Early initiation of norepinephrine in patients with septic shock: A propensity score-based analysis.

BACKGROUND: The use of vasopressors is vital in septic shock. However, the optimal timing of treatment remains unclear. Therefore, we aimed to explore the impact of early norepinephrine initiation on the survival of patients with septic shock. METHODS: We selected 4253 patients from the Medical Information Mart for Intensive Care IV database between 2008 and 2019. The primary outcome was 28-day mortality. Propensity score matching (PSM) was applied to minimize between-group imbalances, and a restricted mean survival time was used to quantify the beneficial impact of early norepinephrine treatment on survival. Sensitivity analyses were conducted to test the robustness of the study results in multiple cohorts. RESULTS: In the PSM cohort, 2862 patients were equally assigned to early (receiving norepinephrine within the first 3 h) and delayed (> 3 h) norepinephrine initiation groups. Patients in the early norepinephrine initiation group received significantly less fluid therapy (0 vs. 79 mL/kg), had lower 28-day mortality (30.0% vs. 37.8%), longer survival days (21.89 vs. 20.37 days), shorter duration of intensive care unit (4.9 vs. 7.2 days) and hospital stays (12.4 vs. 13.6 days), shorter duration of supportive norepinephrine and invasive mechanical ventilation, lower incidence of organ failure progression (64.4% vs. 79.2%) within 24 h after shock onset, and higher mean arterial pressure within 6 and 24 h after shock onset than patients in the delayed norepinephrine initiation group (p < 0.05). CONCLUSIONS: Norepinephrine initiation within the first 3 h, regardless of preload dependency, was associated with longer survival time and shorter duration of supportive norepinephrine and invasive mechanical ventilation and may delay or partially reverse rapid onset organ failure.

Streptococcal Toxic Shock Syndrome in a Pediatric Patient With Intramuscular Venous Malformation in the Neck.

BACKGROUND: Streptococcal toxic shock syndrome (STSS) is diagnosed based on signs of shock with multiorgan system involvement, a generalized erythematous macular rash, and rapidly progressive and destructive soft tissue infection. CASE REPORT: The patient was a 2-year-old girl with intramuscular venous malformation in the neck in which an infection occurred, developing into STSS. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Group A streptococcal infections are common in children and usually have a mild clinical presentation, but may be life threatening in severe cases. Patients with venous malformations are known to have slow-flow anomalies with venous pooling, which can result in hypoxia and possible immune cell dysfunction. Thus, clinicians should be aware of STSS when a patient with venous malformation has a rapidly progressive infection.

[Sepsis with hemolysis due to a liver abscess in a 60-year-old male patient]. / Sepsis mit Hämolyse im Rahmen eines Leberabszesses bei einem 60-jährigen Patienten.

Many cases of Clostridium perfringens sepsis prove to be fatal. We present a case of C. perfringens sepsis with a liver abscess as the focus of infection, which was successfully treated by an interdisciplinary intensive medical care management. The sepsis with this rare pathogen was favored by the presence of a bilioenteric anastomosis and immunosuppressive treatment of a pre-existing Crohn's disease. Antibiotic treatment with clindamycin and penicillin G was initiated and the abscess was drained. Hemodialysis with high cut-off filters was started because of acute kidney failure in the Acute Kidney Injury Network (AKIN) stage III, hemolysis and rhabdomyolysis. Therapeutic plasma exchange was performed due to sepsis and acute liver failure.

PcvCO2-PaCO2/CaO2-CcvO2 Ratio: The Holy Grail in Resuscitation!

How to cite this article: Abraham S. PcvCO2-PaCO2/CaO2-CcvO2 Ratio: The Holy Grail in Resuscitation! Indian J Crit Care Med 2021; 25(12):1337-1338.

Characterization of circulating thrombin in patients with septic shock: a prospective observational study.

