| 1. |
- Friesgaard, Kristian Dahl, et al.
(author)
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Opioids for Treatment of Pre-hospital Acute Pain : A Systematic Review
- 2022
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In: Pain and Therapy. - : Springer. - 2193-8237 .- 2193-651X. ; 11:1, s. 17-36
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Research review (peer-reviewed)abstract
- Introduction Acute pain is a frequent symptom among patients in the pre-hospital setting, and opioids are the most widely used class of drugs for the relief of pain in these patients. However, the evidence base for opioid use in this setting appears to be weak. The aim of this systematic review was to explore the efficacy and safety of opioid analgesics in the pre-hospital setting and to assess potential alternative therapies. Methods The PubMed, EMBASE, Cochrane Library, Centre for Reviews and Dissemination, Scopus, and Epistemonikos databases were searched for studies investigating adult patients with acute pain prior to their arrival at hospital. Outcomes on efficacy and safety were assessed. Risk of bias for each included study was assessed according to the Cochrane approach, and confidence in the evidence was assessed using the GRADE method. Results A total of 3453 papers were screened, of which the full text of 125 was assessed. Twelve studies were ultimately included in this systematic review. Meta-analysis was not undertaken due to substantial clinical heterogeneity among the included studies. Several studies had high risk of bias resulting in low or very low quality of evidence for most of the outcomes. No pre-hospital studies compared opioids with placebo, and no studies assessed the risk of opioid administration for subgroups of frail patients. The competency level of the attending healthcare provider did not seem to affect the efficacy or safety of opioids in two observational studies of very low quality. Intranasal opioids had a similar effect and safety profile as intravenous opioids. Moderate quality evidence supported a similar efficacy and safety of synthetic opioid compared to morphine. Conclusions Available evidence for pre-hospital opioid administration to relieve acute pain is scarce and the overall quality of evidence is low. Intravenous administration of synthetic, fast-acting opioids may be as effective and safe as intravenous administration of morphine. More controlled studies are needed on alternative routes for opioid administration and pre-hospital pain management for potentially more frail patient subgroups.
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| 2. |
- Jalkanen, Ville, et al.
(author)
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The predictive value of soluble urokinase plasminogen activator receptor (SuPAR) regarding 90-day mortality and 12-month neurological outcome in critically ill patients after out-of-hospital cardiac arrest. Data from the prospective FINNRESUSCI study
- 2014
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In: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 85:11, s. 1562-1567
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Journal article (peer-reviewed)abstract
- Aim: The whole body ischaemia-reperfusion after cardiac arrest (CA) induces a systemic inflammation-reperfusion response. The expression of urokinase plasminogen activator receptor (uPAR) is known to be induced after hypoxia and increased levels of soluble form suPAR have been measured after hypoxia and ischaemia. Our aim was to evaluate, whether ischaemia/reperfusion injury after out-of-hospital cardiac arrest (OHCA) increases suPAR concentrations in serum and to evaluate the prognostic value of suPAR regarding 90-day mortality and 12-month neurological outcome. Methods: This is a pre-determined substudy of prospective FINNRESUSCI study. Total of 287 patients treated in the intensive care units after OHCA and with consent from the next-of-kin and serum samples between baseline and day 4 were included. Outcome and neurological outcome were evaluated according the Pittsburgh Cerebral Performance Categories (CPC). Kaplan-Meier survival curves, areas under receiver operational characteristics curves and positive likelihood ratios for mortality and poor neurological outcome were calculated. Results: Non-survivors had higher levels of suPAR after OHCA. Kaplan-Meier survival curves indicated high 90-day mortality in the highest concentration quintiles. LR+ for 1-year CPC 3-5 was 1.8-2.7 for the whole patient cohort and in shockable rhythms 2.0-2.4. In therapeutic hypothermia prognostic value remained. Conclusions: We found that high SuPAR concentrations were associated with poor outcome in patients with OHCA admitted to critical care. However, suPAR alone had inadequate predictive value for poor outcome and did not associate with 12-month neurological outcome.
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| 3. |
- Ottesen, Anett Hellebø, et al.
(author)
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Secretoneurin is a novel prognostic cardiovascular biomarker associated with cardiomyocyte calcium handling.
