Performing central venous catheters in neonates and small infants undergoing cardiac surgery using a wireless transducer for ultrasound guidance: a prospective, observational pilot study.

BACKGROUND: Neonates and small infants with congenital cardiac disease undergoing cardiac surgery represent major challenges facing paediatric anaesthesia and perioperative medicine. AIMS: We here aimed to investigate the success rates in performing ultrasound (US) guided central venous catheter insertion (CVC) in neonates and small infants undergoing cardiac surgery, and to evaluate the practicability and feasibility of thereby using a novel wireless US transducer (WUST). METHODS: Thirty neonates and small infants with a maximum body weight of 10 kg and need for CVC before cardiac surgery were included in this observational trial and were subdivided into two groups according to their weight: < 5 kg and ≥ 5 kg. Cannulation success, failure rate, essential procedure related time periods, and complications were recorded and the clinical utility of the WUST was assessed by a 5-point Likert scale. RESULTS: In total, CVC-insertion was successful in 27 (90%) of the patients and the first attempt was successful in 24 (78%) of patients. Success rates of CVC were 80% < 5 kg and 100% ≥5 kg. Comparing the two groups we found a clear trend towards longer needle insertion time in patients weighing < 5 kg (33 [28-69] vs. 24 [15-37]s, P = .07), whereas, the total time for catheter insertion and the duration of the whole procedure were similar in both groups (199 [167-228] vs. 178 [138-234] and 720[538-818] vs. 660 [562-833]s. In total, we report 3 (10%) cases of local hematoma as procedure-related complications. Assessments of the WUST revealed very good survey results for all parameters of practicability and handling (all ratings between 4.5 and 5.0). CONCLUSION: Although difficulties in CVC-placement seem to relate to vessel size and patient's weight, US guided CVC-insertion represents a valuable, fast, and safe intervention in neonates and small children undergoing cardiac surgery. Using the WUST is feasible for this clinical application and may aid in efforts aiming to optimize perioperative care. TRIAL REGISTRATION: Wireless US-guided CVC placement in infants; Clinicaltrials.gov: NCT04597021 ; Date of Registration: 21October, 2020; retrospectively registered.

Non-pulsatile blood flow is associated with enhanced cerebrovascular carbon dioxide reactivity and an attenuated relationship between cerebral blood flow and regional brain oxygenation.

BACKGROUND: Systemic blood flow in patients on extracorporeal assist devices is frequently not or only minimally pulsatile. Loss of pulsatile brain perfusion, however, has been implicated in neurological complications. Furthermore, the adverse effects of absent pulsatility on the cerebral microcirculation are modulated similarly as CO2 vasoreactivity in resistance vessels. During support with an extracorporeal assist device swings in arterial carbon dioxide partial pressures (PaCO2) that determine cerebral oxygen delivery are not uncommon-especially when CO2 is eliminated by the respirator as well as via the gas exchanger of an extracorporeal membrane oxygenation machine. We, therefore, investigated whether non-pulsatile flow affects cerebrovascular CO2 reactivity (CVR) and regional brain oxygenation (rSO2). METHODS: In this prospective, single-centre case-control trial, we studied 32 patients undergoing elective cardiac surgery. Blood flow velocity in the middle cerebral artery (MCAv) as well as rSO2 was determined during step changes of PaCO2 between 30, 40, and 50 mmHg. Measurements were conducted on cardiopulmonary bypass during non-pulsatile and postoperatively under pulsatile blood flow at comparable test conditions. Corresponding changes of CVR and concomitant rSO2 alterations were determined for each flow mode. Each patient served as her own control. RESULTS: MCAv was generally lower during hypocapnia than during normocapnia and hypercapnia (p < 0.0001). However, the MCAv/PaCO2 slope during non-pulsatile flow was 14.4 cm/s/mmHg [CI 11.8-16.9] and 10.4 cm/s/mmHg [CI 7.9-13.0] after return of pulsatility (p = 0.03). During hypocapnia, non-pulsatile CVR (4.3 ± 1.7%/mmHg) was higher than pulsatile CVR (3.1 ± 1.3%/mmHg, p = 0.01). Independent of the flow mode, we observed a decline in rSO2 during hypocapnia and a corresponding rise during hypercapnia (p < 0.0001). However, the relationship between ΔrSO2 and ΔMCAv was less pronounced during non-pulsatile flow. CONCLUSIONS: Non-pulsatile perfusion is associated with enhanced cerebrovascular CVR resulting in greater relative decreases of cerebral blood flow during hypocapnia. Heterogenic microvascular perfusion may account for the attenuated ΔrSO2/ΔMCAv slope. Potential hazards related to this altered regulation of cerebral perfusion still need to be assessed. TRIAL REGISTRATION: The study was retrospectively registered on October 30, 2018, with Clinical Trial.gov (NCT03732651).

Prognostic Impact of Persistent Thrombocytopenia During Extracorporeal Membrane Oxygenation: A Retrospective Analysis of Prospectively Collected Data From a Cohort of Patients With Left Ventricular Dysfunction After Cardiac Surgery.

OBJECTIVE: The prognostic impact of thrombocytopenia in patients supported by extracorporeal membrane oxygenation after cardiac surgery is uncertain. We investigated whether thrombocytopenia is independently predictive of poor outcome and describe the incidence and time course of thrombocytopenia in extracorporeal membrane oxygenation patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Cardiosurgical ICU at a tertiary referral center. PATIENTS: Three hundred adult patients supported with venoarterial extracorporeal membrane oxygenation for more than 24 hours because of refractory cardiogenic shock after heart surgery between January 2001 and December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-way analysis of variance was used to compare the time course of platelet count changes between survivors and nonsurvivors. Using multiple Cox regression with time-dependent covariates, we investigated the impact of platelet count on 90-day mortality. In nonsurvivors, the daily incidence of moderate (< 100 - 50 × 10/L), severe (49 - 20 × 10/L), and very severe (< 20 × 10/L) thrombocytopenia was 50%, 54%, and 7%, respectively. Platelet count had a biphasic temporal pattern with an initial decrease until day 4-5 after the initiation of extracorporeal membrane oxygenation. Although a significant recovery of the platelet count was observed in survivors, a recovery did not occur in nonsurvivors (p = 0.0001). After adjusting for suspected confounders, moderate, severe, and very severe thrombocytopenia were independently associated with 90-day mortality. The highest risk was associated with severe (hazard ratio, 5.9 [2.7-12.6]; p < 0.0001) and very severe thrombocytopenia (hazard ratio, 25.9 [10.7-62.9], p < 0.0001). CONCLUSION: Thrombocytopenia is an independent risk factor for poor outcome in extracorporeal membrane oxygenation patients after cardiac surgery, with persistent severe thrombocytopenia likely reflecting a high degree of physiologic imbalance.

Different Heparin Contents in Prothrombin Complex Concentrates May Impair Blood Clotting in Outpatients With Ventricular Assist Devices Receiving Phenprocoumon.

OBJECTIVES: Prothrombin complex concentrates (PCCs) are used to rapidly reverse anticoagulation by oral vitamin K antagonists. They differ in the content of clotting factors, endogenous anticoagulants, and heparin. The authors hypothesized that PCCs' specific heparin content may compromise the hemostatic effect. DESIGN: Prospective ex-vivo investigation. SETTING: University hospital. PARTICIPANTS: Venous blood samples were obtained from 8 patients with implanted ventricular assist devices who also were receiving phenprocoumon. INTERVENTIONS: Four different 4-factor PCCs were added to patient blood to attain a calculated increase in prothrombin time by 20%, 40%, and 60% greater than baseline in paired experiments. MEASUREMENTS AND MAIN RESULTS: Clotting was measured using thromboelastometry and endogenous thrombin potential. Two heparin-containing PCCs prolonged the clotting times in a concentration-dependent manner compared with baseline (p<0.01) and compared with PCCs containing significantly less or no heparin (p<0.01). The PCCs containing low or no heparin enhanced the area under the curve of thrombin generation and peak thrombin several fold relative to the heparin-containing PCCs (p<0.01). One of the PCCs containing heparin even decreased peak thrombin generation by ~90% compared with baseline (p<0.01). PCC with low or no heparin shortened the lag phase (p<0.01), whereas 1 heparin containing PCC prolonged the lag phase by 66% (p<0.01). CONCLUSIONS: Physicians should be aware of the differences in heparin contents. Extrapolation of results from one agent to other PCC preparations may be difficult. Patients with an implanted left ventricular assist device and anticoagulated with vitamin-K antagonists could benefit from the use of PCC with low heparin content when surgery or bleeding requires emergency reversal. Further clinical studies are warranted.

