Introduction: ST-elevation myocardial infarction (STEMI) presenting to the ED is a significant health burden. The provision of IV morphine with doses titrated to provide comfort is recommended in the AHA STEMI Guidelines, yet there is limited evidence of safety in this setting. The primary objective of this study was to measure potential harm associated with the provision of IV morphine in STEMI patients presenting to the ED. Methods: This was a two centre retrospective chart review from an urban, inner city, academic ED with an annual census of 85,000 visits, and an affiliated community hospital with 35,000 annual visits. Consecutive patients from April 2009 to January 2015 presenting to the 2 EDs with a diagnosis of STEMI were identified in the ED database. Eight trained research assistants, blinded to the study hypothesis, used standardized data collection templates. The primary investigator double collected 20% of all data to ensure completeness and accuracy. Results: We included 311 patients with STEMI (124 received morphine [M]; 187 no morphine [nM]). The ages of the two groups were similar (mean 64 yrs [M] & 67 yrs [nM]; median 63 yrs [M] & 66 yrs [nM]; IQR 45-81 [M] and 45.5-86.5 [nM]); as were the proportion of female patients (21.0% [M] & 23.5% [nM]. The pre-STEMI Charlson comorbidity scores (mean 2.6), median time to first ECG (11 min [M] & 16 min [nM]), and mean time-to-needle for PCI (96.8 min [M] & 92.0 min [nM]) were similar between groups. The mean CCU length of stay (LOS) (9.3 days vs 6.3 days) and hospital LOS (7.4 days vs 4.6 days) were longer for patients receiving morphine than those not receiving morphine. Rates of congestive heart failure, acute kidney injury and cardiac arrest in hospital were unchanged between the groups. Unadjusted mortality was similar (10.5% [M] vs 13.3% [nM]) between groups. Binary logistic regression controlling for age, Charlson score, first and peak troponin values demonstrated an association between receiving morphine in the ED and an increased risk of death at 30 days (OR 8.1; 95% CI 7.1.-9.1). Conclusion: The provision of morphine to patients with STEMI in the ED may be associated with increased CCU and hospital LOS. When controlling for age, pre-STEMI Charlson score, first and peak troponin values, receiving morphine was associated with an increased risk of death at 30 days. Further research to elucidate this association is warranted.

Adjuvant effects on disease severity caused by the bioherbicide P. papaveracea on opium poppy were evaluated. Tween 20, Tween 80, Triton X-100, Tactic, CelGard, and Keltrol inhibited appressorium formation but not conidial germination on detached leaves. The disease severity varied from 11 to 83% necrosis in field experiments involving eight adjuvants at various concentrations plus 1 × 106 conidia ml−1 or minus pathogen. The three best-performing adjuvants when combined with pathogen, Tactic (1%, v/v), Bond (1%, v/v), and Tween 20 (1%, v/v), were included along with Tween 20 (0.001%, v/v) in field experiments in 1998. Tween 20 (1%, v/v) plus pathogen (1 × 106 conidia ml−1) caused the most severe disease, averaging 68% necrosis within 2 wk of treatment. Overall, plots treated with adjuvant plus P. papaveracea had a 22% reduction in capsule weight per plot as compared to plots treated with the adjuvant alone. Tactic (1%, v/v), Silwet-L77 (0.1%, v/v), Tween 20 (1%, v/v), and Tween 20 (0.001%, v/v) were included in field experiments in 1999. The treatment with Tween 20 (1%, v/v) plus pathogen (2 × 106 conidia ml−1) caused severe disease, averaging 56% necrosis within 2 wk of treatment. In 1999 plots treated with adjuvant plus pathogen averaged a 27% reduction in capsule weight as compared with plots treated with the adjuvants alone. The inclusion of Tween 20 (1%, v/v) with P. papaveracea conidia greatly enhanced efficacy on opium poppy.

Introduction: 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.

Methods: 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).

Results: 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).

Conclusion: 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.

The serotonin syndrome is a potential side-effect of serotonin-enhancing drugs, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). We recently reported a genetic mouse model for the serotonin syndrome, as serotonin transporter (SERT)-deficient mice have exaggerated serotonin syndrome behavioural responses to the MAOI tranylcypromine and the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP). As numerous case reports implicate the atypical opioids tramadol and meperidine in the development of the human serotonin syndrome, we examined tramadol and meperidine as possible causative drugs in the rodent model of the serotonin syndrome in SERT wild-type (+/+), heterozygous (+/−) and knockout (−/−) mice. Comparisons were made with SERT mice treated with either vehicle or morphine, an opioid not implicated in the serotonin syndrome in humans. Here we show that tramadol and meperidine, but not morphine, induce serotonin syndrome-like behaviours in mice, and we show that this response is exaggerated in mice lacking one or two copies of SERT. The exaggerated response to tramadol in SERT−/− mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635. Further, we show that morphine-, meperidine- and tramadol-induced analgesia is markedly decreased in SERT−/− mice. These studies suggest that caution seems warranted in prescribing or not warning patients receiving SSRIs or MAOIs that dangerous side-effects may occur during concurrent use of tramadol and similar agents. These findings suggest that it is conceivable that there might be increased vulnerability in individuals with SERT polymorphisms that may reduce SERT by more than 50%, the level in SERT+/− mice.