Septic shock is characterized by a dysregulated response to infection, hypotension and activation of the coagulation system. Markers of coagulation activation are commonly used to diagnose and monitor ensuing coagulopathies. In this study, we sought to determine levels of circulating thrombin in patients with septic shock. To characterize levels of circulating, active thrombin in patients with septic shock. 48 patients with septic shock were included in this prospective, observational study. Blood samples were obtained on admission, day 1, day 3 and day 6. Levels of active thrombin were measured using a standardized, clinically applicable oligonucleotide (aptamer)-based enzyme-capture assay (OECA). Thrombin levels were correlated with established indirect thrombin parameters, conventional coagulation tests, laboratory parameters, patient characteristics and outcome. Elevated levels of thrombin were detected in 27 patients (56.3%) during the course of the study. Thrombin levels were positively correlated with thrombin-antithrombin complexes (r = 0.30, p < 0.05) and negatively associated with FVII levels (r = - 0.28, p < 0.05). Thrombin levels on admission did not predict 30-day mortality (OR 0.82, 95% CI 0.23-2.92, p = 0.77). Circulating levels of active thrombin can be measured in a subset of patients with septic shock. Although thrombin levels are correlated with established markers of coagulation, they do not provide additional prognostic information.

Usefulness of Antioxidants as Adjuvant Therapy for Septic Shock: A Randomized Clinical Trial.

Background and objectives: Oxidative stress (OS) participates in the pathophysiology of septic shock, which leads to multiple organ failure (MOF), ischemia-reperfusion injury, and acute respiratory distress syndrome. Therefore, antioxidants have been proposed as therapy. Here, we evaluated the effect of antioxidant treatments in patients with septic shock with MOF and determined levels OS before and after treatment. This study was a randomized, controlled, triple-masked, and with parallel assignment clinical trial with a control group without treatment. Materials and Methods: It included 97 patients of either sex with septic shock. 5 treatments were used each in an independent group of 18 patients. Group 1 received vitamin C (Vit C), group 2 vitamin E (Vit E), group 3 n-acetylcysteine (NAC), group 4 melatonin (MT), and group 5 served as control. All antioxidants were administered orally or through a nasogastric tube for five days as an adjuvant to the standard therapy. Results: The results showed that all patients presented MOF due to sepsis upon admission and that the treatment decreased it (p = 0.007). The antioxidant treatment with NAC increased the total antioxidant capacity (p < 0.05). The patients that received Vit C had decreased levels of the nitrate and nitrite ratio (p < 0.01) and C-reactive protein levels (p = 0.04). Procalcitonin levels were reduced by Vit E (p = 0.04), NAC (p = 0.001), and MT (p = 0.04). Lipid-peroxidation was reduced in patients that received MT (p = 0.04). Conclusions: In conclusion, antioxidant therapy associated with standard therapy reduces MOF, OS, and inflammation in patients with septic shock.

[Cardiovascular therapy for sepsis: when, how and how much?] / Kreislauftherapie bei Sepsis ­ wann, wie und wie viel?

The management of hemodynamic instability in the context of sepsis or septic shock is at the forefront in emergency care as well as in the intensive care unit. Cardiovascular instability has a dramatic impact on the rate of organ complications and mortality from sepsis. According to the guideline for the treatment of sepsis, mean arterial pressure should not fall below 65 mm Hg. Crystalloid balanced fluid and catecholamines are the cornerstones of therapy management for septic cardiovascular instability. In this article, the most important points of what, when and how much regarding circulation therapy are presented and critically discussed.

[Extracorporeal techniques for blood purification in sepsis: an update]. / Extrakorporale Blutreinigungsverfahren in der Sepsis ­ Update.

BACKGROUND: Despite ongoing development, mortality in sepsis remains considerable. Various techniques for extracorporeal cytokine removal have been described, but evidence remains conflicting. OBJECTIVES: The aim of this article is to summarize currently used extracorporeal blood purification techniques and their evidence. METHODS: Non-systematic literature review RESULTS: There are currently various blood purification techniques used with different levels of evidence regarding cytokine removal, vasopressor sparing effects and reduction of mortality, including high-volume dialysis with and without high cut-off filters, special adsorption filters (including CytoSorb®, CytoSorbents Europe, Berlin, Germany, and polymyxin­B filters). There is development regarding therapeutic plasma exchange. For some blood purification techniques such as combined plasma filtration and adsorption, multicentric randomized studies found a negative effect on survival. CONCLUSIONS: Despite a theoretical rationale, the use of blood purification methods cannot be recommended for sepsis patients due to the lack of evidence of their efficacy. Heterogeneous inflammatory responses in sepsis render conduction of larger trials difficult. Thus, future studies should cautiously identify appropriate sepsis subtypes to be included. Available techniques should be chosen as individualized complementary treatments and not as competing systems.

[Influencing factors of severe liver disease complicated with toxic shock].

