Incidence Of Neurological Adverse Events Research Articles

Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study

BackgroundCerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications.MethodsThis retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models.ResultsThis study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02–2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan–Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar.ConclusionsIn this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.Graphical abstract

Patterns of neurological adverse events among a retrospective cohort of patients receiving immune checkpoint inhibitors.

Aim: Neurological adverse events (NAEs) are infrequent immune checkpoint inhibitor (ICI) outcomes poorly characterized in extant research, complicating their clinical management. Methods: This study characterized the frequency, severity, patterningand timing of NAEs using a large retrospective registry, including all patients who received at least one dose of an ICI from 2/1/2011-4/7/2022 within our health network. Results: Among 3137 patients, there were 54 NAEs (1.72% any grade; 0.8% grade 3-4). Most NAEs were peripheral (57.4%) versus central (42.6%). Melanoma and renal cell carcinoma were significantly associated with NAEs. Conclusion: The incidence of NAEs was rare though higher than many prior case estimates; the timing was consistent with other AEs. NAEs frequently occurred in tumor types known to favor brain metastases.

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry.

Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD). Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P<0.001) as well as each subtype (transient ischemic attack: 3.3% versus 1.0%, P<0.001; ischemic cerebrovascular accident: 7.7% versus 3.4%, P<0.001; hemorrhagic cerebrovascular accident: 7.2% versus 2.0%, P<0.001) than did patients receiving HM3. A propensity-matched cohort balanced for preimplant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE 82% versus 92%, P<0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio, 5.71 [CI, 3.90-8.36]). HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry.

Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD). Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P<0.001) as well as each subtype (transient ischemic attack: 3.3% versus 1.0%, P<0.001; ischemic cerebrovascular accident: 7.7% versus 3.4%, P<0.001; hemorrhagic cerebrovascular accident: 7.2% versus 2.0%, P<0.001) than did patients receiving HM3. A propensity-matched cohort balanced for preimplant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE 82% versus 92%, P<0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio, 5.71 [CI, 3.90-8.36]). HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

Volume of Disease as a Predictor for Clinical Outcomes in Patients with Melanoma Brain Metastases Treated with Stereotactic Radiosurgery and Immunotherapy

Several clinical trials of anti-PD-1 and CTLA-4 therapies have demonstrated a clinical benefit with a low incidence of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (IT) and stereotactic radiosurgery (SRS) has yielded impressive results with regards to local control and overall survival, it has also been associated with increased rates of radiation necrosis compared to historical series of SRS alone. We retrospectively reviewed patients treated with anti-PD-1, anti-CTLA-4 therapy or the combination and SRS to report on predictors of clinical outcomes. Patients were included if they had MBMs treated with SRS within one year of receiving systemic therapy with anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes such as overall survival (OS), intracranial death (ID), local control of treated lesions (LC) and symptomatic radiation necrosis (RN) were correlated with type and timing of IT with SRS, size of lesions treated, number of lesions treated, total volume of lesions and radiation dose. 29 patients with 171 MBMs were treated over 60 sessions between May 2012 and May 2018. Patients had a median of 5 lesions (range 1-23) treated over a median of 2 courses of SRS. The median volume treated was 6.5 cm3 and the median dose was 21 Gy. Patients were treated with ipilimumab (n = 13), nivolumab-ipilimumab (n = 10), pembrolizumab (n = 5) and pembrolizumab-ipilimumab (n = 1). The majority of patients received at least one fraction of SRS concurrently or within 3 months of receiving immunotherapy (n = 21). 2-year OS and LC were 54.4% and 85.5%, respectively. Overall 14% of patients developed RN; however, only 4.7% of the total number of treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >5 cm3 were found to be at increased risk of intracranial death (p = 0.05) and RN (p = 0.03). The median time to intracranial death was 29 months in patients with tumor volume >5 cm3 and not-yet reached at 60 months in those with tumor volume < 5 cm3. There was no difference in OS, LC, IC or RN with regards to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of lesions treated. In our institutional analysis of patients treated with SRS and IT for MBMs we found overall excellent rates of OS and LC, however, patients with an aggregate tumor volume > 5 cm3 were found to be at increased risk of intracranial death and symptomatic radionecrosis. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.

