David L. McDonagh

Cognitive Function after Major Noncardiac Surgery, Apolipoprotein E4 Genotype, and Biomarkers of Brain Injury

Background:Postoperative cognitive dysfunction (POCD) is a significant cause of morbidity after noncardiac surgery. Identified risk factors are largely limited to demographic characteristics. We hypothesized that POCD was associated with apolipoprotein E4 (APOE4) genotype and plasma biomarkers of brain injury and inflammation. Methods:Three hundred ninety-four patients older than 55 yr undergoing major elective noncardiac surgery were enrolled in this prospective observational study. Apolipoprotein E genotyping was performed at baseline. Plasma was collected at baseline and end of surgery and at 4.5, 24, and 48-h postoperatively. Six protein biomarkers were assayed (B-type natriuretic peptide, C-reactive protein, D-dimer, matrix metalloproteinase-9, neuron-specific enolase, and S-100B). Neurocognitive testing was conducted at baseline and at 6 weeks and 1 yr after surgery; scores were subjected to factor analysis. The association of APOE4 and biomarkers with POCD was tested using multivariable regression modeling. Results:Three hundred fifty patients (89%) completed 6-week neurocognitive testing. POCD occurred in 54.3% of participants at 6 weeks and 46.1% at 1 yr. There was no difference in POCD between patients with or without the APOE4 allele (56.6 vs. 52.6%; P = 0.58). The continuous cognitive change score (mean ± SD) was similar between groups (APOE4: 0.05 ± 0.27 vs. non-APOE4: 0.07 ± 0.28; P = 0.53). Two hundred ninety-one subjects (74%) completed testing at 1 yr. POCD occurred in 45.9% of APOE4 subjects versus 46.3% of non-APOE4 subjects (P = 0.95). The cognitive score was again similar (APOE4: 0.08 ± 0.27 vs. non-APOE4: 0.05 ± 0.25; P = 0.39). Biomarker levels were not associated with APOE4 genotype or cognition at 6 weeks or 1 yr. Conclusion:Cognitive decline after major noncardiac surgery is not associated with APOE4 genotype or plasma biomarker levels.

Anesthesia and Sedation Practices Among Neurointerventionalists during Acute Ischemic Stroke Endovascular Therapy

Background and Purpose: Intra-arterial reperfusion therapies are expanding frontiers in acute ischemic stroke (AIS) management but there is considerable variability in clinical practice. The use of general anesthesia (GA) is one example. We aimed to better understand sedation practices in AIS. Methods: An online survey was distributed to the 68 active members of the Society of Vascular and Interventional Neurology (SVIN). Survey development was based on discussions at the SVIN Endovascular Stroke Round Table Meeting (Chicago, IL, 2008). The final survey contained 12 questions. Questions were developed as single and multiple-item responses; with an option for a free-text response. Results: There was a 72% survey response rate (N = 49/68). Respondents were interventional neurologists in practice 1–5 years (71.4%, N = 35). The mean (±SD) AIS interventions performed per year at the respondents’ institutions was 42.5 ± 25, median 35.0 (IQR 20, 60). The most frequent anesthesia type used was GA (anesthesia team), then conscious sedation (nurse administered), monitored anesthesia care (anesthesia team), and finally local analgesia alone. There was a preference for GA because of eliminating movement (65.3% of respondents; N = 32/49), perceived procedural safety (59.2%, N = 29/49), and improved procedural efficacy (42.9%, N = 21/49). However, cited limitations to GA included risk of time delay (69.4%, N = 34), of propagating cerebral ischemia due to hypoperfusion or other complications (28.6%, N = 14), and lack of adequate anesthesia workforce (20.4%, N = 7). Conclusions: The most frequent type of anesthesia used by Neurointerventionalists for AIS interventions is GA. Prior to making GA standard of care during AIS intervention, more data are needed about effects on clinical outcomes.

Levetiracetam is Neuroprotective in Murine Models of Closed Head Injury and Subarachnoid Hemorrhage

ObjectivesProphylactic treatment with antiepileptic drugs is common practice following subarchnoid hemorrhage (SAH) and traumatic brain injury. However, commonly used antiepileptic drugs have multiple drug interactions, require frequent monitoring of serum levels, and are associated with adverse effects that may prompt discontinuation. In the current study, we test the hypothesis that levetiracetam, an anticonvulsant with favorable interaction and adverse event profiles, is neuroprotective in clinically relevant models of SAH and closed head injury (CHI).MethodsA single intravenous dose of vehicle, low-dose (18 mg/kg), or high-dose (54 mg/kg) levetiracetam was administered intravenously followed CHI. Functional assessments were performed on a daily basis, and histological assessments performed at 24 hours. In a separate series of experiments, mice were randomized to receive in travenous administration of vehicle, low-dose, or high-dose levetiracetam every 12 hours for 3 days following SAH. Functional endpoints were assessed daily, followed by measurement of MCA luminal diameter on day 3.ResultsA single dose of levetiracetam improved functional and histological outcomes after CHI. This effect appeared specific for levetiracetam and was not associated with fosphenytoin treatment. Treatment with levetiracetam also improved functional outcomes and reduced vasospasm following SAH.ConclusionLevetiracetam is neuroprotective in clinically relevant animal models of SAH and CHI. Levetiracetam may be a therapeutic alternative to phenytoin following acute brain injury in the clinical setting when seizure prophylaxis is indicated.

Efficacy, Safety, and Pharmacokinetics of Sugammadex for the Reversal of Rocuronium-induced Neuromuscular Blockade in Elderly Patients

Background:The management of elderly patients can be challenging for anesthesiologists for many reasons, including altered pharmacokinetics and dynamics. This study compared the efficacy, safety, and pharmacokinetics of sugammadex for moderate rocuronium-induced neuromuscular blockade reversal in adult (aged 18–64 yr) versus elderly adult (aged 65 yr or older) patients. Methods:This phase 3a, multicenter, parallel-group, comparative, open-label study enrolled 162 patients aged 18 yr and older, American Society of Anesthesiologists class 1–3, scheduled for surgery with general anesthesia and requiring neuromuscular blockade. After anesthesia induction, patients received rocuronium, 0.6 mg/kg, before tracheal intubation, with maintenance doses of 0.15 mg/kg as required. At the end of surgery, patients received sugammadex, 2.0 mg/kg, at reappearance of the second twitch of the train-of-four (TOF) for reversal. The primary efficacy variable was time from sugammadex administration to recovery of the TOF ratio to 0.9 or greater. Pharmacokinetics and safety were also evaluated. Results:Overall, 150 patients were treated and had at least one postbaseline efficacy assessment; 48 were aged 18–64 yr (adult), 62 were aged 65–74 yr (elderly), and 40 were aged 75 yr or older (old-elderly). The geometric mean time (95% confidence interval) from sugammadex administration to recovery of the TOF ratio to 0.9 increased with age, from 2.3 (2.0–2.6) min (adults) to 2.9 (2.7–3.2) min (elderly/old-elderly groups combined). Recovery of the TOF ratio to 0.9 was estimated to be 0.7 min faster in adults compared with patients aged 65 yr or older (P = 0.022). Sugammadex was well tolerated by all patients. Conclusion:Sugammadex facilitates rapid reversal from moderate rocuronium-induced neuromuscular blockade in adults of all ages.

Measures of Executive Function and Depression Identify Patients at Risk for Postoperative Delirium

Background:Postoperative delirium is associated with increased morbidity and mortality. Preexisting cognitive impairment and depression have been frequently cited as important risk factors for this complication. This prospective cohort study was designed to determine whether individuals who perform poorly on preoperative cognitive tests and/or exhibited depressive symptoms would be at high risk for the development of postoperative delirium. Methods:One hundred nondemented patients, aged 50 yr and older, scheduled to undergo major, elective noncardiac surgery completed a preoperative test battery that included measures of global cognition, executive function, and symptoms of depression. Known preoperative risk factors for delirium were collected and examined with the results of the preoperative test battery to determine the independent predictors of delirium. Results:The overall incidence of delirium was 16% and was associated with increased hospital duration of stay (P < 0.05) and an increased incidence of postoperative complications (P < 0.01). Delirious subjects did not differ from their nondelirious cohorts with regard to their preoperative global cognitive function, preexisting medical comorbidities, age, anesthetic management, or history of alcohol use. Preoperative executive scores (P < 0.001) and depression (P < 0.001), as measured by the Trail Making B test and Geriatric Depression Scale–Short Form, respectively, were found to be independent predictors of postoperative delirium. Conclusions:Low preoperative executive scores and depressive symptoms independently predict postoperative delirium in older individuals. A rapid, simple test combination including tests of executive function and depression could improve physicians’ ability to recognize patients who might benefit from a perioperative intervention strategy to prevent postoperative delirium.

Anesthesia for endovascular treatment of acute ischemic stroke

The initial treatment of patients with acute ischemic stroke (AIS) focuses on rapid recanalization, which often includes the use of endovascular therapies. Endovascular treatment depends upon micronavigation of catheters and devices into the cerebral vasculature, which is easier and safer with a motionless patient. Unfortunately, many stroke patients are unable to communicate and sufficiently cooperate with the procedure. Thus, general anesthesia (GA) with endotracheal intubation provides an attractive means of keeping the patient comfortable and motionless during a procedure that could otherwise be lengthy and uncomfortable. However, several recent retrospective studies have shown an association between GA and poorer outcomes in comparison with conscious sedation for endovascular treatment of AIS, though prospective studies are lacking. The underlying reasons why GA might produce a worse outcome are unknown but may include hemodynamic instability and hypotension, delays in treatment, prolonged intubation with or without neuromuscular blockade, or even neurotoxicity of the anesthetic agent itself. Currently, the choice between GA and conscious sedation should be tailored to the individual patient, on the basis of neurologic deficits, airway and hemodynamic status, and treatment plan. The use of institutional treatment protocols may best support efficient and effective care for AIS patients undergoing endovascular therapy. Important components of such protocols would include parameters to choose anesthetic modality, timeliness of induction, blood pressure goals, minimization of neuromuscular blockade, and planned extubation at the end of the procedure.

Adenosine-induced transient asystole for intracranial aneurysm surgery: a retrospective review.

Brief Summary We describe the use of adenosine-induced cardiac arrest to facilitate intracranial aneurysm clip ligation. Background Cerebral aneurysms are highly variable which may result in difficult surgical exposure for clip ligation in select cases. Secure clip placement is often not feasible without temporarily decompressing the aneurysm. This can be accomplished with temporary clip ligation of proximal vessels, or with deep hypothermic circulatory arrest on cardiopulmonary bypass, although these methods have their own inherent risks. Here we describe an alternate method of decompressing the aneurysm via adenosine-induced transient asystole. Methods We examined the records of 27 patients who underwent craniotomy for cerebral aneurysm clipping in which adenosine was used to induce transient asystole to facilitate clip ligation. Duration of adenosine-induced bradycardia (heart rate <40) and hypotension (SBP<60) recorded on the electronic anesthesia record and outcome data including incidence of successful clipping, intraoperative and postoperative complications, and mortality were recorded. Results Satisfactory aneurysm decompression was achieved in all cases, and all aneurysms were clipped successfully. The median dose of intravenous adenosine resulting in bradycardia greater than 30 seconds was 30 mg. The median dose of adenosine resulting in hypotension greater than 30 seconds was 15 mg, and greater than 60 seconds was 30 mg. One case of prolonged hypotension after rapid redosing of adenosine required brief closed chest compressions before circulation was spontaneously restored. No other adverse events were observed. Conclusions Adenosine cardiac arrest is a relatively novel method for decompression of intracranial aneurysms to facilitate clip application. With appropriate safety precautions, it is a reasonable alternative method when temporary clipping of proximal vessels is not desirable or not possible.

Neurocognitive outcomes after cardiac surgery.

Purpose of review To summarize recent studies of neurocognitive dysfunction after cardiac surgery, as well as to outline efforts and approaches toward advancing the field. Recent findings Observational studies have improved our understanding of the incidence and the trajectory of cognitive decline after cardiac surgery; however, the magnitude of this neurocognitive change remains controversial because of the inconsistent definitions and the lack of a gold-standard diagnostic modality. Nonetheless, physicians commonly see patients with functional and cognitive impairments after cardiac surgery, which utilize healthcare resources and impact quality of life. Novel approaches have utilized advanced neuroimaging techniques as well as innovative monitoring modalities to improve the efficiency of neuroprotective strategies during cardiac surgery. Summary Adverse cognitive and neurologic outcomes following cardiac surgery range from discrete neurocognitive deficits to severe neurologic injury such as stroke and even death. The elderly are at higher risk of suffering these outcomes and the public health dimension of this problem is expected to accelerate. Future studies should combine advanced neuroimaging with genomic, transcriptional, proteomic, and metabolomic profiling to improve our understanding of the pathophysiologic mechanisms and optimize the diagnosis, prevention, and treatment of neurocognitive injury.

A pilot study evaluating presurgery neuroanatomical biomarkers for postoperative cognitive decline after total knee arthroplasty in older adults.

Background:Total knee arthroplasty improves quality of life but is associated with postoperative cognitive dysfunction in older adults. This prospective longitudinal pilot study with a parallel control group tested the hypotheses that (1) nondemented adults would exhibit primary memory and executive difficulties after total knee arthroplasty, and (2) reduced preoperative hippocampus/entorhinal volume would predict postoperative memory change, whereas preoperative leukoaraiosis and lacunae volumes would predict postoperative executive dysfunction. Methods:Surgery (n = 40) and age–education-matched controls with osteoarthritis (n = 15) completed pre- and postoperative (3 weeks, 3 months, and 1 yr) memory and cognitive testing. Hypothesized brain regions of interest were measured in patients completing preoperative magnetic resonance scans (surgery, n = 31; control, n = 12). Analyses used reliable change methods to identify the frequency of cognitive change at each time point. Results:The incidence of postoperative memory difficulties was shown with delay test indices (i.e., story memory test: 3 weeks = 17%, 3 months = 25%, 1 yr = 9%). Postoperative executive difficulty with measures of inhibitory function (i.e., Stroop Color Word: 3 weeks = 21%, 3 months = 22%, 1 yr = 9%). Hierarchical regression analysis assessing the predictive interaction of group (surgery, control) and preoperative neuroanatomical structures on decline showed that greater preoperative volumes of leukoaraiosis/lacunae were significantly contributed to postoperative executive (inhibitory) declines. Conclusions:This pilot study suggests that executive and memory declines occur in nondemented adults undergoing orthopedic surgery. Severity of preoperative cerebrovascular disease may be relevant for understanding executive decline, in particular.

Transient adenosine-induced asystole during the surgical treatment of anterior circulation cerebral aneurysms: technical note.

BACKGROUND: Transient adenosine-induced asystole is a reliable method for producing a short period of relative hypotension during surgical and endovascular procedures. Although the technique has been described in the endovascular treatment of brain arteriovenous malformations, aortic aneurysms, and posterior circulation cerebral aneurysms, little description of its use in anterior circulation aneurysms is available. OBJECTIVE: To assess the benefits of adenosine-induced transient asystole in complex anterior circulation aneurysms, to describe our experience in selected cases, and to provide the first experience of the use of adenosine in anterior circulation aneurysms. METHODS: The adenosine-induced cardiac arrest protocol allows us to titrate the duration of cardiac arrest on the basis of individual patient responses. The operative setup is the same as with all aneurysm clippings, with the addition of the placement of transcutaneous pacemakers as a precaution for prolonged bradycardia or asystole. Escalating doses of adenosine are given to determine the approximate dose that results in 30 seconds of asystole. When requested by the surgeon, the dose of adenosine is administered for definitive dissection and clipping. We present 6 cases in which this technique was used. RESULTS: The use of transient adenosine-induced asystole provided excellent circumferential visualization of the aneurysm neck and safe clip application. All patients did well neurologically and suffered no evidence of perioperative cerebral ischemia or delayed complication from the use of adenosine itself. CONCLUSION: Transient adenosine-induced asystole is a safe and effective technique in select circumstances that may aid in safe and effective aneurysm clipping. Along with the traditional techniques of brain relaxation, skull base approaches, and temporary clipping, adenosine-induced asystole facilitates circumferential visualization of the aneurysm neck and is another technique available to cerebrovascular surgeons.