Rescue stem cell allograft in intensive care unit patients during septic shock with multi-organ failure

This research by Lepretre and colleagues was first published online in the Journal of Critical Care during July 2019.
Purpose:  We describe what we believe to be the first two cases of patients who received an allograft in intensive care unit (ICU) despite severe septic shock with multi-organ failure (MOF).
Results:  One patient had aggressive large B-cell lymphoma. After allograft, the patient initially improved after withdrawing norepinephrine and renal replacement therapy but he subsequently died thirty-two days later because of a new relapse of the disease. The second patient had acute myeloid leukemia type 1 with a need for an allograft after a first complete remission. She was discharged from ICU at D23 after allograft and still alive 7 months later with complete remission. For the two patients, allograft conditioning was performed before admission to our ICU. These two cases highlight one major problem in such situations which is to find the best time to perform the allograft, particularly in ventilated patients with septic shock and MOF. We performed the allograft when we thought that the risk-benefit ratio was in favor of restoring immunity.
Conclusion:  Allograft should be considered as a rescue therapy in ICU for patients with aplasia, during septic shock with multi-organ failure, however close multidisciplinary discussion is required between intensivists and onco-hematologists.
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Quality of life assessment following amputation for septic shock: a long-term descriptive survey after symmetric peripheral gangrene

This article by Labroca and others was published online in the Journal of Critical Care in late June 2019.
Purpose:  To assess health-related quality of life (HRQOL) following rehabilitation of amputees suffering symmetric peripheral gangrene (SPG) after septic shock.
Material and methods:  A retrospective cohort study was conducted in nine French specialized rehabilitation centers. Thirty-two ICU adult patients hospitalized between 2005 and 2015 for septic shock who additionally presented with SPG resulting in at least two major amputations were enrolled. HRQOL was assessed by EQ-5D-3 L questionnaire.
Results:  All patients (mean ICU length of stay 39 ± 22d, SAPS II 58 ± 18) had both lower limbs amputated and 84% were quadruple amputees. HRQOL, assessed 4.8 ± 2.8 years after amputation, was inferior to the French reference. However, patients’ self-rated health status was similar to the reference at the time of HRQOL assessment. The main factor of impaired HRQOL was intense phantom pain, not the mobility or self-care dimensions of EQ-5D. All patients except one preferred to be treated again for SPG despite disability.
Conclusion:  ICU survivors referred to rehabilitation centers after SPG-related amputations had impaired HRQOL. At the time of HRQOL assessment, they considered themselves in good health and preferred to be treated again despite disability. Appraisal of long-term functional outcome should not be used to guide end-of-life decision-making in this situation.
The full text of this article is available to subscribers via this link to the journal’s homepage.  The full text of articles from issues older than sixty days is available via this link to an archive of issues of Journal of Critical Care.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

Impact of timing to source control in patients with septic shock: A prospective multi-center observational study

This work by Kim and others was first published on line during June 2019 in the Journal of Critical Care.
Purpose:  Current guidelines recommend that rapid source control should be adopted in patients not >6–12 h after sepsis is diagnosed. However, evidence level of this guideline is not specified, and there is no previous study on patients with septic shock visiting the emergency department (ED). Therefore, we aimed to assess the impact of rapid source control in patients with septic shock visiting the ED.
Materials and methods:  In a prospective, observational, multicenter, registry-based study in 11 EDs, Cox proportional hazards model was used to assess the independent effect of source control and time to source control on 28-day mortality.
Results:  Cox proportional hazard models revealed that 28-day mortality was significantly lower in patients who underwent source control (HR 0.538 (0.389–0.744), p < .001). However, no significant association between the performance of source control after 6 h or 12 h from enrollment and 28-day mortality was noted.
Conclusions:  Patients with septic shock visiting the ED who underwent source control showed better outcomes than those who did not. We failed to demonstrate the performance of rapid source control reduced the 28-day mortality in septic shock patients. Further studies are required to determine the impact of rapid source control in sepsis and septic shock.
The full text of this article is available to subscribers via this link to the journal’s homepage.  The full text of articles from issues older than sixty days is available via this link to an archive of issues of Journal of Critical Care.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

Effects of short-term hyperoxia on sytemic hemodynamics, oxygen transport, and microcirculation: An observational study in patients with septic shock and healthy volunteers

