Feasibility and postoperative opioid sparing effect of an opioid-free anaesthesia in adult cardiac surgery: a retrospective study.

BACKGROUND: No previous study investigated the dexmedetomidine-based opioid-free anesthesia (OFA) protocol in cardiac surgery. The main objective of this study was to evaluate the feasibility and the postoperative opioid-sparing effect of dexmedetomidine-based OFA in adult cardiac surgery patients. METHODS: We conducted a single-centre and retrospective study including 80 patients above 18 years old who underwent on-pump cardiac surgery between November 2018 and February 2020. Patients were divided into two groups: OFA (lidocaine, ketamine, dexmedetomidine, MgSO4) or opioid-based anaesthesia (remifentanil and anti-hyperalgesic medications such as ketamine and/or MgSO4 and/or lidocaine at the discretion of the anesthesiologist). The primary endpoint was the total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours. Secondary outcomes included perioperative hemodynamics, post-operative maximal pain at rest and during coughing and adverse outcomes. Data are expressed as median [interquartile range]. RESULTS: Patients in the OFA-group had a higher EuroSCORE II, with more diabetes, more dyslipidemia and more non-elective surgery but fewer smoking history. In the OFA group, the median loading dose of dexmedetomidine was 0.6 [0.4-0.6] µg.kg- 1 while the median maintenance dose was 0.11 µg.kg- 1.h- 1 [0.05-0.20]. In 10 (25%) patients, dexmedetomidine was discontinued for a drop of mean arterial pressure below 55 mmHg. The median total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours was lower in the OFA group (15.0 mg [8.5-23.5] versus 30.0 mg [17.3-44.3], p < 0.001). While no differences were seen with rest pain (2.0 [0.0-3.0] versus 0.5 [0.0-5.0], p = 0.60), the maximal pain score during coughing was lower in OFA group (3.5 [2.0-5.0] versus 5.5 [3.0-7.0], p = 0.04). In OFA group the incidence of atrial fibrillation (18% versus 40%, p = 0.03) and non-invasive ventilation use (25% versus 48%, p = 0.04) were lower. The incidence of bradycardia and the intraoperative use of norepinephrine were similar between both groups. CONCLUSION: Dexmedetomidine-based OFA in cardiac surgery patients is feasible and could be associated with a lower postoperative morphine consumption and better postoperative outcomes. Further randomized studies are required to confirm these promising results and determine the optimal associations, dosages, and infusion protocols during cardiac surgery.

Risk Factors of Midterm Mortality After Aortic Valve Replacement for Severe Calcified Tricuspid Aortic Valve Stenosis: A retrospective analysis of Perioperative Events Assessment in Adult Cardiac surgery (PESSAC) Registry.

OBJECTIVE: The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) initially developed for predicting early postoperative mortality of all types of cardiac surgery, is less able to predict, more specifically, long-term outcomes after aortic valve replacement (AVR). The study authors here evaluated the risk factors for three-year mortality after isolated aortic valve replacement (AVR) for severe calcified tricuspid aortic valve stenosis and compared them with EuroSCORE II to predict long-term outcomes. DESIGN: A retrospective study. SETTING: A university teaching hospital. PARTICIPANTS: This study included 1,101 adults who underwent isolated AVR for severe calcified tricuspid aortic valve stenosis between September 2010 to June 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was that of three-year all-cause mortality after AVR. By three years, 168 patients (15.3%) had died. Risk factors for all-cause mortality were: male gender (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.21-2.62; p < 0.01), peripheral arterial disease (OR = 1.77; 95% CI = 1.08-2.92; p = 0.03), age (OR = 1.06 per year increase; 95% CI =1.04-1.09; p < 0.01), pulmonary artery systolic pressure (OR = 1.02 per mmHg increase; 95% CI = 1.01-1.03; p < 0.01), platelet count (OR = 1.003 per G/L increase; 95% CI = 1.000-1.005; p = 0.04), and valve area (OR = 0.97 per cm²/m² increase; 95% CI= 0.95-0.99; p < 0.01). The area under the receiver operating characteristic curves were 0.67 (95% CI = 0.60-0.75) and 0.60 (95% CI = 0.56-0.65) for the authors' logistic regression model and EuroSCORE II, respectively (p = 0.11). CONCLUSIONS: The study authors identified six independent risk factors for three-year mortality after isolated AVR. The logistic regression model had relatively modest predictive performance for three-year mortality.

Independent risk factors for ICU mortality after left ventricular assist device implantation.

