Opioids for Treatment of Pre-hospital Acute Pain: A Systematic Review.

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.

Ketamine for the treatment of prehospital acute pain: a systematic review of benefit and harm.

BACKGROUND: Few 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. METHODS: A 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. RESULTS: We 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, Δvisual analogue scale -0.4 (-0.8 to 0.0) and Δnumeric 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. CONCLUSIONS: This 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. OTHER: Scandinavian 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 NUMBER: CRD42018114399.

[Should all patients with traumatic brain injury receive tranexamic acid?] / Tranexamsyra till alla med akut traumatisk hjärnskada?

Traumatic brain injury (TBI) is a leading cause of death and disability. Progressive intracranial bleeding is common in TBI and worsens outcome. The multicentre, randomized placebo-controlled CRASH-3 study enrolling 12,737 patients showed that early, <3h, administration of tranexamic acid (TXA) decreased mortality in mild-moderate TBI patients. In accordance with large previous trials, thromboembolic complications were not increased. In view of the favourable safety profile of TXA and the devastating effects from intracranial bleeds, the authors argue that TXA be administered within 3h post-injury to moderate-severe TBI patients, and in mild TBI to those with intracranial haemorrhage on acute CT.

Femoral nerve blocks for the treatment of acute pre-hospital pain: A systematic review with meta-analysis.

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.

The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting.

BACKGROUND: Pain is a common condition among prehospital patients. The present study is designed to determine whether adding low-dose ketamine as additional analgesia improves the pain/nausea scores and hemodynamic parameters compared to morphine sulphate alone among patients with bone fractures. METHODS: Prospective, prehospital clinical cohort study. Twenty-seven patients were included with acute pain. Eleven patients received morphine sulphate 0.2 mg/kg (M-group) and 16 patients received morphine sulphate 0.1 mg/kg combined with 0.2 mg/kg ketamine (MK-group). Scores for pain, nausea, sedation (AVPU) and the haemodynamic parameters (systolic blood pressures (BP), heart rate (HR) and peripheral oxygen saturation (SpO2) were recorded at rescue scene before the start of analgesia and subsequently to admission at hospital. RESULTS: Mean treatment time 46 +/- 17 minutes in the M-group and 56 +/- 11 minutes in the MK-group, respectively (ns). Mean doses of morphine sulphate in the M-group were 13.5 +/- 3.2 mg versus 7.0 +/- 1.5 mg in the MK-group. The mean additional doses of ketamine in the MK-group were 27.9 +/- 11.4 mg. There were significantly differences between the M- and the MK-group according to NRS scores for pain (5.4 +/- 1.9 versus 3.1 +/- 1.4) and BP (134 +/- 21 mmHg versus 167 +/- 32 mmHg) at admission at hospital, respectively (P < 0.05). All patients were Alert or respond to Voice and the results were similar between the groups. One patient versus 4 patients reported nausea in the M- and MK-group, respectively, and 3 patients vomited in the Mk-group (ns). CONCLUSION: We conclude that morphine sulphate with addition of small doses of ketamine provide adequate pain relief in patients with bone fractures, with an increase in systolic blood pressure, but without significant side effects.