Goal-Directed Fluid Therapy Enhances Gastrointestinal Recovery after Laparoscopic Surgery: A Systematic Review and Meta-Analysis.

(1) Background: Whether goal-directed fluid therapy (GDFT) provides any outcome benefit as compared to non-goal-directed fluid therapy (N-GDFT) in elective abdominal laparoscopic surgery has not been determined yet. (2) Methods: A systematic literature search was conducted in MEDLINE, Embase, CENTRAL, Web of Science, and Scopus. The main outcomes were length of hospital stay (LOHS), time to first flatus and stool, intraoperative fluid and vasopressor requirements, serum lactate levels, and urinary output. Pooled risks ratios (RRs) with 95% confidence intervals (CI) were calculated for dichotomous outcomes and weighted mean difference (WMD) with 95% CI for continuous outcomes. (3) Results: Eleven studies were included in the quantitative, and fifteen in the qualitative synthesis. LOHS (WMD: -1.18 days, 95% CI: -1.84 to -0.53) and time to first stool (WMD: -9.8 h; CI -12.7 to -7.0) were significantly shorter in the GDFT group. GDFT resulted in significantly less intraoperative fluid administration (WMD: -441 mL, 95% CI: -790 to -92) and lower lactate levels at the end of the operation: WMD: -0.25 mmol L-1; 95% CI: -0.36 to -0.14. (4) Conclusions: GDFT resulted in enhanced recovery of the gastrointestinal function and shorter LOHS as compared to N-GDFT.

Frailty and Emergency Surgery: Results of a Systematic Review and Meta-Analysis.

Background: Frailty, a "syndrome of loss of reserves," is a decade old concept. Initially it was used mainly in geriatrics but lately its use has been extended into other specialties including surgery. Our main objective was to examine the association between frailty and mortality, between frailty and length of hospital stay (LOS) and frailty and readmission within 30 days in the emergency surgical population. Methods: Studies reporting on frailty in the emergency surgical population were eligible. MEDLINE (via PubMed), EMBASE, Scopus, CENTRAL, and Web of Science were searched with terms related to acute surgery and frail*. We searched for eligible articles without any restrictions on the 2nd of November 2020. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI), using a random effect model. Risk of bias assessment was performed according to the recommendations of the Cochrane Collaboration. As the finally selected studies were either prospective or retrospective cohorts, the "Quality In Prognosis Studies" (QUIPS) tool was used. Results: At the end of the selection process 21 eligible studies with total 562.070 participants from 8 countries were included in the qualitative and the quantitative synthesis. Patients living with frailty have higher chance of dying within 30 days after an emergency surgical admission (OR: 1.99; CI: 1.76-2.21; p < 0.001). We found a tendency of increased LOS with frailty in acute surgical patients (WMD: 4.75 days; CI: 1.79-7.71; p = 0.002). Patients living with frailty have increased chance of 30-day readmission after discharge (OR: 1.36; CI: 1.06-1.75; p = 0.015). Conclusions: Although there is good evidence that living with frailty increases the chance of unfavorable outcomes, further research needs to be done to assess the benefits and costs of frailty screening for emergency surgical patients. Systematic Review Registration: The review protocol was registered on the PROSPERO International Prospective Register of Systematic Reviews (CRD42021224689).

Clinical Frailty Scale (CFS) indicated frailty is associated with increased in-hospital and 30-day mortality in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The concept of frailty provides an age-independent, easy-to-use tool for risk stratification. We aimed to summarize the evidence on the efficacy of frailty tools in risk assessment in COVID-19 patients. METHODS: The protocol was registered (CRD42021241544). Studies reporting on frailty in COVID-19 patients were eligible. The main outcomes were mortality, length of hospital stay (LOH) and intensive care unit (ICU) admission in frail and non-frail COVID-19 patients. Frailty was also compared in survivors and non-survivors. Five databases were searched up to 24th September 2021. The QUIPS tool was used for the risk of bias assessment. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI) using a random effect model. Heterogeneity was assessed using the I2 and χ2 tests. RESULTS: From 3640 records identified, 54 were included in the qualitative and 42 in the quantitative synthesis. Clinical Frailty Scale (CFS) was used in 46 studies, the Hospital Frailty Risk Score (HFRS) by 4, the Multidimensional Prognostic Index (MPI) by 3 and three studies used other scores. We found that patients with frailty (CFS 4-9 or HFRS ≥ 5) have a higher risk of mortality (CFS: OR: 3.12; CI 2.56-3.81; HFRS OR: 1.98; CI 1.89-2.07). Patients with frailty (CFS 4-9) were less likely to be admitted to ICU (OR 0.28, CI 0.12-0.64). Quantitative synthesis for LOH was not feasible. Most studies carried a high risk of bias. CONCLUSIONS: As determined by CFS, frailty is strongly associated with mortality; hence, frailty-based patient management should be included in international COVID-19 treatment guidelines. Future studies investigating the role of frailty assessment on deciding ICU admission are strongly warranted.

Extracorporeal Cytokine Removal in Critically Ill COVID-19 Patients: A Case Series.

Introduction: Extracorporeal hemoadsorption (HA) is a potential adjunctive therapy in severe cases of COVID-19 associated pneumonia. In this retrospective study we report data from critically ill patients treated with HA during the first and second wave of the pandemic. Patients and Methods: All patients, who received HA therapy with CytoSorb within the first 96 h of intensive care unit (ICU) admission without hospital-acquired bacterial superinfection, were included. Clinical and laboratory data were collected: on admission, before (TB) and after (TA) HA therapy. Results: Out of the 367 COVID-19 cases, 13 patients were treated with CytoSorb, also requiring mechanical ventilation and renal replacement therapy. All patients were alive at the end of HA, but only 3 survived hospital stay. From TB-TA there was a tendency of decreasing norepinephrine requirement: 193.7 [IQR: 34.8-270.4] to 50.2 [6.5-243.5] ug/kg/day and increasing PaO2/FiO2 ratio 127.8 (95% CI: 96.0-159.6) to 155.0 (115.3-194.6) mmHg but they did not reach statistical significance (p = 0.14 and 0.58, respectively). Treatment related adverse events were not reported. Conclusion: The treatment was well-tolerated, and there was a tendency toward an improvement in vasopressor need and oxygenation during the course of HA. These observations render the need for prospective randomized trials.

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials.

Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33-5.61)] and sCR [OR = 2.29 (CI 1.49-3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39-0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76-10.66)] and sCR [OR = 3.08 (CI 2.00-4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37-0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.

Individualized Hemodynamic Management in Sepsis.

Hemodynamic optimization remains the cornerstone of resuscitation in the treatment of sepsis and septic shock. Delay or inadequate management will inevitably lead to hypoperfusion, tissue hypoxia or edema, and fluid overload, leading eventually to multiple organ failure, seriously affecting outcomes. According to a large international survey (FENICE study), physicians frequently use inadequate indices to guide fluid management in intensive care units. Goal-directed and "restrictive" infusion strategies have been recommended by guidelines over "liberal" approaches for several years. Unfortunately, these "fixed regimen" treatment protocols neglect the patient's individual needs, and what is shown to be beneficial for a given population may not be so for the individual patient. However, applying multimodal, contextualized, and personalized management could potentially overcome this problem. The aim of this review was to give an insight into the pathophysiological rationale and clinical application of this relatively new approach in the hemodynamic management of septic patients.

Plasma somatostatin-like immunoreactivity increases in the plasma of septic patients and rats with systemic inflammatory reaction: experimental evidence for its sensory origin and protective role.

Alterations of somatostatin-like immunoreactivity (SST-LI) in the plasma of 11 systemic inflammatory response syndrome (SIRS) patients were investigated in correlation with cytokines, adhesion molecules and coagulation markers repeatedly during 4 days. The origin and role of SST were studied in the cecum ligation and puncture (CLP) rat SIRS model. Capsaicin-sensitive peptidergic sensory nerves were defunctionalized by resiniferatoxin (RTX) pretreatment 2 weeks earlier, in a separate group animals were treated with the somatostatin receptor antagonist cyclo-somatostatin (C-SOM). Plasma SST-LI significantly elevated in septic patients compared to healthy volunteers during the whole 4-day period. Significantly decreased Horowitz score showed severe lung injury, increased plasma C-reactive protein and procalcitonin confirmed SIRS. Soluble P-selectin, tissue plasminogen activator and the interleukin 8 and monocyte chemotactic protein-1 significantly increased, interleukin 6 and soluble CD40 ligand did not change, and soluble Vascular Adhesion Molecule-1 decreased. SST-LI significantly increased in rats both in the plasma and the lung 6h after CLP compared to sham-operation. After RTX pretreatment SST-LI was not altered in intact animals, but the SIRS-induced elevation was absent. Lung MPO activity significantly increased 6h following CLP compared to sham operation, which was significantly higher both after RTX-desensitization and C-SOM-treatment. Most non-pretreated operated rats survived the 6h, but 60% of the RTX-pretreated ones died showing a significantly worse survival. This is the first comprehensive study in humans and animal experiments providing evidence that SST is released from the activated peptidergic sensory nerves. It gets into the bloodstream and mediates a potent endogenous protective mechanism.

Effects of IgM-enriched immunoglobulin therapy in septic-shock-induced multiple organ failure: pilot study.

Mortality due to septic-shock-induced respiratory failure remains high. A recent meta-analysis suggested that IgM-enriched immunoglobulin treatment may be beneficial in these patients. In this prospective randomised controlled pilot study we investigated the effects of IgM-enriched immunoglobulin treatment in patients with early septic shock accompanied by severe respiratory failure. 33 patients were randomly allocated to receive 5 ml/kg (predicted body weight) IgM-enriched immunoglobulin (16 patients) or placebo (17 patients), respectively, via 8 h IV-infusion for three consecutive days. Daily Multiple Organ Dysfunction Scores (MODS) were calculated. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were monitored daily. For statistical analysis two-way ANOVA was used. Daily MODS showed ongoing multiple system organ failure without significant resolution during the 8 days. Median length of ICU stay, mechanical ventilation, vasopressor support during the ICU stay and 28-day mortality were nearly identical in the two groups. Serum PCT levels showed no significant difference between the two groups, however, CRP levels were significantly lower in the IgM-enriched immunoglobulin group on days 4, 5 and 6, respectively. In this study the use of IgM-enriched immunoglobulin preparation failed to produce any improvement in the organ dysfunction as compared to standard sepsis therapy.

Hemodynamic and respiratory changes during lung recruitment and descending optimal positive end-expiratory pressure titration in patients with acute respiratory distress syndrome.

OBJECTIVES: To investigate respiratory and hemodynamic changes during lung recruitment and descending optimal positive end-expiratory pressure (PEEP) titration. DESIGN: Prospective auto-control clinical trial. SETTING: Adult general intensive care unit in a university hospital. PATIENTS: Eighteen patients with acute respiratory distress syndrome. INTERVENTIONS: Following baseline measurements (T0), PEEP was set at 26 cm H2O and lung recruitment was performed (40/40-maneuver). Then tidal volume was set at 4 mL/kg (T26R) and PEEP was lowered by 2 cm H2O in every 4 mins. Optimal PEEP was defined at 2 cm H2O above the PEEP where Pao2 dropped by > 10%. After setting the optimal PEEP, the 40/40-maneuver was repeated and tidal volume set at 6 mL/kg (T(end)). MEASUREMENTS AND MAIN RESULTS: Arterial blood gas analysis was done every 4 mins and hemodynamic measurements every 8 mins until T(end), then in 30 (T30) and 60 (T60) mins. The Pao2 increased from T0 to T(end) (203 +/- 108 vs. 322 +/- 101 mm Hg, p < .001), but the extravascular lung water (EVLW) did not change significantly. Cardiac index (CI) and the intrathoracic blood volume (ITBV) decreased from T0 to T26R (CI, 3.90 +/- 1.04 vs. 3.62 +/- 0.91 L/min/m2, p < .05; ITBVI, 832 +/- 205 vs. 795 +/- 188 m/m2, p < .05). There was a positive correlation between CI and ITBVI (r = .699, p < .01), a negative correlation between CI and central venous pressure (r = -.294, p < .01), and no correlation between CI and mean arterial pressure (MAP). CONCLUSIONS: Following lung recruitment and descending optimal PEEP titration, the Pao2 improves significantly, without any change in the EVLW up to 1 hr. This suggests a decrease in atelectasis as a result of recruitment rather than a reduction of EVLW. There is a significant change in CI during the maneuver, but neither central venous pressure, heart rate, nor MAP can reflect these changes.

Effects of volumetric vs. pressure-guided fluid therapy on postoperative inflammatory response: a prospective, randomized clinical trial.

OBJECTIVE: To compare intrathoracic blood volume (ITBV) guided fluid management and central venous pressure (CVP) guided therapy in ameliorating the progression of early systemic inflammatory response in patients undergoing major surgery. DESIGN: Prospective, randomized clinical trial. PATIENTS: Forty patients undergoing major abdominal surgery were randomized into CVP and ITBV groups. INTERVENTIONS: In the CVP group the target CVP was 8-12 mmHg while in the ITBV group the goal was to keep the ITBV between 850 and 950 ml/m2 during the operation. MEASUREMENTS AND RESULTS: Hemodynamic parameters were determined by single arterial thermodilution. Measurements were repeated every 30 min intraoperatively. Serum procalcitonin (PCT) and C-reactive protein (CRP) was monitored preoperatively, on ICU admission, and then daily for 3 days. Serum TNF-alpha levels were measured intraoperatively hourly and then daily for 3 days. There was no significant difference between the two groups regarding hemodynamic parameters at any assessment point. In the overall population changes in the stroke volume index showed a significant correlation with changes in CVP and ITBV. TNF-alpha levels remained in the normal range intraoperatively and during the three postoperative days in both groups. Preoperatively normal PCT and CRP levels increased significantly postoperatively, without significant differences between the groups. CONCLUSIONS: ITBV guided fluid therapy did not alter the magnitude of inflammatory response as monitored by serum PCT, CRP, and TNF-alpha in the early postoperative period.

Fluid resuscitation with colloids of different molecular weight in septic shock.

OBJECTIVE: The aim of this study was to investigate the short-term effect of fluid resuscitation with 4% modified fluid gelatine (GEL) versus 6% hydroxyethyl starch (HES) on haemodynamics and oxygenation in patients with septic shock and acute lung injury (ALI). DESIGN: Prospective randomised clinical trial. SETTING: Twenty-bed intensive care unit in a university hospital. PATIENTS: Thirty hypovolemic patients (intrathoracic blood volume index, ITBVI <850 ml/m(2)) in septic shock with ALI were randomised into HES (mean molecular weight: 200,000 Dalton, degree of substitution 0.6) and GEL (mean molecular weight: 30,000 Dalton) groups (15 patients each). INTERVENTIONS: For fluid resuscitation 250 ml/15 min boluses (max. 1,000 ml) were given until the end point of ITBVI >900 ml/m(2) was reached. Repeated haemodynamic measurements were done at baseline (t(b)), at the end point (t(ep)) then at 30 min and 60 min after the end point was reached (t(30), t(60)). Cardiac output, stroke volume, extravascular lung water (EVLW), and oxygen delivery was determined at each assessment point. For statistical analysis two-way ANOVA was used. MEASUREMENTS AND RESULTS: ITBVI, cardiac index, and oxygen delivery index increased significantly at t(ep) and remained elevated for t(30) and t(60), but there was no significant difference between the two groups. The increase in the ITBVI by 100 ml of infusion was similar in both groups (HES: 26+/-19 ml/m(2) vs GEL: 30+/-19 ml/m(2)). EVLW, remained unchanged, and there was no significant difference between the groups (HES, t(b): 8+/-6, t(60): 8+/-6; GEL, t(b): 8+/-3, t(60): 8+/-3 ml/kg). The PaO(2)/FiO(2) did not change significantly over time or between groups (HES, t(b): 207+/-114, t(60): 189+/-78; GEL, t(b): 182+/-85, t(60): 182+/-85 mmHg). CONCLUSION: The results of this study indicate that both HES and GEL infusions caused similar short-term change in ITBVI in septic shock, without increasing EVLW or worsening oxygenation.