Patients with severe liver disease are prone to bacterial and fungal infections, and then develop toxic shock. The onset of the disease may be insidious, but the disease progresses rapidly with a high fatality rate. Current research results show that special conditions such as translocation of intestinal flora and immune paralysis in patients with severe liver disease are susceptible factors for infection and toxic shock. Furthermore, it is currently recognized that the treatment of severe liver disease complicated with toxic shock must be treated with antibiotics and maintenance of hemodynamic stability. Other treatments, such as hydrocortisone and strict glycemic control, are quite controversial and may not necessarily reduce mortality. Herein, we summarize the epidemiology, susceptibility factors; diagnosis and management strategies of severe liver disease complicated with toxic shock, highlighting the characteristics of toxic shock under the background of severe liver disease, so as to detect, prevent and treat septic shock in patients with severe liver disease as early as possible to reduce the fatality rate.

The hollow adrenal gland sign: a newly described enhancing pattern of the adrenal gland on dual-phase contrast-enhanced CT for predicting the prognosis of patients with septic shock.

OBJECTIVE: To investigate the incidence, CT appearance, and implication for prognosis of the hollow adrenal gland sign (HAGS). METHODS: A total of 194 patients with septic shock and 24 patients with hemorrhagic shock (as control group) were retrospectively included in this study and the patients with septic shock were further divided into four subgroups (digestive tract diseases, DTD, n = 49; biliary and pancreatic diseases, BPD, n = 41; postsurgical infection, PI, n = 64; and other diseases, OD, n = 40). All patients underwent a dual-phase contrast-enhanced CT within 1 week after diagnosis. CT findings and clinical records were reviewed. If in the arterial phase the central zone of adrenal gland showed temporally much lower attenuation than the peripheral zone, it was defined as HAGS positive. The incidence of the HAGS in patients with septic shock and hemorrhagic shock, the demographic features, and mortality between HAGS-positive and HAGS-negative patients in each group were respectively compared. RESULTS: The incidence of the HAGS in the septic shock group was nearly 30%, while it was 0 in the hemorrhagic shock group. There was no significant difference in age or gender between HAGS-positive and HAGS-negative patients in all groups, while the mortality of HAGS-positive patients was significantly higher than that of HAGS-negative patients in each group (p < 0.05). The concordance correlation coefficient value showed excellent reproducibility of the two observers (κ = 0.977). CONCLUSION: The HAGS is specific and common on dual-phase contrast-enhanced CT in patients with septic shock and predicts a poor prognosis. KEY POINTS: • The hollow adrenal gland sign (HAGS) newly described in this study is a special enhancing pattern of adrenal gland on dual-phase contrast-enhanced CT in patients with septic shock. • The HAGS is characterized by the much lower-attenuated central zone of the adrenal gland in arterial phase and it showed excellent reproducibility between different observers. • The HAGS is specific and common on dual-phase contrast-enhanced CT in patients with septic shock and predicts a poor prognosis.

[Surviving Sepsis Campaign update 2018: the 1 h bundle : Background to the new recommendations]. / Surviving Sepsis Campaign Update 2018: das 1­h-Bundle : Hintergrund zu den neuen Empfehlungen.

A new update of the sepsis bundle was published by the Surviving Sepsis Campaign (SSC) in April 2018. The original 3 h and 6 h bundles have been restructured and combined into a 1­h bundle. The recommendations comprehensively focus on diagnostic and therapeutic measures which should be carried out within 1 h after recognition of sepsis. This article presents the background and discusses criticisms of the new recommendations.

[Clinical study on the effects of global end-diastolic volume index-directed fluid resuscitation on the prognosis of chronic heart failure patients with septic shock].

