Impact of the pre-illness lipid profile on sepsis mortality

This research by Maile et al was published online in the Journal of Critical Care during January 2020.
Purpose:  To determine if baseline lipid levels contribute to the relationship between lipid levels during sepsis and outcomes.
Materials and methods:  We conducted a retrospective cohort study at a tertiary-care academic medical center. Multi-variable logistic regression models were used to adjust for confounders. Both Systemic Inflammatory Response Syndrome (SIRS) and Sequential Organ Failure Assessment (SOFA) score-based definitions of sepsis were analyzed.
Measurements and main results:  After adjusting for patient characteristics and severity of illness, baseline values for both low density lipoprotein (LDL) cholesterol and triglycerides were associated with mortality (LDL cholesterol odds ratio [OR] 0.44, 95% confidence interval [CI] 0.23–0.84, p = .013; triglyceride OR 0.54, 95% CI 0.37–0.78, p = .001) using a SIRS based definition of sepsis. An interaction existed between these two variables, which resulted in increased mortality with higher baseline low density lipoprotein (LDL) cholesterol values for individuals with triglycerides below 208 mg/dL and the opposite direction of association above this level (interaction OR 1.48, 95% CI 1.02–2.16, p = .039). When using a SOFA score-based definition, only triglycerides remained associated with the mortality (OR 0.55, 95% CI 0.35–0.86, p = .008).
Conclusions:  Baseline lipid values, particularly triglyceride concentrations, are associated with hospital mortality in septic patients.
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Muscle degradation, vitamin D and systemic inflammation in hospitalized septic patients

This article by Borges and colleagues was first published online in the Journal of Critical Care during December 2019.
Purpose:  To date, the relationship between systemic inflammation and muscle changes observed by ultrasonography in septic patients in clinical studies is not known. Furthermore, the role of vitamin D on muscle changes in these patients needs to be investigated.
Materials and methods:  Forty-five patients admitted to the ICU due to severe sepsis or septic shock. Blood samples were collected to evaluate systemic inflammation (interleukin (IL)-10, IL-1β, IL-1α, IL-6, IL-8 and tumor necrosis factor–α(TNF-α)) and vitamin D. Muscle mass was evaluated by ultrasound during hospitalization. Clinical tests of muscle strength (Medical Research Council (MRC) scale and handgrip) were performed after the awakening of patients.
Results:  There was a reduction in day 2 values to hospital discharge on TNF-alpha, IL-8, IL-6 and IL-10 (p < .05). The muscle mass showed a significant decline from day 6 of the ICU. After awakening, the patients had a significant increase in muscle strength (p < .05). There was a positive association between muscle mass variation (day 2 – ICU) with absolute values of IL-8 (r = 0.38 p = .05). For muscle strength, there was a negative association between handgrip strength with IL-8 (r = −0.36 p < .05) on ICU discharge. The vitamin D showed a positive association with the handgrip strength of the day 1 of the awakening (r = 0.51 p < .05).
Conclusions:  In septic patients, there is an association between inflammation and changes in muscle mass and strength during ICU stay, which is similar to those observed in experimental studies. In addition, there was an association of vitamin D with recovery of muscle strength during hospitalization.
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Corticosteroids for treating sepsis in children and adults