A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD).

Background: Heart failure patients are frequently on coagulation-active medications before LVAD implantation and perioperative bleeding is a frequent complication after left ventricular assist device (LVAD) implantation. The role of point-of-care coagulation tests in assessing bleeding risk for LVAD implantation and the early postoperative time course of these tests is not well established. Methods: We prospectively enrolled 25 patients with terminal heart failure undergoing LVAD implantation. Study related TRAP-, ASPI- and ADP- tests of Multiplate® platelet aggregometry, ROTEM® rotational thromboelastometry (INTEM, EXTEM, FIBTEM), thrombin generation assay and conventional laboratory studies were measured at 11 predefined time-points during the first 21 postoperative days. We examined if preoperative TRAP-, ASPI-, ADP- and ROTEM values are correlated with estimated total blood loss (primary outcome parameter) during the first 21 days after LVAD implantation and compared the baseline values of these measurements between patients with a bleeding event to those without. We performed Spearman's correlation and non-parametric tests for paired and non-paired comparisons. Results: 7 out of 25 (28%) patients experienced a bleeding event of which 4 required surgical revision. Of the preoperatively performed measurements the TRAP test [Spearman's Rho (ρ) = -0.5, p = 0.01], INTEM CFT (ρ = 0.72, p < 0.001), INTEM alpha (-0.7, p < 0.001), EXTEM MCF (ρ = -0.63; p < 0.001), EXTEM alpha (ρ = -0.67; p < 0.001), FIBTEM MCF (ρ = -0.41; p = 0.042), Fibrinogen (Clauss) (ρ = -0.5; p = 0.011), Anti-thrombin activity (ρ = -0.49; p = 0.013) and platelet count (ρ = -0.42; p = 0.034) were significantly correlated to total blood loss. Patients undergoing a surgical bleeding revision had significantly reduced values in TRAP-[31.5 IQR (17.25-43.5U) vs. 69 IQR (52.5-87U); p = 0.004], ASPI-[16.5 IQR (5.5-35.7U) vs. 39 IQR (24.5-62.5U); p = 0.038], ADP-[30 IQR (22-69U) vs. 12.5 IQR (8.7-21.5U); p = 0.01], EXTEM MCF-[63 IQR (57.7-63.7) vs. 67 IQR (65-75.5); p = 0.019] and EXTEM alpha [74 IQR (68.75-74) vs. 79 IQR (78-80.5); p = 0.002] values before LVAD implantation. Conclusion: Multiplate® and ROTEM® measurements before LVAD implantation may identify LVAD candidates with platelet dysfunction and alterations of the primary hemostasis and could guide anesthetists and intensive care practitioners in bleeding risk stratification and in the perioperative clinical management.

The Impact of Nonconvulsive Status Epilepticus after Cardiac Surgery on Outcome.

Neurological complications after heart surgery are associated with tremendous morbidity and mortality. Nonconvulsive status epilepticus (NCSE), which can only be verified by EEG, may cause secondary brain damage. Its frequency and its impact on outcomes after cardiac surgery is still unclear. We collected the neurological files and clinical data of all our patients after heart surgery who, in the course of their ICU stay, had been seen by a neurologist who ordered an EEG. Within 18 months, 1457 patients had cardiac surgery on cardiopulmonary bypass. EEG was requested for 89 patients. Seizures were detected in 39 patients and NCSE was detected in 11 patients. Open heart surgery was performed in all 11 NSCE patients, of whom eight showed concomitant brain insults. None had a history of epilepsy. Despite the inhibition of seizure activity with antiseizure medication, clinical improvement was only noted in seven NCSE patients, three of whom were in cerebral performance category 2 and four in category 3 at hospital discharge. The four patients without neurological benefit subsequently died in the ICU. The occurrence of NCSE after open cardiac surgery is significant and frequently associated with brain injury. It seems prudent to perform EEG studies early to interrupt seizure activity and mitigate secondary cerebral injury.

Early sST2 Liberation after Implantation of a Left Ventricular Assist Device in Patients with Advanced Heart Failure.

