- The A6V polymorphism of the human μ-opioid receptor negatively impacts signalling of morphine and endogenous opioids in vitro. [JOURNAL ARTICLE]
- Br J Pharmacol 2014 Dec 17.
Polymorphisms of the μ-opioid receptor (MOPr) may contribute to the variation in responses to opioid drugs in clinical and unregulated situations. The A6V variant of MOPr (MOPr-A6V) is present in up to 20% of individuals in some populations, and may be associated with heightened susceptibility to drug abuse. There are no functional studies examining the acute signalling of MOPr-A6V in vitro, so we investigated potential functional differences between MOPr and MOPr-A6V at several signalling pathways using structurally distinct opioid ligands.CHO and AtT-20 cells stably expressing MOPr and MOPr-A6V used. Adenylyl cyclase (AC) inhibition and ERK1/2 phosphorylation assays were conducted in CHO cells, assays of K channel activation in AtT-20 cells.Buprenorphine did not inhibit AC or stimulate ERK1/2 phosphorylation in CHO cells expressing MOPr-A6V, but buprenorphine activation of K channels in AtT-20 cells was preserved. DAMGO, morphine and β-endorphin inhibition of AC was significantly reduced via MOPr-A6V, as was signalling of all opioids to ERK1/2. However, there was little effect of the A6V variant on K channel activation.This study shows that signalling to AC and ERK via MOPr-A6V is reduced for many opioids, including the clinically significant drugs morphine, buprenorphine and fentanyl, as well endogenous opioids. The MOPr-A6V variant can be common and this compromised signalling may affect individual responses to opioid therapy, while the possible disruption of the endogenous opioid system may contribute to susceptibility to substance abuse.
- Morphine and nicotine addiction and withdrawal influence baroreflex sensitivity and blood pressure in two-kidney one clip hypertensive (2K1C) rats. [JOURNAL ARTICLE]
- Bratisl Lek Listy 2014; 115(12):743-748.
Objective: This study aimed to investigate the effects of addiction to morphine and nicotine as well as their withdrawal on both baroreflex sensitivity and blood pressure in hypertensive rats. Methods: In this experimental study 40 male rats were divided into two main groups as follows: in group I, hypertensive rats received saline for 8 weeks; in group II, hypertensive rats were treated with morphine and nicotine for 8 weeks. At the end of 8 weeks group II rats were divided into four sub-groups including, 3 sub-groups of those were put on drug withdrawal protocol. At the end of experiment, blood pressure, heart rate, plasma renin activity (PRA), serum NO concentration and baroreflex sensitivity (BRS) were measured. Results: Results demonstrated that BP and BRS were significantly lower in addicted to morphine and nicotine hypertensive rats compared to control (p < 0.05). Addiction withdrawal (in morphine and nicotine withdrawal rats) completely reversed BP and BRS to the pre-addiction levels (p < 0.05). Withdrawal in the only nicotine treated group lowered BP and BRS compared to group that had received morphine and nicotine together (p < 0.05). Conclusion: Results of current study may propose simultaneous morphine and nicotine withdrawal can prevent cardiovascular complications raised due to withdrawal (Fig. 5, Ref. 58). Keywords: hypertension, baroreflex sensitivity, morphine, nicotine.