Left ventricular assist devices (LVADs) are used as an alternative therapy for heart transplantation in patients with advanced heart failure. However, the mortality rate of these patients remains relatively high. A large proportion of deaths after LVAD implantation occur during intensive care unit (ICU) stay. We conducted a retrospective study to identify the risk factors for all-cause ICU mortality in patients with an implanted LVAD. Between January 1, 2008 and December 31, 2016, 70 consecutive patients who had received an LVAD were analyzed. The median ICU length of stay was 14 days (IQR: 8-31) and 16 patients (22.9% [95%CI: 13.1-32.7]) died in the ICU. The 90-day mortality rate was 25.7% (95%CI: 15.5-35.9). The main causes of ICU mortality were: multiple organ failure, stroke, and hemorrhagic events. The univariate analysis identified the following perioperative risk factors for all-cause ICU mortality: hypertension, preoperative platelet count, preoperative white cell count, inotropic support before LVAD implantation, mechanical ventilation before LVAD implantation, renal replacement therapy before LVAD implantation, short-term mechanical support before LVAD implantation, INTERMACS class 1 to 2, low intraoperative platelet count, low early postoperative hemoglobin level, low early postoperative platelet count, low early postoperative pH, and massive perioperative blood transfusion. In the multivariate logistic regression analysis, only mechanical ventilation before LVAD implantation was retained as an independent risk factor for ICU mortality (OR = 11.96 [95%CI: 2.67-53.45], P < .01). These findings confirm that most deaths after LVAD implantation occur in the ICU. Patients that receive mechanical ventilation preoperatively have the highest risk of death. This confirms the need to actively treat respiratory failure and to wean patients from respiratory support before LVAD implantation. Such a strategy offers the best opportunity to initiate active rehabilitation.

U-shaped relationship between pre-operative plasma fibrinogen levels and severe peri-operative bleeding in cardiac surgery.

BACKGROUND: An inverse linear relationship has been reported between pre-operative fibrinogen levels and postoperative blood loss in cardiac surgery. However, recently high pre-operative fibrinogen levels have also been reported to be associated with increased blood transfusion and re-operation. OBJECTIVE: We tested the hypothesis that the relationship between pre-operative fibrinogen levels and severe peri-operative bleeding is not linear. DESIGN: A large-scale (n = 3883) single-centre retrospective study. SETTING: A tertiary care teaching hospital. PATIENTS: We analysed data from our institutional database which includes all patients above 18 years who underwent on-pump cardiac surgery through a sternotomy between September 2010 and May 2014. MAIN OUTCOME MEASURES: Peri-operative severe bleeding adapted from the Universal Definition of Peri-operative Bleeding, class 3 or 4. The relationship between pre-operative fibrinogen levels and peri-operative severe bleeding was analysed by binary logistic regression. A cubic B-spline transformation was used to estimate the relationship between pre-operative fibrinogen level associated with excessive peri-operative bleeding. RESULTS: Severe peri-operative bleeding was observed in 957 (24.6%) patients. An L-shaped relationship was observed between pre-operative fibrinogen levels and 24-h postoperative blood loss. The relationship between pre-operative fibrinogen levels and severe peri-operative bleeding (i.e. Universal Definition of Peri-operative Bleeding class 3 or 4) was U-shaped: the risk of severe peri-operative bleeding bottomed at 3.3 g l when the upward sloping curve started at 5.8 g l with a steeper increase above 8.2 g l. CONCLUSION: We reported a U-shaped relationship between severe peri-operative bleeding and pre-operative fibrinogen levels. While a low-level of fibrinogen appears to be associated with a high risk of bleeding, a high level does not necessarily protect the patient against such a risk and could even be a risk factor for peri-operative bleeding.

Reduced Length of Hospital Stay for Cardiac Surgery-Implementing an Optimized Perioperative Pathway: Prospective Evaluation of an Enhanced Recovery After Surgery Program Designed for Mini-Invasive Aortic Valve Replacement.

