Abstract Lactate levels are commonly evaluated in acutely ill patients. Although most often used in the context of evaluating shock, lactate levels can be elevated for many reasons. While tissue ...hypoperfusion may be the most common cause of elevation, many other etiologies or contributing factors exist. Clinicians need to be aware of the many potential causes of lactate level elevation as the clinical and prognostic importance of an elevated lactate level varies widely by disease state. Moreover, specific therapy may need to be tailored to the underlying cause of elevation. The present review is based on a comprehensive PubMed search between the dates of January 1, 1960, to April 30, 2013, using the search term lactate or lactic acidosis combined with known associations, such as shock, sepsis, cardiac arrest, trauma, seizure, ischemia, diabetic ketoacidosis, thiamine, malignancy, liver, toxins, overdose, and medication. We provide an overview of the pathogenesis of lactate level elevation followed by an in-depth look at the varied etiologies, including medication-related causes. The strengths and weaknesses of lactate as a diagnostic/prognostic tool and its potential use as a clinical end point of resuscitation are discussed. The review ends with some general recommendations on the management of patients with elevated lactate levels.
BACKGROUND:Cardiac arrest in hospitalized children is associated with poor outcomes, but no contemporary study has reported whether the trends in survival have changed over time. In this study, we ...examined temporal trends in survival for pediatric patients with an in-hospital pulseless cardiac arrest and pediatric patients with a nonpulseless cardiopulmonary resuscitation event from 2000 to 2018.
METHODS:This was an observational study of hospitalized pediatric patients (≤18 years of age) who received cardiopulmonary resuscitation from January 2000 to December 2018 and were included in the Get With The Guidelines-Resuscitation registry, a United States–based in-hospital cardiac arrest registry. The primary outcome was survival to hospital discharge, and the secondary outcome was return of spontaneous circulation (binary outcomes). Generalized estimation equations were used to obtain unadjusted trends in outcomes over time. Separate analyses were performed for patients with a pulseless cardiac arrest and patients with a nonpulseless event (bradycardia with poor perfusion) requiring cardiopulmonary resuscitation. A subgroup analysis was conducted for shockable versus nonshockable initial rhythms in pulseless events.
RESULTS:A total of 7433 patients with a pulseless cardiac arrest and 5751 patients with a nonpulseless event were included for the analyses. For pulseless cardiac arrests, survival was 19% (95% CI, 11%–29%) in 2000 and 38% (95% CI, 34%–43%) in 2018, with an absolute change of 0.67% (95% CI, 0.40%–0.95%; P<0.001) per year, although the increase in survival appeared to stagnate following 2010. Return of spontaneous circulation also increased over time, with an absolute change of 0.83% (95% CI, 0.53%–1.14%; P<0.001) per year. We found no interaction between survival to hospital discharge and the initial rhythm. For nonpulseless events, survival was 57% (95% CI, 39%–75%) in 2000 and 66% (95% CI, 61%–72%) in 2018, with an absolute change of 0.80% (95% CI, 0.32%–1.27%; P=0.001) per year.
CONCLUSIONS:Survival has improved for pediatric events requiring cardiopulmonary resuscitation in the United States, with a 19% absolute increase in survival for in-hospital pulseless cardiac arrests and a 9% absolute increase in survival for nonpulseless events between 2000 and 2018. However, survival from pulseless cardiac arrests appeared to have reached a plateau following 2010.
