Abstract

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28 days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

Abstract

BACKGROUND Whether to use limited fluid resuscitation (LFR) in patients with hemorrhagic shock or septic shock remains controversial. This research was aimed to assess the pros and cons of utilizing LFR in hemorrhagic shock or septic shock patients. METHODS PubMed, Cochrane Library, Embase, Web of science, CNKI, VIP, and Wan Fang database searches included for articles published before December 15, 2020. Randomized controlled trials of LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients were selected. RESULT This meta-analysis including 28 randomized controlled trials (RCTs) and registered 3288 patients. The 7 of 27 RCTs were the patients with septic shock. Others were traumatic hemorrhagic shock patients. Comparing LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients, the summary odds ratio (OR) was 0.50 (95% confidence interval [CI] 0.42-0.60, P < .00001) for mortality, 0.46 (95% CI 0.31-0.70, P = .0002) for multiple organ dysfunction syndrome (MODS), 0.35 (95% CI 0.25-0.47) for acute respiratory distress syndrome (ARDS), and 0.33 (95% CI 0.20-0.56) for disseminated intravascular coagulation (DIC). CONCLUSION Limited fluid resuscitation is the benefit of both traumatic hemorrhagic shock patients and septic shock patients.

Abstract

PURPOSE This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock. METHODS Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care. RESULTS Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010). CONCLUSION The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.

Abstract

BACKGROUND After being used for more than a decade the use of hydroxyethyl starch (HES) 130/0.38-0.45 in clinical practice was discouraged because of serious adverse events including bleeding, acute kidney injury and death. But could these adverse effects have been discovered sooner? By comparing the summary effect estimates of the adverse effects of HES 130/0.38-0.45 in different study designs we aimed to disclose any signal of this. METHODS We systematically searched MEDLINE, EMBASE and Cochrane Library and hand-searched the reference lists of relevant studies to identify studies for inclusion. Eligible trials were randomised clinical trials (RCTs) and observational studies in patients with sepsis and randomised trials in animals with induced sepsis comparing HES 130/0.38-0.45 to any type of crystalloid. Relevant outcomes were all-cause mortality at longest follow-up, renal replacement therapy (RRT), acute kidney injury (AKI) and bleeding. We extracted data, conducted conventional meta-analyses and assessed risk of bias and the quality of evidence. RESULTS We included 8 RCTs including 3,273 patients, 1 observational study including 379 patients and 5 randomised animal trials including 94 test animals. There was no suggestion of interaction in subgroup analyses comparing the different study designs for any outcomes (all-cause mortality at longest follow-up P=0.33; RRT P=0.70; AKI P=0.63; bleeding P=0.20). CONCLUSIONS We observed no interaction between the summary effect estimates of RCTs, observational studies in patients and randomised animal trials for any of the outcomes. Accordingly, we found no evidence indicating that the adverse effects of HES 130/0.38-0.45 could have been discovered sooner.

Abstract

Current evidences in resuscitation of adult sepsis have pointed to the importance of types of crystalloid fluid-related complications on resuscitation outcomes, but evidences are lacking in pediatric populations. In this study, the authors aimed to compare outcomes of pediatric sepsis resuscitation with different types of crystalloid. They randomly assigned pediatric sepsis patients requiring fluid bolus into three groups to receive either normal saline solution (NSS), Ringer lactate solution (RLS), or Sterofundin as fluid bolus therapy. Forty-two patients were included in the study. Median age was 29 mo and, weight 13 kg. After fluid bolus, the complications were not different among groups. However, in the RLS group, the patients who received large dose of the fluid showed significant reduction in urinary neutrophil gelatinase-associated lipocalin (uNGAL) level. It is concluded that fluid bolus therapy with different types of crystalloid solution did not result in different outcomes but large dose of RLS was associated with greater reduction of uNGAL level, compared to other fluids.Trial Registration: Thai Clinical Trial Registry (TCTR) identification number TCTR20170605001 (retrospectively registered on 1st June 2017). https://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task20=search&task2=view1&id=2576.

Abstract

OBJECTIVES The purpose of this research was to determine the effectiveness of Pentaglobin® as adjuvant therapy in the treatment of sepsis in preterm newborns. MATERIALS AND METHODS It was a prospective, observational, randomized study for 272 premature neonates and very low birth weight (VLBW) that were diagnosed with sepsis carried at neonatal intensive care units. The patients randomized into control group who received standard sepsis antibiotic treatments, and an intervention group who received Pentaglobin® 5 ml/kg daily for 3 consecutive days as an adjunct therapy to a standard sepsis antibiotic treatment. RESULTS Multiple organisms that isolated from culture specimens were Gram-negative bacteria, Gram-positive, and candida (56.25%, 42.28%, and 1.47%, respectively). The disease duration was distinctively longer in patients who were treated by the standard antibiotic protocol (mean ± standard deviation [SD]: 30.76 ± 3.97, odds ratio [OR]: 30.76, 95% confidence interval [CI]: 30.051, 31.473) comparing to the patients who received Pentaglobin adjuvant therapy (mean ± SD: 26.48 ± 5.55, OR: 26.48, 95% CI: 25.489, 27.477) (P < 0.000). Patients treated by standard antibiotic protocol were associated to a substantially increased risk of death (11.76%, hazard ratio 4.400, 95% CI: 1.432, 13.529, P = 0.009). CONCLUSION Neonatal sepsis is more common in premature and VLBW newborns, and Pentaglobin® management of newborn nosocomial sepsis might be used in addition to other therapies.

Abstract

INTRODUCTION The ultrasound measurement of inferior vena cava (IVC) diameter change during respiratory phase to guide fluid resuscitation in shock patients is widely performed, but the benefit on reducing the mortality of sepsis patients is questionable. The study objective was to evaluate the 30-day mortality rate of patients with sepsis-induced tissue hypoperfusion (SITH) and septic shock (SS) treated with ultrasound-guided fluid management (UGFM) using ultrasonographic change of the IVC diameter during respiration compared with those treated with the usual-care strategy. METHODS This was a randomized controlled trial conducted in an urban, university-affiliated tertiary-care hospital. Adult patients with SITH/SS were randomized to receive treatment with UGFM using respiratory change of the IVC (UGFM strategy) or with the usual-care strategy during the first six hours after emergency department (ED) arrival. We compared the 30-day mortality rate and other clinical outcomes between the two groups. RESULTS A total of 202 patients were enrolled, 101 in each group (UGFM vs usual-care strategy) for intention-to-treat analysis. There was no significant difference in 30-day overall mortality between the two groups (18.8% and 19.8% in the usual-care and UGFM strategy, respectively; p > 0.05 by log rank test). Neither was there a difference in six-hour lactate clearance, a change in the sequential organ failure assessment score, or length of hospital stay. However, the cumulative fluid amount given in 24 hours was significantly lower in the UGFM arm. CONCLUSION In our ED setting, the use of respiratory change of IVC diameter determined by point-of-care ultrasound to guide initial fluid resuscitation in SITH/SS ED patients did not improve the 30-day survival probability or other clinical parameters compared to the usual-care strategy. However, the IVC ultrasound-guided resuscitation was associated with less amount of fluid used.

Abstract

AIMS: Sepsis and septic shock are common causes of hospitalization and mortality in patients with cirrhosis. There is no data on the choice of fluid and resuscitation protocols in sepsis-induced hypotension in cirrhosis. METHODS In this open-label trial conducted at a single center, we enrolled 308 cirrhotics with sepsis-induced hypotension and randomized them to receive either 5% albumin or normal saline. The primary endpoint was a reversal of hypotension [mean arterial pressure, MAP, ≥ 65 mmHg] at 3 h. Secondary endpoints included serial effects on heart rate, arterial lactate and urine output. RESULTS 154 patients each received 5% albumin (males, 79.8%, mean MAP 52.9 ± 7.0 mm Hg) or 0.9% saline (85.1%, 53.4 ± 6.3 mm Hg) with comparable baseline parameters and liver disease severity. Reversal of hypotension was higher in patients receiving 5% albumin than saline at the end of one hour [25.3% and 11.7%, p = 0.03, Odds ratio (95% CI)-1.9 (1.08-3.42)] and at the end of three hours [11.7% and 3.2%, p = 0.008, 3.9 (1.42-10.9)]. Sustained reduction in heart rate and hyperlactatemia (p < 0.001) was better in the albumin group. At one week, the proportion of patients surviving was higher in the albumin group than those receiving saline (43.5% vs 38.3%, p = 0.03). Female gender and SOFA ≥ 11 were predictors of non-response to fluid. CONCLUSIONS 5% human albumin is safe and beneficial in reversing sepsis-induced hypotension compared to normal saline in patients with cirrhosis improving clinically assessable parameters of systemic hemodynamics, tissue perfusion and in-hospital short-term survival of cirrhosis patients with sepsis.

Abstract

BACKGROUND The best fluid replacement strategy and the role of albumin in immunocompromised patients with sepsis is unclear. METHODS We performed a secondary analysis of immunocompromised patients enrolled in the ALBIOS trial which randomized patients with severe sepsis or septic shock to receive either 20% albumin (target 30 g per liter or more) and crystalloid or crystalloid alone during ICU stay. RESULTS Of 1818 patients originally enrolled, 304 (16.4%) were immunocompromised. One-hundred-thirty-nine (45.7%) patients were randomized in the albumin while 165 (54.2%) in the crystalloid group. At 90 days, 69 (49.6%) in the albumin group and 89 (53.9%) in the crystalloids group died (hazard ratio - HR - 0.94; 95% CI 0.69-1.29). No differences were observed with regards to 28-day mortality, SOFA score (and sub-scores), length of stay in the ICU and in the hospital, proportion of patients who had developed acute kidney injury or received renal replacement therapy, duration of mechanical ventilation. Albumin was not independently associated with a higher or lower 90-day mortality (HR 0.979, 95% CI 0.709-1.352) as compared to crystalloid. CONCLUSION Albumin replacement during the ICU stay, as compared with crystalloids alone, did not affect clinical outcomes in a cohort of immunocompromised patients with sepsis.

Abstract

Red blood cell transfusion is thought to improve cell respiration during septic shock. Nevertheless, its acute impact on oxygen transport and metabolism in this condition remains highly debatable. The objective of this study was to evaluate the impact of red blood cell transfusion on microcirculation and oxygen metabolism in patients with sepsis and septic shock. We conducted a search in the MEDLINE®, Elsevier and Scopus databases. We included studies conducted in adult humans with sepsis and septic shock. A systematic review and meta-analysis were performed using the DerSimonian and Laird random-effects model. A p value < 0.05 was considered significant. Nineteen manuscripts with 428 patients were included in the analysis. Red blood cell transfusions were associated with an increase in the pooled mean venous oxygen saturation of 3.7% (p < 0.001), a decrease in oxygen extraction ratio of -6.98 (p < 0.001) and had no significant effect on the cardiac index (0.02L/minute; p = 0,96). Similar results were obtained in studies including simultaneous measurements of venous oxygen saturation, oxygen extraction ratio, and cardiac index. Red blood cell transfusions led to a significant increase in the proportion of perfused small vessels (2.85%; p = 0.553), while tissue oxygenation parameters revealed a significant increase in the tissue hemoglobin index (1.66; p = 0.018). Individual studies reported significant improvements in tissue oxygenation and sublingual microcirculatory parameters in patients with deranged microcirculation at baseline. Red blood cell transfusions seemed to improve systemic oxygen metabolism with apparent independence from cardiac index variations. Some beneficial effects have been observed for tissue oxygenation and microcirculation parameters, particularly in patients with more severe alterations at baseline. More studies are necessary to evaluate their clinical impact and to individualize transfusion decisions.