BackgroundEndothelial progenitor cells (EPCs) have been suggested to constitute a restoration index of the disturbed endothelium in ICU patients. Neuromuscular electric stimulation (NMES) is increasingly employed in ICU to prevent comorbidities such as ICU-acquired weakness, which is related to endothelial dysfunction. The role of NMES to mobilize EPCs has not been investigated yet. The purpose of this study was to explore the NMES-induced effects on mobilization of EPCs in septic ICU patients.MethodsThirty-two septic mechanically ventilated patients (mean ± SD, age 58 ± 14 years) were randomized to one of the two 30-min NMES protocols of different characteristics: a high-frequency (75 Hz, 6 s on–21 s off) or a medium-frequency (45 Hz, 5 s on–12 s off) protocol both applied at maximally tolerated intensity. Blood was sampled before and immediately after the NMES sessions. Different EPCs subpopulations were quantified by cytometry markers CD34+/CD133+/CD45−, CD34+/CD133+/CD45−/VEGFR2+ and CD34+/CD45−/VEGFR2+.ResultsOverall, CD34+/CD133+/CD45− EPCs increased from 13.5 ± 10.2 to 20.8 ± 16.9 and CD34+/CD133+/CD45−/VEGFR2+ EPCs from 3.8 ± 5.2 to 6.4 ± 8.5 cells/106 enucleated cells (mean ± SD, p < 0.05). CD34+/CD45−/VEGFR2+ EPCs also increased from 16.5 ± 14.5 to 23.8 ± 19.2 cells/106 enucleated cells (mean ± SD, p < 0.05). EPCs mobilization was not affected by NMES protocol and sepsis severity (p > 0.05), while it was related to corticosteroids administration (p < 0.05).ConclusionsNMES acutely mobilized endothelial progenitor cells, measures of the endothelial restoration potential, in septic ICU patients.

BackgroundIntensive care unit-acquired weakness (ICUAW) is a common complication, associated with significant morbidity. Neuromuscular electrical stimulation (NMES) has shown promise for prevention. NMES acutely affects skeletal muscle microcirculation; such effects could mediate the favorable outcomes. However, optimal current characteristics have not been defined. This study aimed to compare the effects on muscle microcirculation of a single NMES session using medium and high frequency currents.MethodsICU patients with systemic inflammatory response syndrome (SIRS) or sepsis of three to five days duration and patients with ICUAW were studied. A single 30-minute NMES session was applied to the lower limbs bilaterally using current of increasing intensity. Patients were randomly assigned to either the HF (75 Hz, pulse 400 μs, cycle 5 seconds on - 21 seconds off) or the MF (45 Hz, pulse 400 μs, cycle 5 seconds on - 12 seconds off) protocol. Peripheral microcirculation was monitored at the thenar eminence using near-infrared spectroscopy (NIRS) to obtain tissue O2 saturation (StO2); a vascular occlusion test was applied before and after the session. Local microcirculation of the vastus lateralis was also monitored using NIRS.ResultsThirty-one patients were randomized. In the HF protocol (17 patients), peripheral microcirculatory parameters were: thenar O2 consumption rate (%/minute) from 8.6 ± 2.2 to 9.9 ± 5.1 (P = 0.08), endothelial reactivity (%/second) from 2.7 ± 1.4 to 3.2 ± 1.9 (P = 0.04), vascular reserve (seconds) from 160 ± 55 to 145 ± 49 (P = 0.03). In the MF protocol: thenar O2 consumption rate (%/minute) from 8.8 ± 3.8 to 9.9 ± 3.6 (P = 0.07), endothelial reactivity (%/second) from 2.5 ± 1.4 to 3.1 ± 1.7 (P = 0.03), vascular reserve (seconds) from 163 ± 37 to 144 ± 33 (P = 0.001). Both protocols showed a similar effect. In the vastus lateralis, average muscle O2 consumption rate was 61 ± 9%/minute during the HF protocol versus 69 ± 23%/minute during the MF protocol (P = 0.5). The minimum amplitude in StO2 was 5 ± 4 units with the HF protocol versus 7 ± 4 units with the MF protocol (P = 0.3). Post-exercise, StO2 increased by 6 ± 7 units with the HF protocol versus 5 ± 4 units with the MF protocol (P = 0.6). These changes correlated well with contraction strength.ConclusionsA single NMES session affected local and systemic skeletal muscle microcirculation. Medium and high frequency currents were equally effective.

Objectives: There is mounting evidence that delays in appropriate antimicrobial administration are responsible for preventable deaths in patients with sepsis. Herein, we examine the association between potentially modifiable antimicrobial administration delays, measured by the time from the first order to the first administration (antimicrobial lead time), and death among people who present with new onset of sepsis. Design: Observational cohort and case-control study. Setting: The emergency department of an academic, tertiary referral center during a 3.5-year period. Patients: Adult patients with new onset of sepsis or septic shock. Interventions: None. Measurements and Main Results: We enrolled 4,429 consecutive patients who presented to the emergency department with a new diagnosis of sepsis. We defined 0–1 hour as the gold standard antimicrobial lead time for comparison. Fifty percent of patients had an antimicrobial lead time of more than 1.3 hours. For an antimicrobial lead time of 1–2 hours, the adjusted odds ratio of death at 28 days was 1.28 (95% CI, 1.07–1.54; p = 0.007); for an antimicrobial lead time of 2–3 hours was 1.07 (95% CI, 0.85–1.36; p = 0.6); for an antimicrobial lead time of 3–6 hours was 1.57 (95% CI, 1.26–1.95; p < 0.001); for an antimicrobial lead time of 6–12 hours was 1.36 (95% CI, 0.99–1.86; p = 0.06); and for an antimicrobial lead time of more than 12 hours was 1.85 (95% CI, 1.29–2.65; p = 0.001). Conclusions: Delays in the first antimicrobial execution, after the initial clinician assessment and first antimicrobial order, are frequent and detrimental. Biases inherent to the retrospective nature of the study apply. Known biologic mechanisms support these findings, which also demonstrate a dose-response effect. In contrast to the elusive nature of sepsis onset and sepsis onset recognition, antimicrobial lead time is an objective, measurable, and modifiable process.

IntroductionElectrical muscle stimulation (EMS) is an FDA-approved thromboprophylactic method. Thrombus pathogenesis is considered to depend on factors related to components of the vessel wall, the velocity of blood, and blood consistency—collectively known as, the Virchow’s triad.ObjectiveThe testimony supporting the thromboprophylactic effects of the EMS is reviewed. An emphasis is placed on the fact that, EMS has demonstrated, in certain circumstances, an efficacy rate that cannot be fully explained by the Virchow’s triad; also that, in reviewing relevant evidence and the theorized pathophysiological mechanisms, several findings collectively point to a potentially missed point. Remarkably, venous thromboembolic disease (VTE) is extremely more common in the lower versus the upper extremities even when the blood velocities equalize; EMS had synergistic effects with intermittent compressive devices, despite their presumed identical mechanism of action; sleep is not thrombogenic; non-peroperative EMS is meaningful only if applied ≥5 times daily; neural insult increases VTEs more than the degree expected by the hypomobility-related blood stasis; etc. These phenomena infer the presence of a 4th thrombogenetic factor: neural supply to the veins provides direct antithrombic effects, by inducing periodic vessel diameter changes and/or by neuro-humoral, chemically acting factors. EMS may stimulate or substitute the 4th factor. This evidence-based hypothesis is analyzed.ConclusionA novel pathophysiologic mechanism of thrombogenesis is supported; and, based on this, the role of EMS in thromboprophylaxis is expanded. Exploration of this mechanism may provide new targets for intervention.

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Epstein-Barr virus (EBV)-related haemophagocytic lymphohistiocytosis (EBVr-HLH) has a better prognosis when the virus is rapidly cleared, but the best antiviral approach is controversial. We present a patient to whom the therapeutic standard rituximab was co-administered with valacyclovir and an HLH-specific treatment with favourable viral and clinical responses. We conducted an extensive literature review and contacted several world reference centres and experts to inquire about their approaches and experience. We conclude that antivirals are infrequently used for EBVr-HLH, despite their laboratory-proven and likely clinical beneficial effect on some EBV-related diseases. However, the role of antivirals remains obscure. Concerns about their lack of efficacy are based on observational data and reports of the cellular tropism of EBV. Therefore, the adjunct use of antivirals may be considered when myelotoxicity is not the primary concern, and related outcomes should be systematically recorded to produce higher quality evidence.

Any advanced shock eventually degenerates into vasoplegia, which responds weakly to vasopressors. The highest reported norepinephrine flow rate is 3 μg/kg/min. We present the case of a young explosion victim, who was transferred in late haemorrhagic shock. Apart from usual treatment (hydration, mass transfusion protocol), single-agent norepinephrine was used to maintain a mean arterial pressure (MAP) of >60–65 mm Hg. For several hours, norepinephrine flow was 7–10 times the aforementioned (highest reported) in order to achieve our goal; during which, further hydration or transfusion would not contribute to MAP elevation. Sequential Organ Failure Assessment (SOFA) severity score was 18 (expected mortality >99%). The patient survived without underperfusion-related damage. We conclude that norepinephrine dosages could potentially be greatly increased in late shock. We must resist giving up flow escalation based on its numerical value.

Background Computer-assisted communication is shown to prevent critical omissions (“errors”) in the handoff process. Objective The aim of the study was to study this effect and related provider satisfaction, using a standardized software. Methods Fourteen internal medicine house officers staffed 6 days and 1 cross-covering teams were randomized to either the intervention group or control, employing usual handoff, so that handoff information was exchanged only between same-group subjects (daily, for 28 days). Results In the intervention group, fewer omissions (among those studied) occurred intravenous access (17 versus 422, P < 0.001), code status (1 versus 158, P < 0.001), diet/nothing per mouth (28 versus 477, P < 0.001), and deep venous thrombosis prophylaxis (17 versus 284, P < 0.001); duration to compose handoff was similar; and physicians perceived less workload adjusted for patient census and provider characteristics (P = 0.004) as well as better handoff quality (P < 0.001) and clarity (P < 0.001). Conclusions The intervention was associated with fewer errors and superior provider satisfaction.