In general, treatment effects can be measured on a relative (i.e., odds ratio or risk ratio) or absolute (i.e., risk difference) scale when an outcome is binary. A randomized trial of epinephrine in ...out-of-hospital cardiac arrest. An empirical study of the effect of the control rate as a predictor of treatment efficacy in meta-analysis of clinical trials.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
IMPORTANCE: Tracheal intubation is common during adult in-hospital cardiac arrest, but little is known about the association between tracheal intubation and survival in this setting. OBJECTIVE: To ...determine whether tracheal intubation during adult in-hospital cardiac arrest is associated with survival to hospital discharge. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of adult patients who had an in-hospital cardiac arrest from January 2000 through December 2014 included in the Get With The Guidelines–Resuscitation registry, a US-based multicenter registry of in-hospital cardiac arrest. Patients who had an invasive airway in place at the time of cardiac arrest were excluded. Patients intubated at any given minute (from 0-15 minutes) were matched with patients at risk of being intubated within the same minute (ie, still receiving resuscitation) based on a time-dependent propensity score calculated from multiple patient, event, and hospital characteristics. EXPOSURE: Tracheal intubation during cardiac arrest. MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC) and a good functional outcome. A cerebral performance category score of 1 (mild or no neurological deficit) or 2 (moderate cerebral disability) was considered a good functional outcome. RESULTS: The propensity-matched cohort was selected from 108 079 adult patients at 668 hospitals. The median age was 69 years (interquartile range, 58-79 years), 45 073 patients (42%) were female, and 24 256 patients (22.4%) survived to hospital discharge. Of 71 615 patients (66.3%) who were intubated within the first 15 minutes, 43 314 (60.5%) were matched to a patient not intubated in the same minute. Survival was lower among patients who were intubated compared with those not intubated: 7052 of 43 314 (16.3%) vs 8407 of 43 314 (19.4%), respectively (risk ratio RR = 0.84; 95% CI, 0.81-0.87; P < .001). The proportion of patients with ROSC was lower among intubated patients than those not intubated: 25 022 of 43 311 (57.8%) vs 25 685 of 43 310 (59.3%), respectively (RR = 0.97; 95% CI, 0.96-0.99; P < .001). Good functional outcome was also lower among intubated patients than those not intubated: 4439 of 41 868 (10.6%) vs 5672 of 41 733 (13.6%), respectively (RR = 0.78; 95% CI, 0.75-0.81; P < .001). Although differences existed in prespecified subgroup analyses, intubation was not associated with improved outcomes in any subgroup. CONCLUSIONS AND RELEVANCE: Among adult patients with in-hospital cardiac arrest, initiation of tracheal intubation within any given minute during the first 15 minutes of resuscitation, compared with no intubation during that minute, was associated with decreased survival to hospital discharge. Although the study design does not eliminate the potential for confounding by indication, these findings do not support early tracheal intubation for adult in-hospital cardiac arrest.
Utstein-style reporting templates provide a structured framework with which to compare systems of care for cardiac arrest. The 2004 Utstein reporting template encompassed both out-of-hospital and ...in-hospital cardiac arrest. A 2015 update of the Utstein template focused on out-of-hospital cardiac arrest, which makes this update of the in-hospital template timely. Representatives of the International Liaison Committee on Resuscitation developed an updated in-hospital Utstein reporting template iteratively by meeting face-to-face, by teleconference, and by online surveys between 2013 and 2018. Data elements were grouped by hospital factors, patient variables, pre-event factors, cardiac arrest and postresuscitation processes, and outcomes. Elements were classified as core or supplemental by use of a modified Delphi process. Variables were described as core if they were considered essential. Core variables should enable reasonable comparisons between systems and are considered essential for quality improvement programs. Together with core variables, supplementary variables are considered useful for research.
The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with ...sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.
IMPORTANCE: Tracheal intubation is common during pediatric in-hospital cardiac arrest, although the relationship between intubation during cardiac arrest and outcomes is unknown. OBJECTIVE: To ...determine if intubation during pediatric in-hospital cardiac arrest is associated with improved outcomes. DESIGN, SETTING, AND PARTICIPANTS: Observational study of data from United States hospitals in the Get With The Guidelines–Resuscitation registry. Pediatric patients (<18 years) with index in-hospital cardiac arrest between January 2000 and December 2014 were included. Patients who were receiving assisted ventilation, had an invasive airway in place, or both at the time chest compressions were initiated were excluded. EXPOSURES: Tracheal intubation during cardiac arrest . MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation and neurologic outcome. A favorable neurologic outcome was defined as a score of 1 to 2 on the pediatric cerebral performance category score. Patients being intubated at any given minute were matched with patients at risk of being intubated within the same minute (ie, still receiving resuscitation) based on a time-dependent propensity score calculated from multiple patient, event, and hospital characteristics. RESULTS: The study included 2294 patients; 1308 (57%) were male, and all age groups were represented (median age, 7 months 25th-75th percentiles, 21 days, 4 years). Of the 2294 included patients, 1555 (68%) were intubated during the cardiac arrest. In the propensity score–matched cohort (n = 2270), survival was lower in those intubated compared with those not intubated (411/1135 36% vs 460/1135 41%; risk ratio RR, 0.89 95% CI, 0.81-0.99; P = .03). There was no significant difference in return of spontaneous circulation (770/1135 68% vs 771/1135 68%; RR, 1.00 95% CI, 0.95-1.06; P = .96) or favorable neurologic outcome (185/987 19% vs 211/983 21%; RR, 0.87 95% CI, 0.75-1.02; P = .08) between those intubated and not intubated. The association between intubation and decreased survival was observed in the majority of the sensitivity and subgroup analyses, including when accounting for missing data and in a subgroup of patients with a pulse at the beginning of the event. CONCLUSIONS AND RELEVANCE: Among pediatric patients with in-hospital cardiac arrest, tracheal intubation during cardiac arrest compared with no intubation was associated with decreased survival to hospital discharge. Although the study design does not eliminate the potential for confounding, these findings do not support the current emphasis on early tracheal intubation for pediatric in-hospital cardiac arrest.