Background: The use of left ventricular assist device (LVAD) has increased considerably over the past decade; however, there is limited literature to assist in patient selection and monitoring. The frequency of adverse events remains high. We examined the early expression of circulating soluble ST2 (sST2), a biomarker with immunosuppressive and profibrotic activity, and assessed the risk of death at 1 year in patients receiving LVAD implant. Methods: We prospectively enrolled 20 heart failure patients and measured sST2, IL-33, and IL-6 serum concentrations over three weeks after LVAD implantation. We compared the kinetics of IL-6, sST2, and IL-33 release in survivors with those of nonsurvivors using mixed model two-way analysis of variance for repeated measures. We also collected data on hemodynamic parameters (i.e., cardiac output) and frequency of infections during the hospital stay. Results: LVAD therapy led to an immediate and significant improvement of the hemodynamic parameters in 1-year survivors and nonsurvivors alike. The 1-year survival rate was 65%. IL-6 concentrations showed a significant (p = 0.03) peak at admission to the intensive care unit following LVAD implantation, whereas sST2 levels were massively increased (p < 0.0003) on day 1. While 1-year survivors had persistently lower sST2 values compared to nonsurvivors during the first 3 weeks after LVAD implantation (p = 0.012), no differences were observed in the temporal pattern of IL-6 or IL-33. The odds of detecting Candida species in the bronchoalveolar lavage fluid were 14 times higher in nonsurvivors than in survivors (OR 13.7, CI 1.4-127, p = 0.02). Conclusion: In patients implanted with LVAD, circulating sST2 levels and frequency of Candida colonisation were associated with higher mortality. Awareness of this early immune response can guide physicians in risk-benefit analysis.

Limitations of Cerebral Oximetry in a Patient With an Intracerebral Hemorrhage and Brain Edema on Extracorporeal Membrane Oxygenation: A Case Report.

Regional cerebral tissue saturation monitoring is frequently used in patients on mechanical cardiac assist devices with the intention to promptly detect critical imbalances between cerebral oxygen delivery and oxygen extraction and ultimately circumvent permanent brain injury. We report a case where an intraparenchymal bleed in the supply zone of the middle cerebral artery-followed by severe hemispherical brain edema, leading to life-threatening intracranial hypertension-escaped cerebral oximetry monitoring using near-infrared spectroscopy. Potential explanations for our observation, as well as the specific limitations of these devices, are discussed.

Discriminatory power of scoring systems for outcome prediction in patients with extracorporeal membrane oxygenation following cardiovascular surgery†.

OBJECTIVES: Although extracorporeal membrane oxygenation (ECMO) represents a rapidly evolving treatment option in patients with refractory heart or lung failure, survival remains poor and appropriate risk stratification challenging because established risk prediction models have not been validated for this specific population. METHODS: This observational single-centre registry included a total of 240 patients treated with venoarterial ECMO therapy following cardiovascular surgery and analysed the discriminatory power of the European System of Cardiac Operative Risk Evaluation (EuroSCORE) additive, the EuroSCORE II, the Sequential Organ Failure Assessment (SOFA) score, the Simplified Acute Physiology Score (SAPS) II, the SAPS III, the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage renal failure (RIFLE) classification, the survival after venoarterial ECMO (SAVE) score, the prEdictioN of Cardiogenic shock OUtcome foR AMI patients salvaGed by VA-ECMO (ENCOURAGE) score and the Society of Thoracic Surgeons (STS) risk model for outcome prediction. RESULTS: During a median follow-up time of 37 months (interquartile range 19-67), 65% of the patients died. Only the SAVE score and the SAPS II were significantly associated with the 30-day mortality rate with a hazard ratio (HR) of 1.06 [95% confidence interval (CI) 1.02-1.11; P = 0.002] for the SAVE score and an HR of 1.02 (95% CI 1.01-1.03; P = 0.004) for the SAPS II with a modest discriminatory power displayed by a C-index of 0.61 and 0.57, respectively. Seven out of 10 scoring systems revealed significant association with long-term mortality, with the SAVE score and the SAPS II remaining the strongest predictors of long-term mortality with an HR of 1.06 (95% CI 1.03-1.09; P < 0.001, C-index 0.61) for the SAVE score and an HR of 1.02 (95% CI 1.01-1.03; P < 0.001, C-index 0.58) for the SAPS II. CONCLUSIONS: Risk assessment based on established risk models in patients with ECMO remains difficult. Only the SAPS II and the SAVE score were exclusively found to be suitable for short- and long-term outcome prediction in this specific vulnerable patient population.

Duration of extracorporeal membrane oxygenation support and survival in cardiovascular surgery patients.

