Diastology in the intensive care unit: Challenges for the assessment and future directions.

Myocardial dysfunction is common in patients admitted to the intensive care unit (ICU). Septic disease frequently results in cardiac dysfunction, and sepsis represents the most common cause of admission and death in the ICU. The association between left ventricular (LV) systolic dysfunction and mortality is not clear for critically ill patients. Conversely, LV diastolic dysfunction (DD) seems increasingly recognized as a factor associated with poor outcomes, not only in sepsis but also more generally in critically ill patients. Despite recent attempts to simplify the diagnosis and grading of DD, this remains relatively complex, with the need to use several echocardiographic parameters. Furthermore, the current guidelines have several intrinsic limitations when applied to the ICU setting. In this manuscript, we discuss the challenges in DD classification when applied to critically ill patients, the importance of left atrial pressure estimates for the management of patients in ICU, and whether the study of cardiac dysfunction spectrum during critical illness may benefit from the integration of left ventricular and left atrial strain data to improve diagnostic accuracy and implications for the treatment and prognosis.

Inferior vena cava distensibility during pressure support ventilation: a prospective study evaluating interchangeability of subcostal and trans­hepatic views, with both M­mode and automatic border tracing.

The Inferior Vena Cava (IVC) is commonly utilized to evaluate fluid status in the Intensive Care Unit (ICU),with more recent emphasis on the study of venous congestion. It is predominantly measured via subcostal approach (SC) or trans-hepatic (TH) views, and automated border tracking (ABT) software has been introduced to facilitate its assessment. Prospective observational study on patients ventilated in pressure support ventilation (PSV) with 2 × 2 factorial design. Primary outcome was to evaluate interchangeability of measurements of the IVC and the distensibility index (DI) obtained using both M-mode and ABT, across both SC and TH. Statistical analyses comprised Bland-Altman assessments for mean bias, limits of agreement (LoA), and the Spearman correlation coefficients. IVC visualization was 100% successful via SC, while TH view was unattainable in 17.4% of cases. As compared to the M-mode, the IVC-DI obtained through ABT approach showed divergences in both SC (mean bias 5.9%, LoA -18.4% to 30.2%, ICC = 0.52) and TH window (mean bias 6.2%, LoA -8.0% to 20.4%, ICC = 0.67). When comparing the IVC-DI measures obtained in the two anatomical sites, accuracy improved with a mean bias of 1.9% (M-mode) and 1.1% (ABT), but LoA remained wide (M-mode: -13.7% to 17.5%; AI: -19.6% to 21.9%). Correlation was generally suboptimal (r = 0.43 to 0.60). In PSV ventilated patients, we found that IVC-DI calculated with M-mode is not interchangeable with ABT measurements. Moreover, the IVC-DI gathered from SC or TH view produces not comparable results, mainly in terms of precision.

Effect of Prewarming on Perioperative Hypothermia in Patients Undergoing Loco-Regional or General Anesthesia: A Randomized Clinical Trial.

Background and Objectives: Redistribution hypothermia occurs during anesthesia despite active intraoperative warming. Prewarming increases the heat absorption by peripheral tissue, reducing the central to peripheral heat gradient. Therefore, the addition of prewarming may offer a greater preservation of intraoperative normothermia as compared to intraoperative warming only. Materials and Methods: A single-center clinical trial of adults scheduled for non-cardiac surgery. Patients were randomized to receive or not a prewarming period (at least 10 min) with convective air devices. Intraoperative temperature management was identical in both groups and performed according to a local protocol. The primary endpoint was the incidence, the magnitude and the duration of hypothermia (according to surgical time) between anesthetic induction and arrival at the recovery room. Secondary outcomes were core temperature on arrival in operating room, surgical site infections, blood losses, transfusions, patient discomfort (i.e., shivering), reintervention and hospital stay. Results: In total, 197 patients were analyzed: 104 in the control group and 93 in the prewarming group. Core temperature during the intra-operative period was similar between groups (p = 0.45). Median prewarming lasted 27 (17-38) min. Regarding hypothermia, we found no differences in incidence (controls: 33.7%, prewarming: 39.8%; p = 0.37), duration (controls: 41.6% (17.8-78.1), prewarming: 45.2% (20.6-71.1); p = 0.83) and magnitude (controls: 0.19 °C · h-1 (0.09-0.54), prewarming: 0.20 °C · h-1 (0.05-0.70); p = 0.91). Preoperative thermal discomfort was more frequent in the prewarming group (15.1% vs. 0%; p < 0.01). The interruption of intraoperative warming was more common in the prewarming group (16.1% vs. 6.7%; p = 0.03), but no differences were seen in other secondary endpoints. Conclusions: A preoperative prewarming period does not reduce the incidence, duration and magnitude of intraoperative hypothermia. These results should be interpreted considering a strict protocol for perioperative temperature management and the low incidence of hypothermia in controls.

Full and simplified assessment of left ventricular diastolic function in covid-19 patients admitted to ICU: Feasibility, incidence, and association with mortality.

PURPOSE: Left ventricular diastolic dysfunction (LVDD) is associated with poor outcomes in the intensive care unit (ICU). Nonetheless, precise reporting of LVDD in COVID-19 patients is currently lacking and assessment could be challenging. METHODS: We performed an echocardiography study in COVID-19 patients admitted to ICU with the aim to describe the feasibility of full or simplified LVDD assessment and its incidence. We also evaluated the association of LVDD or of single echocardiographic parameters with hospital mortality. RESULTS: Between 06.10.2020 and 18.02.2021, full diastolic assessment was feasible in 74% (n = 26/35) of patients receiving a full echocardiogram study. LVDD incidence was 46% (n = 12/26), while the simplified assessment produced different results (incidence 81%, n = 21/26). Nine patients with normal function on full assessment had LVDD with simplified criteria (grade I = 2; grade II = 3; grade III = 4). Nine patients were hospital-survivors (39%); the incidence of LVDD (full assessment) was not different between survivors (n = 2/9, 22%) and non-survivors (n = 10/17, 59%; p = .11). The E/e' ratio lateral was lower in survivors (7.4 [3.6] vs. non-survivors 10.5 [6.3], p = .03). We also found that s' wave was higher in survivors (average, p = .01). CONCLUSION: In a small single-center study, assessment of LVDD according to the latest guidelines was feasible in three quarters of COVID-19 patients. Non-survivors showed a trend toward greater LVDD incidence; moreover, they had significantly worse s' values (all) and higher E/e' ratio (lateral).

Association of weaning failure from mechanical ventilation with transthoracic echocardiography parameters: a systematic review and meta-analysis.

BACKGROUND: Weaning from mechanical ventilation is a challenging step during recovery from critical illness. Weaning failure or early reintubation are associated with increased morbidity and mortality, exposing patients to life-threatening complications. Cardiac dysfunction represents the most common cause of weaning failure. We conducted a systematic review and meta-analysis to evaluate the association between transthoracic echocardiographic parameters and weaning failure. METHODS: We performed a systematic search of MEDLINE and EMBASE screening for prospective studies providing echocardiographic data collected just before the beginning of spontaneous breathing trial and outcome of the weaning attempt. We primarily focused on parameters currently recommended for evaluation of left ventricular (LV) systolic or diastolic dysfunction. RESULTS: We included 11 studies in our primary analysis, which included data on LV ejection fraction (LVEF, n=10 studies) and parameters recommended for the assessment of LV diastolic function (E/e' ratio n=10; E/A ratio n=9; E wave n=8; and e' wave n=7). Weaning failure was significantly associated to a higher E/e' ratio (standardised mean difference [SMD]=1.70, 95% confidence interval [CI; 0.78-2.62]; P<0.001), lower e' wave (SMD=-1.22, 95% CI [-2.33 to -0.11]; P=0.03), and higher E wave (SMD=0.97, 95% CI [0.29-1.65]; P=0.005). We found no association between weaning failure and LVEF (SMD=-0.86, 95% CI [-1.92-0.20]; P=0.11) and E/A ratio (SMD=0.00, 95% CI [-0.30-0.31]; P=0.98). CONCLUSIONS: Weaning failure is associated with parameters indicating worse LV diastolic function (E/e', e' wave, E wave) and increased LV filling pressure (E/e' ratio). The association between weaning failure and LV systolic dysfunction as evaluated by LVEF is more unclear. More studies are needed to clarify this aspect and regarding the role of right ventricular function.

Echocardiographic Parameters and Mortality in Pediatric Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the prognostic value of echocardiographic parameters in pediatric septic patients. DATA SOURCES: MEDLINE, PubMed, and EMBASE (last update April 5, 2020). STUDY SELECTION: Observational studies of pediatric sepsis providing echocardiographic parameters in relation to mortality. DATA EXTRACTION: Echocardiography data were categorized as those describing left ventricular systolic or diastolic function, right ventricular function, and strain echocardiography parameters. Data from neonates and children were considered separately. Analysis is reported as standardized mean difference and 95% CI. DATA SYNTHESIS: We included data from 14 articles (n = 5 neonates, n = 9 children). The fractional shortening was the most commonly reported variable (11 studies, n = 555 patients) and we did not identify an association with mortality (standardized mean difference 0.22, 95% CI [-0.02 to 0.47]; p = 0.07, I2 = 28%). In addition, we did not find any association with mortality also for left ventricular ejection fraction (nine studies, n = 417; standardized mean difference 0.06, 95% CI [-0.27 to 0.40]; p = 0.72, I2 = 51%), peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave (four studies, n = 178; standardized mean difference -0.01, 95% CI [-0.34 to 0.33]; p = 0.97, I2 = 0%), and myocardial performance index (five studies, n = 219; standardized mean difference -0.51, 95% CI [-1.10 to 0.08]; p = 0.09, I2 = 63%). However, in regard to left ventricular diastolic function, there was an association with mortality for higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging ratio (four studies, n = 189, standardized mean difference -0.45, 95% CI [-0.80 to -0.10]; p = 0.01, I2 = 0%) or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging wave (three studies, n = 159; standardized mean difference 0.49, 95% CI [0.13-0.85]; p = 0.008, I2 = 0%). We did not find any association with mortality for early wave of transmitral flow/late (atrial) wave of trans-mitral flow ratio (six studies, n = 273; standardized mean difference 0.28, 95% CI [-0.42 to 0.99]; p = 0.43, I2 = 81%) and peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave measured at the tricuspid annulus (three studies, n = 148; standardized mean difference -0.18, 95% CI [-0.53 to 0.17]; p = 0.32, I2 = 0%). Only a few studies were conducted with strain echocardiography. CONCLUSIONS: This meta-analysis of echocardiography parameters in pediatric sepsis failed to find any association between the measures of left ventricular systolic or right ventricular function and mortality. However, mortality was associated with higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging, indicating possible importance of left ventricular diastolic dysfunction. These are preliminary findings because of high clinical heterogeneity in the studies to date.

Systolic-dicrotic notch pressure difference can identify tachycardic patients with septic shock at risk of cardiovascular decompensation following pharmacological heart rate reduction.

BACKGROUND: During sepsis, heart rate (HR) reduction could be a therapeutic target, but identification of responders (non-compensatory tachycardia) and non-responders (compensatory for 'fixed' stroke volume [SV]) is challenging. We tested the ability of the difference between systolic and dicrotic pressure (SDPdifference), which reflects the coupling between myocardial contractility and a given afterload, in discriminating the origin of tachycardia. METHODS: In this post hoc analysis of 45 patients with septic shock with persistent tachycardia, we characterised features of haemodynamic response focusing on SDPdifference, classifying patients according to variations in arterial dP/dtmax after 4 h of esmolol administration to maintain HR <95 beats min-1. A cut-off value of 0.9 mm Hg ms-1 was used for group allocation. RESULTS: After reducing HR, arterial dP/dtmax remained above the cut-off in 23 patients, whereas it decreased below the cut-off in 22 patients (from 0.99 [0.37] to 0.63 [0.16] mm Hg ms-1; mean [SD], P<0.001). At baseline, patients with decreased dP/dtmax after esmolol had lower SDPdifference than those with higher dP/dtmax (40 [19] vs 53 [16] mm Hg, respectively; P=0.01). The SDPdifference remained unchanged after esmolol in the higher dP/dtmax group (49 [16] mm Hg), whereas it decreased significantly in patients with lower dP/dtmax (29 [11] mm Hg; P<0.001). In the latter, the HR reduction resulted in a significant cardiac output reduction with unchanged SV, whereas in patients with higher dP/dtmax SV increased (from 48 [12] to 67 [14] ml; P<0.001) with maintained cardiac output. CONCLUSIONS: A decrease in SDPdifference could discriminate between compensatory and non-compensatory tachycardia, revealing a covert loss of myocardial contractility not detected by conventional echocardiographic parameters and deteriorating after HR reduction with esmolol. CLINICAL TRIAL REGISTRATION: NCT02188888.

The Effect of Propofol and Dexmedetomidine Sedation on Norepinephrine Requirements in Septic Shock Patients: A Crossover Trial.

OBJECTIVES: Propofol-based sedation may increase hemodynamic instability by decreasing vascular tone and venous return. Incremental exogenous catecholamines doses may be required to counteract such effects, aggravating the deleterious effects of sympathetic overstimulation. α-2 adrenergic agonists have been reported to decrease norepinephrine requirements in experimental septic shock. The aim of the present study is to test the hypothesis that switching from sedation with propofol to the α-2 agonist dexmedetomidine may decrease norepinephrine doses in septic shock. DESIGN: Prospective open-label crossover study. SETTINGS: University hospital, ICU. PATIENTS: Thirty-eight septic shock patients requiring norepinephrine to maintain adequate mean arterial pressure and needing deep sedation with propofol and remifentanil to maintain a Richmond Agitation-Sedation Scale score between -3 and -4. INTERVENTIONS: An initial set of measurements including hemodynamics, norepinephrine doses, and depth of sedation were obtained during sedation with propofol. Propofol was then replaced by dexmedetomidine and a second set of data was obtained after 4 hours of dexmedetomidine infusion. Sedation was switched back to propofol, and a final set of measurements was obtained after 8 hours. A Richmond Agitation-Sedation Scale score between -3 and -4 was maintained during the study period. MEASUREMENTS AND MAIN RESULTS: Norepinephrine requirements decreased from 0.69 ± 0.72 µg/kg/min before dexmedetomidine to 0.30 ± 0.25 µg/kg/min 4 hours after dexmedetomidine infusion, increasing again to 0.42 ± 0.36 µg/kg/min while on propofol 8 hours after stopping dexmedetomidine (p < 0.005). Dexmedetomidine dosage was 0.7 ± 0.2 µg/kg/hr. Before and after dexmedetomidine infusion, sedative doses remained unchanged (propofol 2.6 ± 1.2 vs 2.6 ± 1.2 mg/kg/hr; p = 0.23 and remifentanil 1.27 ± 0.17 vs 1.27 ± 0.16 µg/kg/hr; p = 0.52, respectively). Richmond Agitation-Sedation Scale was -4 (-4 to -3) before, -4 (-4 to -3) during, and -4 (-4 to -4) after dexmedetomidine (p = 0.07). CONCLUSIONS: For a comparable level of sedation, switching from propofol to dexmedetomidine resulted in a reduction of catecholamine requirements in septic shock patients.

The Effects of On-Pump and Off-Pump Coronary Artery Bypass Surgery on Respiratory Function in the Early Postoperative Period.

BACKGROUND:: Respiratory complications are common after cardiac surgery and the use of extracorporeal circulation is one of the main causes of lung injury. We hypothesized a better postoperative respiratory function in off-pump coronary artery bypass grafting (OPCABG) as compared with "on-pump coronary artery bypass grafting" (ONCABG). METHODS:: This is a retrospective, single-center study at a cardiothoracic intensive care unit (ICU) in a tertiary university hospital. Consecutive data on 339 patients undergoing elective CABG (n = 215 ONCABG, n = 124 OPCABG) were collected for 1 year from the ICU electronic medical records. We compared respiratory variables (Pao2, Pao2/Fio2 ratio, Sao2, and Paco2) at 7 predefined time points (ICU admission, postoperative hours 1, 3, 6, 12, 18, and 24). We also evaluated time to extubation, rates of reintubation, and use of noninvasive ventilation (NIV). We used mixed-effects linear regression models (with time as random effect for clustering of repeated measures) adjusted for a predetermined set of covariates. RESULTS:: The values of Pao2 and Pao2/Fio2 were significantly higher in the OPCABG group only at ICU admission (mean differences: 9.7 mm Hg, 95% confidence interval [CI] 3.1-16.2; and 27, 95% CI 6.1-47.7, respectively). The OPCABG group showed higher Paco2, overall ( P = .02) and at ICU admission (mean difference 1.8 mm Hg, 95% CI: 0.6-3), although mean values were always within normal range in both groups. No differences were seen in Sao2 values, time to extubation, rate of reintubation rate, and use of postoperative NIV. Extubation rate was higher in OPCABG only at postoperative hour 12 (92% vs ONCABG 82%, P = .02). CONCLUSION:: The OPCABG showed only marginal improvements of unlikely clinical meaning in oxygenation as compared to ONCABG in elective low-risk patients.

Anticoagulation and Transfusions Management in Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Assessment of Factors Associated With Transfusion Requirements and Mortality.

PURPOSE: We describe an approach for anticoagulation and transfusions in veno-venous-extracorporeal membrane oxygenation (VV-ECMO), evaluating factors associated with higher transfusion requirements, and their impact on mortality. METHODS: Observational study on consecutive adults supported with VV-ECMO for acute respiratory distress syndrome (ARDS). We targeted an activated partial thromboplastin time of 40 to 50 seconds and a hematocrit of 24% to 30%. Univariate and multiple analyses were done to evaluate factors associated with transfusion requirements and the influence of increasing transfusions on mortality during ECMO. RESULTS: In a cohort of 82 VV-ECMO patients (PRedicting dEath for SEvere ARDS on VV-ECMO [PRESERVE] score: 4, Interquartile range [IQR]: 3-5, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction [RESP] score: 2, IQR: 2-4), 76 (92.7%) patients received at least 1 unit of packed red blood cells (PRBCs) during the intensive care unit stay related to ECMO (median PRBC/d 156 mL, IQR: 93-218; median ECMO duration 14 days, IQR: 8-22). A higher requirement of PRBC transfusions was associated with pre-ECMO hematocrit, and with the following conditions during ECMO: platelet nadir, antithrombin III (ATIII), and stage 3 of acute kidney injury (all P < .05). Sixty-two (75.6%) patients survived ECMO. Pre-ECMO hospital stay, PRBC transfusion, and septic shock were associated with mortality (all P < .05). The adjusted odds ratio for each 100mL/d increase in PRBC transfusion was 1.9 (95% confidence interval [CI]: 1.1-3.2, P = .01); for the development of septic shock it was 15.4 (95% CI: 1.7-136.8, P = .01), and for each day of pre-ECMO stay it was 1.1 (95% CI: 1-1.2, P = .04). CONCLUSION: Implementation of a comprehensive protocol for anticoagulation and transfusions in VV-ECMO for ARDS resulted in a low PRBC requirement, and an ECMO survival comparable to data in the literature. Lower ATIII emerged as a factor associated with increased need for transfusions. Higher PRBC transfusions were associated with ECMO mortality. Further investigations are needed to better understand the right level of anticoagulation in ECMO, and the factors to take into account in order to manage personalized transfusion practice in this select setting.

Levosimendan for patients with severely reduced left ventricular systolic function and/or low cardiac output syndrome undergoing cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Previous studies have shown beneficial effects of levosimendan in high-risk patients undergoing cardiac surgery. Two large randomized controlled trials (RCTs), however, showed no advantages of levosimendan. METHODS: We performed a systematic review and meta-analysis (MEDLINE and Embase from inception until March 30, 2017), investigating whether levosimendan offers advantages compared with placebo in high-risk cardiac surgery patients, as defined by preoperative left ventricular ejection fraction (LVEF) ≤ 35% and/or low cardiac output syndrome (LCOS). The primary outcomes were mortality at longest follow-up and need for postoperative renal replacement therapy (RRT). Secondary postoperative outcomes investigated included myocardial injury, supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI), duration of mechanical ventilation, intensive care unit and hospital lengths of stay, and incidence of hypotension during drug infusion. RESULTS: Six RCTs were included in the meta-analysis, five of which investigated only patients with LVEF ≤ 35% and one of which included predominantly patients with LCOS. Mortality was similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR 0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02), and a trend toward lower mechanical support, both overall (p = 0.07) and in patients with LVEF < 35% (p = 0.05). CONCLUSIONS: Levosimendan reduces mortality in patients with preoperative severely reduced LVEF but does not affect overall mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

Bivalirudin for Alternative Anticoagulation in Extracorporeal Membrane Oxygenation: A Systematic Review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) offers therapeutic options in refractory respiratory and/or cardiac failure. Systemic anticoagulation with heparin is routinely administered. However, in patients with heparin-induced thrombocytopenia or heparin resistance, the direct thrombin inhibitor bivalirudin is a valid option and has been increasingly used for ECMO anticoagulation. We aimed at evaluating its safety and its optimal dosing for ECMO. METHODS: Systematic web-based literature search of PubMed and EMBASE performed via National Health Service Library Evidence and manually, updated until January 30, 2016. RESULTS: The search revealed 8 publications relevant to the topic (5 case reports). In total, 58 patients (24 pediatrics) were reported (18 received heparin as control groups). Bivalirudin was used with or without loading dose, followed by infusion at different ranges (lowest 0.1-0.2 mg/kg/h without loading dose; highest 0.5 mg/kg/h after loading dose). The strategies for monitoring anticoagulation and optimal targets were dissimilar (activated partial thromboplastin time 45-60 seconds to 42-88 seconds; activated clotting time 180-200 seconds to 200-220 seconds; thromboelastography in 1 study). CONCLUSION: Bivalirudin loading dose was not always used; infusion range and anticoagulation targets were different. In this systematic review, we discuss the reasons for this variability. Larger studies are needed to establish the optimal approach with the use of bivalirudin for ECMO.

Mitral Regurgitation Grading in the Operating Room: A Systematic Review and Meta-analysis Comparing Preoperative and Intraoperative Assessments During Cardiac Surgery.

OBJECTIVE: To assess differences in mitral regurgitation (MR) grade between the preoperative and the intraoperative evaluations. DESIGN: Systematic review and meta-analysis of 6 observational studies found from MEDLINE and EMBASE. SETTING: Cardiac surgery. PARTICIPANTS: One hundred thirty-seven patients. INTERVENTION: Comparison between the preoperative MR assessment and the intraoperative evaluation conducted under general anesthesia (GA), with or without "hemodynamic matching" (HM) (artificial increase of afterload). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the difference between the preoperative and intraoperative MR grade under "GA-only" or "after-HM." Secondary analyses addressed differences according to effective regurgitant orifice area (EROA), regurgitant volume (RVol), color-jet area, and vena contracta width. Risk of MR underestimation was found under "GA-only" (SMD: 0.55; 95% confidence interval [CI], 0.31-0.79, p < 0.00001), but not "after-HM" (SMD: -0.16; 95% CI, -0.46 to 0.13, p = 0.27). Under "GA-only", EROA had a trend toward underestimation (p = 0.07), RVol was reliable (p = 0.17), while reliance on color-jet area and vena contracta width incur risk of underestimation (both p = 0.003). After HM, EROA accurately reflected preoperative MR (p = 0.68) while RVol had a trend toward overestimation (p = 0.05). The overall reported incidence of misdiagnoses was slightly more common under "GA-only" (mean 48%, 39% underestimation, 9% overestimation; range: 32%-57%) than "after-HM" (mean 41%, 12% underestimation, 29% overestimation; range: 33%-50%). Only the minority of misdiagnoses were clinically relevant: underestimation was around 10% (both approaches), but 18% had clinically significant overestimation "after-HM" as compared with 3% under GA-only. CONCLUSIONS: Intraoperative assessment under "GA-only" significantly underestimated MR. A more accurate intraoperative evaluation can be obtained with afterload manipulation, although HM strategy carries high risk of clinically significant overestimation.

The Effects of On-Pump and Off-Pump Coronary Artery Bypass Surgery on Metabolic Profiles in the Early Postoperative Period.

OBJECTIVE: Hyperlactatemia and base deficit (BD) are markers of adverse outcome after cardiac surgery, and their derangement can be influenced by the use of extracorporeal circulation. The authors hypothesized a better postoperative metabolic profile in off-pump coronary artery bypass grafting (OPCABG) compared with "on-pump" coronary artery bypass grafting (ONCABG). DESIGN: This was a retrospective study, with consecutive data collected for 1 year from electronic medical records. SETTING: Cardiothoracic intensive care unit at a tertiary university hospital. PARTICIPANTS: The study comprised 339 patients who underwent elective coronary artery bypass grafting (ONCABG [n = 215], OPCABG [n = 124]). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The metabolic (arterial lactatemia, pH, and BD) and hemodynamic (inotropic/vasopressor support) parameters of OPCABG and ONCABG patients were compared at 7 predefined time points (intensive care admission and the 1st, 3rd, 6th, 12th, 18th, and 24th postoperative hours). For each output of interest, mixed-effects linear regression models were used (with time as random-effect to allow for clustering of repeated measures) and adjusted for a predetermined set of covariates. Arterial lactatemia and pH were comparable at all time points; BD was worse in the ONCABG group overall (p = 0.01) and at most time points (except at the 1st and 24th postoperative hours). For the whole period, inotropic support was more common in ONCABG patients (p<0.05), whereas vasopressor use was more frequent in the OPCABG group (p< 0.05). CONCLUSIONS: Improved postoperative BD values were demonstrated in the OPCABG group, although pH and lactatemia were similar between groups. Inotropic support was less common in the OPCABG group at the expense of more frequent vasopressor support.

The role of neuromuscular blockade in patients with traumatic brain injury: a systematic review.

Management of Traumatic Brain Injury (TBI) focuses on controlling intracranial pressure (ICP), while other treatments, such as the use of neuromuscular blocking agents (NMBAs), need scientific evidence. We conducted a systematic review to investigate the usefulness of NMBAs in the context of TBI and/or increased ICP. We searched MEDLINE and EMBASE databases up to January 31st 2014, including both clinical and experimental findings. We found a total of 34 articles, of which 22 were prospective clinical trials. No systematic review/meta-analyses were found. Seven studies evaluated NMBA boluses in preventing stimulation-related ICP surges: paralysis was effective during tracheal suctioning and physiotherapy but not during bronchoscopy. Fourteen small studies (8 to 25 patients) assessed the effect of NMBA boluses on ICP. Two studies showed an ICP increase by succinylcholine and one found a decrease in ICP after atracurium. No ICP changes were observed in the other studies. One prospective study confirmed that discontinuing paralysis increases energy expenditure. Two retrospective studies investigated mortality/morbidity: one found that early paralysis (continued for >12 h) was not beneficial and potentially associated with extra-cranial complications, while the second demonstrated a correlation between continuous infusion of NMBA and time spent with ICP > 20 mmHg. Eight animal studies were also retrieved. In most studies, NMBA bolus was beneficial in controlling ICP, especially when performing stimulating procedures. However, retrospective evidence found potential harm by continuous NMBA infusion. In the context of TBI patients, we discuss the potentially positive effects of paralysis with its negative ones. Well-conducted randomized controlled trials and/or large pharmaco-epidemiologic studies are warranted.

C-reactive protein kinetics after major surgery.

BACKGROUND: Diagnosis of sepsis in the postoperative period is a challenge. Measurements of inflammatory markers, such as C-reactive protein (CRP), have been proposed in medical patients, but the interpretation of these values in surgical patients is more difficult. We evaluated the changes in blood CRP levels and white blood cell count in postoperative patients with and without infection. METHODS: All patients admitted to our 34-bed Department of Intensive Care after major (elective or emergency) cardiac, neuro-, vascular, thoracic, or abdominal surgery during a 4-month period were prospectively included. Patients were screened daily and characterized as infected or noninfected. CRP levels and white blood cell counts were recorded daily in all patients for up to 7 days after the surgical intervention. RESULTS: Of the 151 patients enrolled, 115 underwent elective surgery and 36 emergency surgery; cardiac surgery was performed in 49 patients, neurosurgery in 65, abdominal surgery in 25, vascular surgery in 7, and thoracic surgery in 5. In noninfected patients (n = 117), mean CRP values increased from baseline to postoperative day (POD) 3 (P < 0.0001, estimated mean difference [EMD] = 99.7 mg/L [95% confidence interval, 85.6-113.8]) and then decreased until POD 7 but remained higher than the level at baseline (P < 0.0001, EMD = 49.2 mg/L [95% confidence interval, 27.1-71.2]). Postoperative infection occurred in 20 patients (13.2%). In these patients, CRP values were already higher on POD 1 than in noninfected patients (P = 0.0054). CONCLUSIONS: CRP levels increase in the first week after major surgery but to a much larger extent in infected than in noninfected patients. Persistently high CRP levels after POD 4, especially when >100 mg/L, suggest the presence of a postoperative infection.

Morning or Afternoon Scheduling for Elective Coronary Artery Bypass Surgery: Influence of Longer Fasting Periods from Metabolic and Hemodynamic Perspectives.

BACKGROUND: Prolonged preoperative fasting may worsen postoperative outcomes. Cardiac surgery has higher perioperative risk, and longer fasting periods may be not well-tolerated. We analysed the postoperative metabolic and hemodynamic variables in patients undergoing elective coronary artery bypass grafting (CABG) according to their morning or afternoon schedule. METHODS: Single-centre retrospective study at University teaching hospital (1-year data collection from electronic medical records). Using a mixed-effects linear regression model adjusted for several covariates, we compared metabolic (lactatemia, pH, and base deficit [BD]) and haemodynamic values (patients on vasoactive support, and vasoactive inotropic score [VIS]) at 7 prespecified time-points (admission to intensive care, and 1st, 3rd, 6th, 12th, 18th, and 24th postoperative hours). RESULTS: 339 patients (n = 176 morning, n = 163 afternoon) were included. Arterial lactatemia and BD were similar (overall P = 0.11 and P = 0.84, respectively), while pH was significantly lower in the morning group (overall P < 0.05; mean difference -0.01). Postoperative urine output, fluid balance, mean arterial pressure, and central venous pressure were similar (P = 0.59, P = 0.96, P = 0.58 and P = 0.53, respectively). A subgroup analysis of patients with diabetes (n = 54 morning, n = 45 afternoon) confirmed the same findings. The VIS values and the proportion of patients on vasoactive support was higher in the morning cases at the 18th (P = 0.002 and p=0.04, respectively) and 24th postoperative hours (P = 0.003 and P = 0.04, respectively). Mean intensive care length of stay was 1.94 ± 1.36 days versus 2.48 ± 2.72 days for the afternoon and morning cases, respectively (P = 0.02). CONCLUSIONS: Patients undergoing elective CABG showed similar or better metabolic and hemodynamic profiles when scheduled for afternoon surgery.

Ciprofol as compared to propofol for sedation and general anesthesia: a systematic review of randomized controlled trials.

BACKGROUND: Propofol is the most commonly used hypnotic agent used during sedation and general anesthesia (GA) practice, offering faster recovery compared to benzodiazepines. However, cardiovascular impact of propofol and pain at injection are commonly encountered side effects. Ciprofol is a novel disubstituted phenol derivative, and there is growing evidence regarding its clinical use. METHODS: We conducted a systematic literature search (updated on 23 July 2023) to evaluate safety and efficacy of ciprofol in comparison to propofol in patients undergoing procedures under sedation or GA. We focused on randomized controlled trials (RCTs) only, extrapolating data on onset and offset, and on the side effects and the pain at injection. RESULTS: The search revealed 14 RCTs, all conducted in China. Eight RCTs studied patients undergoing sedation, and six focused on GA. Bolus of ciprofol for sedation or induction of GA varied from 0.2 to 0.5 mg/kg. In four studies using ciprofol for maintenance of GA, it was 0.8-2.4 mg/kg/h. Ciprofol pharmacokinetics seemed characterized by slower onset and offset as compared to propofol. Pain during injection was less frequent in the ciprofol group in all the 13 studies reporting it. Eight studies reported "adverse events" as a pooled outcome, and in five cases, the incidence was higher in the propofol group, not different in the remaining ones. Occurrence of hypotension was the most commonly investigated side effects, and it seemed less frequent with ciprofol. CONCLUSION: Ciprofol for sedation or GA may be safer than propofol, though its pharmacokinetics may be less advantageous.

Mortality in Patients With Sepsis Treated With Esmolol or Landiolol: A Systematic Review and Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis.

BACKGROUND: The latest meta-analysis indicated potential survival benefits from ultra-short-acting ß-blockers in patients with sepsis with persistent tachycardia. However, subsequent multicenter randomized controlled trials (RCTs) have reported conflicting findings, prompting the need for an updated meta-analysis to incorporate these newly published RCTs. RESEARCH QUESTION: Does the use of ultra-short-acting ß-blockers (esmolol or landiolol) in patients with sepsis with persistent tachycardia improve mortality? STUDY DESIGN AND METHODS: We conducted an updated systematic search through April 2, 2024, exploring the MEDLINE, Cochrane Central Register of Controlled Trials, and Embase databases for RCTs reporting mortality in adult patients with sepsis treated with esmolol or landiolol as compared with those treated with neither of these or receiving placebo and published in English. Meta-analyses were conducted with the random effects model. The primary outcome was mortality at the longest follow-up, with subgroup analysis separating single-center RCTS from large multicenter RCTs. RESULTS: Eight RCTs (885 patients) were included in the primary analysis. Ultra-short-acting ß-blockers did not improve mortality significantly at the longest follow-up (risk ratio [RR], 0.84; 95% CI, 0.68-1.02; P = .08; I2 = 51%; very low certainty of the evidence) and 28-day mortality (RR, 0.77; 95% CI, 0.59-1.00; P = .05; I2 = 62%). Subgroup analyses of mortality outcomes pointed toward different results between single-center and multicenter RCTs. Trial sequence analyses showed that both mortality outcomes were not robust. The sensitivity analyses suggested a significant reduction in mortality by adding RCTs published in non-English languages. INTERPRETATION: In this updated meta-analysis, the use of esmolol or landiolol did not reduce mortality in patients with sepsis with persistent tachycardia. However, results were not robust and outcomes differed between single-center and multicenter RCTs. Moreover, sensitivity analyses showed the fragility of the primary outcome. Further studies regarding ultra-short-acting ß-blockers with advanced cardiac monitoring or serial echocardiography are warranted. TRIAL REGISTRY: International Prospective Register of Systematic Reviews; No.: CRD42024503570; URL: https://www.crd.york.ac.uk/prospero/.