- 2015
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 65:4, s. 339-51
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Journal article (peer-reviewed)abstract
- BACKGROUND: Secretoneurin (SN) levels are increased in patients with heart failure (HF), but whether SN provides prognostic information and influences cardiomyocyte function is unknown.OBJECTIVES: This study sought to evaluate the merit of SN as a cardiovascular biomarker and assess effects of SN on cardiomyocyte Ca(2+) handling.METHODS: We assessed the association between circulating SN levels and mortality in 2 patient cohorts and the functional properties of SN in experimental models.RESULTS: In 143 patients hospitalized for acute HF, SN levels were closely associated with mortality (n = 66) during follow-up (median 776 days; hazard ratio [lnSN]: 4.63; 95% confidence interval: 1.93 to 11.11; p = 0.001 in multivariate analysis). SN reclassified patients to their correct risk strata on top of other predictors of mortality. In 155 patients with ventricular arrhythmia-induced cardiac arrest, SN levels were also associated with short-term mortality (n = 51; hazard ratio [lnSN]: 3.33; 95% confidence interval: 1.83 to 6.05; p < 0.001 in multivariate analysis). Perfusing hearts with SN yielded markedly increased myocardial levels and SN internalized into cardiomyocytes by endocytosis. Intracellularly, SN reduced Ca(2+)/calmodulin (CaM)-dependent protein kinase II δ (CaMKIIδ) activity via direct SN-CaM and SN-CaMKII binding and attenuated CaMKIIδ-dependent phosphorylation of the ryanodine receptor. SN also reduced sarcoplasmic reticulum Ca(2+) leak, augmented sarcoplasmic reticulum Ca(2+) content, increased the magnitude and kinetics of cardiomyocyte Ca(2+) transients and contractions, and attenuated Ca(2+) sparks and waves in HF cardiomyocytes.CONCLUSIONS: SN provided incremental prognostic information to established risk indices in acute HF and ventricular arrhythmia-induced cardiac arrest.
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| 4. |
- Ottesen, Anett H., et al.
(author)
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Secretoneurin Is an Endogenous Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor That Attenuates Ca2+-Dependent Arrhythmia
- 2019
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In: Circulation. - : Lippincott Williams & Wilkins. - 1941-3149 .- 1941-3084. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Circulating SN (secretoneurin) concentrations are increased in patients with myocardial dysfunction and predict poor outcome. Because SN inhibits CaMKII delta (Ca2+/calmodulin-dependent protein kinase II delta) activity, we hypothesized that upregulation of SN in patients protects against cardiomyocyte mechanisms of arrhythmia. METHODS: Circulating levels of SN and other biomarkers were assessed in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT; n=8) and in resuscitated patients after ventricular arrhythmia-induced cardiac arrest (n=155). In vivo effects of SN were investigated in CPVT mice (RyR2 [ryanodine receptor 2]-R2474S) using adeno-associated virus-9-induced overexpression. Interactions between SN and CaMKII delta were mapped using pull-down experiments, mutagenesis, ELISA, and structural homology modeling. Ex vivo actions were tested in Langendorff hearts and effects on Ca2+ homeostasis examined by fluorescence (fluo-4) and patchclamp recordings in isolated cardiomyocytes. RESULTS: SN levels were elevated in patients with CPVT and following ventricular arrhythmia-induced cardiac arrest. In contrast to NT-proBNP (N-terminal proB- type natriuretic peptide) and hs-TnT (high-sensitivity troponin T), circulating SN levels declined after resuscitation, as the risk of a new arrhythmia waned. Myocardial pro-SN expression was also increased in CPVT mice, and further adeno-associated virus-9-induced overexpression of SN attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies mapped SN binding to the substrate binding site in the catalytic region of CaMKII delta. Accordingly, SN attenuated isoproterenol induced autophosphorylation of Thr287-CaMKII delta in Langendorff hearts and inhibited CaMKII delta-dependent RyR phosphorylation. In line with CaMKII delta and RyR inhibition, SN treatment decreased Ca2+ spark frequency and dimensions in cardiomyocytes during isoproterenol challenge, and reduced the incidence of Ca2+ waves, delayed afterdepolarizations, and spontaneous action potentials. SN treatment also lowered the incidence of early afterdepolarizations during isoproterenol; an effect paralleled by reduced magnitude of L-type Ca2+ current. CONCLUSIONS: SN production is upregulated in conditions with cardiomyocyte Ca2+ dysregulation and offers compensatory protection against cardiomyocyte mechanisms of arrhythmia, which may underlie its putative use as a biomarker in at-risk patients.
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| 5. |
- Raatiniemi, Lasse, et al.