OBJECTIVE: The overall therapeutic goal of venoarterial extracorporeal membrane oxygenation (ECMO) in patients with postcardiotomy shock is bridging to myocardial recovery. However, in patients with irreversible myocardial damage prolonged ECMO treatment would cause a delay or even withholding of further permanent potentially life-saving therapeutic options. We therefore assessed the prognostic effect of duration of ECMO support on survival in adult patients after cardiovascular surgery. METHODS: We enrolled into our single-center registry a total of 354 patients who underwent venoarterial ECMO support after cardiovascular surgery at a university-affiliated tertiary care center. RESULTS: Through a median follow-up period of 45 months (interquartile range, 20-81 months), 245 patients (69%) died. We observed an increase in mortality with increasing duration of ECMO support. The association between increased duration of ECMO support and mortality persisted in patients who survived ECMO support with a crude hazard ratio of 1.96 (95% confidence interval, 1.40-2.74; P < .001) for 2-year mortality compared with the third tertile and the second tertile of ECMO duration. This effect was even more pronounced after multivariate adjustment using a bootstrap-selected confounder model with an adjusted hazard ratio of 2.30 (95% confidence interval, 1.52-3.48; P < .001) for 2-year long-term mortality. CONCLUSIONS: Prolonged venoarterial ECMO support is associated with poor outcome in adult patients after cardiovascular surgery. Our data suggest reevaluation of therapeutic strategies after 7 days of ECMO support because mortality disproportionally increases afterward.

Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent.

INTRODUCTION: The high shear rates induced by left ventricular assist devices cause acquired von Willebrand disease (aVWD). We hypothesised that an ex vivo model could be established to study whether mechanical shear stress alone causes aVWD or whether this process depends also on the VWF cleavage protein ADAMTS-13 and on platelets. MATERIALS AND METHODS: Healthy volunteers and two patients with congenital ADAMTS-13 deficiency donated blood. In vitro closed extracorporeal circuits were established using medically approved left ventricular assist devices (LVAD). VWF multimers were quantified by gel electrophoresis; VWF antigen, ristocetin cofactor activity (VWF:RCo), ADAMTS-13 levels and platelet function were assessed. RESULTS: The high shear stress in the extracorporeal circulation rapidly decreased VWF:RCo and thereby the VWF:RCo/VWF:Ag ratio by 47% (p<0.01) to pathologically low values. Concomitantly, high molecular weight multimers (HMWM) decreased: up to 14-15 mers were visible on the gels at baseline, which were reduced by a maximum of 6-7 mers, corresponding to an average 68% lower densitometry signal of HMWM (p<0.001). This was accompanied by marked reduction of aggregation by various agonists (p<0.005). In contrast, the two patients with congenital thrombocytopenic purpura with virtually complete deficiency of ADAMTS-13 activity had only a minimal or no decrease in multimers (p<0.005 vs. healthy controls). Similarly, no or minimal depletion of large multimers occurred, when normal plasma circulated without platelets. CONCLUSION: An in vitro model for LVAD associated aVWD demonstrated that ADAMTS-13 and platelets contribute to the depletion of HMWM of VWF.

The neuroprotective effect of magnesium sulphate during iatrogenically-induced ventricular fibrillation.

UNLABELLED: We studied the neuroprotective effect of magnesium sulphate (MgSO4) administered before ventricular fibrillation was induced for internal cardioverter defibrillator threshold testing, and continued during reperfusion. METHODS: With the intention of increasing serum magnesium (Mg) to >1.2 mmol/L, 15 patients received 16 mmol of MgSO4, IV, followed by 5 mmol over two hours. Fifteen patients received placebo. Serum neuron-specific enolase (NSE) was assessed, as well as pre- and postoperative neurocognitive function. RESULTS: NSE increased in all patients, reaching a peak at 24 hours. The target Mg level was maintained throughout surgery in only nine of the Mg patients, and mainly in those with low lean body mass (LBM). In these patients, increased Mg levels were related to altered NSE release (P<0.05). NSE increased when serum Mg dropped to <1.2 mmol/L, finally exceeding levels of inadequately or untreated patients. Neurocognitive function after surgery was similar between groups. CONCLUSIONS: Insufficient dosing could account for our results, as NSE release could be inhibited by Mg >1.2 mmol/L. For neuroprotection, the Mg dosage should be adjusted according to LBM and infusion be extended to >2 hours.