Severe Calcification of the Ascending Aorta Detected Incidentally in Patients Undergoing Cardiac Surgery.

Incidentally discovered severe calcified ascending aorta (CAA) is a major challenge faced by surgeons during cardiac surgery. The aim of this study was to evaluate the outcome in patients undergoing cardiac surgery in this condition with the additional replacement of the CAA. A retrospective study on a cohort of 74 patients (28.4% females; mean age: 73 ± 7 years) underwent cardiac surgery and initial replacement of an incidentally discovered CAA using moderate hypothermic circulatory arrest. A control group was matched according to age, gender, and procedure. No significant differences were noted with regard to preoperative risk factors. Due to the additional replacement of CAA, the extracorporeal circulation and cross-clamping time were significantly longer in the study group (p < 0.001). Postoperatively, no significant differences in complications were observed between the groups. There was no significant difference in regard to incidence of neurologic adverse events (5.4 vs. 2.7%; p = 0.68) or 30-day mortality (6.7 vs. 4.1%; p = 0.72). Our study showed that the initial replacement of incidental CAA in patients undergoing cardiac surgery was not associated with increased risks for neurologic adverse events and mortality.

(OA15) Clinical Outcomes of Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immunotherapy

Several clinical trials of anti-PD-1 and CTLA-4 therapies have demonstrated a clinical benefit in patients with melanoma brain metastases (MBMs) and a low incidence of neurologic adverse events. The combined effect of these immunotherapies and stereotactic radiosurgery (SRS) on toxicity and survival in patients with MBMs is not well understood. We retrospectively reviewed patients treated with anti-PD-1, anti-CTLA-4 therapy or the combination and SRS to report on these outcomes. Patients were included if they had MBMs treated with SRS within one year of receiving systemic therapy with anti-PD-1 and/or CTLA-4 therapy. The primary objective was to assess rates of radionecrosis with regards to treatment regimen and timing. Other end points analyzed were time to progression and overall survival. Twenty-six patients with 150 MBMs were treated over 58 sessions between May 2012 and July 2016. Patients had a median of 4.5 lesions (range 1-23) treated with a median of 2 courses of radiation. The mean tumor volume per treated lesion was 1.48 cm3 and the mean dose was 2100 cGy. Patients were treated with ipilimumab (n = 11), nivolumab-ipilimumab (n = 8), pembrolizumab (n = 5) and pembrolizumab-ipilimumab (n = 2). The majority of patients received SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Overall 15% of patients developed radionecrosis. The median time to development of radionecrosis was 14.4 months. Patients who received combination anti-PD-1 and ipilimumab therapy were more likely to develop radionecrosis compared to other treatment regimens (p = 0.028). Radiation necrosis events occurred more frequently when patients were treated with anti-PD-1 and ipilimumab within 3 months of SRS (p = 0.023). One patient developed radionecrosis at the surgical bed while the rest developed radionecrosis at intact metastases. There was no difference in overall survival, percent of patients alive at 12, 18 or 24 months, or time to progression (local or systemic) between treatment groups or with regards to timing of radiation and immunotherapy. In our institutional analysis of patients treated with SRS and immunotherapy for melanoma brain metastases, radionecrosis was primarily observed in patients treated with combination anti-PD-1 and ipilimumab within three months of SRS. Given the efficacy of combination anti-PD-1/CTLA-4 therapy for MBM management and observed radiation necrosis events, prospective evaluation of the role of SRS in this setting is warranted.

Safety of Pedicle Screws in Adolescent Idiopathic Scoliosis Surgery.

