β1-blocker in sepsis.
Hasegawa Daisuke,Sato Ryota,Nishida Osamu
Journal of intensive care
BACKGROUND:The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers. MAIN BODY:A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation. CONCLUSION:Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted.
Timing of Antibiotic Administration in Pediatric Sepsis.
Creedon Jessica K,Vargas Sigella,Asaro Lisa A,Wypij David,Paul Raina,Melendez Elliot
Pediatric emergency care
OBJECTIVES:Antibiotic administration within 1 hour of hypotension has been shown to reduce mortality. It is unknown whether antibiotics before hypotension in children who eventually meet criteria for septic shock improves outcomes. This study assesses whether antibiotic timing from the time of meeting criteria for sepsis in children with septic shock impacts morbidity and mortality. METHODS:This is a retrospective study of children 18 years or younger presenting to a tertiary free-standing children's hospital emergency department with sepsis that subsequently progressed to septic shock and were admitted to an intensive care unit from 2008 to 2012. The time when the patient met criteria for sepsis to the time of first antibiotic administration was assessed and correlated with patient morbidity and mortality. RESULTS:Among 135 children (median age, 13.1 years), 34 (25%) were previously healthy, whereas 49 (36%) had 2 or more medical comorbidities. Twenty-seven children (20%) had positive blood cultures, 17 (13%) had positive urine cultures, and 34 (25%) had chest x-ray findings that were interpreted as pneumonia. Among the 42 (31%) with antibiotics within 1 hour from criteria for sepsis, there was higher mortality (4/42 vs 0/93, P = 0.009), more organ dysfunction, longer time on a vasoactive infusion, and increased intensive care unit and hospital lengths of stay (all P < 0.05). CONCLUSIONS:Children with criteria for sepsis who subsequently progressed to septic shock who received antibiotics within 1 hour of meeting sepsis criteria had increased mortality, length of stay, and organ dysfunction.
Dysregulated Immunity and Immunotherapy after Sepsis.
Darden Dijoia B,Kelly Lauren S,Fenner Brittany P,Moldawer Lyle L,Mohr Alicia M,Efron Philip A
Journal of clinical medicine
Implementation of protocolized surveillance, diagnosis, and management of septic patients, and of surgical sepsis patients in particular, is shown to result in significantly increased numbers of patients surviving their initial hospitalization. Currently, most surgical sepsis patients will rapidly recover from sepsis; however, many patients will not rapidly recover, but instead will go on to develop chronic critical illness (CCI) and experience dismal long-term outcomes. The elderly and comorbid patient is highly susceptible to death or CCI after sepsis. Here, we review aspects of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) endotype to explain the underlying pathobiology of a dysregulated immune system in sepsis survivors who develop CCI; then, we explore targets for immunomodulatory therapy.
Analysis of Noninvasive Ventilation in Subjects With Sepsis and Acute Respiratory Failure.
Drescher Gail S,Al-Ahmad Ma'moon M
BACKGROUND:Acute respiratory failure is among the sequelae of complications that can develop in response to severe sepsis. Research into sepsis-related respiratory failure has focused on ARDS and invasive mechanical ventilation. We studied the factors associated with success and failure of noninvasive ventilation (NIV) in the treatment of sepsis-related acute respiratory failure. METHODS:This retrospective study included 136 subjects with a diagnosis of acute respiratory failure and intrapulmonary or extrapulmonary sepsis who were placed on NIV. Subjects were divided into 2 groups based on the need for intubation from NIV: NIV failure ( = 70) and NIV success ( = 66). Demographic, clinical, and outcome data were collected and compared between groups, with the development of multivariate models to predict NIV failure and mortality. RESULTS:The overall NIV failure rate in subjects with a diagnosis of sepsis was 51%. There were no between-group differences in demographic or baseline characteristics. However, there were significant differences in clinical variables, with higher SOFA scores (NIV failure: 6.4 [± 3.0] vs NIV success: 4.9 [± 2.1]; = .002), 2nd lactate levels (NIV failure: 2.6 [1.7 - 4.3] vs NIV success: 1.9 [1.4 - 2.6] mmol/L; = .007), and initial NIV F settings (NIV failure: 0.50 [0.40 - 0.70] vs NIV failure: 0.40 [0.35 - 0.50]; = .003) in subjects who failed NIV. There were also more subjects in the NIV failure group who had a lactate ≥ 4 mmol/L prior to NIV start compared to those who succeeded on NIV (33% vs 15%, = .02). At NIV start, subjects in the NIV failure group had lower mean arterial pressure (85 mm Hg [IQR 74-96] vs 91.7 mm Hg [IQR 78-108], = .042) and Glasgow coma scale scores (14 [IQR 13-15] vs 15 [IQR 14-15], < .002), while fewer subjects in the NIV failure group received a fluid bolus in the 24 h prior to NIV start (33% vs 53%, = .02) or had signs of volume overload (36% vs 64%, < .001). Multivariate analysis indicated that age (odds ratio 1.05 [95% CI 1.01-1.09], = .02), SOFA score (odds ratio 1.49 [95% CI 1.15-1.94], = .002), first systolic blood pressure (odds ratio 0.97 [95% CI 0.95-0.99], = .02), signs of volume overload (odds ratio 0.23 [95% CI 0.07-0.68], = .008], fluids prior to NIV (odds ratio 0.08 [95% CI 0.02-0.31], < .001), and initial F on NIV (odds ratio 1.04 [95% CI 1.01-1.08, = .002) independently predicted NIV failure with an area under the curve of 0.88. Only NIV failure independently predicted death in multivariate analysis (area under the curve = 0.70). CONCLUSIONS:NIV failure in sepsis-related acute respiratory failure was independently predicted by patient acuity, first systolic blood pressure after sepsis alert, initial F settings on NIV, fluid resuscitation, and signs of volume overload. However, only NIV failure independently predicted death in this cohort of subjects.
Meta-analysis of the diagnostic value of procalcitonin in adult burn sepsis.
Chen Zhao,Turxun Nurlan,Ning Fangyan
Advances in clinical and experimental medicine : official organ Wroclaw Medical University
Sepsis is one of the main causes of death in burn patients, and many studies have suggested that procalcitonin (PCT) is a biomarker for the early diagnosis of sepsis, but the results are controversial. The aim of this study was to evaluate the diagnostic value of serum PCT in adult burn sepsis by conducting a meta-analysis of published studies. The PubMed, Embase, Web of Science, CNKI and China Wanfang databases were searched, and studies on PCT as a marker for the diagnosis of adult burn sepsis from the establishment of the database, to February 1, 2020 were screened. The data were analyzed using Stata v. 15.0 software. A total of 10 studies and 704 patients were included. The combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 0.67 (95% CI: 0.48-0.81), 0.87 (95% CI: 0.72-0.95), 5.20 (95% CI: 2.49-10.84), 0.38 (95% CI: 0.24-0.61) and 13.70 (95% CI: 5.72-32.82), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.85 (95% CI: 0.82-0.88), and the diagnostic threshold was the main source of heterogeneity. Results demonstrate that serum PCT may be used as a useful biomarker for the early diagnosis of burn sepsis in adults, and may be combined with other diagnostic indexes to further improve the sensitivity and specificity.
Dantrolene repurposed to treat sepsis or septic shock and COVID-19 patients.
Wei H,Liang G,Vera R M
European review for medical and pharmacological sciences
OBJECTIVE:Disruption of intracellular Ca2+ homeostasis via excessive and pathological Ca2+ release from the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR) through ryanodine receptor (RyRs) Ca2+ channels play a critical role in the pathology of systemic inflammatory response syndrome (SIRS) and associated multiple organ dysfunction syndrome (MODS) in sepsis or septic shock. Dantrolene, a potent inhibitor of RyRs, is expected to ameliorate SIRS and MODS and decrease mortality in sepsis or septic shock patients. This review summarized the potential mechanisms of therapeutic effects of dantrolene in sepsis or septic shock at molecular, cell, and organ levels and provided suggestions and strategies for future clinical studies.
Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment.
Peerapornratana Sadudee,Manrique-Caballero Carlos L,Gómez Hernando,Kellum John A
Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill patient and is associated with unacceptable morbidity and mortality. Prevention of S-AKI is difficult because by the time patients seek medical attention, most have already developed acute kidney injury. Thus, early recognition is crucial to provide supportive treatment and limit further insults. Current diagnostic criteria for acute kidney injury has limited early detection; however, novel biomarkers of kidney stress and damage have been recently validated for risk prediction and early diagnosis of acute kidney injury in the setting of sepsis. Recent evidence shows that microvascular dysfunction, inflammation, and metabolic reprogramming are 3 fundamental mechanisms that may play a role in the development of S-AKI. However, more mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials.
Maternal sepsis update.
Abir Gillian,Bauer Melissa E
Current opinion in anaesthesiology
PURPOSE OF REVIEW:Maternal sepsis is the second leading cause of maternal death in the United States. A significant number of these deaths are preventable and the purpose of this review is to highlight causes such as delays in recognition and early treatment. RECENT FINDINGS:Maternal sepsis can be difficult to diagnose due to significant overlap of symptoms and signs of normal physiological changes of pregnancy, and current screening tools perform poorly to identify sepsis in pregnant women. Surveillance should not only include during pregnancy, but also throughout the postpartum period, up to 42 days postpartum. Education and awareness to highlight this importance are not only vital for obstetric healthcare provides, but also for nonobstetric healthcare providers, patients, and support persons. SUMMARY:Through education and continual review and analysis of evidence-based practice, a reduction in maternal morbidity and mortality secondary to maternal sepsis should be attainable with dedication from all disciplines that care for obstetric and postpartum patients. Education and vigilance also extend to patients and support persons who should be empowered to escalate care when needed.