Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease.

Dehydration is an important cause of death in patients with Ebola virus disease (EVD). Parenteral fluids are often required in patients with fluid requirements in excess of their oral intake. The peripheral intravenous route is the most commonly used method of parenteral access, but inserting and maintaining an intravenous line can be challenging in the context of EVD. Therefore it is important to consider the advantages and disadvantages of different routes for achieving parenteral access (e.g. intravenous, intraosseous, subcutaneous and intraperitoneal). To compare the reliability, ease of use and speed of insertion of different parenteral access methods. We ran the search on 17 November 2014. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid MEDLINE(R) and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), CINAHL (EBSCOhost), clinicaltrials.gov and screened reference lists. Randomised controlled trials comparing different parenteral routes for the infusion of fluids or medication. Two review authors examined the titles and abstracts of records obtained by searching the electronic databases to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. Outcome measures of interest were success of insertion; time required for insertion; number of insertion attempts; number of dislodgements; time period with functional access; local site reactions; clinicians' perception of ease of administration; needlestick injury to healthcare workers; patients' discomfort; and mortality. For trials involving the administration of fluids we also collected data on the volume of fluid infused, changes in serum electrolytes and markers of renal function. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the following outcomes: success of insertion, time required for insertion, number of dislodgements, volume of fluid infused and needlestick injuries. We included 17 trials involving 885 participants. Parenteral access was used to infuse fluids in 11 trials and medications in six trials. None of the trials involved patients with EVD. Intravenous and intraosseous access was compared in four trials; intravenous and subcutaneous access in 11; peripheral intravenous and intraperitoneal access in one; saphenous vein cutdown and intraosseous access in one; and intraperitoneal with subcutaneous access in one. All of the trials assessing the intravenous method involved peripheral intravenous access.We judged few trials to be at low risk of bias for any of the assessed domains.Compared to the intraosseous group, patients in the intravenous group were more likely to experience an insertion failure (risk ratio (RR) 3.89, 95% confidence interval (CI) 2.39 to 6.33; n = 242; GRADE rating: low). We did not pool data for time to insertion but estimates from the trials suggest that inserting intravenous access takes longer (GRADE rating: moderate). Clinicians judged the intravenous route to be easier to insert (RR 0.15, 95% CI 0.04 to 0.61; n = 182). A larger volume of fluids was infused via the intravenous route (GRADE rating: moderate). There was no evidence of a difference between the two routes for any other outcomes, including adverse events.Compared to the subcutaneous group, patients in the intravenous group were more likely to experience an insertion failure (RR 14.79, 95% CI 2.87 to 76.08; n = 238; GRADE rating: moderate) and dislodgement of the device (RR 3.78, 95% CI 1.16 to 12.34; n = 67; GRADE rating: low). Clinicians also judged the intravenous route as being more difficult to insert and patients were more likely to be agitated in the intravenous group. Patients in the intravenous group were more likely to develop a local infection and phlebitis, but were less likely to develop erythema, oedema or swelling than those in the subcutaneous group. A larger volume of fluids was infused into patients via the intravenous route. There was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine if the risk of insertion failure differed between the saphenous vein cutdown (SVC) and intraosseous method (RR 4.00, 95% CI 0.51 to 31.13; GRADE rating: low). Insertion using SVC took longer than the intraosseous method (MD 219.60 seconds, 95% CI 135.44 to 303.76; GRADE rating: moderate). There were no data and therefore there was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine the relative effects of intraperitoneal or central intravenous access relative to any other parenteral access method. There are several different ways of achieving parenteral access in patients who are unable meet their fluid requirements with oral intake alone. The quality of the evidence, as assessed using the GRADE criteria, is somewhat limited because of the lack of adequately powered trials at low risk of bias. However, we believe that there is sufficient evidence to draw the following conclusions: if peripheral intravenous access can be achieved easily, this allows infusion of larger volumes of fluid than other routes; but if this is not possible, the intraosseous and subcutaneous routes are viable alternatives. The subcutaneous route may be suitable for patients who are not severely dehydrated but in whom ongoing fluid losses cannot be met by oral intake.A film to accompany this review can be viewed here (http://youtu.be/ArVPzkf93ng)

Use of tranexamic acid in major trauma: a sex-disaggragated analysis of the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2 and CRASH-3) trials and UK trauma registry (Trauma and Audit Research Network) data.