(author)
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Femoral nerve blocks for the treatment of acute pre-hospital pain: A systematic review with meta-analysis
- 2020
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In: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 64:8, s. 1038-1047
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Research review (peer-reviewed)abstract
- Background Pain management is one of the most important interventions in the emergency medical services. The femoral nerve block (FNB) is, among other things, indicated for pre- and post-operative pain management for patients with femoral fractures but its role in the pre-hospital setting has not been determined. The aim of this review was to assess the effect and safety of the FNB in comparison to other forms of analgesia (or no treatment) for managing acute lower extremity pain in adult patients in the pre-hospital setting. Methods A systematic review (PROSPERO registration (CRD42018114399)) was conducted. The Cochrane and GRADE methods were used to assess outcomes. Two authors independently reviewed each study for eligibility, extracted the data and performed risk of bias assessments. Results Four studies with a total of 252 patients were included. Two RCTs (114 patients) showed that FNB may reduce pain more effectively than metamizole (mean difference 32 mm on a 100 mm VAS (95% CI 24 to 40)). One RCT (48 patients) compared the FNB with lidocaine and magnesium sulphate to FNB with lidocaine alone and was only included here for information regarding adverse effects. One case series included 90 patients. Few adverse events were reported in the included studies. The certainty of evidence was very low. We found no studies comparing FNB to inhaled analgesics, opioids or ketamine. Conclusions Evidence regarding the effectiveness and adverse effects of pre-hospital FNB is limited. Studies comparing pre-hospital FNB to inhaled analgesics, opioids or ketamine are lacking.
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| 6. |
- Sandberg, Marten, et al.
(author)
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Ketamine for the treatment of prehospital acute pain: a systematic review of benefit and harm
- 2020
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In: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 10:11
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Research review (peer-reviewed)abstract
- BackgroundFew publications have addressed prehospital use of ketamine in analgesic doses. We aimed to assess the effect and safety profile of ketamine compared with other analgesic drugs (or no drug) in adult prehospital patients with acute pain.MethodsA systematic review of clinical trials assessing prehospital administration of ketamine in analgesic doses compared with other analgesic drugs or no analgesic treatment in adults. We searched PubMed, EMBASE, Cochrane Library and Epistemonikos from inception until 15 February 2020, including relevant articles in English and Nordic languages. We used the Cochrane and Grading of Recommendations Assessment, Development and Evaluation methodologies and exclusively assessed patient-centred outcomes. Two independent authors screened trials for eligibility, extracted data and assessed risk of bias.ResultsWe included eight studies (2760 patients). Ketamine was compared with various opioids given alone, and intranasal ketamine given with nitrous oxide was compared with nitrous oxide given alone. Four randomised controlled trials (RCTs) and one cluster randomised trial included 699 patients. One prospective cohort included 27 patients and two retrospective cohorts included 2034 patients. Five of the eight studies had high risks of bias. Pain score with ketamine is probably lower than after opioids as demonstrated in a cluster-RCT (308 patients) and a retrospective cohort (158 patients) study, Delta visual analogue scale -0.4 (-0.8 to 0.0) and Delta numeric pain rating scale -3.0 (-3.86 to -2.14), respectively. Ketamine probably leads to less nausea and vomiting (risk ratio (RR) 0.24 (0.11 to 0.52)) but more agitation (RR 7.81 (1.85 to 33)) than opioids.ConclusionsThis systematic literature review finds that ketamine probably reduces pain more than opioids and with less nausea and vomiting but higher risk of agitation. Risk of bias in included studies is high.OtherScandinavian society of anaesthesiology and intensive care medicine funded meetings and software. The Norwegian Air Ambulance Foundation funded publication. Otherwise this research received no grant from any agency in the public, commercial or not-for-profit sectors.PROSPERO registration numberCRD42018114399.
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| 7. |
- Vaahersalo, Jukka, et al.
(author)
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Therapeutic hypothermia after out-of-hospital cardiac arrest in Finnish intensive care units : the FINNRESUSCI study
- 2013
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 39:5, s. 826-837
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Journal article (peer-reviewed)abstract
- We aimed to evaluate post-resuscitation care, implementation of therapeutic hypothermia (TH) and outcomes of intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients in Finland. We included all adult OHCA patients admitted to 21 ICUs in Finland from March 1, 2010 to February 28, 2011 in this prospective observational study. Patients were followed (mortality and neurological outcome evaluated by Cerebral Performance Categories, CPC) within 1 year after cardiac arrest. This study included 548 patients treated after OHCA. Of those, 311 patients (56.8 %) had a shockable initial rhythm (incidence of 7.4/100,000/year) and 237 patients (43.2 %) had a non-shockable rhythm (incidence of 5.6/100,000/year). At ICU admission, 504 (92 %) patients were unconscious. TH was given to 241/281 (85.8 %) unconscious patients resuscitated from shockable rhythms, with unfavourable 1-year neurological outcome (CPC 3-4-5) in 42.0 % with TH versus 77.5 % without TH (p < 0.001). TH was given to 70/223 (31.4 %) unconscious patients resuscitated from non-shockable rhythms, with 1-year CPC of 3-4-5 in 80.6 % (54/70) with TH versus 84.0 % (126/153) without TH (p = 0.56). This lack of difference remained after adjustment for propensity to receive TH in patients with non-shockable rhythms. One-year unfavourable neurological outcome of patients with shockable rhythms after TH was lower than in previous randomized controlled trials. However, our results do not support use of TH in patients with non-shockable rhythms.
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