Blind spot in sepsis management - Tissue level changes in microcirculation.

In sepsis cytokine-mediated inflammation, clotting cascade activation and glycocalyx shedding impair both function and structure of the microcirculation, compromising adequate tissue oxygenation/perfusion. Such mismatch results in "dysoxia", an imbalance in mitochondrial respiration.Microvessel injuries can be grouped into four types: cytotoxic oedema, micro-vessel heterogeneity, sluggish/absent flow, and focal anaemia. Recognition of such diversity in microcirculatory pathology, alongside with the implementation of novel biomarkers might reveal previously unobserved heterogeneity in adults diagnosed with sepsis. Early identification of distinct subtypes may help not only to better stratify disease severity but may also provide explanation to the often seen insufficient/absent response to resuscitative treatment. Experimental evidence suggests that impaired microcirculatory flow may correlate with organ dysfunction and mortality. Therefore, reliable/reproducible diagnostic tools, that provide real-time information about the dynamic state of the microcirculation, might be practice changers in managing the critically ill.The sublingual mucosa and the nailfolds provide easy access to microcirculation via hand-held, point-of-care devices. Accessing these windows, clinicians may recognise, understand and potentially correct the underlying tissue oxygenation/perfusion mismatch. This new clinical information might facilitate an individualised approach vs protocolised care aiming to administer the right balance of intravenous fluids/vasopressors, time/dose auxiliary treatment modalities and, most importantly, might also guide determining the optimal duration of resuscitation to avoid/minimise harm and maximise benefits in sepsis management. However, before every-day clinical use of such point-of-care microcameras, validation studies are needed to establish not only feasibility but reliability and reproducibility as well.

Differentiating sepsis from similar groups of symptoms at triage level in emergency care.

OBJECTIVES: Conditions that have similar initial presentations as sepsis may make early recognition of sepsis in an emergency room (ER) difficult. We investigated whether selected physiologic and metabolic parameters can be reliably used in the emergency department to differentiate sepsis from other disease states that mimic it, such as dehydration and stroke. METHODS: Loess regression on retrospective follow-up chart data of patients with sepsis-like symptoms (N = 664) aged 18+ in a large ER in Hungary was used to visualize/identify cutoff points for sepsis risk. A multivariate logistic regression model based on standard triage data was constructed with its corresponding receiver operating characteristic (ROC) curve and compared with another model constructed based on current sepsis guidelines. RESULTS: Age, bicarbonate, HR, lactate, pH, and body temperature had U, V, W, or reverse U-shaped associations with identifiable inflexion points, but the cutoff values we identified were slightly different from guideline cutoff values. In contrast to the guidelines, no inflexion points could be observed for the association of sepsis with SBP, DPB, MAP, and RR and therefore were treated as continuous variables. Compared to the guidelines-based model, the triage data-driven final model contained additional variables (age, pH, bicarbonate) and did not include lactate. The data-driven model identified about 85% of sepsis cases correctly, while the guidelines-based model identified only about 70% of sepsis cases correctly. CONCLUSION: Our findings contribute to the growing body of evidence for the necessity of finding improved tools to identify sepsis at early time points, such as in the ER.

Mapping nursing interventions using the Therapeutic Intervention Scoring System in bloodless liver transplantations.

BACKGROUND: The Simplified Therapeutic Intervention Scoring System adapted to liver transplantation by King's College Hospital rank 138 activities to determine the nursing workload, diagnostic, monitoring and therapeutic needs. OBJECTIVES: To evaluate nursing activities of "King's-TISS" score grouped in organ systems and nurse patient ratio in the perioperative 48 hours of blood product free liver transplantations (LT). METHODS: The "King's-TISS" score's were analysed by nursing procedures and grouped, scored according to organ systems. The nursing workloads were studied during LT (T1), on arrival on the ICU (T2) and 12-24-48 hours after LT (T3-T4-T5). RESULTS: The total of "King's-TISS" score points were decreased by ≥20% daily (p = 0.001). The mean score of 104 ± 3.5 points (CI:104-105) during LT decreased to 84.7 ± 12 points (CI:83-86) in 48 hours (T5). The "metabolic" and "haemostasis" points increased (p = ).01), the "immunology" points unchanged (T2-T5) postoperatively. A slight decrease was observed in case of "basic nursing care", "monitoring", "neurologic support", "renal support" and "cardiovascular support" points (T2-T5, p < .01). The "invasive intervention" and "ventilatory support" points strongly decreased (T2-T5, p < .001). One "King's-TISS" point was found to equal 7.4 minutes with a nurse patient ratio of 2:1 intraoperatively and 1:1 postoperatively. CONCLUSION: Absence of blood product administration in LT decreases the total and organ specific workload, except the metabolic, haemostasis, immunology and basic support requirement. It was not within the scope of the King's-TISS score to analyse the application of viscoelastic haemostasis test and coagulation factor concentrate administration.

