Tranexamic Acid in Upper Gastrointestinal Bleeding is Associated With Venous and Arterial Thromboembolic Events.

OBJECTIVES: To determine the risk difference of arterial and venous thromboembolic events between patients with upper gastrointestinal bleeding (UGIB) who received and did not receive tranexamic acid. DESIGN: Retrospective cohort study. SETTING: The TriNetX Analytics (Cambridge, MA) Research Network, a deidentified mixed electronic health record and claims-derived database with over 110 million patients, primarily located in the United States. PATIENTS: A total of 2,016,763 patients diagnosed with hematemesis or melena between October 31, 2003, and October 31, 2023. INTERVENTIONS: Receipt of tranexamic acid within 7 days of a UGIB diagnosis. MEASUREMENTS AND MAIN RESULTS: We measured the incidence of thromboembolic events, both venous (deep venous thrombosis [DVT] and pulmonary embolism [PE]) and arterial (cerebrovascular accident [CVA] and myocardial infarction [MI]), within either 7 days of tranexamic acid (for recipients) or 7 days of UGIB diagnosis (for nonrecipients). Subsequently, we developed similar subcohorts using propensity score matching (PSM) for demographic and comorbidity data and reexamined the incidence of thromboembolic events, both before and after excluding any patients with any prior episodes of the outcomes. In all analyses, tranexamic acid recipients experienced significantly more adverse thromboembolic outcomes, with the post-PSM cohorts' risk difference generating an odds ratio of 1.4 for MI (95% CI, 1.2-1.7), 1.6 in CVA (95% CI, 1.3-1.9), 1.8 in PE (95% CI, 1.5-2.3), and 2.1 in DVT (95% CI, 1.8-2.5); all p values of less than 0.001. CONCLUSIONS: Leveraging data from a large, multi-institutional database, we identified a correlation between tranexamic acid use in patients with UGIB and the occurrence of both venous and arterial thromboembolic events. Although the former is well-attested in the literature, the latter finding is more novel, underscoring the need for further prospective research to better characterize the risk-benefit profile of tranexamic acid in the management of gastrointestinal bleeding.

Sepsis and Adrenal Insufficiency.

In sepsis, dysregulation of the hypothalamic-pituitary-adrenal axis, alterations in cortisol metabolism, and tissue resistance to glucocorticoids can all result in relative adrenal insufficiency or critical illness-related corticosteroid insufficiency (CIRCI). The symptoms and signs of CIRCI during sepsis are nonspecific, generally including decreased mental status, unexplained fever, or hypotension refractory to fluids, and the requirement of vasopressor therapy to maintain adequate blood pressure. While we have been aware of this syndrome for over a decade, it remains a poorly understood condition, challenging to diagnose, and associated with significantly diverging practices among clinicians, particularly regarding the optimal dosing and duration of corticosteroid therapy. The existing literature on corticosteroid use in patients with sepsis and septic shock is vast with dozens of randomized controlled trials conducted across the past 4 decades. These studies have universally demonstrated reduced duration of shock, though the effects of corticosteroids on mortality have been inconsistent, and their use has been associated with adverse effects including hyperglycemia, neuromuscular weakness, and an increased risk of infection. In this article, we aim to provide a thorough, evidence-based, and practical review of the current recommendations for the diagnosis and management of patients with sepsis who develop CIRCI, explore the controversies surrounding this topic, and highlight what lies on the horizon as new evidence continues to shape our practice.

Demographic Undertones for Sepsis Mortality in a Community-Based Hospital.

BACKGROUND: Sepsis continues to take main stage in healthcare. Therefore, it remains crucial to elucidate contributors to sepsis mortality. The aim of this study is to determine the impact of race, insurance type, and code status on sepsis mortality in a community health system. METHODS: We conducted a retrospective cohort study of inpatient adults of any sex, race, and insurance type with a diagnosis of sepsis, severe sepsis, septic shock, or pneumonia. RESULTS: We included 913 patients, with an average age of 69 years for expired patients and 62 years for non-expiring patients (P < 0.0001). After controlling for other variables, patients who presented as comfort care arrest were 4.3 (95% confidence interval (CI): 1.8 to 9.9, P = 0.0007) times more likely to have died than full code patients. Those who were comfort care only were 10.6 (95% CI: 0.8 to 140.6, P = 0.0741) times more likely to have died than the full code, although this was not statistically significant. CONCLUSIONS: The results suggest that patients who are comfort care arrest have an increased risk of sepsis mortality. The results show no impact of insurance type or race on sepsis mortality, which is in contrast to some existing literature. The study suggests that institutions may need to investigate internal variables related to sepsis mortality.

Artificial hyperventilation normalizes haemodynamics and arterial oxygen content in hypoxic rats.

INTRODUCTION: Although humans are capable of enduring critically low levels of oxygen, many hypoxaemic patients die despite aggressive therapies. Mimicking the physiological hyperventilation necessary to survive extreme hypoxic conditions could minimize the derangements caused by acute hypoxic-hypoxia. The objective of this study was to measure the haemodynamic-biochemical response to artificially induced hyperventilation in hypoxic rats. MATERIAL AND METHODS: Twenty-four deeply anaesthetized and mechanically ventilated rats were allocated to 3 groups: control (n = 5, FiO2 = 1); hypoxic spontaneously hyperventilating (n = 10, FiO2 = 0.08); and hypoxic artificially induced hyperventilation (n = 9, targeting PaCO2 = 10 mm Hg, FiO2 = 0.08). We compared the spontaneously and artificially hyperventilating groups. P-values < 0.01 were considered statistically significant. Mean arterial pressure (MAP) and serum chemistry were measured for 180 minutes. RESULTS: The control group remained stable throughout the experiment. The hypoxic groups developed profound hypotension after the decrease in FiO2. However, the artificially induced hyperventilated rats recovered their MAP to levels higher than the spontaneously hyperventilating group (117.1 ± 17.2 vs. 68.1 ± 16.0, P = 0.0048). In regard to the biochemical derangements, even though the serum lactate and PaO2 were not different among the hypoxic groups, the artificially hyperventilated group achieved significantly higher SaO2 (94.3 ± 3.6 vs. 58.6 ± 9.6, P = 0.005), pH (7.87 ± 0.04 vs. 7.50 ± 0.13, P = 0.005), and CaO2 (17.7 ± 2.6 vs. 10.2 ± 1.3, P = 0.005) at 180 minutes. CONCLUSIONS: Artificially induced hyperventilation led to the correction of arterial oxygen content, severe serum chemistry, and haemodynamic derangements. These findings may represent a novel rescue manoeuvre and serve as a bridge to a permanent form of support, but should be further studied before being translated to the clinical setting.

Pain management during the withholding and withdrawal of life support in critically ill patients at the end-of-life: a systematic review and meta-analysis.

PURPOSE: To review and summarize the most frequent medications and dosages used during withholding and withdrawal of life-prolonging measures in critically ill patients in the intensive care unit. METHODS: We searched PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Virtual Health Library from inception through March 2019. We considered any study evaluating pharmaceutical interventions for pain management during the withholding or withdrawing of life support in adult critically ill patients at the end-of-life. Two independent investigators performed the screening and data extraction. We pooled data on utilization rate of analgesic and sedative drugs and summarized the dosing between the moment prior to withholding or withdrawal of life support and the moment before death. RESULTS: Thirteen studies met inclusion criteria. Studies were conducted in the United States (38%), Canada (31%), and the Netherlands (31%). Eleven studies were single-cohort and twelve had a Newcastle-Ottawa Scale score of less than 7. The mean age of the patients ranged from 59 to 71 years, 59-100% were mechanically ventilated, and 47-100% of the patients underwent life support withdrawal. The most commonly used opioid and sedative were morphine [utilization rate 60% (95% CI 48-71%)] and midazolam [utilization rate 28% (95% CI 23-32%)], respectively. Doses increased during the end-of-life process (pooled mean increase in the dose of morphine: 2.6 mg/h, 95% CI 1.2-4). CONCLUSIONS: Pain control is centered on opioids and adjunctive benzodiazepines, with dosages exceeding those recommended by guidelines. Despite consistency among guidelines, there is significant heterogeneity among practices in end-of-life care.