Benefits of ultra-fast-track anesthesia in left ventricular assist device implantation: a retrospective, propensity score matched cohort study of a four-year single center experience

A retrospective data search and analysis of prospectively collected data from all patients who underwent implantation of LVAD between March, 2010 and March, 2012 was performed. Informed consent was waived by our ethical board (Ethik-Komission RWTH) due to the retrospective nature of the analysis. The following data were collected from the electronic database: demographics, comorbidities, preoperative diagnostic results from left and right heart catheterization, echocardiographic findings, spirometry, radiographic finding, laboratory results, perioperative surgical and anesthesia protocols, hemodynamic and ventilation parameters from monitoring during the operation and in the ICU, and packed red blood cells (PRBCs) given in the operating room (OR) and during the remaining hospital stay. European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) were calculated for all patients. Ambulatory patients were routinely followed up every two months from March, 2010 until March, 2016 according to our standardized follow-up protocol for LVAD patients.

All patients underwent cardiac surgery through full median sternotomy. LVAD implantation and, if necessary, concomitant tricuspid valve repair (TVR) and/or coronary artery bypass grafting (CABG) were performed with on-pump beating heart in 38 cases. In 5 cases with concomitant aortic valve replacement (AVR), myocardial protection was ensured through antegrade crystalloid cardioplegia with mild hypothermia (32–34 °C). Prior to cardiopulmonary bypass (CPB), heparin was given to achieve an activated clotting time (ACT) of ≥ 400 s. Patients, who underwent UFTA_, were rewarmed to a minimal body temperature of >36.5 °C before weaning from CPB. At the end of surgery, all patients were transferred to the ICU.

Within the mentioned period, the patients were individually selected for the UFTA protocol at the discretion of the attending anesthetists and cardiac surgeons. The exclusion criteria for UFTA included age ≥ 70 years, INTERMACS levels 1 and 2, chronic obstructive pulmonary disease (COPD) > grade II, body mass index ≥ 30 kg/m² (BMI), impaired preoperative pulmonary function with a reduced forced expiratory volume in 1 s (FEV1)/Forced vital capacity (FVC) ratio = FEV1% < 65%, cerebrovascular accident (CVA) in medical history and preoperative hemodialysis. Due to the fact that this is the first systematic approach to this new technique, we deliberately chose a pilot design: Only patients deemed suitable for this new strategy on an expert consensus between surgeon and anesthetist were recruited. This of course poses a source of bias, yet from an ethical point of view, it remains the only plausible strategy to determine non-inferiority before entering a randomized controlled trial design.

To avoid inappropriate comparison, patients classified as INTERMACS Level 1 or 2, were excluded, due to the fact that patients with INTERMACS level 1 and 2 are high risk patients, hemodynamically unstable, some of them already are intubated and on positive inotropic support preoperatively, all other LVAD patients who were extubated according to our regular institutional protocol during the first 12 h. postoperatively or later in the ICU formed our historical control group (LVAD _conv ). Patients, who had successful UFTA, formed (LVAD _ultra ) group and were retrospectively compared to matched patients from the LVADconv group (LVAD _match ) (Fig. 1), for detailed information of patient's data please refer to the Additional file 1. This excludes the two patients who failed UFTA despite an intention to treat. Those cases are further described in the following paragraph UFTA failure.

All patients scheduled for LVAD implantation received no premedication prior to surgery. Cardiac medication was continued until the morning of surgery. In both groups, anesthesia was induced with sufentanil 0.25–0.5 μg/kg, propofol 1 to 1.5 mg/kg and rocuronium 1 mg/kg. Muscle relaxants were not repeated during the operation. Anesthesia was maintained with propofol 2–4 mg/kg/h and sufentanil 0.5–2.0 μg/kg/h. When the surgeon started the actual LVAD implantation procedure, sufentanil was stopped, and remifentanyl (continuous infusion 0.2 μg/kg/min) was used for analgesia in the LVAD _ultra group. At the end of surgery, before skin closure, remifentanyl application was stopped, and the patients received piritramid 0.1 mg/kg. Propofol was discontinued, and patients were put in a beach-chair position. A remaining neuromuscular block was excluded. On arousal, the patients were asked to obey simple commands and tasks, e.g., move arms and legs, swallow and lift head. Finally, after negotiation of pain, the patient’s trachea was extubated. Oxygen was given via a facemask (target SpO₂ 94–100%), and carbon dioxide retention was excluded.