This research by Espinoza and others was published in Journal of Critical Care online in June 2019.
Purpose:  To characterize the microvascular effects of a brief period of hyperoxia, in patients with septic shock and in healthy volunteers.
Materials and methods:  In 20 patients with septic shock, we assessed systemic hemodynamics, sublingual microcirculation by SDF-videomicroscopy, and skin perfusion by capillary refill time (CRT), central-peripheral temperature (ΔT°), and perfusion index. Measurements were performed at baseline and after 5 min of inspired oxygen fraction of 1.00. Additionally, we studied 8 healthy volunteers, in whom hyperoxia was prolonged to 30 min.
Results:  In septic patients, hyperoxia increased mean arterial pressure and systemic vascular resistance, but cardiac output remained unchanged. The only significant change in sublingual microcirculation was a decreased heterogeneity flow index (1.03 [1.01–1.07] vs 1.01 [0.34–1.05], P = .002). Perfused vascular density (13.1 [12.0–15.0] vs 14.0 [12.2–14.8] mm/mm2, P = .21) and the other sublingual microvascular variables were unmodified. CRT and ΔT° did not change but perfusion index slightly decreased. In healthy volunteers, sublingual microcirculation and skin perfusion were stable.
Conclusions:  Short-term hyperoxia induced systemic cardiovascular changes but was not associated with noticeable derangement in sublingual microcirculation and skin perfusion. Nevertheless, longer exposures to hyperoxia might have produced different results.
The full text of this article is available to subscribers via this link to the journal’s homepage.  The full text of articles from issues older than sixty days is available via this link to an archive of issues of Journal of Critical Care.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

Effect of physostigmine on recovery from septic shock following intra-abdominal infection – Results from a randomized, double-blind, placebo-controlled, monocentric pilot trial (Anticholium® per Se)

This research by Pinder et al was published online during April 2019 in the Journal of Critical Care.
Purpose:  The cholinergic anti-inflammatory pathway has been shown to be accessible by physostigmine salicylate in animal models. However, the cholinesterase inhibitor is not approved for adjunctive therapy in sepsis, and tolerability and safety of high initial doses followed by continuous infusion have not been investigated.
Materials and methods:  In this trial, 20 patients with perioperative septic shock due to intra-abdominal infection were eligible. The physostigmine group received an initial dose of 0.04 mg/kg physostigmine salicylate, followed by continuous infusion of 1 mg/h for 120 h; the placebo group was treated with 0.9% sodium chloride. Primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score during treatment and up to 14 days.
Results:  Administration of physostigmine salicylate was well tolerated. Mean SOFA scores were 8.9 ± 2.5 and 11.3 ± 3.6 (mean ± SD) for physostigmine and placebo group, respectively. Adjusted for age, difference between means was not statistically significant (−2.37, 95% CI: -5.43 to 0.70, p = 0.121). Norepinephrine doses required only appeared lower in the physostigmine group (p = 0.064), along with a more rapid reduction from an elevated heart rate possibly indicating less hemodynamic instability.
Conclusions:  Treatment with physostigmine salicylate was feasible and safe. Further studies are justified to assess the effect on recovery from septic shock.
The full text of this article is available to subscribers via this link to the journal’s homepage.  The full text of articles from issues older than sixty days is available via this link to an archive of issues of Journal of Critical Care.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial.

This article by Hernandez and others was published in JAMA in February 2019 (volume 321 number 7 pages 654-664)
Importance:  Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established.
Objective:  To determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality.
Design, Setting, and Participants:  Multi-centre, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018.
Interventions: Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period.
Main Outcomes and Measures:  The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay.
Results:  Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, -1.00 [95% CI, -1.97 to -0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed.
Conclusions and Relevance:  Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

Association of septic shock definitions and standardized mortality ratio in a contemporary cohort of critically ill patients

This research by Kashyap and colleagues was first published on line in the “Journal of Critical Care” during January 2019.
Purpose:  The newly proposed septic shock definition has provoked a substantial controversy in the emergency and critical care communities. We aim to compare new (SEPSIS-III) versus old (SEPSIS-II) definitions for septic shock in a contemporary cohort of critically ill patients.
Material and methods:  Retrospective cohort of consecutive patients, age ≥ 18 years admitted to intensive care units at the Mayo Clinic between January 2009 and October 2015. We compared patients who met old, new, both, or neither definition of sepsis shock. SMR were calculated using APACHE IV predicted mortality.
Results:  The initial cohort consisted of 16,720 patients who had suspicion of infection, 7463 required vasopressor support. The median (IQR) age was 65(54–75) years and 4167(55.8%) were male. Compared to patients with old definition, the patients with new definition had higher APACHE III score (median IQR); (73 (57–92) vs. 70 (56–89), p < .01); SOFA score; (6 (4–10) vs. 6 (4–9), p < .01), were older (70 (59–79) vs. 64 (54–74) years, p = .03). They also had higher hospital mortality, N (%) 71, (19.7%) vs. 40 (12.6%), p < .01) and a higher SMR (0.66 vs. 0.45, p < .01).
Conclusions:  Compared to SEPSIS-II, SEPSIS-III definition of septic shock identifies patients further along disease trajectory with higher likelihood of poor outcome.
The full text of articles from issues older than sixty days is available via this link to an archive of issues of Journal of Critical Care.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.