Can absence of cardiac activity on point-of-care echocardiography predict death in out-of-hospital cardiac arrest? A systematic review and meta-analysis.

AIM: The purpose of this systematic review and meta-analysis was to evaluate the accuracy of the absence of cardiac motion on point-of-care echocardiography (PCE) in predicting termination of resuscitation (TOR), short-term death (STD), and long-term death (LTD), in adult patients with cardiac arrest of all etiologies in out-of-hospital and emergency department setting. METHODS: A systematic review and meta-analysis was conducted based on PRISMA guidelines. A literature search in Medline, EMBASE, Cochrane, WHO registry, and ClinicalTrials.gov was performed from inspection to August 2022. Risk of bias was evaluated using QUADAS-2 tool. Meta-analysis was divided into medical cardiac arrest (MCA) and traumatic cardiac arrest (TCA). Sensitivity and specificity were calculated using bivariate random-effects, and heterogeneity was analyzed using I2 statistic. RESULTS: A total of 27 studies (3657 patients) were included in systematic review. There was a substantial variation in methodologies across the studies, with notable difference in inclusion criteria, PCE timing, and cardiac activity definition. In MCA (15 studies, 2239 patients), the absence of cardiac activity on PCE had a sensitivity of 72% [95% CI 62-80%] and specificity of 80% [95% CI 58-92%] to predict LTD. Although the low numbers of studies in TCA preluded meta-analysis, all patients who lacked cardiac activity on PCE eventually died. CONCLUSIONS: The absence of cardiac motion on PCE for MCA predicts higher likelihood of death but does not have sufficient accuracy to be used as a stand-alone tool to terminate resuscitation. In TCA, the absence of cardiac activity is associated with 100% mortality rate, but low number of patients requires further studies to validate this finding. Future work would benefit from a standardized protocol for PCE timing and agreement on cardiac activity definition.

EFSUMB Clinical Practice Guidelines for Point-of-Care Ultrasound: Part One (Common Heart and Pulmonary Applications) SHORT VERSION.

OBJECTIVE: To evaluate the evidence and produce a summary and recommendations for the most common heart and lung point-of-care ultrasound (PoCUS). METHODS: We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendations were produced, including assigning levels of evidence (LoE) and grading of recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement of the summary and recommendation for each question (using a 5-point Likert scale), which was approved in the case of a level of agreement of greater than 75 %. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses. FINDINGS AND RECOMMENDATIONS: One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1), the remaining 9 questions achieved broad agreement with an assigned LoE of 4 and a weak GRADE recommendation (question 2), three achieved an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8) and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). CONCLUSION: These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings.

EFSUMB Clinical Practice Guidelines for Point-of-Care Ultrasound: Part One (Common Heart and Pulmonary Applications) LONG VERSION.

AIMS: To evaluate the evidence and produce a summary and recommendations for the most common heart and lung applications of point-of-care ultrasound (PoCUS). METHODS: We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendation were produced, including assignment of levels of evidence (LoE) and grading of the recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement regarding the summary and recommendation for each question (using a 5-point Likert scale), which was approved if a level of agreement of greater than 75 % was reached. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses. FINDINGS AND RECOMMENDATIONS: One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1). The remaining 9 questions achieved broad agreement with one assigned an LoE of 4 and weak GRADE recommendation (question 2), three achieving an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8), and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). CONCLUSION: These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings.

