Post Cardiac Arrest Care in the Cardiac Intensive Care Unit.

PURPOSE OF REVIEW: Cardiac arrests constitute a leading cause of mortality in the adult population and cardiologists are often tasked with the management of patients following cardiac arrest either as a consultant or primary provider in the cardiac intensive care unit. Familiarity with evidence-based practice for post-cardiac arrest care is a requisite for optimizing outcomes in this highly morbid group. This review will highlight important concepts necessary to managing these patients. RECENT FINDINGS: Emerging evidence has further elucidated optimal care of post-arrest patients including timing for routine coronary angiography, utility of therapeutic hypothermia, permissive hypercapnia, and empiric aspiration pneumonia treatment. The complicated state of multi-organ failure following cardiac arrest needs to be carefully optimized by the clinician to prevent further neurologic injury and promote systemic recovery. Future studies should be aimed at understanding if these findings extend to specific patient populations, especially those at the highest risk for poor outcomes.

Reduced Intracerebral Hemorrhage and Perihematomal Edema Volumes in Diabetics on Sulfonylureas.

Background and Purpose- Sulfonylurea medications have been linked to reduced brain edema and improved outcome following ischemic stroke, but their effects on primary intracerebral hemorrhage (pICH) have not been thoroughly explored. Increasing ICH volume and perihematomal edema (PHE) volume are predictors of poor outcome in pICH. We investigated whether preexisting sulfonylurea use influenced ICH volume, PHE volume, and discharge disposition in patients with type 2 diabetes mellitus presenting with pICH. Methods- We performed a retrospective chart review of all diabetic patients presenting with pICH to 2 tertiary academic centers from 2006 to 2016. All patients with diabetes mellitus, pICH, admission computed tomography scan, and sulfonylurea use on admission were included in our study. For each case, 2-matched controls (admission date, age, hematoma location [deep versus lobar], use of antiplatelet, or anticoagulant) with diabetes mellitus and pICH were consecutively selected. ICH and PHE volumes were measured via region of interest analysis on admission computed tomography. To mitigate the influence of ICH volume on PHE, the PHE/ICH surface area ratio was calculated. Hospital discharge disposition was determined via chart abstraction. We used the Wilcoxon rank-sum test and Fisher exact test to compare cases and controls. Results- Of 317 patients screened, 21 sulfonylurea cases and 42-matched controls met criteria for study inclusion. Sulfonylurea cases had significantly lower admission ICH volumes (median, 4 mL; interquartile range [IQR], 2-30 versus median, 25 mL; IQR, 6-60; P=0.011), PHE volumes (median, 4 mL; IQR, 0.9-24 versus median, 17; IQR, 6-37; P=0.0095), and PHE/ICH surface area ratios (median, 0.28; IQR, 0.1-0.4 versus median, 0.43; IQR, 0.3-0.6; P=0.013) as compared with controls. Sulfonylureas were associated with improved discharge disposition ( P=0.0062). Conclusions- In patients with diabetes mellitus and pICH, sulfonylurea use predicted lower ICH and PHE volumes, lower relative PHE, and improved discharge disposition. Given the paucity of treatment options for pICH, further study of sulfonylureas is warranted.

Neuroscience step-down unit admission criteria for patients with intracerebral hemorrhage.

OBJECTIVES: The goal of our study is to determine optimal criteria which can be used to avoid admission to neuroscience intensive care units for patients with intracerebral hemorrhage (ICH). PATIENTS AND METHODS: This is a retrospective cohort study of 431 patients with primary ICH from January 2013 to the end of December 2015 and reviewed multiple admitting characteristics. Based on these needs, we tested the following step-down unit admission criteria: Supratentorial ICH, ICH volume <20 cc, no Intraventricular hemorrhage (IVH), systolic BP <200mmHg, no respiratory failure, GCS≥12. We classified 431 patients into two groups; 1-Patients who met step-down unit admission Criteria (71 patients). 2-Patients who didn't meet the criteria (360 patients). RESULTS: In our patients, 16.5% fulfilled the criteria. Length of stay in the ICU was 1.43days in step-down unit admission criteria patients. None of the patients who fulfilled the criteria were readmitted to the ICU, compared to 3 readmissions among the group of patients who did not fulfill the criteria (P=0.82). None of these patients required a neurosurgical procedure vs 47 patients (10.9%) in the other group (P=0.04). Among patients who met the criteria, 83.1% were discharged home or rehab RR 0.33 CI (0.19-0.55), (P<0.0001). CONCLUSION: We propose that patients who fulfill step-down unit admission criteria can be safely monitored in stroke unit and they have no need for ICU admission. Further studies are needed to validate these criteria in a prospective manner.

Low-frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes.

Power spectral analysis of heart rate variability has often been used to assess cardiac autonomic function; however, the relationship of low-frequency (LF) power of heart rate variability to cardiac sympathetic tone has been unclear. With or without adjustment for high-frequency (HF) power, total power or respiration, LF power seems to provide an index not of cardiac sympathetic tone but of baroreflex function. Manipulations and drugs that change LF power or LF:HF may do so not by affecting cardiac autonomic outflows directly but by affecting modulation of those outflows by baroreflexes.

Cardiac sympathetic denervation preceding motor signs in Parkinson disease.

There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[(18)F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD.

Functional effects of cardiac sympathetic denervation in neurogenic orthostatic hypotension.

BACKGROUND: Diseases characterized by neurogenic orthostatic hypotension (NOH), such as Parkinson disease (PD) and pure autonomic failure (PAF), are associated with cardiac sympathetic denervation, as reflected by low myocardial concentrations of 6-[(18)F]fluorodopamine-derived radioactivity. We studied the impact of such denervation on cardiac chronotropic and inotropic function. METHODS: Cardiac inotropic function was assessed by the pre-ejection period index and the systolic time ratio index in response to the directly acting beta-adrenoceptor agonist, isoproterenol, and to the indirectly acting sympathomimetic amine, tyramine, in patients with PD+NOH or PAF (PD+NOH/PAF group, N=13). We compared the results to those in patients with multiple system atrophy, which usually entails NOH with normal cardiac sympathetic innervation (MSA, N=15), and in normal control subjects (N=5). RESULTS: The innervated and denervated groups did not differ in baseline mean pre-ejection period index or systolic time ratio index. Tyramine increased cardiac contractility in the MSA patients and controls but not in the PD+NOH/PAF group. For similar heart rate responses, the PD+NOH/PAF group required less isoproterenol (p<0.01) and had lower plasma isoproterenol levels (p<0.01) than did the MSA group. CONCLUSIONS: Among patients with NOH those with cardiac sympathetic denervation have an impaired inotropic response to tyramine and exaggerated responses to isoproterenol. This pattern suggests that cardiac denervation is associated with decreased ability to release endogenous norepinephrine from sympathetic nerves and with supersensitivity of cardiac beta-adrenoreceptors.

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy.

OBJECTIVE: Biomarkers are increasingly important to diagnose and test treatments of neurodegenerative diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical, and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA). METHODS: In 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra (SN) were measured 2h after 6-[18F]fluorodopa injection, septal myocardial radioactivity measured 8min after 6-[18F]fluorodopamine injection, CSF and plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification Test (UPSIT)). Receiver operating characteristic curves were constructed, showing test sensitivities at given specificities. RESULTS: PUT:OCC, CAU:OCC, and SN:OCC ratios of 6-[18F]fluorodopa-derived radioactivity were similarly low in PD and MSA (p<0.0001, p<0.0001, p=0.003 compared to controls), as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA concentrations (p<0.0001, each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA (p=0.004; p=0.005). CSF DOPAC correlated positively with PUT:OCC ratios (r=0.61, p<0.0001). Myocardial 6-[18F]fluorodopamine-derived radioactivity distinguished PD from MSA (83% sensitivity at 80% specificity, 100% sensitivity among patients with neurogenic orthostatic hypotension). Only PD patients were anosmic; only MSA patients had normal olfaction (61% sensitivity at 80% specificity). CONCLUSIONS: PD and MSA feature low PUT:OCC ratios of 6-[18F]fluorodopa-derived radioactivity and low CSF DOPAC and DOPA concentrations, cross-validating the neuroimaging and neurochemical approaches but not distinguishing the diseases. PUT:SN and PUT:CAU ratios of 6-[18F]fluorodopa-derived radioactivity, cardiac 6-[18F]fluorodopamine-derived radioactivity, and olfactory testing separate PD from MSA.

Attenuated pre-ejection period response to tyramine in patients with cardiac sympathetic denervation.

Stress is a well-known factor affecting cardiac contractility through the cardiac sympathetic nerves. A positive inotropic effect of the cardiac sympathetic nerves on the myocardium is reflected by pre-ejection period (PEP) shortening. Patients with Parkinson disease (PD) and neurogenic orthostatic hypotension (NOH) (PD + NOH) or with pure autonomic failure (PAF) have markedly decreased myocardial 6-[(18)F]Fluorodopamine-derived radioactivity, reflecting cardiac sympathetic denervation. The functional effects of the cardiac sympathetic denervation have been unknown. We measured PEP and heart rate-corrected PEP (PEPI) responses to i.v. tyramine (1 mg/min) in 13 patients (9 PD + NOH and 4 PAF) with low 6-[(18)F]Fluorodopamine-derived radioactivity and in subjects with normal radioactivity (15 multiple system atrophy with NOS patients (MSA + NOS). Baseline PEP and PEPI did not differ between the groups. By 10 min after initiation of tyramine infusion, PEP and PEPI were significantly lower (P < 0.01) in MSA + NOS, compared to base line, whereas PEP and PEPI remained unchanged in the PD + NOH/PAF group. The PEP and PEPI decrease was larger in the MSA + NOS group than in the PD + NOH/PAF group (P < 0.05). One of the functional consequences of cardiac sympathetic denervation is failure to increase contractility in response to stimuli that depend on endogenous norepinephrine release.

Sympathoadrenal function in patients with paroxysmal hypertension: pseudopheochromocytoma.

OBJECTIVES: The causes of paroxysmal hypertension in patients in whom pheochromocytoma has been excluded ('pseudopheochromocytoma') usually remain unclear. Blood pressure disturbances and symptoms of catecholamine excess in these patients may reflect activation of the sympathetic nervous and adrenal medullary systems. We therefore examined sympathoadrenal function in patients with pseudopheochromocytoma compared with age-matched control subjects in whom there was no suspicion of pheochromocytoma. METHODS: Plasma catecholamines and hemodynamics were examined in response to intravenous glucagon, yohimbine, and trimethaphan in 11 patients with pseudopheochromocytoma and a comparison group of nine normotensive and five hypertensive volunteers. Adrenomedullary function was also assessed by abdominal F-fluorodopamine positron emission tomography and measurements of plasma metanephrine, the O-methylated metabolite of epinephrine. RESULTS: Compared with controls, patients with pseudopheochromocytoma had normal plasma concentrations of norepinephrine, but 120% higher (P < 0.05) baseline plasma concentrations of epinephrine, 80% higher (P < 0.01) baseline plasma concentrations of metanephrine, and sixfold larger (P < 0.05) increases in plasma epinephrine after glucagon. Adrenal 18F-fluorodopamine-derived radioactivity did not differ between groups. Compared with changes in plasma norepinephrine, falls in blood pressure after trimethaphan were 13-fold larger (P < 0.005) and increases in blood pressure after yohimbine were threefold larger (P < 0.01) in pseudopheochromocytoma patients than in controls. CONCLUSION: Patients with pseudopheochromocytoma exhibit a pattern of normal sympathetic noradrenergic outflow, adrenomedullary activation, and augmented blood pressure responses to changes in the sympathoneural release of norepinephrine.

Cardiac sympathetic denervation preceding motor signs in Parkinson disease.

There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[(18)F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD.