Haptoglobin Administration for Intravascular Hemolysis: A Systematic Review.

Introduction Exogenous haptoglobin administration may enhance plasma-free hemoglobin (pfHb) clearance during hemolysis, and reduce its end-organ damage: we sought to systematically review and summarize available evidence on the use of haptoglobin as a treatment for hemolysis of any cause. Methods We included studies describing haptoglobin administration as treatment or prevention of hemolysis-related complications. Only studies with a control group reporting at least one of the outcomes of interest were included in the quantitative synthesis. Primary outcome was the change in pfHb concentration 1 hour after haptoglobin infusion. Results Among 573 articles, 13 studies were included in the review (677 patients, 52.8% received haptoglobin). Median initial haptoglobin intravenous bolus was 4000 (2000, 4000) IU. Haptoglobin was associated with lower pfHb 1 hour (SMD -11.28; 95% CI -15.80 to -6.75; p<0.001) and 24 hours (SMD -2.65; 95% CI -4.73 to -0.57; p=0.001) after infusion. There was no difference in all-cause mortality between haptoglobin-treated patients and control group (OR 1.41; 95% CI 0.49 to 4.95; p=0.520). Haptoglobin was associated with a lower incidence of acute kidney injury (OR 0.64; 95% CI 0.44-0.93; p=0.020). No adverse events or side effects associated with haptoglobin use were reported. Conclusions Haptoglobin administration has been used in patients with hemolysis from any cause to treat or prevent hemolysis-associated adverse events. Haptoglobin may reduce levels of pfHb and preserve kidney function without increase in adverse events.

Effect of Urine Output on the Predictive Precision of NephroCheck in On-Pump Cardiac Surgery With Crystalloid Cardioplegia: Insights from the PrevAKI Study.

OBJECTIVES: Previous studies in other settings suggested that urine output (UO) might affect NephroCheck predictive value. We investigated the correlation between NephroCheck and UO in cardiac surgery patients. DESIGN: Post hoc analysis of a multicenter study. SETTING: University hospital. PARTICIPANTS: Patients who underwent cardiac surgery using cardiopulmonary bypass (CPB) and crystalloid cardioplegia. MEASUREMENTS AND MAIN RESULTS: All patients underwent NephroCheck testing 4 hours after CPB discontinuation. The primary outcome was the correlation between UO, NephroCheck results, and acute kidney injury (AKI, defined according to Kidney Disease: Improving Global Outcomes). Of 354 patients, 337 were included. Median NephroCheck values were 0.06 (ng/mL)2/1,000) for the overall population and 0.15 (ng/mL)2/1,000) for patients with moderate to severe AKI. NephroCheck showed a significant inverse correlation with UO (ρ = -0.17; p = 0.002) at the time of measurement. The area under the receiver characteristic curve (AUROC) for NephroCheck was 0.60 (95% confidence interval [CI], 0.54-0.65), whereas for serum creatinine was 0.82 (95% CI, 0.78-0.86; p < 0.001). When limiting the analysis to the prediction of moderate to severe AKI, NephroCheck had a AUROC of 0.82 (95% CI, 0.77 to 0.86; p<0.0001), while creatinine an AUROC of 0.83 (95% CI, 0.79-0.87; p = 0.001). CONCLUSIONS: NephroCheck measured 4 hours after the discontinuation from the CPB predicts moderate to severe AKI. However, a lower threshold may be necessary in patients undergoing cardiac surgery with CPB. Creatinine measured at the same time of the test remains a reliable marker of subsequent development of renal failure.

A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Association of Impedance Aggregometry-Measured Platelet Aggregation With Thromboembolic Events in Patients Who Undergo Carotid Endarterectomy: A Pilot Study.