OBJECTIVES: Presently, there is enthusiasm for the Enhanced Recovery After Surgery (ERAS) program. The literature clearly indicates this type of program could shorten hospital length of stay and improve patient outcome. However, most of the studies conducted have encompassed mainly colorectal and orthopedic surgeries. Thus, in an effort to provide more evidence to the literature, the authors prospectively investigated the feasibility and clinical effectiveness of a dedicated ERAS program for mini-invasive aortic valve replacements (MIAVRs). DESIGN: Observational before-and-after trial. SETTING: University hospital. PARTICIPANTS: Consecutive patients scheduled for an MIAVR via a mini-sternotomy during 2 time periods-before (MIAVR group) and after implementation of an ERAS program (MIAVR-ERAS group). INTERVENTIONS: Patients in the dedicated MIAVR-ERAS group followed a dedicated pathway specifically designed for this procedure, which encompasses several evidence-based medicine elements for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Data on patient demographics, patient characteristics, compliance to the ERAS protocol, postoperative morphine consumption, postoperative pain scores, postoperative complications, hospital length of stay, and hospital readmission rate were collected and compared. Twenty-three patients were enrolled in each group. Patients enrolled in the new protocol had significantly lower postoperative pain scores (p = 0.03). The median hospital length of stay was 10 (9-13.5) and 7 (6.5-8) days in the traditional MIAVR group and in the MIAVR-ERAS group, respectively (p < 0.001). CONCLUSIONS: An ERAS pathway planned for MIAVR seems feasible and was associated with a shorter length of hospital stay with trends toward both less opioid consumption and less postoperative complications.

Intraoperative changes in blood lactate levels are associated with worse short-term outcomes after cardiac surgery with cardiopulmonary bypass.

BACKGROUND: A high perioperative blood lactate level has been reported to be associated with poor outcomes after cardiac surgery. More than isolated peaks of lactate values, it should be more interesting to take into account changes in intraoperative blood lactate level (∆Lact). This large-scale retrospective study evaluated the relationship between ∆Lact and overall intensive care unit morbidity and 30-day all-cause mortality. METHODS: Perioperative data from consecutive patients undergoing on-pump cardiac surgery between September 2010 and June 2016 were retrospectively analysed through our institutional database including clinical, transfusion and laboratory test results implemented prospectively by physicians. Blood lactate levels were initially measured after induction of anaesthesia (baseline) and periodically during the surgery. The ∆Lact was defined as the difference between the highest intraoperative blood lactate and the baseline lactate level and offered the opportunity to stratify patients into four subgroups: ⩽0, 0.1-0.9, 1-1.9 and ⩾2 mmol L-1. RESULTS: From the 7,795 patients found eligible during the study period, 7,447 patients were analysed. The median ∆Lact of our patients was 0.6 (0.3-1) mmol L-1. Most of the studied patients (65.9%) exhibited a ∆Lact between 0.1 and 0.9 mmol L-1. A concentration-dependent relationship was observed between ∆Lact and intensive care unit morbidity and 30-day mortality. After adjustment for co-variables, all ∆Lact > 0 was associated with an increase in overall intensive care unit morbidity. An independent relationship was also found between ∆Lact and 30-day mortality as of a 1 mmol L-1 increase. CONCLUSION: Our results suggest that ∆Lact is associated with poor short-term outcomes in adult cardiac surgical patients.

Feasibility of Automated Propofol Sedation for Transcatheter Aortic Valve Implantation: A Pilot Study.

BACKGROUND: Recently, several trials have shown that closed-loop sedation is feasible. No study has used automated sedation in extremely frail patients, such as those scheduled for transcatheter aortic valve implantation (TAVI). We developed and tested a novel automated sedation system for this kind of population and surgery. The system integrates a decision support system that detects respiratory and hemodynamic events via smart alarms, which provide pertinent/related clinical suggestions and treatment options. The main objective was the feasibility of closed-loop sedation, defined as successful automated sedation without manual override. Secondary qualitative observations were clinical and controller performance. METHODS: Twenty patients scheduled for elective TAVI were enrolled. Sedation was administered via a closed-loop delivery system designed for propofol. The clinical performance of sedation was the efficacy to maintain a bispectral index (BIS) of 65. To evaluate the sedation performance, BIS values were stratified into 4 categories: excellent, very good, good, and inadequate sedation control, defined as BIS values within 10%, ranging from 11% to 20%, ranging from 21% to 30%, or >30% from the target value, respectively. The controller performance was calculated using Varvel parameters. Critical respiratory and hemodynamic events were documented. The former was defined as peripheral oxygen saturation <92% and/or respiratory rate <8/min, whereas the latter was considered a mean arterial pressure <60 mm Hg and/or heart rate <40 bpm. RESULTS: Automated sedation was successful in 19 patients undergoing TAVI. One patient was excluded from the final analysis because of conversion to general anesthesia. The secondary observations revealed that the clinical performance allowed an excellent to good control during 69% (99% confidence interval, 53%-77%; interquartile range, 59%-79%) of the sedation time. Fifteen patients presented critical respiratory episodes, with a median of 3 events per hour of sedation. Six patients presented critical hemodynamic episodes, with a median of 2 events per hour of procedure. CONCLUSIONS: The automated closed-loop sedation system tested could be used successfully for patients scheduled for a TAVI procedure. The results showed a satisfactory clinical performance of sedation control.