The ever-growing availability of computing power and the sustained development of advanced computational methods have contributed much to recent scientific progress. These developments present new ...challenges driven by the sheer amount of calculations and data to manage. Next-generation exascale supercomputers will harden these challenges, such that automated and scalable solutions become crucial. In recent years, we have been developing AiiDA (aiida.net), a robust open-source high-throughput infrastructure addressing the challenges arising from the needs of automated workflow management and data provenance recording. Here, we introduce developments and capabilities required to reach sustained performance, with AiiDA supporting throughputs of tens of thousands processes/hour, while automatically preserving and storing the full data provenance in a relational database making it queryable and traversable, thus enabling high-performance data analytics. AiiDA's workflow language provides advanced automation, error handling features and a flexible plugin model to allow interfacing with external simulation software. The associated plugin registry enables seamless sharing of extensions, empowering a vibrant user community dedicated to making simulations more robust, user-friendly and reproducible.
Andersen and Granfeldt discuss the pragmatic cluster-crossover randomized trials regarding airway management during cardiac arrest. The pragmatic cluster-crossover randomized trial (N = 3004) ...conducted in the US comparing a strategy of laryngeal tube insertion with a strategy of endotracheal intubation. The investigators found that the laryngeal tube strategy was associated with a clinical and statistically significant increase in 72-hour survival. In the other trial conducted in the UK comparing an airway management strategy using a different type of supraglottic airway with a strategy of endotracheal intubation. In contrast to the findings of the first trial, found no significant difference in the primary outcome of a favorable neurological outcome at 30 days, which occurred in 6.4% of patients in the supraglottic airway group and 6.8% in the endotracheal intubation group.95% CI, -1.6% to 0.4%).
BACKGROUND Cigarette smoking during pregnancy is associated with negative reproductive consequences for male fetuses in adult life such as reduced testicular volume and sperm concentration. The ...present study evaluates the number of germ and somatic cells present in human embryonic first-trimester gonads in relation to maternal smoking. METHODS The study includes 24 human first-trimester testes, aged 37–68 days post-conception, obtained from women undergoing legal termination of pregnancy. A questionnaire was used to obtain information about smoking and drinking habits during pregnancy. Validated stereological methods were used to estimate gonadal cell numbers in histological sections. Results were also evaluated in the context of previously published data on ovaries from our laboratory. RESULTS A significant reduction in the number of germ cells by 55% 95% confidence interval (CI) 74–21% reduction, P = 0.004 and somatic cells by 37% (95% CI 59–3%, P = 0.023) was observed in testes prenatally exposed to maternal cigarette smoking, compared with unexposed. The effect of maternal smoking was dose-dependent being higher in the heavy smokers and remained consistent after adjusting for possible confounders such as alcohol and coffee consumption (P = 0.002). The number of germ cells in embryonic gonads, irrespective of gender, was also significantly reduced by 41% (95% CI 58–19%, P = 0.001) in exposed versus non-exposed embryonic gonads. CONCLUSIONS Prenatal exposure to maternal cigarette smoke reduces the number of germ and somatic cells in embryonic male and female gonads. This effect may have long-term consequences on the future fertility of exposed offspring. These findings may provide one potential cause of the reduced fertility observed during recent years.
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