Timothy I. Morgenthaler

Clinical Characteristics of Fatal Pulmonary Embolism in a Referral Hospital

OBJECTIVE To determine the clinical characteristics of hospitalized patients who died of pulmonary embolism, confirmed by evaluative autopsy. DESIGN We retrospectively analyzed a series of autopsy cases of pulmonary embolism at a tertiary-care center for the period Jan. 1, 1985, through Dec. 31, 1989. MATERIAL AND METHODS The medical and autopsy records of all hospitalized patients with autopsy-proven fatal pulmonary embolism were reviewed. Cases of tumor emboli, fat emboli, and contributory-only thromboembolic disease were excluded from the study. Specific symptoms and signs, diagnostic studies, and prophylactic measures were noted. RESULTS Among 2,427 autopsies performed during the 5-year study period, death in 92 (3.8%) was clinically and pathologically judged to be caused by pulmonary embolism. No risk factors were noted in only 11 patients (12%). Prophylaxis against thromboembolism was used in 46%. Classic symptoms were often absent: dyspnea was present in only 59%, chest pain in only 17%, and hemoptysis in 3%. Pulmonary embolism was considered in 49% of the 92 patients and was correctly assigned as the cause of death on the death certificate or in the medical records in 32%. Testing for venous thromboembolic disease was performed in 22%. Comorbidity was present in most patients: 54% had guarded or poor prognoses independent of pulmonary embolism. CONCLUSION The usual signs and symptoms associated with pulmonary embolism did not adequately identify most of our patients who died of pulmonary embolism. The reasons included the absence of these signs and symptoms, inability to communicate (for example, sedated or comatose patient), sudden death from acute massive pulmonary embolism, and presence of comorbid factors.

Amnestic sleep-related eating disorder associated with zolpidem

OBJECTIVE To describe the association of amnestic nocturnal eating behavior with use of zolpidem for insomnia. BACKGROUND Sleep-related eating disorder is increasingly recognized in relationship to other diagnosable sleep disorders. Many of these disorders, like restless legs syndrome (RLS), give rise to complaints of insomnia. Zolpidem is the most commonly prescribed drug for insomnia complaints, and although it has sometimes been associated with side effects of transient amnesia and sleep walking, an association with sleep-related eating has not been previously emphasized. METHODS Consecutive case series of five patients who were using zolpidem and evaluated with nocturnal eating behaviors. RESULTS We evaluated five patients over 11 months with problematic amnestic nocturnal eating associated with zolpidem used for complaints of insomnia. All five patients had RLS, three had obstructive sleep apnea syndrome, two had sleep walking, and one had psychophysiologic insomnia. With discontinuation of zolpidem and effective treatment of their sleep disorders, nocturnal eating resolved. CONCLUSIONS Zolpidem, at least in patients with underlying sleep disorders that cause frequent arousals, may cause or augment sleep-related eating behavior. This report demonstrates the importance of arriving at a specific diagnosis for insomnia complaints, and alerts the sleep practitioner to this unusual side effect of zolpidem.

Reducing Iatrogenic Risk in Thoracentesis: Establishing Best Practice Via Experiential Training in a Zero-Risk Environment

BACKGROUND We studied the reasons why patients undergoing thoracenteses performed in our outpatient pulmonary clinic had a higher frequency of iatrogenic pneumothorax compared to that in the concurrent radiology practice in our institution, which utilizes ultrasound guidance. We reviewed our practice model and implemented a unique experiential training paradigm in a zero-risk simulation environment to improve efficacy, timeliness, service orientation, and safety. METHODS We retrospectively determined the rate of clinically significant pneumothoraces in our practice (phase I, July 1, 2001, to June 30, 2002). The training system redesign included the following: (1) a designated group of pulmonologist instructors dedicated to treating pleural disease and reducing the number of iatrogenic complications; (2) the use of ultrasound image guidance for all thoracenteses; and (3) structured proficiency and competency standards for proceduralists. Postintervention (phase II) data were prospectively collected (January 2005 to December 2006) and compared with our baseline data. RESULTS The baseline rate of pneumothorax was 8.6% (5 of 58 patients) in our pulmonary practice. Following intervention (phase II), the rate of pneumothorax declined to 1.1% (p = 0.0034). During phase II, the number of thoracenteses performed increased (186 vs 58 per year, respectively; p < 0.05). The iatrogenic pneumothorax rate was stable in the 2 years following intervention (2005, 0.7% [1 of 137 pneumothoraces]; 2006, 1.3% [3 of 226 pneumothoraces]; p > 0.9). Postintervention complications included procedure-related pain (n = 19), cough (n = 4), and hypotension (n = 10). CONCLUSIONS An improvement program that included simulation, ultrasound guidance, competency testing, and performance feedback reduced iatrogenic risk to patients. We recommend application of this process to procedural practices.

Early Anticoagulation Is Associated With Reduced Mortality for Acute Pulmonary Embolism

BACKGROUND Acute pulmonary embolism (PE) may be rapidly fatal if not diagnosed and treated. IV heparin reduces mortality and recurrence of PE, but the relationship between survival and timing of anticoagulation has not been extensively studied. METHODS We studied 400 consecutive patients in the ED diagnosed with acute PE by CT scan angiography and treated in the hospital with IV unfractionated heparin from 2002 to 2005. Patients received heparin either in the ED or after admission. Time from ED arrival to therapeutic activated partial thromboplastin time (aPTT) was calculated. Outcomes included in-hospital and 30-day mortality, hospital and ICU lengths of stay, hemorrhagic events on heparin, and recurrent venous thromboembolism within 90 days. RESULTS In-hospital and 30-day mortality rates were 3.0% and 7.7%, respectively. Patients who received heparin in the ED had lower in-hospital (1.4% vs 6.7%; P = .009) and 30-day (4.4% vs 15.3%; P < .001) mortality rates as compared with patients given heparin after admission. Patients who achieved a therapeutic aPTT within 24 h had lower in-hospital (1.5% vs 5.6%; P = .093) and 30-day (5.6% vs 14.8%; P = .037) mortality rates as compared with patients who achieved a therapeutic aPTT after 24 h. In multiple logistic regression models, receiving heparin in the ED remained predictive of reduced mortality, and ICU admission remained predictive of increased mortality. CONCLUSIONS We report an association between early anticoagulation and reduced mortality for patients with acute PE. We advocate further study with regard to comorbidities to assess the usefulness of modifications to hospital protocols.

Obstructive Sleep Apnea-Hypopnea Syndrome

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repetitive episodes of airflow reduction (hypopnea) or cessation (apnea) due to upper airway collapse during sleep. Increasing recognition and a greater understanding of the scope of this condition have substantially affected the practices of many clinicians. This review provides practical information for physicians assessing patients with OSAHS. It discusses complications, clinical recognition, the polysomnographic report, and treatment of OSAHS, including strategies for troubleshooting problems associated with continuous positive airway pressure therapy.

Zolpidem is independently associated with increased risk of inpatient falls.

BACKGROUND Inpatient falls are associated with significant morbidity and increased healthcare costs. Zolpidem has been reported to decrease balance and is associated with falls. Yet, it is a commonly used hypnotic agent in the inpatient setting. Zolpidem use in hospitalized patients may be a significant and potentially modifiable risk factor for falling. OBJECTIVE To determine whether inpatients administered zolpidem are at greater risk of falling. DESIGN Retrospective cohort study. SETTING Adult non-intensive care unit (non-ICU) inpatients at a tertiary care center. METHODS Adult inpatients who were prescribed zolpidem were identified. Electronic medical records were reviewed to capture demographics and other risk factors for falls. The fall rate was compared in those administered zolpidem versus those only prescribed zolpidem. Multivariate analyses were performed to determine whether zolpidem was independently associated with falls. RESULTS The fall rate among patients who were prescribed and received zolpidem (n = 4962) was significantly greater than among patients who were prescribed but did not receive zolpidem (n = 11,358) (3.04% vs 0.71%; P < 0.001). Zolpidem use continued to remain significantly associated with increased fall risk after accounting for age, gender, insomnia, delirium status, dose of zolpidem, Charlson comorbidity index, Hendrichs fall risk score, length of hospital stay, presence of visual impairment, gait abnormalities, and dementia/cognitive impairment (adjusted odds ratio [OR] 4.37, 95% confidence interval [CI] = 3.34-5.76; P < 0.001). Additionally, patients taking zolpidem who experienced a fall did not differ from other hospitalized adult patients who fell in terms of age, opioids, antidepressants, sedative-antidepressants, antipsychotics, benzodiazepine, or antihistamine use. CONCLUSION Zolpidem use was a strong, independent, and potentially modifiable risk factor for inpatient falls.

Sirolimus-associated diffuse alveolar hemorrhage.

Sirolimus is an immunosuppressive medication used in transplant recipients. To our knowledge, we describe the third reported case of alveolar hemorrhage in association with sirolimus. Fever, dyspnea, hemoptysis, and lung infiltrates resolved rapidly with cessation of sirolimus therapy both initially and after reinstitution of the drug. Unlike previous reports, our patient had no evidence of lymphocytic alveolitis but rather marked macrophage hemosiderosis, suggesting that sirolimus pulmonary toxicity may manifest through 2 separate mechanisms. Our case highlights an uncommon but potentially lethal manifestation of sirolimus pulmonary toxicity.

Does Autotitrating Positive Airway Pressure Therapy Improve Postoperative Outcome in Patients at Risk for Obstructive Sleep Apnea Syndrome?: A Randomized Controlled Clinical Trial

BACKGROUND Obstructive sleep apnea has been associated with postoperative complications. We hypothesized that postoperative autotitrating positive airway pressure (APAP) applied to patients at high risk for obstructive sleep apnea would shorten hospital stay and reduce postoperative complications. METHODS Included were patients aged 18 to 100 years scheduled for elective total knee or hip arthroplasty who were able to give informed consent. Patients without contraindication to positive airway pressure therapy were divided into a high- or low-risk group on the basis of the Flemons sleep apnea clinical score. Low-risk patients received standard care. High-risk patients were randomized to receive standard care or standard care plus postoperative APAP. All patients were administered a predismissal cardiorespiratory sleep study. The primary end point was length of stay, and secondary end points were a range of postoperative complications. RESULTS One hundred thirty-eight patients were enrolled in the study (52 in the low-risk group, 86 in the high-risk group). Within the high-risk group, 43 were randomized to standard care and 43 to standard care plus postoperative APAP. There were no significant differences in the length of stay (P=.65) or any of the secondary end points between the randomized groups. On subgroup analysis of patients with an apnea-hypopnea index of ≥15, patients randomized to APAP had a longer postoperative stay (median, 5 vs 4 days; P=.02). CONCLUSIONS The role for empirical postoperative APAP requires further study, but the findings did not show benefit for APAP applied postoperatively to positive airway pressure-naive patients at high risk for sleep apnea.

Use of Exhaled Nitric Oxide in Predicting Response to Inhaled Corticosteroids for Chronic Cough

OBJECTIVE To evaluate our experience with patients who presented with chronic cough and how exhaled nitric oxide predicted response to inhaled corticosteroid (ICS) therapy. PATIENTS AND METHODS This retrospective observational study of 114 patients evaluated for chronic cough with measured exhaled nitric oxide and methacholine challenge testing was conducted from December 1, 2004, through November 30, 2005. Clinical records were extracted. Patients with no documented follow-up were contacted by telephone and administered a questionnaire. RESULTS In 64 patients, ICS therapy was started or the current ICS dose increased. Forty-one patients had elevated exhaled nitric oxide levels (defined as >or=35 ppb), 36 (88%) of whom had significant improvement in their chronic cough (likelihood ratio of a positive response, 4.9; 95% confidence interval, 2.2-10.9). Twenty-three patients with exhaled nitric oxide levels in the reference range were also prescribed ICS, and only 2 had cough improvement (likelihood ratio of a negative response, 0.07; 95% confidence interval, 0.02-0.25). Patients had documented follow-up that ranged from 4 weeks to 16 months. A cutoff of 38 ppb was found to best differentiate ICS responders and nonresponders. CONCLUSIONS Measurement of exhaled nitric oxide accurately predicted response to ICS therapy for chronic cough. Patients with a positive exhaled nitric oxide test result had a strong likelihood of response to ICS, whereas a negative exhaled nitric oxide test result indicated an unlikely response to ICS. This finding may potentially have an impact on how patients with chronic cough are evaluated and treated.

The complex sleep apnea resolution study: A prospective randomized controlled trial of continuous positive airway pressure versus adaptive servoventilation therapy

INTRODUCTION Prior studies show that adaptive servoventilation (ASV) is initially more effective than continuous positive airway pressure (CPAP) for patients with complex sleep apnea syndrome (CompSAS), but choosing therapies has been controversial because residual central breathing events may resolve over time in many patients receiving chronic CPAP therapy. We conducted a multicenter, randomized, prospective trial comparing clinical and polysomnographic outcomes over prolonged treatment of patients with CompSAS, with CPAP versus ASV. METHODS Qualifying participants meeting criteria for CompSAS were randomized to optimized CPAP or ASV treatment. Clinical and polysomnographic data were obtained at baseline and after 90 days of therapy. RESULTS We randomized 66 participants (33 to each treatment). At baseline, the diagnostic apnea-hypopnea index (AHI) was 37.7 ± 27.8 (central apnea index [CAI] = 3.2 ± 5.8) and best CPAP AHI was 37.0 ± 24.9 (CAI 29.7 ± 25.0). After second-night treatment titration, the AHI was 4.7 ± 8.1 (CAI = 1.1 ± 3.7) on ASV and 14.1 ± 20.7 (CAI = 8.8 ± 16.3) on CPAP (P ≤ 0.0003). At 90 days, the ASV versus CPAP AHI was 4.4 ± 9.6 versus 9.9 ± 11.1 (P = 0.0024) and CAI was 0.7 ± 3.4 versus 4.8 ± 6.4 (P < 0.0001), respectively. In the intention-to-treat analysis, success (AHI < 10) at 90 days of therapy was achieved in 89.7% versus 64.5% of participants treated with ASV and CPAP, respectively (P = 0.0214). Compliance and changes in Epworth Sleepiness Scale and Sleep Apnea Quality of Life Index were not significantly different between treatment groups. CONCLUSION Adaptive servoventilation (ASV) was more reliably effective than CPAP in relieving complex sleep apnea syndrome. While two thirds of participants experienced success with CPAP, approximately 90% experienced success with ASV. Because both methods produced similar symptomatic changes, it is unclear if this polysomnographic effectiveness may translate into other desired outcomes. CLINICAL TRIALS Clinicaltrials.Gov NCT00915499.