This systematic review by Annane and colleagues was first published online during December 2019
Review question:  We reviewed the evidence on the effect on death of using corticosteroids in children and adults with sepsis.
Background:  Sepsis is present when an infection is complicated by organ failure. People develop rapid breathing, hypotension (low blood pressure), and mental confusion. Sepsis can interfere with the effectiveness of the body’s corticosteroids, which serve as a key defence against infection. Corticosteroids have been given for decades to people with infection resulting from various causes.
Search date:  The evidence provided in this review is current to July 2019.
Study characteristics:  This review included 61 trials (12,192 participants). Fifty‐eight trials compared corticosteroids to no corticosteroids (placebo or usual care in 48 and nine trials, respectively); three trials also compared continuous versus bolus administration of corticosteroids.
Study funding sources:  Three trials were funded by a drug company, 27 by public organizations or through charitable funding, and six by both a drug company and public organizations or charitable funding; 25 did not declare the source of funding.
Key results:  We have analysed the following two comparisons.
• Corticosteroids versus placebo/usual care.
Corticosteroids probably reduce the risk of death at 28 days by 9% (50 trials; 11,233 participants), with consistent treatment effects between children and adults. They also probably slightly reduce the risk of dying in hospital. There may be little or no effect of corticosteroids on risk of dying over the long term (longer than three months), but these results are less certain. Corticosteroids result in a large reduction in length of stay in the intensive care unit (ICU) and in hospital. Corticosteroids increase the risk of muscle weakness and hypernatraemia. They probably increase the risk of hyperglycaemia. They probably do not increase the risk of superinfection. There may be little or no effect of corticosteroids on risk of gastroduodenal bleeding, neuropsychiatric events, stroke, or cardiac events.
• Continuous infusion versus intermittent boluses of corticosteroids.
We are uncertain about the effects of continuous infusion of corticosteroids compared with intermittent bolus administration. Three studies reported data for this comparison, and the certainty of evidence for all outcomes was very low.
Certainty of evidence
• Corticosteroids versus placebo/usual care
We judged the certainty of evidence for 28‐day mortality as moderate due to some inconsistency related to differences among study populations, types of corticosteroids and how they were given, and use of additional interventions.
• Continuous infusion versus intermittent boluses of corticosteroids
We judged the certainty of evidence for 28‐day mortality as very low due to inconsistency and imprecision.
Implications for practice:  Moderate‐certainty evidence indicates that corticosteroids probably reduce 28‐day, 90‐day, and hospital mortality among patients with sepsis. Corticosteroids result in a large reduction in ICU and hospital length of stay (high‐certainty evidence). There may be little or no difference in the risk of major complications; however, corticosteroids increase the risk of muscle weakness and hypernatraemia (high‐certainty evidence), and probably increase the risk of hyperglycaemia (moderate‐certainty evidence). The effects of continuous versus intermittent bolus administration of corticosteroids are uncertain.
Implications for research:  The criteria for critical illness‐related corticosteroid insufficiency in septic shock remain to be defined.
Subgroup analyses suggest that additional studies are needed to address these topics related to the use of corticosteroids in patients with sepsis.

  • The role of a long course of low‐dose corticosteroids for treatment of septic shock in children.
  • The role of a long course of low‐dose corticosteroids for treatment of patients with sepsis without shock, or with a mild form of septic shock; patients with ARDS; and patients with sepsis related to community‐acquired pneumonia.
  • The role of mineralocorticoid replacement.
  • Optimal timing of initiation of treatment.
  • Optimal dose and duration of hydrocortisone (or equivalent).
  • Optimal modality to administer treatment that is continuous versus intermittent bolus.
  • Optimal modality to stop treatment with or without taper off.
  • The role of a long course of low‐dose corticosteroids for treatment of sepsis caused by different types of infections.
  • Long‐term neuromuscular effects of steroids.
    The full details of this Cochrane Systematic Review are available via this link.

C-reactive protein as a prognostic factor in intensive care admissions for sepsis: A Swedish multicenter study

This article by Koozi and others was first published online in the Journal of Crtical Care during December 2019
Purpose:  C-reactive protein (CRP) is not included in the major intensive care unit (ICU) prognostic tools such as the Simplified Acute Physiology Score (SAPS). We assessed CRP on ICU admission as a SAPS-3 independent risk marker for short-term mortality and length of stay (LOS) in ICU patients with sepsis.
Materials and methods:  Adult ICU admissions satisfying the Sepsis-3 criteria to four southern Swedish hospitals were retrospectively identified and divided into a low CRP group (<100 mg/L) and a high CRP group (>100 mg/L) based on the admission CRP level. The standardized mortality ratio (SMR) was calculated.
Results:  A total of 851 admissions were included. The SMR was higher in the high CRP group (0.85 vs. 0.67, P = .001 in the whole sepsis group and 0.85 vs. 0.59, P = .003 in the culture-positive subgroup). The CRP levels also correlated with ICU and hospital LOS in survivors (P < .001 and P = .002), again independent of SAPS-3.
Conclusion:  An admission CRP level >100 mg/L is associated with an increased risk of ICU and 30-day mortality as well as prolonged LOS in survivors, irrespective of morbidity measured with SAPS-3. Thus, CRP may be a simple, early marker for prognosis in ICU admissions for sepsis.
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.