In the conventional group, both sufentanil and propofol were continued in the ICU. These patients were ventilated and weaned from ventilation according to clinical standards, including lung protective ventilation. Extubation criteria included: 1. Normothermia and normovolemia; 2. Absence of surgical bleeding with adequate hemostasis with normal activated coagulation time; 3. Complete reversal of the neuromuscular blockade assessed by limb movements and spontaneous ventilation sufficient to maintain arterial oxygen saturation over 95% with 40% FiO₂ and end-tidal carbon dioxide under 50 mmHg; 4. Hemodynamic stability without significant inotropic support; and 5. A conscious patient obeying simple verbal commands.

In addition to basic monitoring (ECG, pulse oximetry, invasive blood pressure measurements, temperature measurements and arterial and central venous blood gas analysis with a sampling frequency of 30 min or as determined by clinical protocol), all patients received an additional pulmonary artery catheter (PAC) to control cardiac index (CI) and central venous oxygen saturation (ScvO₂). Transesophageal echocardiography (TEE) was routinely used in all procedures.

With no universally accepted definition of RVF after LVAD placement, we used the following definition: 1. ≥ 48 h. nitric oxide (NO) (or other pulmonary vasodilator, such as iloprost); 2. Multi-organ failure from persistent hypotension without evidence of sepsis; 3. Positive inotropic agents for ≥14 days post-LVAD or late re-institution of inotropes (>14 days post-LVAD); or 4. Needing right ventricular assist device. This model was used by Kalogeropoulos et al. [19] and is consistent with the Kormos et al. model [14].

The definition of delirium is based on the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) from the American Psychiatric Association [20]. We use the Confusion Assessment Method (CAM) for the ICU (CAM-ICU) [21, 22]. The CAM-ICU was estimated for each patient in the ICU at least twice a day during both day and night shift rounds.

Continuous variables are expressed as the means ± standard deviation (SD) and categorical variables as absolute numbers and percentages. Due to non-normally distributed data the comparisons between groups before matching were performed with the Mann-Whitney-U-test for continuous variables and Fisher’s exact test or χ2 test, where appropriate, for categorical variables. Due to the small group of patients who had successful UFTA (LVAD _ultra ) and to reduce selection bias, we performed propensity score matching to match all 13 patients in the LVAD _ultra group with the appropriate patients in the LVAD _conv group after excluding patients classified as INTERMACS level 1–2 from LVAD _conv group. Propensity scores were calculated for each patient using multivariate logistic regression based on the following preoperative covariates: Age, BMI, COPD ≤ grade II, FEV1%, peripheral arterial disease (PAD), preoperative creatinine, Re-do procedures, European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), left ventricular ejection fraction (EF), pulmonary artery mean pressure (PAMP), pulmonary capillary wedge pressure (PCWP), CI, and right ventricular end-diastolic basal-diameter from a four chamber view (RVEDD1), measured according to the American Society of Echocardiography guidelines [23]. Variables were chosen for the propensity matching according to known preoperative risk-factors, which promote prolonged mechanical ventilation, prolonged ICU stay after open heart cardiac surgery [10, 24] and right heart failure after LVAD implantation [14, 18, 19]. LVAD _ultra patients were matched to LVAD _conv patients with the closest propensity score with the nearest-neighbor algorithm without replacement and with a 0.2 matching tolerance. The LVAD _conv patients who could be matched formed the matched group LVAD _match . Figure 1 describes the design of the study and the patient groups. Kaplan–Meier analyses were used to estimate the survival functions for patients in both groups. Differences in survival were evaluated using the log-rank test. Patients were censored for transplantation. After matching, categorical outcomes were compared with the McNemar’s test, and continuous outcomes were compared with Wilcoxon signed-rank test. For the comparisons of continuous variables with repeated measurements (CI, ScvO₂, CVP, MPAP) a One-Way ANOVA test with Sidak’s correction were performed. All statistical analyses were performed using SPSS software, version 23.0 (Chicago, IL, USA). Propensity matching was performed with the extension package of the statistical program R version 3.1. A two-tailed p-value of < 0.05 was considered significant. All p-values were reported as three digit numbers.