Distinguishing in-hospital and out-of-hospital status epilepticus: clinical implications from a 10-year cohort study.

BACKGROUND AND PURPOSE: The aim was to determine differences of clinical, treatment and outcome characteristics between patients with in-hospital and out-of-hospital status epilepticus (SE). METHODS: From 2005 to 2014, clinical data were assessed in adults with SE treated in an academic medical care centre. Clinical characteristics, treatment and outcomes were compared between patients with in-hospital and out-of-hospital SE. RESULTS: Amongst 352 patients, 213 were admitted with SE and 139 developed in-hospital SE. Patients with in-hospital SE had more acute/fatal aetiologies (60% vs. 35%, P < 0.001), fewer previous seizures (33% vs. 50%, P = 0.002), a higher median Charlson Comorbidity Index (3 vs. 2, P < 0.001), longer median SE duration (1 vs. 0.5 days, P = 0.001), more refractory SE (52% vs. 39%, P = 0.022), less return to functional baseline (38% vs. 54%, P = 0.006) and increased mortality (29% vs. 19%, P = 0.001). Whilst in multivariable analyses an increasing Status Epilepticus Severity Score (STESS) was an independent predictor for death in both groups, increased Charlson Comorbidity Index and treatment refractory SE were associated with death only in patients with in-hospital SE. Continuous anaesthesia for refractory SE was associated with increased mortality only in patients with out-of-hospital SE. The area under the receiver operating curve was 0.717 for prediction of death by STESS in patients with in-hospital SE and 0.811 in patients with out-of-hospital SE. CONCLUSIONS: Patients with in-hospital SE had more fatal aetiologies and comorbidities, refractory SE, less return to functional baseline, and increased mortality compared to patients with out-of-hospital SE. Whilst the STESS was a robust predictor for death in both groups, the association between continuous anaesthesia and death was limited to out-of-hospital SE.

Early predictors of refractory status epilepticus: an international two-center study.

BACKGROUND AND PURPOSE: Status epilepticus (SE) refractory to first- and second-line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE)­an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults. METHODS: Clinical and laboratory data on consecutive intensive care unit patients with SE from two academic care centers (a derivation data set from a Swiss center and a validation data set from a US center) were assessed. Multivariable analysis was performed with the derivation set to identify RSE predictors at SE onset. Their external validity was evaluated with an independent validation set. Measures of calibration and discrimination were assessed. RESULTS: In all, 302 patients were analyzed (138 with and 164 without RSE), 171 in the derivation data set and 131 in the validation data set. Acute SE etiology, coma/stupor and serum albumin <35 g/l at SE onset were independent predictors for RSE in the derivation data set [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.01-4.07; OR 4.83, 95% CI 2.42-9.68; OR 2.45, 95% CI 1.16-5.16]. The prediction model showed good measures of calibration (Hosmer-Lemesow goodness-of-fit test P = 0.99) and discrimination (area under the receiver operating characteristic curve 0.8) on the derivation data set­results that were similar in the validation data set (Hosmer-Lemeshow P = 0.24; area under the receiver operating characteristic curve 0.73). CONCLUSIONS: This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system.

Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated delirium in septic patients.

BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100ß from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100ß from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100ß, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

Under Armour - Use of personal protective equipment for simulated CPR of COVID-19 patients: an observational study.

BACKGROUND: Personal protective equipment (PPE) protects healthcare workers and patients. Data on guideline compliance on how to dress (donning) or remove (doffing) PPE and the assistance among multiple participants (buddying) are limited. This study assesses the quality of donning, doffing, and buddying of PPE in a simulated medical emergency. METHOD: Physicians handling a simulated cardiac arrest of a COVID-19 patient. Adjacent to the victim, PPE was available. The appropriateness of PPE choice was assessed by using video recordings, with each individual participant being analyzed from the beginning of the simulation scenario from two perspectives regarding the selection of items during donning and doffing, hygiene aspects, time, and team support (buddying). The primary outcome was the number of participants being appropriately protected, defined as both wearing (a) all PPE items provided, and (b) all PPE items correctly at the time of first patient contact (FPC). Secondary outcomes included the timing of participants being appropriately protected. Statistical analysis was performed using SPSS (version 28). Mann-Whitney test, chi-square test, and linear regression analysis were performed as appropriate. RESULTS: At first patient contact 21% (91/437) were correctly protected. One or more incorrect PPE items were found in 4% (19/437), whereas 61% (265/437) wore one or more PPE items incorrectly. In 14% (62/437), one or more PPE items were missing. The time interval between donning start and FPC was 66 (55-78) sec. Time to FPC was longer in correctly than in incorrectly protected participants 77 (66-87) vs. 64 (54-75) sec; p < 0.001) and decreased by 7 ± 2 s per PPE item omitted (P = 0.002). Correct doffing was observed in 192/345 (56%), while buddying occurred in 120 participants (27%), indicating that they either assisted other participants in some manner (verbally or physically) or received assistance themselves. CONCLUSIONS: Our findings imply a need for education in correct and timely PPE donning and doffing. Donning PPE as intended delayed FPC. This and the influence of buddying needs further investigation (German study register number DRKS00023184).

Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP.

Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.

[Patients in intensive care after a suicide attempt with legal drugs - risk profile and course]. / Patienten mit Intensivpflichtigen Medikamentösen Suizidversuchen - Risikoprofil und Verlauf.

Little is known about the risk profile and the further history of patients who attempted suicide by severe medicinal intoxication.All patients residing in Basel (n = 190) admitted to the intensive care unit between 01/01/1998 and 12/31/2001 because of a suicide attempt with legal drugs were investigated regarding psychopathology and sociodemographic features. Also, until the end of 2005, further suicide attempts as well as potential cases of death were followed up.All 190 patients had psychiatric disorders. Compared to the general population, female sex, single status, low educational level, unemployment and invalidity were found significantly more often. Until the end of 2005 almost half of 118 patients followed up in our outpatient department committed further suicide attempts. 28 patients died, 6 of these by suicide.These patients should preferably not be prescribed medication with a low therapeutic range and they should receive intensive follow-up care.

Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study.

In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.

Intracranial pressure in patients with sepsis.

INTRODUCTION: In sepsis the brain is frequently affected although there is no infection of the CNS (septic encephalopathy). One possible cause of septic encephalopathy is failure of the blood-brain barrier. Brain edema has been documented in animal models of sepsis. Aggressive fluid resuscitation in the early course of sepsis improves survival and is standard practice. We hypothesized that aggressive fluid administration will increase intracranial pressure (ICP) and may cause critical reductions in cerebral perfusion pressure (CPP). MATERIALS AND METHODS: Patients with sepsis were investigated daily on up to four consecutive days in the intensive care unit. Mean arterial blood pressure (MAP) and blood flow velocity in the middle cerebral artery were monitored for one hour each day. ICP was calculated non-invasively from MAP and flow velocity data. S-100beta was determined daily. FINDINGS: Fifty-two measurements were performed in 16 patients. ICP could be determined in 45 measurements in 15 patients. Seven patients had an ICP > 15 mmHg and 11 patients had a CPP < 60 mmHg on at least 1 day. We found no significant correlation between ICP and fluid administration, but low CPP was significantly correlated with elevated S-100beta (r = -0.47, p = 0.001). CONCLUSIONS: Further research is needed to determine the role of ICP/CPP monitoring in patients with sepsis.

Impact of MALDI-TOF-MS-based identification directly from positive blood cultures on patient management: a controlled clinical trial.

OBJECTIVES: Rapid identification of pathogens directly from positive blood cultures (BC) in combination with an antimicrobial stewardship programme (ASP) is associated with improved antibiotic treatment and outcomes, but the effect of each individual intervention is less clear. The current study investigated the impact of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) versus conventional identification on antibiotic management in a setting with a well-established ASP and low resistance rates. METHODS: In this single-centre open label, controlled clinical trial 425 patients with positive BCs were allocated by weekday during a 1-year period to either MALDI-TOF directly from positive BCs or conventional processing. ASP was identical throughout the study period. The primary outcome was duration of intravenous antimicrobial therapy and was analysed in an intention-to-treat approach. RESULTS: In all, 368 patients were analysed (MALDI-TOF n = 168; conventional n = 200) with similar baseline characteristics. Mean duration of intravenous antimicrobial therapy (12.9 versus 13.2 days, p 0.9) and length of stay (16.1 versus 17.9 days, p 0.3) were comparable. In the clinically significant bloodstream infection subgroup (n = 242) mean time from Gram-stain to active treatment was significantly shorter (3.7 versus 6.7 h, p 0.003). Admission to the intensive care unit after bloodstream infection onset was less frequent in the MALDI-TOF group (23.1 versus 37.2%, p 0.02). CONCLUSIONS: Rapid identification of contaminated BCs (n = 126) resulted in a shorter duration of intravenous antimicrobial therapy (mean 4.8 versus 7.5 days, p 0.04). Rapid identification using MALDI-TOF directly from positive BCs did not impact on duration of intravenous antimicrobial therapy, but provided fast and reliable microbiological results and may improve treatment quality in the setting of an established ASP.

Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction.

BACKGROUND: Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS: We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. CONCLUSIONS: Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.

Graded myocardial ischemia is associated with a decrease in diastolic distensibility of the remote nonischemic myocardium in the anesthetized dog.

OBJECTIVES: This study was designed to investigate the changes in regional distensibility of the ischemic segment and of a remote nonischemic segment brought about by graded myocardial ischemia. BACKGROUND: Ventricular distensibility is a major determinant of left ventricular end-diastolic pressure. The effects of graded myocardial ischemia on the regional distensibility of the ischemic area have not been studied. Moreover, there are few data on the effects of myocardial ischemia on the regional distensibility of the nonischemic myocardium. METHODS: Nine anesthetized open chest mongrel dogs were fitted with instruments to measure left ventricular pressure and circumferential length (sonomicrometry) in the ischemic segment and in a nonischemic segment. The pressure-length relation was modified by stepwise infusion and withdrawal of 200 ml of each dog's own blood over 30 min in five consecutive stages of regional ischemia. Unstressed dimensions were obtained by repeated inferior vena cava occlusions. In both segments, regional distensibility was assessed at end-diastole by means of the constants of the pressure-length (chamber stiffness), the pressure-strain and the force-strain (myocardial stiffness) relations. RESULTS: In the ischemic segment, partial and complete coronary occlusions were associated with a twofold increase in the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant, whereas in the nonischemic segment the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant increased by 50%. CONCLUSIONS: Regional myocardial ischemia is associated with a decrease in distensibility of both the ischemic and the remote nonischemic myocardium.

Effects of esmolol on patients with left ventricular dysfunction.

This study examined the effect of esmolol, an ultrashort-acting beta-receptor blocker, in 10 patients with severe left ventricular dysfunction. Simultaneous hemodynamic and radionuclide angiographic measurements were obtained at incremental doses of esmolol (2, 4, 8, 12 and 16 mg/min). At a dose of 4 mg/min, esmolol produced beats blockade: a decrease in heart rate from 91 +/- 4 to 83 +/- 4 beats/min (p less than 0.05) (mean +/- SEM) and a decrease in systolic aortic pressure from 133 +/- 5 to 128 +/- 5 mm Hg (p less than 0.05). At the maximal dose, the heart rate decreased to 79 +/- 3 beats/min (p less than 0.05) and biventricular function was depressed; the left ventricular ejection fraction decreased from 27 +/- 2 to 21 +/- 2% (p less than 0.05) and the right ventricular ejection fraction decreased from 38 +/- 2 to 29 +/- 2% (p less than 0.05). These changes were accompanied by increases in left ventricular end-diastolic volume (p less than 0.05), left ventricular end-systolic volume (p less than 0.05) and pulmonary artery wedge pressure (p less than 0.05), as well as a decrease in cardiac output (p less than 0.05). The hemodynamic abnormalities (which showed considerable interindividual variability) returned to near baseline levels 10 to 30 minutes after infusion was stopped. Thus, esmolol can be administered to patients with severe left ventricular dysfunction. The beneficial effect (beta-adrenergic blockade) is usually achieved with small doses without clinically important hemodynamic changes. At larger doses, however, significant changes in biventricular function may be observed.

Life-threatening orolingual angioedema during thrombolysis in acute ischemic stroke.

BACKGROUND: Orolingual angioedema can occur during thrombolysis with alteplase in stroke patients. However, data about its frequency, severity and the significance of concurrent use of angiotensin-converting-enzyme inhibitors (ACEi) are sparse. OBJECTIVE: (1), to alert to the potentially life-threatening complication of orolingual angioedema. (2), to present CT-scans of the tongue which exclude lingual hematoma. (3), to estimate the frequency of orolingual angioedema. (4), to evaluate the risk associated with the concurrent use of ACEi. METHODS: Single center, databank-based observational study on 120 consecutive patients with i. v. alteplase for acute stroke. Meta-analysis of all stroke studies on alteplase-associated angioedema, which provided detailed information about the use of ACE-inhibitors. Across studies, the Peto odds ratio of orolingual angioedema for "concurrent use of ACEi" was calculated. RESULTS: Orolingual angioedema occurred in 2 of 120 patients (1.7%, 95% CI 0.2-5.9 %). Angioedema was mild in one, but rapidly progressive in another patient. Impending asphyxia prompted immediate intubation. CT showed orolingual swelling but no bleeding. One of 19 (5%) patients taking ACEi had orolingual angioedema, compared to 1 of 101 (1%) patients without ACEi. Medline search identified one further study about the occurrence of alteplase-associated angioedema in stroke patients stratified to the use of ACEi. Peto odds ratio of 37 (95 % CI 8-171) indicated an increased risk of alteplasetriggered angioedema for patients with ACEi (p <0.001). CONCLUSION: Orolingual angioedema is a potentially life-threatening complication of alteplase treatment in stroke patients, especially in those with ACEi. Orolingual hematoma as differential diagnosis can be excluded by CT-scan.

Exercise thallium-201 scintigraphy in men with nondiagnostic exercise electrocardiograms. Prognostic implications.

We studied the prognostic value of exercise thallium-201 imaging in 196 men with suspected or known coronary artery disease who had nondiagnostic exercise electrocardiograms. The perfusion images in each of three projections were divided into three segments; each segment was assessed for perfusion defects (fixed or reversible). There were 12 cardiac events at a mean follow-up of 15 months (range, one to 66 months). Of those, five patients died of cardiac causes and seven had nonfatal acute myocardial infarctions (MIs). Only the number of perfusion defects significantly predicted cardiac events; clinical presentation, history of MI, presence of Q-wave MI, exercise duration, and exercise heart rate and double product did not predict cardiac events or add to information provided by the number of defects. Furthermore, actuarial life-table analysis showed that patients with three or more perfusion defects had significantly worse prognoses than patients with fewer than three defects. Exercise thallium-201 imaging helps in risk stratification of men with nondiagnostic exercise electrocardiograms.

Exercise thallium imaging in patients with diabetes mellitus. Prognostic implications.

We used exercise thallium 201 imaging in 123 patients with diabetes mellitus (77 men and 46 women, aged 56 +/- 8 years), 75% of whom had angina pectoris (typical or atypical). During exercise testing, 18 patients (15%) had angina pectoris, 28 (23%) had ischemic ST changes, and 69 (56%) had abnormal thallium images. During follow-up (up to 36 months), there were 12 cardiac events; four patients died of cardiac causes and eight had nonfatal acute myocardial infarction. Univariate and multivariate survival analysis identified two independent predictors of cardiac events: the event rate was significantly less in patients with normal images and exercise heart rate over 120 beats per minute than in patients with abnormal images and exercise heart rate of 120 beats per minute or less (0% vs 22%). The patients with abnormal images or exercise heart rate of 120 beats per minute or less had an intermediate event rate (11.5%). Furthermore, two of the 54 patients with normal images and ten of 69 patients with abnormal images had subsequent cardiac events. Thus, exercise thallium imaging is useful in risk stratification in patients with diabetes mellitus.

Role of exercise thallium 201 imaging in decision making.

This prospective study examined the impact of results of exercise thallium 201 imaging on the estimation of probability of coronary artery disease (CAD) and patient management among cardiologists and internists in our institution. Before exercise testing, the probability of CAD in the 100 patients enrolled in this study was considered low in 31, intermediate in 28, and high in 41 patients. The probability of CAD after exercise thallium imaging was different in four patients (10%) in the high group, 22 patients (79%) in the intermediate group, and three patients (10%) in the low group. Further, the results of exercise testing resulted in changes in patient management in 29 patients (71%) in the high group, 26 patients (93%) in the intermediate group, and 16 patients (52%) in the low group. Overall, the management changed in 71% of the patients. This change included changes in medications, physical activity, frequency of office visits, need for cardiac catheterization, and need for coronary arterial bypass grafting. Thus, exercise thallium imaging is useful in clinical decision making: the diagnostic certainty is improved in patients with intermediate pretest probability of CAD; and some degree of change in patient management is observed, even in patients in whom the probability of CAD is not altered.

Platelet-activating factor (PAF) does not affect diastolic function in isolated rat hearts.

Platelet-activating factor might be responsible for the alterations of diastolic function observed in different disease states and these potential effects have not been studied. The effect of incremental concentrations of platelet-activating factor (to a maximum of 200 nM) was therefore examined in isolated perfused rat heart. Platelet-activating factor decreased coronary flow rate and contractility in a dose-dependent manner. Although high-dose platelet-activating factor decreased peak -dP/dt compared to baseline, this was not significant when compared to vehicle-administered control. There were no changes in the time constant of left ventricular relaxation and the chamber stiffness constant. These results do not support a major direct role of platelet-activating factor in diastolic dysfunction.

Synthesis and cytotoxic evaluation of cycloheximide derivatives as potential inhibitors of FKBP12 with neuroregenerative properties.

On the basis of the new finding that the protein synthesis inhibitor cycloheximide (1, 4-[2-(3, 5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]-2,6-piperidinedione) is able to competitively inhibit hFKBP12 (K(i) = 3.4 microM) and homologous enzymes, a series of derivatives has been synthesized. The effect of the compounds on the activity of hFKBP12 and their cytotoxicity against eukaryotic cell lines (mouse L-929 fibroblasts, K-562 leukemic cells) were determined. As a result, several less toxic or nontoxic cycloheximide derivatives were identified by N-substitution of the glutarimide moiety and exhibit IC(50) values in the range of 22.0-4.4 microM for inhibition of hFKBP12. Among these compounds cycloheximide-N-(ethyl ethanoate) (10, K(i) = 4.1 microM), which exerted FKBP12 inhibition to an extent comparable to that of cycloheximide (1), was found to cause an approximately 1000-fold weaker inhibitory effect on eukaryotic protein synthesis (IC(50) = 115 microM). Cycloheximide-N-(ethyl ethanoate) (10) was able to significantly speed nerve regeneration in a rat sciatic nerve neurotomy model at dosages of 30 mg/kg.

Use of technetium-99m isonitrile (RP-30A) in assessing left ventricular perfusion and function at rest and during exercise in coronary artery disease, and comparison with coronary arteriography and exercise thallium-201 SPECT imaging.

This study compared the results of stress and rest single-photon emission computed tomography imaging of myocardial perfusion using technetium-99m isonitrile (RP-30A) with the results of stress and redistribution tomographic thallium imaging and the results of coronary arteriography in 39 patients, 11 without and 28 with coronary artery disease (CAD). Each patient underwent 2 exercise studies at identical workload, heart rate and double product. In a subset of 13 patients, concomitant evaluation of left ventricular (LV) function using first-pass radionuclide angiography with a multi-crystal camera also was performed with bolus injections of isonitrile. Isonitrile had similar sensitivity (82 vs 82%, difference not significant), a slightly--but not significantly--higher specificity (100 vs 82%) and similar predictive accuracy (87 vs 82%) to thallium-201. The tracer uptake was assessed in 20 segments/study. There was concordance between the isonitrile and thallium-201 images in 723 of the 780 segments (93%) (kappa = 0.83 +/- 0.02). In general, the isonitrile images were considered of better quality than the thallium-201 images. All 10 patients with CAD who underwent concomitant first-pass radionuclide angiography had either perfusion abnormalities or an abnormal ejection fraction response to exercise. Thus, technetium-99m isonitrile provides a reliable method of assessment of CAD with a sensitivity, specificity and predictive accuracy comparable to that of exercise thallium-201 imaging. Additional advantages include better image quality and the ability to obtain concomitant assessment of LV function with the use of first-pass radionuclide angiography.

Effects of intravenous infusion of esmolol and propranolol on biventricular performance at rest and during exercise as assessed by quantitative radionuclide angiography.

This double-blind, randomized, crossover study examined the effects of intravenous infusion of esmolol (a new ultra-short-acting beta-receptor blocking agent) and propranolol on cardiovascular performance at rest and during peak upright exercise in 15 patients. Biventricular function was assessed by means of first-pass radionuclide ventriculography with a computerized multicrystal camera. At rest, significant treatment differences between esmolol and propranolol vs baseline were found for the heart rate, systolic blood pressure, double product, left ventricular ejection fraction (EF), systolic blood pressure to end-systolic volume ratio, cardiac index and right ventricular EF. During exercise, significant treatment differences were also found for the heart rate, systolic blood pressure, double product, right ventricular EF and cardiac index. The mean baseline measurements were higher than the mean treatment measurements, but no significant differences were found between mean esmolol and mean propranolol measurements at rest and during exercise except for the exercise systolic blood pressure, which was lower during esmolol infusion. The magnitude of drug effect was greater at the time of exercise than at rest. The blood level of esmolol decreased markedly by 30 minutes after infusion. Esmolol was well tolerated, with no important local, systemic or laboratory abnormalities. Thus, the effects of esmolol on cardiovascular performance at rest and exercise are similar to those of propranolol.