Double inter-hospital transfer in Sepsis patients presenting to the ED does not worsen mortality compared to single inter-hospital transfer

This article by Arulraja and colleagues was first published online in the Journal of Critical Care during December 2019.
Purpose:  Sepsis is a leading cause of hospital deaths. Inter-hospital transfer is frequent in sepsis and is associated with increased mortality. Some sepsis patients undergo two inter-hospital transfers (double transfer). This study assessed the (1) prevalence, (2) associated risk factors, (3) associated mortality, and (4) hospital length-of-stay and costs of double-transfer of sepsis patients.
Materials and methods:  Retrospective cohort study using 2005–2014 administrative claims data in Iowa. Multivariable generalized estimating equations adjusted for potential confounding variables, with a primary outcome of mortality. Secondary outcomes included hospital length-of-stay and costs. Hospital-specific cost-to-charge ratios estimated hospital costs. Hospitals were categorized into quintiles based on sepsis-volume.
Results:  Of 15,182 sepsis subjects, there were 45.2% non-transfers and 2.1% double-transfers. Double-transfers had worse mortality than non-transfers but not single-transfers. Of the non-transfers, 44.9% presented to a top sepsis-volume hospital compared to 22.8% of double-transfers and 25.1% of single-transfers. After transfer from first to second hospital, 93.4% of the single-transfers and 92.2% of the double-transfers were at a top sepsis-volume hospital. Double-transfers had longer length-of-stay and more in total hospital costs than single-transfers.
Conclusions:  Double-transfer occurs in 2.1% of Iowa sepsis patients. Double-transfers had similar mortality and increased length of stay and costs compared to single-transfers.
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 Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial.

This article by Fowler et al was published in JAMA during October 2019 in volume 322 issue 13.
Importance:  Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS).
Objective:  To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS.
Design, Setting, and Participants:  The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018.InterventionsPatients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours.
Main Outcomes and Measures:  The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours.
Results:  Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours.
Conclusions and Relevance:  In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

Fluid resuscitation in patients with end-stage renal disease on hemodialysis presenting with severe sepsis or septic shock: A case control study

This research by Rajdev and colleagues was first published in October 2019 in the online edition of Journal of Critical Care.
Due to the potential risk of volume overload, physicians are hesitant to aggressively fluid-resuscitate septic patients with end-stage renal disease (ESRD) on hemodialysis (HD). Primary objective: To calculate the percentage of ESRD patients on HD (Case) who received ≥30 mL/Kg fluid resuscitation within the first 6 h compared to non-ESRD patients (Control) that presented with severe sepsis (SeS) or septic shock (SS). Secondary objectives: Effect of fluid resuscitation on intubation rate, need for urgent dialysis, hospital length of stay (LOS), intensive care unit (ICU) admission and LOS, need for vasopressors, and hospital mortality. Medical records of 715 patients with sepsis, SeS, SS, and ESRD were reviewed. We identified 104 Case and 111 Control patients. In the Case group, 23% of patients received ≥30 mL/Kg fluids compared to 60% in the Control group (p < 0.001). There was no significant difference in mortality, need for urgent dialysis, intubation rates, ICU LOS, or hospital LOS between the two groups. Subgroup analysis between ESRD patients who received ≥30 mL/Kg (N = 80) vs those who received <30 mL/Kg (N = 24) showed no significant difference in any of the secondary outcomes. Compliance with 30 mL/Kg fluids was low for all patients but significantly lower for ESRD patients. Aggressive fluid resuscitation appears to be safe in ESRD patients.
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.