How Much Is the Inevitable Loss of Different Coagulation Factors During Blood Product-Free Liver Transplantations?

BACKGROUND: Bloodless liver transplantations (LT) have already been reported, but special characteristics of hemostatic changes remain less defined. The aim of this study was to evaluate the "inevitable" loss of coagulation factors (CF) in blood product-free LT. METHODS: Blood product and CF concentrate-free LT patient data were analyzed in terms of the first 2 days of perioperative hemostasis kinetics (N = 59). CF levels (FI, II, V, VII, X, and XIII), platelet (PLT) levels, and hemoglobin levels were measured before LT (T1), on arrival at the intensive care unit (T2), and 12, 24, and 48 hours after LT (T3, T4, and T5, respectively). Thromboelastographic (TEG) parameters were determined before and at the end of LT (T1-T2). RESULTS: Fibrinogen levels decreased by 1.2 ± 0.6 g/L, prothrombin levels by 26% ± 14%, factor V levels by 40% ± 23%, VII levels by 29% ± 19%, and X levels by 39% ± 22% (P < .001). From T2 to T4 fibrinogen increased by 0.9 ± 0.6g/L for 24 hours (P < .001). Factor II, V, and VII levels increased by 20% ± 16%, 31% ± 32%, and 12% ± 27%, respectively, between T3 and T5 (P < .001). However, factor X reached only half of the T1 level (T3-T5, P < .001). Platelet count increased in 34 (58%) patients at T2 (P < .001). The TEG parameters remained in the normal range during LT (T1-T2). CONCLUSION: The major findings of this study advocate that "inevitable" levels of CF decrease during LT by an average of 1.2 g/L in terms of fibrinogen and 23% to 40% regarding factors II, V, VII, and X. The authors suggest that knowing the "magic numbers" and comparing them against baseline laboratory results might predict the possibility of blood product-free transplant, providing confidence and safety to the surgeon and the anesthetist.

Effects of repeated surgical stress on daily changes of body core temperature in mice.

Daily body core temperature rhythm has been known to become blunted for several days following intra-abdominal implantation of biotelemetry transmitters in small rodents and about a week is required for re-establishment of stable body core temperature oscillation. In the present study carried out on mice it was found that a repetition of the same minor surgical intervention (laparotomy) several days apart could speed up the stabilization of body temperature oscillations. Melatonin supplied with the drinking water continuously was found to speed up the return of stable daily body temperature rhythm further on consecutive laparotomies, while daily injections of methylprednisolone resulted in some delay in the development of stable body core temperature oscillations. It is concluded that in C57BL/6 mice possessing low plasma levels of melatonin exhibit an adaptive response to repeated stresses influencing the dynamics of daily body temperature rhythm.

Energetics of fasting heterothermia in TRPV1-KO and wild type mice.

To learn the possible role of TRPV1 in the changes of temperature regulation induced by short-term energy lack, TRPV1-KO and wild type mice were exposed to complete fasting for 2 or 3 days while their core temperature and locomotor activity were recorded using a biotelemetry method. In both types of mice, fasting led to progressive daytime hypothermia with night-time core temperature being maintained at normothermia (collectively called heterothermia). During fasting rises of locomotor activity were observed parallel to night-time normothermia with occasional increases of both parameters recorded every 2 to 3 hours (ultradian rhythms). The daytime fall of core temperature was significantly greater in wild type than in TRPV1-KO mice, in the former an advance of the temperature/activity rhythm having been observed in spite of the presence of a 12/12 hour light/darkness schedule. Re-feeding applied at the beginning of the light-period led to rapid reappearance of normothermia in both types of mice without a large increase in locomotor activity. It is concluded that the TRPV1-gene may have a role in the development of adaptive daytime hypothermia (and hence saving some energy) in mice during complete fasting but still allowing normothermia maintained at night, a strategy probably serving survival under natural conditions in small size rodents such as the mouse. The possible role of muscle thermogenesis either with or without gross bodily movement during fasting or on re-feeding, respectively, may be based on different mechanisms yet to be clarified.