To review existing publications on the safety of pedicle screw insertions in adolescent idiopathic scoliosis (AIS). Despite having increased risk for neurological and visceral injuries, the use of pedicle screws have led to increased correction rates in scoliosis surgery. A review was performed on topics pertinent to pedicle screw insertion in AIS, which included pedicle morphometry in AIS, structures at risk during pedicle screw insertion, and accuracy and safety of various pedicle screw insertion techniques. The importance of computer navigation and future research regarding pedicle screw placement in AIS were also briefly reviewed. Many authors have reported abnormal pedicle anatomy in AIS. Injury to the neural structures was highest over the apical region, whereas aortic injury was the highest at T5 and T10. In the proximal thoracic spine, the esophagus could be injured even with screws as short as 25 mm. Overall pedicle perforation rates for perforations >0 and >2 mm (assessed by computed tomography) ranged from 6.4% to 65.0% and 3.7% to 29.9%, respectively. The critical pedicle perforation (>2 mm excluding lateral thoracic) and anterior perforation (>0 mm) rates was reported to range from 1.5% to 14.5% and 0.0% to 16.1%, respectively. Pedicle perforation rates were lower with the use of computer navigation. The incidence of neurological adverse events after scoliosis surgery was 0.06%–1.9%. Aortic injury has only been observed in case reports. According to the available literature, pedicle screw insertion in AIS is considered safe with low rates of clinical adverse events. Moreover, the use of navigation technology has been shown to reduce pedicle perforation rates.

Neuropathic Pain and Foot Drop Related to Nerve Injury After Short Duration Surgery and Caudal Analgesia

Caudal anesthesia is the most common type of regional anesthetic technique performed in children. The incidence of neurologic adverse events is extremely rare. A postoperative complication of a mild but permanent neurologic deficit after administration of a caudal anesthetic in a previously well 9-year-old boy who required emergency scrotal exploration for a testicular torsion is reported. The caudal injection provided good postoperative analgesia, which probably resulted in the patient remaining in the same position overnight. This may have contributed to the development of the neurologic deficit, probably owing to a compressive neuropathy. We suggest that, as anesthesiologists obtaining informed consent for anesthetic interventions, we now need to inform guardians/carers of pediatric patients who are to receive caudal analgesia of the extremely small material risk of neurologic damage after caudal anesthesia. Additionally, the anesthetic community may need to consider revising postoperative care instructions to prevent the future occurrence of this rare outcome, particularly if using additives that prolong analgesic block duration.

Repair of aortic arch and the impact of cross-clamping time, New York Heart Association stage, circulatory arrest time, and age on operative outcome

Aortic arch replacement is associated with high morbidity and mortality. We evaluated the postoperative complications and risk factors in 32 consecutive patients after aortic arch replacement. The mean age was 61+/-15 years and male to female ratio was 24/8. Diameter of ascending aorta was 6.0+/-0.8 cm and diameter of aortic arch was 5.2+/-1.2 cm. The average New York heart association (NYHA) class was 2+/-1. The 30-day mortality was 6.2% (2 of 32 patients), one patient died intraoperatively (3%); all surviving 30 patients had f/u for at least six months, a total of 3 of 32 patients had died within six months, actuarial survival was 90% at six months. The overall incidence of neurologic adverse events was 9%; however, only one patient had a cerebrovascular accident (CVA) with a focal deficit (3%). The other two patients had global neurologic dysfunction. Other significant postoperative complications included atrial fibrillation in 15 patients (46%), ventricular fibrillation requiring cardiopulmonary resuscitation (CPR) in one patient (3%), and pericardial effusion requiring pericardicentesis in eight patients (25%). The need for blood transfusion correlated with the cross-clamping length (Pearson r 0.62; 95% confidence interval (CI), 0.35-0.79; P-value 0.0001; R(2)=0.38). Cross-clamp time (139+/-58 min) did not have an impact on length of intensive care unit (ICU) stay (Pearson r -0.09; 95% CI -0.39-0.23; P=0.58; R(2)=0.008) nor did the length of circulatory arrest (95% CI -0.44-0.21, P=0.44). The length of stay in the ICU (142+/-128 h) correlated with the NYHA stage of the patient (95% CI 0.001-0.62, P=0.04). The length of stay (LOS) (12+/-6 days) correlated with age of the patients (95% CI 0.03-0.57, P=0.03). Elderly patients and patients with high NYHA class need close postoperative monitoring in the ICU. A short circulatory arrest and aortic clamp time do not extend the LOS in ICU or in the hospital.