Objective: To investigate the effect of global end-diastolic volume index (GEDI)-guided fluid resuscitation on the prognosis of patients with chronic heart failure and septic shock. Methods: This study was a prospective randomized controlled study. Consecutive eligible patients were divided into 2 groups according to the random number table method: control group (n=21) and experimental group (n=20). On the basis of routine treatment, patients in the control group received early goal-directed therapy until the central venous pressure (CVP) reaching 8-12 mmHg (1 mmHg=0.133 kPa), mean arterial pressure reaching over 65 mmHg, urine volume reaching over 0.5 ml·kg(-1)·h(-1), and central venous oxygen saturation reaching more than 70%. On the basis of routine treatment, patients in the experimental group were monitored continuously on cardiac output with pulse indication and fluid resuscitation guided by volume index GEDI. The GEDI should be maintained on the range of 680-800 ml/m(2). The remaining resuscitation goals were the same as control group. General clinical data of the two groups were collected at admission. Negative fluid balance onset time, duration of mechanical ventilation, ICU mortality and 28-day mortality were compared between the two groups. The outcomes were recorded as listed: start time of negative fluid balance, duration of mechanical ventilation, mortality in ICU and 28-day mortality. Results: There was no significant difference in age, sex, weight, APACHE Ⅱ score, SOFA score and NYHA functional class score between the two groups (all P>0.05). The negative liquid balance onset time in the control group was 3.5 (2.5, 4.0) days, which was significantly longer than that in the experimental group (2.6 (2.0, 3.0) days,U=115.0, P=0.012). The duration of mechanical ventilation was 355 (118, 552) hours in the control group, which was significantly longer than that in the experimental group (132 (36.75, 233.3) hours, U=130, P=0.038). The ICU mortality was 38.1% (8/21) in the control group, tended to be higher than that in the experimental group (20.0%(4/20), χ(2)=1.620, P=0.203). The 28-day mortality was 42.9% (9/21) in the control group, similar as in the experimental group (25.0%(5/20), χ(2)=1.482,P=0.477). Conclusion: Fluid resuscitation guided by volume index (GEDI) may improve the prognosis of patients with chronic heart failure complicated with septic shock.

A paradigm shift in the provision of improved critical care in the emergency department.

With Hong Kong's ageing population, advancement of medical technologies and hospital congestion, it is not uncommon for emergency physicians to encounter complicated critically ill patients in daily practice. It becomes a fundamental role of emergency physicians to initiate timely diagnostic and therapeutic interventions to save a patient's life and improve their prognosis. It is the reason a critical care service has been developed in emergency departments worldwide over the last decade. This article shares how emergency department intensivists can contribute to this novel model of care with some illustrative cases. Advanced airway and peri-intubation management, difficult mechanical ventilation, treatment of shock, circulatory arrest, and metabolic disturbances can be safely and efficiently handled in the current emergency department setting. Obstacles, barriers, and the road ahead will be discussed.

[The effects of levosimendan on the cardiac function and prognosis in elderly patients with septic shock and myocardial contractility impairment].

Objective: To investigate the effect of levosimendan on cardiac function and prognosis in elderly patients with septic myocardial contractility impairment. Methods: A prospective, randomized, controlled study was conducted. The elderly patients with septic myocardial contractility impairment who were admitted to Intensive Care Unit in Zhejiang Hospital were consecutively enrolled from January 2017 to September 2017. The key inclusive criterion was left ventricular ejection fraction (LVEF) ≤50% after fluid resuscitation. A total of 30 patients were randomly assigned to levosimendan group (n=15) and dobutamine group (n=15). Based onconventional treatment, intravenous dobutamine (5 µg per kilogram of body weight per minute) or levosimendan (0.2 µg per kilogram of body weight per minute)were continuously administrated for 24 hours in two groups. At 0 h,24 h,48 h, 72 h after injection, the following parameters or values were recorded including serum lactic acid (Lac), and echocardiographic parameters such as LVEF, stroke volume (SV). The time of mechanical ventilation, length of stay in ICU and 28-day mortality were compared in two groups. Results: Compared with dobutamine group, blood Lac at 24 h [(1.97±1.10)mmol/L vs. (2.73±2.06) mmol/L, P=0.002] decreased significantlyin levosimendan group. LVEF and SV were significantly higher in levosimendan group at 24 h [LVEF:(47.93±5.01)% vs.(45.60±5.47)%, P=0.004;SV:(47.73±14.01) ml vs. (44.80±16.89) ml, P=0.035;respectively], 48 h [LVEF:(51.07±5.05)% vs.(46.73±6.34)%, P=0.004;SV: (49.87±14.15) ml vs. (45.07±16.94) ml, P=0.005;respectively] and 72 h [LVEF:(53.20±5.92)% vs. (47.70±6.71)%, P=0.002;SV:(51.27±14.98) ml vs. (45.73±17.34) ml, P=0.010]. The time of mechanical ventilation, length of stay in ICU and 28-day mortality were comparable between two groups (P>0.05). Conclusions: Levosimendan improves cardiac systolic function and tissue perfusion in elderly patients with septic myocardial contractility impairment. However, cardiac diastolic function, liver and kidney function are not further improved by levosimendan compare with dubutamine. Time of mechanical ventilation, length of stay in ICU and 28-day mortality in two groups are similar.

