Infectious Disease & Sepsis

Do We Need to Administer Fludrocortisone in Addition to Hydr... : Critical Care Medicine (lww.com)

This systematic review and Bayesian network meta-analysis, involving 19 studies and 95,841 patients, assessed hydrocortisone with/without fludrocortisone versus placebo in septic shock. Hydrocortisone plus fludrocortisone was associated with reduced short-term mortality (OR: 0.79; 95% CrI: 0.64-0.99; NNT: 21) compared to placebo, showing potential benefits with minimal adverse events. However, findings suggest cautious interpretation due to low certainty evidence and a broad NNT range, indicating the need for further large-scale RCTs.

Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as Adjunctive Therapy in Septic Shock:

A Retrospective Cohort Study" by Lock AE et al., published in the Annals of Pharmacotherapy in 2023, explored whether adding fludrocortisone (FC) to hydrocortisone (HC) would improve the time to septic shock reversal in patients. Conducted as a single-center, retrospective cohort study from March 2017 to May 2020, it included adult ICU patients who received either HC plus FC or HC alone, excluding those with prior corticosteroid use, corticosteroids for other indications, single-dose corticosteroid treatment, or shock due to non-sepsis causes. The primary measure was time to shock reversal, with secondary outcomes including mortality and hyperglycemia rates.

The study found no significant difference in time to shock reversal between the two groups, with 251 patients participating (114 in the HC + FC group and 137 in the HC group). The Cox proportional hazards model did indicate a shorter…

The results of this study do not support the use of landiolol (a beta blocker) for managing patients with tachycardia treated with norepinephrine for established septic shock.

Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial | Resuscitation | JAMA | JAMA Network

Vitamin C for Patients With COVID-19

The LOVIT-COVID trial and the vitamin C section of the REMAP-CAP trial were synchronized to enhance the efficiency of the research. They included 1568 critically ill patients (1037 on vitamin C and 531 in the control group) and 1022 non-critically ill patients (456 on vitamin C and 566 in the control group). Patients were given 50 mg/kg of vitamin C through an IV every 6 hours for a maximum of 96 hours. While both trials were planned together, LOVIT-COVID used a placebo, whereas REMAP-CAP compared vitamin C to standard care. The study was halted once set criteria for potential harm and lack of effectiveness were reached. Among the critically ill patients, those on vitamin C had a median of 7 days without organ support, compared to 10 days in the control group, with an 8.6% probability of effectiveness, 91.4% of potential harm, and 99.9%…

Reliability of Admission Procalcitonin Testing for Capturing Bacteremia Across the Sepsis Spectrum: Real-World Utilization and Performance Characteristics, 65 U.S. Hospitals, 2008–2017

Procalcitonin-on-admission testing for patients with suspected bloodstream infections (BSIs) is often conducted, but its performance remains disputed. 📊 This research paper represents the largest study to date on the use of procalcitonin for identifying patients with bloodstream infections (BSI) in U.S. hospitals. Here are the key points:

• 🩺The study was a retrospective cohort study utilizing the Cerner HealthFacts Database from 2008 to 2017, and included all adult inpatients (≥ 18 years) who had blood cultures and procalcitonin tests within 24 hours of admission.

• ⚕️The study assessed the testing frequency of procalcitonin, sensitivity for detecting BSIs caused by different pathogens, and the discriminatory ability of procalcitonin-on-admission for BSI in patients with or without fever/hypothermia, ICU admission, and sepsis.

A two-day course of antibiotics for complicated appendicitis Appendicitis

This open-label, non-inferiority trial conducted across 15 Dutch hospitals assessed the efficacy and safety of reducing postoperative intravenous antibiotic duration from 5 days to 2 days in patients aged ≥8 years with complex appendicitis, amidst rising concerns regarding antimicrobial resistance. The primary endpoint was a composite of infectious complications and mortality within a 90-day post-appendicectomy period. The trial showed no significant difference in the primary endpoint between the two groups, suggesting that a shorter antibiotic course is non-inferior to a longer one, with additional benefits of lowered adverse effects, and potentially reduced hospital stay and costs.