OBJECTIVES: The aim of the current study was to assess the relationship among thrombin receptor activator peptide 6 (TRAP test), adenosine-5'-diphosphate (ADP test), arachidonic acid (ASPI test), and stroke/transient ischemic attack (TIA), using the multiple electrode aggregometry (Multiplate) in patients undergoing carotid thromboendarterectomy (CEA). DESIGN: A retrospective study. SETTING: Vascular surgery operating rooms of a university hospital. PARTICIPANTS: One hundred thirty-one out of 474 patients undergoing CEA between November 2020 and October 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A preoperative blood sample of all enrolled patients was analyzed using the Multiplate analyzer. Receiver operating characteristics curves, were generated to test the ability of TRAP, ADP, and ASPI in discriminating perioperative thromboembolic stroke/TIA. A logistic LASSO regression model was used to identify factors independently associated with stroke/TIA. Eight patients experienced a perioperative stroke/TIA. Although all the platelet functional assays showed excellent predictive performance, an ADP value exceeding 72 U showed the highest specificity (87%) and sensitivity (68%) in discriminating patients who had a perioperative thromboembolic stroke/TIA, with a negative predictive value of 99% and a positive predictive value of 15%. After LASSO regression, an ADP >72 U and the need for a shunt during CEA were the only 2 variables independently associated with perioperative stroke/TIA. CONCLUSION: Because the ADP test was independently associated with perioperative stroke/TIA, the assessment of platelet reactivity using Multiplate may offer potential utility in monitoring patients undergoing CEA.

High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.

BACKGROUND: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. METHODS: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. DISCUSSION: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.

Del Nido Cardioplegia in Adult Cardiac Surgery: Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: To compare the outcomes of patients receiving del Nido solution versus any other type of cardioplegia. DESIGN: A systematic review and meta-analysis of randomized trials. SETTING: Cardiac operating rooms. PARTICIPANTS: Adult patients (≥18 years old) undergoing cardiac surgery. INTERVENTIONS: The EMBASE, MEDLINE, and CENTRAL databases were searched systematically from their inception until August 2022 for randomized controlled trials comparing del Nido versus other cardioplegias. MEASUREMENTS AND MAIN RESULTS: Ten studies were included, including 1,812 patients (871 in the del Nido group and 941 in the control group), and published after 2017. There were significant reductions in postoperative stroke and/or transient ischemic attack rate in the del Nido group: 9/467 (1.9%) v 25/540 (4.6%); odds ratio (OR), 0.43; 95% CI, 0.20-0.92 (p = 0.007). Del Nido cardioplegia was also associated with significantly shorter aortic cross-clamp time (mean difference, -8.99 minutes; 95% CI, -17.24 to -0.73 [p < 0.001]), significantly reduced need for defibrillation (89/582 [15%] v 252/655 [38%]; OR, 0.33; 95% CI, 0.15-0.72 [p < 0.001]), significantly lower risk of postoperative acute kidney injury (21/235 [8.9%] v 34/301 [11%]; OR, 0.50; 95% CI, 0.26-0.97 [p = 0.04]), with no effect on mortality (14/607 [2.3%] v 12/681 [1.8%]; p = 0.5). CONCLUSION: According to the authors' meta-analysis of recent randomized clinical trials, del Nido is a safe cardioplegic solution, which might provide better organ protection in adult cardiac surgery without differences in mortality when compared to other cardioplegic solutions.

Heart Rate Variability in Subjects with Severe Allergic Background Undergoing COVID-19 Vaccination.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination is the world's most important strategy for stopping the pandemic. Vaccination challenges the body's immune response and can be complicated by hypersensitivity reactions. The autonomic nervous system can modulate the inflammatory immune response, therefore constituting a potential marker to characterize individuals at high risk of hypersensitivity reactions. Autonomic nervous system functionality was assessed through measurement of the heart rate variability (HRV) in subjects with a history of severe allergic reactions and 12 control subjects. HRV parameters included the mean electrocardiograph RR interval and the standard deviation of all normal R-R intervals (SDNN). All measurements were performed immediately before the anti-SARS-CoV-2 vaccination. The median RR variability was lower in the study than in the control group: 687 ms (645-759) vs. 821 ms (759-902); p = 0.02. The SDNN was lower in the study group than in the control group: 32 ms (23-36) vs. 50 ms (43-55); p < 0.01. No correlation was found between age and the SDNN. Autonomic nervous system activity is unbalanced in people with a severe allergy background.

Dexmedetomidine versus remifentanil for sedation under monitored anesthetic care in complex endovascular aortic aneurysm repair: a single center experience with mid-term follow-up.

BACKGROUND: Sedation protocols in patients undergoing complex endovascular aortic aneurysm repair are not fully investigated. The aim of this study was to compare a dexmedetomidine (DEX) based sedation protocol with a remifentanil-based sedation protocol. METHODS: Seventy-nine consecutive patients undergoing complex endovascular aortic repair were enrolled and retrospectively analyzed. Forty-two received 0.03 mg/kg midazolam intravenous bolus with remifentanil (0.075-0.1 µg/kg/min for 10 minutes followed by continuous infusion 0.050-0.25 µg/kg/min) and 37 DEX (1 µg/kg over 10 minutes and continuous infusion 0.50-0.75 µg/kg/hour) to achieve an Observer Assessment of Alertness/Sedation Scale (OAAS) ≤4, a Richmond Agitation/Sedation Scale (RASS) ≤-2 and a Visual Analogic Scale (VAS) <4. The primary endpoint was patients' satisfaction. Secondary endpoints included assessment of sedation and pain, the incidence of perioperative hemodynamic or gas exchange imbalance, and 36 month-mortality. RESULTS: Remifentanil group showed a higher satisfaction rate than DEX (P<0.001). Patients on DEX were more sedated than remifentanil according to OAAS (3 [2-3] vs. 4 [3-4]; P=0.001) and RASS (-2[-3/-2] vs. -2[-2/-2]; P=0.001) with no difference in VAS (2 [1-3] vs. 2 [1-3]; P=0.41). DEX provides reliable sedation with lower patient's satisfaction. A higher number of patients were discharged from the recovery room on vasopressors in the DEX group compare with the remifentanil group (5 vs. 0; P=0.045, respectively). The two groups showed a non-significant difference in the survival rate at 36-month (DEX 67% vs. remifentanil 73%; (P=0.90). CONCLUSIONS: In this setting remifentanil provides reliable sedation with higher patient's satisfaction and less hemodynamic effect than DEX.

Association Between Type of Anaesthesia and Clinical Outcome in Patients Undergoing Endovascular Repair of Thoraco-Abdominal Aortic Aneurysms by Fenestrated and Branched Endografts.

OBJECTIVE: Although endovascular repair of thoraco-abdominal aortic aneurysm (TAAA) is the treatment of choice in the high risk population that is ineligible for an open surgical approach, little is known about the association between the type of anaesthesia and complications. This study compared the short term clinical outcomes of patients undergoing the visceral step of TAAA with fenestrated endograft aortic repair (FEVAR) and branched endograft aortic repair (BEVAR) under general anaesthesia (GA) with sedation with monitored care anaesthesia (MAC). METHODS: This single centre, retrospective, observational study recruited 124 consecutive patients undergoing elective F/BEVAR from 2014 - 2021. The primary endpoint was the short term complication rate according to the type of anaesthesia. Secondary endpoints included: need for inotropes or vasopressors for hypotension, time spent in the operating room, and admission to the intensive care unit. Propensity score matching was generated to account for the between group imbalance in the pre-operative covariables. RESULTS: After propensity score matching, 42 patients under GA were matched with 42 under MAC. The two groups showed no difference in cardiac and non-cardiac complications. Among the secondary outcomes, a higher number of patients in the GA group required inotropes or vasopressors compared with MAC (33% vs. 9%; p = .031). Although GA and MAC showed the same 30 day technical success (81% vs. 83%; p = .078), non-significant lower rates of major adverse events (10% vs. 12%; p = .72), one year re-intervention (14% vs. 21%; p = .39), and one year target vessel instability (10% vs. 21%; p = .39) were observed in the GA group. Overall, the in hospital mortality rate was 4%, with no difference between GA and MAC (2% vs. 5%; p = 1.0). CONCLUSION: The type of anaesthesia seemed to have no effect on procedure success, peri-operative morbidity, or mortality in patients undergoing F/BEVAR.