The Feasibility of a Completely Automated Total IV Anesthesia Drug Delivery System for Cardiac Surgery.

BACKGROUND: In this pilot study, we tested a novel automatic anesthesia system for closed-loop administration of IV anesthesia drugs for cardiac surgical procedures with cardiopulmonary bypass. This anesthesia drug delivery robot integrates all 3 components of general anesthesia: hypnosis, analgesia, and muscle relaxation. METHODS: Twenty patients scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Propofol, remifentanil, and rocuronium were administered using closed-loop feedback control. The main objective was the feasibility of closed-loop anesthesia defined as successful automated cardiac anesthesia without manual override by the attending anesthesiologist. Secondary qualitative observations were clinical and controller performances. The clinical performance of hypnosis control was the efficacy to maintain a bispectral index (BIS) of 45. To evaluate the hypnosis performance, BIS values were stratified into 4 categories: "excellent," "good," "poor," and "inadequate" hypnosis control defined as BIS values within 10%, ranging from 11% to 20%, ranging from 21% to 30%, or >30% of the target value, respectively. The clinical performance of analgesia was the efficacy to maintain NociMap values close to 0. The analgesia performance was assessed classifying the NociMap values in 3 pain control groups: -33 to +33 representing excellent pain control, -34 to -66 and +34 to +66 representing good pain control, and -67 to -100 and +67 to +100 representing insufficient pain control. The controller performance was calculated using the Varvel parameters. RESULTS: Robotic anesthesia was successful in 16 patients, which is equivalent to 80% (97.5% confidence interval [CI], 53%-95%) of the patients undergoing cardiac surgery. Four patients were excluded from the final analysis because of technical problems with the automated anesthesia delivery system. The secondary qualitative observations revealed that the clinical performance of hypnosis allowed an excellent and good control during 70% (97.5% CI, 63%-76%) of maintenance time and an insufficient clinical performance of analgesia for only 3% (97.5% CI, 1%-6%) of maintenance time. CONCLUSIONS: The completely automated closed-loop system tested in this investigation could be used successfully and safely for cardiac surgery necessitating cardiopulmonary bypass. The results of the present trial showed satisfactory clinical performance of anesthesia control.

The effect of local anesthetic continuous wound infusion for the prevention of postoperative pneumonia after on-pump cardiac surgery with sternotomy: the STERNOCAT randomized clinical trial.

PURPOSE: Postoperative pain after cardiac surgery, exacerbated by cough and sternal mobilization, limits clearance of bronchopulmonary secretions and may predispose to postoperative pneumonia. In this study, we tested the ability of local anesthetic continuous wound infusion to prevent pneumonia after cardiac surgery with sternotomy and cardiopulmonary bypass (CPB) owing to better analgesia and bronchopulmonary drainage. METHODS: In this randomized, double-blind, placebo-controlled trial conducted in five academic centers, patients undergoing cardiac surgery with sternotomy and CPB were enrolled from February 2012 until November 2014, and were followed over 30 days. Patients were assigned to a 48-h infusion (10 ml h-1) of L-bupivacaine (12.5 mg h-1) or placebo (saline) via a pre-sternal multiperforated catheter. Anesthesia and analgesia protocols were standardized. The primary end point was the incidence of pneumonia during the study period, i.e., until hospital discharge or 30 days. We hypothesized a 30% reduction in the incidence of pneumonia. RESULTS: Among 1493 randomized patients, 1439 completed the trial. Pneumonia occurred in 36/746 patients (4.9%) in the L-bupivacaine group and in 42/739 patients (5.7%) in the placebo group (absolute risk difference taking into account center and baseline risk of postoperative pneumonia, - 1.3% [95% CI - 3.4; 0.8] P = 0.22). In the predefined subgroup of patients at high risk, L-bupivacaine decreased the incidence of pneumonia (absolute risk difference, - 5.6% [95% CI - 10.0; - 1.1], P = 0.01). CONCLUSIONS: After cardiac surgery with sternotomy, continuous wound infusion of L-bupivacaine failed to decrease the incidence of pneumonia. These findings do not support the use of local anesthetic continuous wound infusion in this indication. Further study should investigate its effect in high-risk patients. TRIAL REGISTRATION: EudraCT Number: 2011-003292-10; Clinicaltrials.gov Identifier: NCT01648777.

Hypoprothrombinemia and severe perioperative haemorrhagic complications in cardiac surgery patients treated with high-dose cefazolin for infective endocarditis.