Women are less likely than men to receive some emergency treatments. This study examines whether the effect of tranexamic acid (TXA) on mortality in trauma patients varies by sex and whether the receipt of TXA by trauma patients varies by sex. First, we conducted a sex-disaggregated analysis of data from the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH)-2 and CRASH-3 trials. We used interaction tests to determine whether the treatment effect varied by sex. Second, we examined data from the Trauma and Audit Research Network (TARN) to explore sex differences in the receipt of TXA. We used logistic regression models to estimate the odds ratio for receipt of TXA in females compared with males. Results are reported as n (%), risk ratios (RR), and odds ratios (OR) with 95% confidence intervals. Overall, 20 211 polytrauma patients (CRASH-2) and 12 737 patients with traumatic brain injuries (CRASH-3) were included in our analysis. TXA reduced the risk of death in females (RR=0.69 [0.52-0.91]) and in males (RR=0.80 [0.71-0.90]) with no significant heterogeneity by sex (P=0.34). We examined TARN data for 216 364 patients aged ≥16 yr with an Injury Severity Score ≥9 with 98 879 (46%) females and 117 485 (54%) males. TXA was received by 7198 (7.3% [7.1-7.4%]) of the females and 19 697 (16.8% [16.6-17.0%]) of the males (OR=0.39 [0.38-0.40]). The sex difference in the receipt of TXA increased with increasing age. Administration of TXA to patients with bleeding trauma reduces mortality to a similar extent in women and men, but women are substantially less likely to be treated with TXA

The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis

Introduction: The Antifibrinolytic Trialists Collaboration aims to increase knowledge about the effectiveness and safety of antifibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of antifibrinolytics for acute intracranial haemorrhage. Methods: The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42016052155). We will conduct an individual patient data meta-analysis of randomised controlled trials with 1000 patients or more assessing the effects of antifibrinolytics in acute intracranial haemorrhage. We will assess the effect on two co-primary outcomes: 1) death in hospital at end of trial follow-up, and 2) death in hospital or dependency at end of trial follow-up. The co-primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of antifibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of antifibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis. Conclusions: This IPD meta-analysis will examine important clinical questions about the effects of antifibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice

The WOMAN trial: clinical and contextual factors surrounding the deaths of 483 women following post-partum haemorrhage in developing countries.

BACKGROUND: Post-partum haemorrhage (PPH) is a leading cause of maternal death worldwide. The WOMAN trial assessed the effects of tranexamic acid (TXA) on death and surgical morbidity in women with PPH. The trial recorded 483 maternal deaths. We report the circumstances of the women who died. METHODS: The WOMAN trial recruited 20,060 women with a clinical diagnosis of PPH after a vaginal birth or caesarean section. We randomly allocated women to receive TXA or placebo. When a woman died, we asked participating clinicians to report the cause of death and to provide a short narrative of the events surrounding the death. We collated and edited for clarity the narrative data. RESULTS: Case fatality rates were 3.0% in Africa and 1.7% in Asia. Nearly three quarters of deaths were within 3 h of delivery and 91% of these deaths were from bleeding. Women who delivered outside a participating hospital (12%) were three times more likely to die (OR = 3.12, 95%CI 2.55-3.81) than those who delivered in hospital. Blood was often unavailable due to shortages or because relatives could not afford to buy it. Clinicians highlighted late presentation, maternal anaemia and poor infrastructure as key contributory factors. CONCLUSIONS: Although TXA use reduces bleeding deaths by almost one third, mortality rates similar to those in high income countries will not be achieved without tackling late presentation, maternal anaemia, availability of blood for transfusion and poor infrastructure

Point of care coagulometry in prehospital emergency care: an observational study

Background: Haemostatic impairment can have a crucial impact on the outcome of emergency patients, especially in cases of concomitant antithrombotic drug treatment. In this prospective observational study we used a point of care (POC) coagulometer in a prehospital physician-based emergency medical system in order to test its validity and potential value in the treatment of emergency patients. Methods: During a study period of 12 months, patients could be included if venous access was mandatory for further treatment. The POC device CoaguChek® was used to assess international normalized ratio (INR) after ambulance arrival at the scene. Results were compared with in-hospital central laboratory assessment of INR. The gain of time was analysed as well as the potential value of POC testing through a questionnaire completed by the responsible prehospital emergency physician. Results: A total of 103 patients were included in this study. POC INR results were highly correlated with results of conventional assessment of INR (Bland-Altman-bias: 0.014). Using a cutoff value of INR >1.3, the device’s sensitivity to detect coagulopathy was 100 % with a specificity of 98.7 %. The median gain of time was 69 min. Treating emergency physicians considered the value of prehospital POC INR testing ‘high’ in 9 % and ‘medium’ in 21 % of all patients. In patients with tracer diagnosis ‘neurology’, the value of prehospital INR assessment was considered ‘high’ or ‘medium’ (63 %) significantly more often than in patients with non-neurological tracer diagnoses (24 %). Conclusions: Assessment of INR through a POC coagulometer is feasible in prehospital emergency care and provides valuable information on haemostatic parameters in patients. Questionnaire results suggest that POC INR testing may present a valuable technique in selected patients. Whether this information translates into an improved management of respective patients has to be evaluated in further studies

Cost-Effectiveness Analysis of Administering Tranexamic Acid to Bleeding Trauma Patients Using Evidence from the CRASH-2 Trial

OBJECTIVE: To assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings. METHODS: The CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. FINDINGS: Administering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was$17,483 in Tanzania, $19,550 in India and$30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was $18,025 in Tanzania,$20,670 in India and $48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is$48, $66 and$64 in Tanzania, India and the UK respectively. CONCLUSION: Early administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings. TRIAL REGISTRATION: This paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.govNCT00375258 and South African Clinical Trial Register DOH-27-0607-1919

Risk factors for peripartum hysterectomy among women with postpartum haemorrhage: analysis of data from the WOMAN trial.

BACKGROUND: Peripartum hysterectomy can cause significant morbidity and mortality. Most studies of peripartum hysterectomy are from high income countries. This cohort study examined risk factors for peripartum hysterectomy using data from Africa, Asia, Europe and the Americas. METHODS: We used data from the World Maternal Antifibrinolytic (WOMAN) trial carried out in 193 hospitals in 21 countries. Peripartum hysterectomy was defined as hysterectomy within 6 weeks of delivery as a complication of postpartum haemorrhage. Univariable and multivariable random effects logistic regression models were used to analyse risk factors. A hierarchical conceptual framework guided our multivariable analysis. RESULTS: Five percent of women had a hysterectomy (1020/20,017). Haemorrhage from placenta praevia/accreta carried a higher risk of hysterectomy (17%) than surgical trauma/tears (5%) and uterine atony (3%). The adjusted odds ratio (AOR) for hysterectomy in women with placenta praevia/accreta was 3.2 (95% CI: 2.7-3.8), compared to uterine atony. The risk of hysterectomy increased with maternal age. Caesarean section was associated with fourfold higher odds of hysterectomy than vaginal delivery (AOR 4.3, 95% CI: 3.6-5.0). Mothers in Asia had a higher hysterectomy incidence (7%) than mothers in Africa (5%) (AOR: 1.2, 95% CI: 0.9-1.7). CONCLUSIONS: Placenta praevia/accreta is associated with a higher risk of peripartum hysterectomy. Other risk factors for hysterectomy are advanced maternal age, caesarean section and giving birth in Asia