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

BACKGROUND: In people with sickle cell disease, sickled red blood cells cause the occlusion of small blood vessels, which presents as episodes of severe pain known as pain crises or vaso-occlusive crises. The pain can occur in the bones, chest, or other parts of the body, and may last several hours to days. Pain relief during crises includes both pharmacologic and non-pharmacologic treatments. The efficacy of inhaled nitric oxide in pain crises has been a subject of controversy; hypotheses have been made suggesting a beneficial response due to its vasodilator properties, yet no conclusive evidence has been presented. This review aimed to evaluate the available randomised controlled studies addressing this topic. OBJECTIVES: To capture the body of evidence evaluating the efficacy and safety of the use of inhaled nitric oxide in treating pain crises in people with sickle cell disease, and to assess the relevance, robustness, and validity of the treatment to better guide medical practice in the fields of haematology and palliative care (since the recent literature seems to favour the involvement of palliative care for such people). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register. We searched for unpublished work in the abstract books of the European Haematology Association conference, the American Society of Hematology conference, the British Society for Haematology Annual Scientific Meeting, the Caribbean Health Research Council Meetings, and the National Sickle Cell Disease Program Annual Meeting. The most recent search was conducted on 1 September 2021. We also searched ongoing study registries on 19 November 2021. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing inhaled nitric oxide with placebo for treating pain crises in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data (including adverse event data), with any disagreements resolved by consulting a third review author. When the data were not reported in the text, we attempted to extract the data from available tables or figures. We contacted trial authors for additional information. We assessed the certainty of the evidence using the GRADE criteria. MAIN RESULTS: We included three trials involving a total of 188 participants in the review. There were equal numbers of males and females. Most participants were adults, although one small trial was conducted in a children's hospital and recruited children over the age of 10 years. All three parallel trials compared inhaled nitric oxygen (80 parts per million (ppm)) to placebo (nitrogen gas mixed with oxygen or room air) for four hours; one trial continued administering nitric oxide (40 ppm) for a further four hours. This extended trial had an overall low risk of bias; however, we had concerns about risk of bias for the remaining two trials due to their small sample size, and additionally a high risk of bias due to financial conflicts of interest in one of these smaller trials. We were only able to analyse some limited data from the eight-hour trial, reporting the remaining results narratively. Evidence from one trial (150 participants) suggested that inhaled nitric oxide may not reduce the time to pain resolution: inhaled nitric oxide median 73.0 hours (95% confidence interval (CI) 46.0 to 91.0) and with placebo median 65.5 hours (95% CI 48.1 to 84.0) (low-certainty evidence). No trial reported on the duration of the initial pain crisis. Only one large trial reported on the frequency of pain crises in the follow-up period and found there may be little or no difference between the inhaled nitric oxide and placebo groups for return to the emergency department (risk ratio (RR) 0.73, 95% CI 0.31 to 1.71) and rehospitalisation (RR 0.53, 95% CI 0.25 to 1.11) (150 participants; low-certainty evidence). There may be little or no difference between treatment and placebo in terms of reduction in pain score at any time point up to eight hours (150 participants). The two smaller trials reported a beneficial effect of inhaled nitric oxide in reducing the visual analogue pain score after four hours of the intervention. Analgesic use was reported not to differ greatly between the inhaled nitric oxide group and placebo group in any of the three trials, but no analysable data were provided. Two trials reported the median duration of hospitalisation: in the largest trial the placebo group had the shorter duration, whilst in the second smaller (paediatric) trial hospitalisation was shorter in the treatment group. Only the largest trial (150 participants) reported serious adverse events, with no increase in the inhaled nitric oxide group during or after the intervention compared to the control group (acute chest syndrome occurred in 5 out of 75 participants from each group, pyrexia in 1 out of 75 participants from each group, and dysphagia and a drop in haemoglobin were each reported in 1 out of 75 participants in the inhaled nitric oxide group) (low-certainty evidence). AUTHORS' CONCLUSIONS: The currently available evidence is insufficient to determine the effects (benefits or harms) of using inhaled nitric oxide to treat pain (vaso-occlusive) crises in people with sickle cell disease. Large-scale, long-term trials are needed to provide more robust data in this area. Patient-important outcomes (e.g. measures of pain and time to pain resolution and amounts of analgesics used), as well as use of healthcare services, should be measured and reported in a standardised manner.

Assessing left ventricular systolic function by emergency physician using point of care echocardiography compared to expert: systematic review and meta-analysis.

Assessing left ventricular systolic function (LVSF) by echocardiography assists in the diagnosis and management of a diverse range of patients presenting to the emergency department (ED). We evaluated the agreement between ED-based clinician sonographers and apriori-defined expert sonographers. We conducted a systematic review and meta-analysis based on Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. We searched Medline, EMBASE, Cochrane, ClinicalTrials.gov, TRIP and Google Scholar for eligible studies from inception to February 2021. Risk of bias was evaluated using Quality Assessment Tool for Diagnostic Accuracy Studies-2 tool. The level of agreement between clinician and expert sonographers was measured using kappa, sensitivity, specificity, positive and negative likelihood ratio statistics using random-effects models. Twelve studies were included (1131 patients, 1229 scans and 159 clinician sonographers). Significant heterogeneity was identified in patient selection, methods of assessment of LVSF, reference standards and statistical methods for assessing agreement. The overall quality of studies was low, with most being small, single centre convenience samples. A meta-analysis including seven studies (786 scans) where visual estimation method was used by clinician sonographers demonstrated simple Kappa of 0.68 [95% confidence interval (CI), 0.57-0.79], and sensitivity, specificity, positive and negative likelihood ratio of 89% (95% CI, 80-94%), 85% (95% CI, 80-89%), 5.98 (95% CI, 4.13-8.68) and 0.13 (95% CI, 0.06-0.24), respectively, between clinician sonographer and expert sonographer for normal/abnormal LVSF. The weighted kappa for five studies (429 scans) was 0.70 (95% CI, 0.61-0.80) for normal/reduced/severely reduced LVSF. There is substantial agreement between ED-based clinician sonographers and expert sonographers for assessing LVSF using visual estimation and ranking it as normal/reduced, or normal/reduced/severely reduced, in patients presenting to ED.

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

BACKGROUND: In people with sickle cell disease, sickled red blood cells cause the occlusion of small blood vessels which presents as episodes of severe pain known as pain crises or vaso-occlusive crises. The pain can occur in the bones, chest, or other parts of the body, and may last several hours to days. Pain relief during crises includes both pharmacologic and non-pharmacologic treatments. The efficacy of inhaled nitric oxide in pain crises has been a controversial issue and hypotheses have been made suggesting a beneficial response due to its vasodilator properties. Yet no conclusive evidence has been presented.This review aims to evaluate the available randomised controlled studies which address this topic. OBJECTIVES: To capture the available body of evidence evaluating the efficacy and safety of the use of inhaled nitric oxide in treating pain crises in people with sickle cell disease; and to assess the treatment's relevance, robustness, and validity, in order to better guide medical practice in the fields of haematology and palliative care (since recent literature seems to favour the involvement of palliative care for those people). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. Unpublished work is identified by searching the abstract books of the European Haematology Association conference; the American Society of Hematology conference; the British Society for Haematology Annual Scientific Meeting; the Caribbean Health Research Council Meetings; and the National Sickle Cell Disease Program Annual Meeting.Date of most recent search: 19 September 2019.We also searched ongoing study registries, date of most recent search: 26 September 2019. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing inhaled nitric oxide with placebo, or standardized way of treatment of pain crises in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data (including adverse event data). A third author helped clarify any disagreement. When the data were not reported in the text, we attempted to extract the data from any table or figure available. We contacted trial authors for additional information. We assessed the quality of the evidence using the GRADE criteria MAIN RESULTS: We identified six trials, three of which (188 participants) were eligible for inclusion in the review. There were equal numbers of males and females; and most participants were adults, although one small trial was conducted in a children's hospital and recruited children over the age of 10 years. All three parallel trials compared inhaled nitric oxygen (80 ppm) to placebo (room air) for four hours; one trial continued administering nitric oxide (40 ppm) for a further four hours. This extended trial had an overall low risk of bias; however, in the remaining two trials we had concerns about the risk of bias from the small sample size and additionally a high risk of bias due to financial conflicts of interest in one of these smaller trials. We were only able to analyse some limited data from the eight-hour trial and report the remaining results narratively.The time to pain resolution was only reported in one trial (150 participants), showing there may be little or no difference between the two groups: with inhaled nitric oxide median 73.0 hours (95% confidence interval (CI) 46.0 to 91.0) and with placebo median 65.5 hours (95% CI 48.1 to 84.0) (low-quality evidence). No trial reported on the duration of the initial pain crisis. Only one large trial reported on the frequency of pain crises in the follow-up period and found there may be little or no difference between the inhaled nitric oxide and placebo groups for a return to the ED, risk ratio 0.73 (95% CI 0.31 to 1.71) or for re-hospitalisation, risk ratio 0.53 (95% CI 0.25 to 1.11) (150 participants; low-quality evidence).There may be little or no difference between treatment and placebo in terms of reduction in pain score at any time point up to eight hours (150 participants). The two smaller trials reported a beneficial effect of inhaled nitric oxide in reducing the visual analogue pain score after four hours of the intervention, but these trials were small and limited compared to the first trial.Analgesic use was reported not to differ greatly between the inhaled nitric oxide group and placebo group in any of the three trials, but no analysable data were provided. The median duration of hospitalisation was reported by two trials, in the largest trial the placebo group had the shorter duration and in the second smaller (paediatric) trial hospitalisation was shorter in the treatment group.Only the largest trial (150 participants) reported serious adverse events, with no increase in the inhaled nitric oxide group during or after the intervention compared to the control group (acute chest syndrome occurred in 5 out of 75 participants from each group, pyrexia in 1 out of 75 participants from each group, dysphagia and a drop in haemoglobin were each reported in 1 out of 75 participants in the inhaled nitric oxide group, but not in the placebo group) (low-quality evidence). AUTHORS' CONCLUSIONS: The currently available trials do not provide sufficient evidence to determine the effects (benefits or harms) of using inhaled nitric oxide to treat pain (vaso-occlusive) crises in people with sickle cell disease. Large-scale, long-term trials are needed to provide more robust data in this area. Patient-important outcomes (e.g. measures of pain and time to pain resolution and amounts of analgesics used), as well as use of healthcare services should be measured and reported in a standardized form.