Endocarditis is a serious and common disease that requires prolonged antimicrobial therapy. The recent shortage of oxacillin has led to the use of other antimicrobial agents such as cefazolin to treat endocarditis due to methicillin-sensitive Staphylococcus aureus. We describe four cases of life-threatening haemorrhagic complications (fatal in two cases) in patients treated with high-dose cefazolin. All of these patients with major bleeding presented with hypoprothrombinemia secondary to hypovitaminosis K. This adverse event may be due to inhibition of vitamin K epoxide reductase and/or gamma-glutamyl-carboxylase by the 2-methyl-1,2,3-thiadiazol-5-thiol group of cefazolin. This inhibition may result in hypoprothrombinemia by altering the synthesis of vitamin K-dependent coagulation factors. The increasing use of cefazolin, especially at a high dose and for a prolonged period of time, should be accompanied by regular monitoring of coagulation, including prothrombin index, and vitamin K supplementation.

A combined approach for the early recognition of acute kidney injury after adult cardiac surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a frequent complication. The current criteria to detect CSA-AKI rise only when organic dysfunction has occurred. The Doppler Renal Resistive Index (RRI) and the urinary G1 cell cycle arrest proteins (TIMP-2 and IGFBP7) have been advocated to predict CSA-AKI at an early stage after cardiac surgery. The primary objective was to determine the predictive value of these new markers to detect CSA-AKI after elective heart surgery in patients at risk to develop AKI. METHODS: In a prospective observational trial, we studied 50 patients scheduled for elective on-pump heart surgery at high risk for CSA-AKI. The primary outcome was the incidence of AKI according to the KDIGO criteria recording the urine output every hour until ICU discharge and measuring the serum creatinine levels on each postoperative day until the post-procedure peak values were reached or until the 7th postoperative day. The RRI and the urinary proteins [TIMP-2]*[IGFBP7] were measured concomitantly: before surgery, 1hour (H1), 4-hour (H4), 12-hour (H12), and 24-hour (H24) after surgery. RESULTS: Thirty-seven patients (74%) developed CSA-AKI. Urinary [TIMP-2]*[IGFBP7] at H12 were significantly higher in patients that developed AKI (0.62, [interquartile] [0.20-1.18] vs. 0.30 [0.07-0.47] P=0.044) with an area under the receiver-operating characteristic curve of 0.69 [0.53-0.84]. The best sensitivity (65%) and specificity (62%) was achieved for a cutoff value of 0.3 (ng.mL-1)2.1000-1. The H12 time-point was the only in which the RRI values measured showed a trend toward statistical significance in patients that developed AKI (0.72 (Standard deviation)±(0.06) vs. 0.68±(0.07) P=0.065). The combination of the two markers ([TIMP-2]*[IGFBP7]+RRI) at H12 showed an increased performance of the accuracy with an area under the receiver-operating characteristic curve of 0.78 [0.62-0.93]. CONCLUSIONS: In a population at risk of developing CSA-AKI, neither the RRI nor urinary [TIMP-2]*[IGFBP7] detect CSA-AKI occurring in the first post-operative week within the first 24 postoperative hours.

New markers for early detection of acute kidney injury after transcatheter aortic valve implantation.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication after a transcatheter aortic valve implantation (TAVI). Biomarkers such as urinary G1 cell cycle arrest proteins (TIMP-2 and IGFBP7) and sonographic evaluation (Doppler Renal Resistive Index [RRI]) have been advocated to predict AKI at an early stage after a TAVI-procedure. The primary aim was to determine the predictive value of these markers to detect AKI after a TAVI-procedure at an early phase. PATIENTS AND METHODS: In a prospective observational study, 62 consecutive patients were scheduled for a TAVI. AKI was assessed based on the KDIGO criteria. Biomarkers and RRI were measured concomitantly before TAVI, at the first micturition post-implantation and the first micturition on the morning after the procedure. RESULTS: Twenty-two patients (35%) developed AKI. On the first day after the TAVI-procedure, urinary TIMP-2 and IGFBP7 concentrations increased significantly in patients who developed AKI (0.1, [interquartile] [0.1-0.35] to 0.40 [0.10-1.00] vs. 0.2 [0.1-0.5] to 0.10 [0.10-0.20], P=0.012) with an area under the receiver-operating characteristic curve of 0.71 [0.55-0.83]. Sensitivity was 0.57 and specificity was 0.83 for a cut-off value of 0.35. No significant increases in RRI were found in patients who developed AKI. CONCLUSIONS: Based on the current guidelines for the diagnosis of AKI, the urinary proteins TIMP-2 and IGFBP7 do not detect AKI at an early stage accurately in patients undergoing a TAVI-procedure.