[Correlation of transcutaneous oxygen pressure and blood lactate in patients with septic shock].

To analyze the correlation between transcutaneous oxygen pressure (P(tc)O(2)) and blood lactate in patients with septic shock. Fifty-sixpatients with septic shock were prospectively investigated. P(tc)O(2) was monitored continuously for 6 hours, and arterial blood gas was measured at baseline (T0) and 6 hours(T6). Records of P(tc)O(2),were analyzed for the correlation with lactate level and lactate clearance rate. P(tc)O(2) valuesin the high lactate clearance group and the low one were compared.The lowest value of P(tc)O(2) at T6 and duration of P(tc)O(2)<40 mmHg (1 mmHg=0.133 kPa) were both correlated with lactate level and lactate clearance rateat T6.The low predictive value of P(tc)O(2) was 29 mmHg of lactate clearance under 20% with a sensitivity 85.2% and a specificity 65.5%. The low predictive value of P(tc)O(2) in high lactate clearance group was significantly higher than that in low lactate clearance group, while the duration of P(tc)O(2)<40 mmHg was shorter than the latter. During 6 h continuous monitoring, patients with a significant low P(tc)O(2) or prolonged duration of low P(tc)O(2) have relatively high lactate or low lactate clearance after resuscitation.

[International guidelines from the Surviving Sepsis Campaign : 2016 update]. / Internationale Leitlinien der Surviving Sepsis Campaign : Update 2016.

An update to the international guidelines for sepsis therapy was published by the Surviving Sepsis Campaign (SSC) in March 2017. The guidelines have been completely restructured and comprehensively deal with new evidence. The guidelines discuss sepsis-specific therapeutic measures and provide detailed recommendations on general intensive care measures for sepsis. This article summarizes the most important amendments and suggests delving deeper into the guidelines.

[The ROSE concept: modern fluid management in intensive care medicine]. / Das ROSE-Konzept ­ modernes Flüssigkeitsmanagement in der Intensivmedizin.

The ROSE concept, which is the acronym of resuscitation, optimization, stabilization and evacuation, describes the phases of fluid therapy, based on the pathophysiology of septic shock. During the first two phases, aggressive fluid therapy that is guided by clinical and hemodynamic parameters is mandatory. During the stabilization phase, recovery from shock and microcirculatory injury occurs, which enables the depletion of fluid overload in the fourth and final phase. Ultimately, euvolemia needs to be regained, which reverts interstitial edema and organ dysfunction.

Emerging infection: streptococcal toxic shock-like syndrome caused by group B Streptococcus (GBS), Streptococcus agalactiae.

Streptococcus agalactiae or Group B Streptococcus (GBS) infections are commonly associated with infections in neonates and pregnant women. However, there has been a rising incidence in nonpregnant adults. The risk of GBS infection in nonpregnant adults is increased for patients of advanced age and those with underlying medical conditions such as diabetes mellitus and cancer. We present a 77-year-old female with type-2 diabetes mellitus, hypertension, and bilateral foot ulcers that presented in probable septic shock with necrotic foot ulcers and necrotizing fasciitis and underwent bilateral lower limb amputations. The patient fulfilled the Streptococcal Toxic Shock Syndrome (STSS) criteria as defined by The Working Group on Severe Streptococcal Infections. These criteria were created for group A Streptococcus (Streptococcus pyogenes). Our patient fulfilled the Working Group's criteria, except that the blood culture was positive for group B Streptococcus (Streptococcus agalactiae). Numerous studies demonstrate the importance of early detection and antibiotic treatment for GBS infections in general and early surgical management for necrotizing soft tissue infections (NSTIs) such as necrotizing fasciitis.

Mixed Shock Complicating Cardiogenic Shock: Frequency, Predictors, and Clinical Outcomes.

BACKGROUND: Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity. METHODS: We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters. RESULTS: Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure (P=0.043), hepatic injury (P=0.049), and suspected/definite infection (P=0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P=0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P=0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; Padj=0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; Padj<0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; Padj=0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; Padj=0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; Padj=0.008). CONCLUSIONS: MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality.