M. Bridget Zimmerman

Nocturnal Arterial Hypotension and Its Role in Optic Nerve Head and Ocular Ischemic Disorders

We measured 24-hour ambulatory blood pressure monitoring and diurnal curve of the intraocular pressure in 166 white patients with anterior ischemic optic neuropathy, normal-tension glaucoma, primary open-angle glaucoma, and other optic nerve head disorders. Hourly average blood pressure data analyses showed a significant (P < .0001) decrease in mean systolic (26%) and diastolic (33%) blood pressure measurements at night. A significantly (P = .0028) lower nighttime mean diastolic blood pressure and a significantly (P = .0044) greater mean percentage decrease in diastolic blood pressure were noted in normal-tension glaucoma than in anterior ischemic optic neuropathy. Patients with arterial hypertension taking oral hypotensive therapy showed a significant association between progressive visual field deterioration and nocturnal hypotension, particularly in anterior ischemic optic neuropathy. Intraocular pressure showed no significant correlation with visual field deterioration in any of these conditions. Our findings suggest that nocturnal hypotension, in the presence of other vascular risk factors, may reduce the optic nerve head blood flow below a critical level, and thereby may play a role in the pathogenesis of anterior ischemic optic neuropathy and glaucomatous optic neuropathy; that is, nocturnal hypotension may be the final insult in a multifactorial situation. The same mechanisms may be true of a number of other ocular ischemic disorders. This finding opens a new dimension in the understanding and management of these visually disabling diseases.

Investigating the Relationship Between Stroke and Obstructive Sleep Apnea

BACKGROUND AND PURPOSE We aimed to prospectively determine whether the incidence of obstructive sleep apnea in patients with recent stroke was significantly different from that of a sex- and age-matched control group with no major medical problems. METHODS We prospectively performed overnight polysomnography in 24 patients with a recent stroke (13 men and 11 women; mean age [+/- SD], 64.6 +/- 10.4 years) and 27 subjects without stroke (13 men and 14 women; mean age, 61.6 +/- 8.8 years). Patients with either ischemic or hemorrhagic stroke were entered into this study. Polysomnographic evaluations were performed within approximately 2 to 5 weeks after each patients stroke. RESULTS Obstructive sleep apnea was found in 10 of 13 men with stroke (77%) and in only 3 of 13 male subjects without stroke (23%) (P=.0169). Seven of 11 women with stroke (64%) had obstructive sleep apnea, while only 2 of 14 female subjects without stroke (14%) had obstructive sleep apnea (P=.0168). For men with stroke, the mean apnea/hypopnea index (+/- SE) was 21.5 +/- 4.2 events per hour, while for male subjects without stroke it was 4.8 +/- 1.8 events per hour (P=.0014). For women with stroke the mean apnea/hypopnea index was 31.6 +/- 8.8 events per hour, while for female subjects without stroke it was 2.9 +/- 1.6 events per hour (P=.0024). The 4-year mortality for patients with stroke was 20.8%. All patients with stroke who died had obstructive sleep apnea. CONCLUSIONS Patients with stroke have an increased incidence of obstructive sleep apnea compared with normal sex- and age-matched control subjects. Hypoxia and hemodynamic responses to obstructive sleep apnea may have predisposed these patients to stroke.

Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants.

Objective. Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years, the benefits and adverse consequences of allowing lower hematocrit levels have not been systematically evaluated. The objective of this study was to determine if restrictive guidelines for red blood cell (RBC) transfusions for preterm infants can reduce the number of transfusions without adverse consequences. Design, Setting, and Patients. We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion. Intervention. The infants were assigned randomly to either the liberal- or the restrictive-transfusion group. For each group, transfusions were given only when the hematocrit level fell below the assigned value. In each group, the transfusion threshold levels decreased with improving clinical status. Main Outcome Measures. We recorded the number of transfusions, the number of donor exposures, and various clinical and physiologic outcomes. Results. Infants in the liberal-transfusion group received more RBC transfusions (5.2 ± 4.5 [mean ± SD] vs 3.3 ± 2.9 in the restrictive-transfusion group). However, the number of donors to whom the infants were exposed was not significantly different (2.8 ± 2.5 vs 2.2 ± 2.0). There was no difference between the groups in the percentage of infants who avoided transfusions altogether (12% in the liberal-transfusion group versus 10% in the restrictive-transfusion group). Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia, and they had more frequent episodes of apnea, including both mild and severe episodes. Conclusions. Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants.

Incidence of Various Types of Retinal Vein Occlusion and Their Recurrence and Demographic Characteristics

We analyzed data on 1,108 patients (1,229 eyes) with various types of retinal vein occlusion. Retinal vein occlusion was classified into six distinct clinical types: (I) nonischemic and (II) ischemic central retinal vein occlusion, (III) nonischemic and (IV) ischemic hemicentral retinal vein occlusion, and (V) major and (VI) macular branch retinal vein occlusion. Retinal vein occlusion occurred more often in men than women. The age range of patients was between 14 and 92 years, with 570 of 1,108 patients (51%) 65 years or older; however, 99 of 620 (16%), 15 of 154 (10%), and 17 of 375 (5%) of the patients with central, hemicentral, and branch retinal vein occlusion, respectively, were younger than 45 years. The cumulative probability of developing a second episode of the same or a different type of retinal vein occlusion in the same eye was 0.9% within two years and 2.5% within four years, and in the fellow eye was 7.7% and 11.9%, respectively. The cumulative probability of conversion of nonischemic to ischemic central retinal vein occlusion at six months and 18 months was 13.2% and 18.6%, respectively, in persons 65 years of age or older and 6.7% and 8.1%, respectively, in persons 45 to 64 years of age.

Rate of visual field loss and long-term visual outcome in primary open-angle glaucoma.

PURPOSE To evaluate long-term visual field outcome in primary open-angle glaucoma. METHODS In this retrospective cohort study, 40 eyes of 40 patients with primary open-angle glaucoma with elevated intraocular pressure and a minimum of 8-year longitudinal series of visual fields were plotted with Goldmann perimeter. Eyes with any other ocular disease except cataract were excluded. Manual grid templates were used to quantify the visual fields. Linear regression was performed to estimate the rate of visual field decline. Pertinent clinical factors were evaluated for statistical association with the rate of decline. Long-term clinical outcome including visual acuity, rate of legal blindness, and rate of medical and surgical interventions was also measured. RESULTS In the 40 eyes studied, with a mean follow-up of 14 years, the visual field score decreased at the rate of -1.5% per year. Overall, 68% showed significant decrease, and the rate of decrease among these eyes was -2.1% per year. Five eyes became legally blind from glaucoma; the cumulative rate of blindness from glaucoma was 19% at 22 years. Higher intraocular pressure and greater number of antiglaucoma medications on initial presentation were associated with faster and slower deterioration of visual field (compared with the average), respectively. CONCLUSIONS With standard glaucoma therapy, the rate of visual field loss in primary open-angle glaucoma is slow. Lower intraocular pressure and more antiglaucoma medications are associated with slower visual field decline. Legal blindness from glaucoma is 19% over a follow-up of 22 years.

A comparison of spatial semivariogram estimators and corresponding ordinary Kriging predictors

Predicting values of a spatially distributed variable, such as the concentration of a mineral throughout an ore body or the level of contamination around a toxic-waste dump, can be accomplished by a regression procedure known as kriging. Kriging and other types of statistical inference for spatially distributed variables are based on models of stochastic processes {Y t: t ∊ D} called random-field models. A commonly used class of random-field models are the intrinsic models, for which the mean is constant, and half of the variance of Yt , – Ys . is a function, called the semivariogram, of the difference t – s. The type of kriging corresponding to an intrinsic model is called ordinary kriging. The semivariogram, which typically is taken to depend on one or more unknown parameters, must be estimated prior to ordinary kriging. Various estimators of the semivariograms parameters have been proposed. For two Gaussian intrinsic random-field models, we compare, by a Monte Carlo simulation study, the performance o...

Retinal Artery Occlusion: Associated Systemic and Ophthalmic Abnormalities

OBJECTIVE To investigate systematically the various associated systemic and ophthalmic abnormalities in different types of retinal artery occlusion (RAO). DESIGN Cohort study. PARTICIPANTS We included 439 consecutive untreated patients (499 eyes) with RAO first seen in our clinic from 1973 to 2000. METHODS At first visit, all patients underwent detailed ophthalmic and medical history, and comprehensive ophthalmic evaluation. Visual evaluation was done by recording visual acuity, using the Snellen visual acuity chart, and visual fields with a Goldmann perimeter. Initially they also had carotid Doppler/angiography and echocardiography. The same ophthalmic evaluation was performed at each follow-up visit. MAIN OUTCOME MEASURES Demographic features, associated systemic and ophthalmic abnormalities, and sources of emboli in various types of RAO. RESULTS We classified RAO into central (CRAO) and branch (BRAO) artery occlusion. In both nonarteritic (NA) CRAO and BRAO, the prevalence of diabetes mellitus, arterial hypertension, ischemic heart disease, and cerebrovascular accidents were significantly higher compared with the prevalence of these conditions in the matched US population (all P<0.0001). Smoking prevalence, compared with the US population, was significantly higher for males (P = 0.001) with NA-CRAO and for women with BRAO (P = 0.02). Ipsilateral internal carotid artery had > or =50% stenosis in 31% of NA-CRAO patients and 30% of BRAO, and plaques in 71% of NA-CRAO and 66% of BRAO. An abnormal echocardiogram with an embolic source was seen in 52% of NA-CRAO and 42% of BRAO. Neovascular glaucoma developed in only 2.5% of NA-CRAO eyes. CONCLUSIONS This study showed that, in CRAO as well as BRAO, the prevalence of various cardiovascular diseases and smoking was significantly higher compared with the prevalence of these conditions in the matched US population. Embolism is the most common cause of CRAO and BRAO; plaque in the carotid artery is usually the source of embolism and less commonly the aortic and/or mitral valve. The presence of plaques in the carotid artery is generally of much greater importance than the degree of stenosis in the artery. Contrary to the prevalent misconception, we found no cause-and-effect relationship between CRAO and neovascular glaucoma.

Hypothermia Improves Defibrillation Success and Resuscitation Outcomes From Ventricular Fibrillation

Background—Induced hypothermia is recommended to improve neurological outcomes in unconscious survivors of out-of-hospital ventricular fibrillation (VF) cardiac arrest. Patients resuscitated from a VF arrest are at risk of refibrillation, but there are few data on the effects of already existing hypothermia on defibrillation and resuscitation. Methods and Results—Thirty-two swine (mean±SE weight, 23.0±0.6 kg) were divided into 4 groups: normothermia (n=8), mild hypothermia (35°C) (n=8), moderate hypothermia (33°C) (n=8), and severe hypothermia (30°C) (n=8). Hypothermia was induced by surrounding the animal with ice, and VF was electrically induced. After 8 minutes of unsupported VF (no CPR), the swine were defibrillated (biphasic waveform) with successive shocks as needed and underwent CPR until resumption of spontaneous circulation or no response (≥10 minutes). First-shock defibrillation success was higher in the moderate hypothermia group (6 of 8 hypothermia versus 1 of 8 normothermia; P=0.04). The number of shocks needed for late defibrillation (≥1 minute after initial shock) was less in all 3 hypothermia groups compared with normothermia (all P<0.05). None of the 8 animals in the normothermia group achieved resumption of spontaneous circulation compared with 3 of 8 mild hypothermia (P=NS), 7 of 8 moderate hypothermia (P=0.001), and 5 of 8 severe hypothermia (P=0.03) animals. Coronary perfusion pressure during CPR was not different between the groups. Conclusions—When VF was induced in the setting of moderate or severe hypothermia, resuscitative measures were facilitated with significantly improved defibrillation success and resuscitation outcome. The beneficial effect of hypothermia was not due to alteration of coronary perfusion pressure, which suggests that changes in the mechanical, metabolic, or electrophysiological properties of the myocardium may be responsible.

Beta-blocker eyedrops and nocturnal arterial hypotension.

PURPOSE To investigate the effects of topical beta-blocker eyedrops on nocturnal arterial hypotension and heart rate and on visual field deterioration. METHODS We prospectively investigated 275 white patients, 161 with glaucomatous optic neuropathy and 114 with nonarteritic anterior ischemic optic neuropathy, by 24-hour ambulatory blood pressure monitoring and diurnal curve of intraocular pressure, in addition to detailed ophthalmic evaluation. Of the patients with glaucomatous optic neuropathy, 131 had normal-tension glaucoma and 30 had primary open-angle glaucoma. Of the 275 patients, 114 were using topical beta-blocker eyedrops twice daily (76 with normal-tension glaucoma, 26 with primary open-angle glaucoma, and 12 with anterior ischemic optic neuropathy). RESULTS Hourly average blood pressure data analyses showed overall a drop in blood pressure as well as heart rate during sleep, and a significantly greater drop in mean diastolic blood pressure (P = .009) at night in normal-tension glaucoma than in anterior ischemic optic neuropathy. Also, patients using beta-blocker eyedrops experienced a significantly greater percentage drop in diastolic blood pressure at night (P = .028), lower minimum nighttime diastolic blood pressure (P = .072), and lower minimum nighttime heart rate (P = .002) than did those not using them. In normal-tension glaucoma, eyes receiving beta-blocker eyedrops showed visual field progression significantly (P = .0003) more often than those not receiving beta-blockers. CONCLUSIONS The findings of our studies, as well as those of others, suggest that any factor that increases nocturnal arterial hypotension is a potential risk factor in vulnerable individuals with glaucomatous optic neuropathy or anterior ischemic optic neuropathy. The present study suggests that the use of beta-blocker eyedrops, by aggravating nocturnal arterial hypotension and reducing the heart rate, may be a potential risk factor in susceptible individuals.

A Prospective Study of Outcomes, Healthcare Resource Utilization, and Costs Associated With Postoperative Nosocomial Infections

OBJECTIVE We evaluated 4 important outcomes associated with postoperative nosocomial infection: costs, mortality, excess length of stay, and utilization of healthcare resources. DESIGN The outcomes for patients who underwent general, cardiothoracic, and neurosurgical operations were recorded during a previous clinical trial. Multivariable analyses including significant covariates were conducted to determine whether nosocomial infection significantly affected the outcomes. SETTING A large tertiary care medical center and an affiliated Veterans Affairs Medical Center. PATIENTS A total of 3,864 surgical patients. RESULTS The overall nosocomial infection rate was 11.3%. Important covariates included age, Karnofsky score, McCabe and Jackson classification of the severity of underlying disease, National Nosocomial Infection Surveillance system risk index, and number of comorbidities. After accounting for covariates, nosocomial infection was associated with increased postoperative length of stay, increased costs, increased hospital readmission rate, and increased use of antimicrobial agents in the outpatient setting. Nosocomial infection was not associated independently with a significantly increased risk of death in this surgical population. CONCLUSION Postoperative nosocomial infection was associated with increased costs of care and with increased utilization of medical resources. To accurately assess the effects of nosocomial infections, one must take into account important covariates. Surgeons seeking to decrease the cost of care and resource utilization must identify ways to decrease the rate of postoperative nosocomial infection.