The IMMUNOCITRE Trial

Enteral citrulline supplementation does not improve SOFA score on day 7 in mechanically ventilated critically ill patients!

The authors conducted a multicenter, randomized, double-blind trial in four French ICUs from September 2016 to February 2019. They evaluated the effect of enteral L-citrulline on organ dysfunction and selected immune parameters in mechanically ventilated ICU patients who did not have sepsis or septic shock. The main outcome was the Sequential Organ Failure Assessment (SOFA) score on day 7. The results showed no significant difference in the SOFA score on day 7 between the L-citrulline and placebo groups (4 [IQR, 2-6] vs. 4 [IQR, 2-7]; p = 0.9). However, the L-citrulline group had significantly higher plasma arginine levels on day 3, without any observed effect on immune parameters.

Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial…

Lower vs Higher Fluid Volumes in Adult Patients With Sepsis

In a systematic review updating the optimal IV fluid volume strategy for adult sepsis patients, the study compared lower vs. higher fluid volumes. The results, based on trials with low risk of bias, indicated that lower IV fluid volumes have minimal to no impact on all-cause mortality (Relative Risk: 0.99, 97% CI, 0.89-1.10) or serious adverse events (Relative Risk: 0.95, 97% CI, 0.83-1.07) compared to higher volumes. However, these conclusions come with some imprecision, not ruling out potential benefits or risks. Notably, the trials did not report on health-related quality of life.

Lower vs Higher Fluid Volumes in Adult Patients With Sepsis - CHEST (chestnet.org)

Probiotics in AKI and Sepsis: A Clinical Insight

During acute kidney injury (AKI) stemming from sepsis, a dysbiotic change in the intestinal microbiota is observed, impacting kidney function recovery. To evaluate the therapeutic potential of probiotics in alleviating this dysbiosis and potentially enhancing kidney function recovery, a double-blind clinical trial was conducted. 92 patients with sepsis-associated AKI were treated with either probiotics or a placebo for one week. The primary outcomes investigated were kidney function recovery and mortality at 6 months, while secondary outcomes included markers like urea, urine volume, need for kidney replacement therapy, and any adverse events. The study found no significant benefits of probiotics in improving KFR or reducing 6-month mortality. However, a notable reduction in urea levels was observed in the probiotics group.

Full article: Probiotics in septic acute kidney injury, a double blind, randomized control trial (tandfonline.com)

Effect of Ultrashort-Acting β-Blockers on Mortality in Patients With Sepsis With Persistent Tachycardia Despite Initial Resuscitation

This systematic review and meta-analysis examined the use of ultrashort-acting β-blockers (esmolol and landiolol) in patients with sepsis and septic shock and persistent tachycardia despite initial resuscitation. Seven randomized controlled trials with 613 patients were analyzed. The results showed that using esmolol or landiolol was associated with significantly lower 28-day mortality (RR: 0.68, 95% CI: 0.54-0.85, P < .001). The absolute risk reduction was 0.18, and the number needed to treat to prevent one death was 5.5.

The meta-analysis reported that ultrashort-acting β1-blockers can increase stroke volume index and reduce heart rate without changing the cardiac index, mean arterial pressure, or norepinephrine requirement at 24 hours. This suggests that these drugs can improve cardiovascular efficiency in septic patients and may improve mortality outcomes in such patients. However, the exact mechanisms behind these effects and…

Timing of Vasopressin Addition to Norepinephrine and Efficacy Outcomes in Patients With Septic Shock

1. 🏥 The trial examined the effect of the timing of vasopressin (AVP) addition to norepinephrine (NE) on septic shock patients' clinical outcomes, conducted retrospectively in a single health system over several sites from January 2018 to December 2019. 🕰️

2. 👥 The trial included 243 patients out of the initial 497, with patients being above 18, diagnosed with septic shock, and having received NE followed by AVP. Those with certain medical conditions or who were pregnant were excluded. 🚫

3. 🕑 Two groups were formed based on when AVP was added to NE treatment: an early group (within 3 hours) and a late group (after 3 hours). ⌛

4. 📊 Both groups had balanced characteristics at NE initiation. Still, differences were noticed in the SOFA score, weight, administration of hydrocortisone and vitamin C, and fluid dose prior to NE…

How Fast Should a Fluid Bolus be Given? (icureach.com)

1. 📚 A systematic review included 85 studies and 3601 patients, investigating the impact of rapid infusion rates (completed within 30 minutes) on stroke volume or cardiac output. It found a potential enhancement of these parameters due to effectively increased venous return and preload. 🔎✅🏥

2. 💧 Fluid volumes used in the review's trials varied: less than 500 mL in 12.7% of cases, 500 mL in 79.4%, and more than 500 mL in 7.9% of cases. 📏📊💧

3. 📈 Despite positive hemodynamic outcomes, the impact of rapid infusion rates on patient-centered outcomes remains uncertain, signaling a need for more research in this area. 🔄❔🚑

4. ⏱ A randomized controlled trial involving 10,520 critically ill patients compared infusion rates of 333 mL/hour (slower) vs. 999 mL/hour (faster). Mortality rates showed no significant difference between the groups, indicating that infusion rates don't dramatically impact survival. ☠️⚖️🕓

5. 💡…

Efficacy and safety of sulbactam–durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii–calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK) - The Lancet Infectious Diseases

The urgent need for effective antibiotics against carbapenem-resistant Acinetobacter baumannii–calcoaceticus complex (ABC) infections led to a phase 3 randomized controlled trial comparing the efficacy and safety of sulbactam–durlobactam versus colistin. The trial involved adults with confirmed ABC-related infections, such as hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bloodstream infections. Patients received either sulbactam–durlobactam or colistin, in combination with imipenem–cilastatin, as background therapy for 7-14 days.

The primary efficacy endpoint was 28-day all-cause mortality in patients with confirmed carbapenem-resistant ABC. The study concluded that sulbactam–durlobactam was non-inferior to colistin (28-day all-cause mortality of 19% versus 20%). Additionally, sulbactam–durlobactam showed a significantly lower incidence of nephrotoxicity compared to colistin. The trial demonstrated that sulbactam–durlobactam could…

HEMOPERFUSION USING THE LPS-SELECTIVE MESOPOROUS POLYMERIC ADSORBENT IN SEPTIC SHOCK: A MULTICENTER RANDOMIZED CLINICAL TRIAL

This multicenter randomized controlled trial evaluated the efficacy and safety of Efferon LPS hemoperfusion cartridges in patients with intra-abdominal sepsis (IAS) and septic shock. The study included a group undergoing EHP procedures (n = 38) and a control group receiving conventional protocols (n = 20). EHP resulted in significant improvements, including increased mean arterial pressure (MAP) and partial pressure arterial oxygen/fraction of inspired oxygen ratio (PaO2/FiO2), decreased norepinephrine doses, and improved multiorgan function based on Sequential Organ Failure Assessment (SOFA) scores. Notably, EHP facilitated faster weaning from mechanical ventilation. Early 3-day mortality was reduced in the Efferon LPS group, and laboratory tests showed rapid normalization of biomarkers. These findings demonstrate that EHP with Efferon LPS is a safe procedure for resolving septic shock and restoring clinical biomarkers in IAS patients.

Rey S, Kulabukhov VM, Popov…

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De-resuscitation in septic shock refers to the process of actively removing excess fluids from a patient after their condition has been stabilized. Does this improve outcomes?

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De-resuscitation in septic shock refers to the process of actively removing excess fluids from a patient after their condition is stabalized