The study objective was to determine whether acetazolamide is effective in prophylaxis of acute mountain sickness (AMS) at moderate altitude in ambulatory travelers not undergoing vigorous exercise. Volunteers vacationing in La Paz, Bolivia (3630 m), immediately after arrival from sea level were studied. The design was a double-blind, randomized trial of two doses of acetazolamide (125 mg twice daily, 250 mg twice daily) versus placebo twice daily over a 24-h period. The main outcome measure was AMS score and score trend, using the Lake Louise consensus questionnaire. Nine of 32 subjects (28%) had symptom scoring diagnostic of AMS at 0 h. At 0 and 24 h (respectively), the mean Lake Louise scores were 1.73 and 1.09 for the 11 subjects receiving placebo, 1.45 and 1.36 for the 11 subjects receiving the 125-mg dose, and 2.7 and 0.6 for the 11 subjects receiving the 250-mg dose. The absolute change in these mean scores was not significant for placebo (p = 0.21) or the 125-mg dose (p = 0.88), but was significant for the 250-mg dose (p = 0.008). A comparison of a difference in decline in average AMS score over time showed a statistically significant decline for the 250-mg dosing group versus placebo (p = 0.002). The 250-mg dose of acetazolamide twice daily (but not 125 mg twice daily) was effective in inducing a significant decline in AMS symptoms over the 24-h period after arrival to 3630 m. These results suggest that the dosing of acetazolamide for AMS prevention in nonmountaineering tourists at altitudes below 3700 m should not be lowered below 250 mg twice daily.
Abstract Background Treatment of Mycobacterium avium complex pulmonary disease (MAC-PD) involves prolonged courses of multiple antibiotics that are variably tolerated and commonly cause adverse drug reactions (ADR). The purpose of this retrospective, single-center study was to identify demographic and disease-related variables associated with significant ADRs among patients treated with antibiotics against MAC-PD. Methods We reviewed all patients treated with antibiotic therapy for MAC-PD at a single center from 2000 to 2021. Patients were included if they met diagnostic criteria for MAC-PD, were prescribed targeted antibiotic therapy for any length of time and had their treatment course documented in their health record. We compared patients who completed antibiotics as originally prescribed (tolerant) with those whose antibiotic treatment course was modified or terminated secondary to an ADR (intolerant). Results Over the study period, 235 patients were prescribed antibiotic treatment with their clinical course documented in our center’s electronic health record, and 246 treatment courses were analyzed. One hundred forty-three (57%) tolerated therapy versus 108 (43%) experienced ADRs. Among the 108 intolerant courses, 67 (63%) required treatment modification and 49 (46%) required premature treatment termination. Treatment intolerance was associated more frequently with smear positive sputum cultures (34% vs. 20%, p = 0.009), a higher Charlson Comorbidity Index (CCI) (4 vs. 6, p = 0.007), and existing liver disease (7% vs. 1%, p = 0.03). There was no between-group difference in BMI (21 vs. 22), fibrocavitary disease (24 vs. 19%), or macrolide sensitivity (94 vs. 80%). The use of daily therapy was not associated with intolerance (77 vs. 79%). Intolerant patients were more likely to be culture positive after 6 months of treatment (44 vs. 25%). Conclusions Patients prescribed antibiotic therapy for MAC-PD are more likely to experience ADRs if they have smear positive sputum cultures at diagnosis, a higher CCI, or existing liver disease. Our study’s rate of early treatment cessation due to ADR’s was similar to that of other studies (20%) but is the first of its kind to evaluate patient and disease factors associated with ADR’s. A systematic approach to classifying and addressing ADRs for patients undergoing treatment for MAC-PD is an area for further investigation.
Lyme disease is a tick-borne spirochaete infection which, in a proportion of patients, can lead to neuropathy. This article describes a case of diaphragmatic paralysis due to Lyme disease. A 39-yr-old male presented to the hospital because of an acute left facial palsy. Six weeks prior to admission he had developed a circular rash on his left flank during a camping holiday. He also complained of shortness of breath and arthralgia for 1 week. His chest radiograph demonstrated a raised right hemi-diaphragm. Diaphragmatic paralysis was confirmed by fluoroscopy (a positive sniff test). Serology revealed evidence of recent infection by Borrelia burgdorferi. On the basis of the patient's clinical presentation, a recent history of erythema migrans, and positive Lyme serology, a diagnosis of neuroborreliosis was made. He received oral doxycycline therapy (200 mg x day(-1)) for three weeks. Facial and diaphragmatic palsies resolved within eight weeks. On the basis of this case, a diagnosis of Lyme disease should be considered in patients from endemic regions with otherwise unexplained phrenic nerve palsy.
1 Divsion of Critical Care Medicine and Adult Cardiothoracic Anesthesiology, Department of Anesthesiology, Pain, and Perioperative Medicine, Stanford University School of Medicine, Stanford, CA 2 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA The authors have disclosed that they do not have any potential conflicts of interest.
Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients.
Section 1 Introduction *Emergency Critical Care - Robert Rodriguez Section 2 Hemodynamic Monitoring *Tissue Oxygenation and Cardiac Output - Catherine S. Reid, Geoffrey K. Lighthall*Non-Invasive Hemodynamic Monitoring - Chad Myers*Arterial Blood Pressure Monitoring - Vidya Rao, John E. Arbo*The Central Venous and Pulmonary Artery Catheter - Carlos Brun, Geoffrey K. Lighthall Section 3 Critical Care Ultrasonography *Principles of Critical Care Ultrasonography - Philips Perera, Laleh Gharahbaghian, Thomas Mailhot, Sarah Williams, Diku P. Mandavia *Pulmonary Ultrasonography - Feras Khan, Anne-Sophie Beraud Section 4 Pulmonary Critical Care *Respiratory Failure and Mechanical Ventilation - John-Emile Kenny, Stephan J. Ruoss*Ventilation Strategies in COPD, Asthma, and Pulmonary Arterial Hypertension - Jey Chung, Paul Mohabir, Stephen J. Ruoss*Acute Pulmonary Edema - Nina Patel, Margaret Neff*High Risk Pulmonary Embolism - Tsuyoshi Mitari *Acute Respiratory Distress Syndrome - Darryl Abrams, Daniel Brodie*Extracorporeal Cardiopulmonary Membrane Oxygenation - Vidya Rao, Darryl Abrams, Cara Agerstrand, Daniel Brodie Section 5 Cardiac Critical Care * Heart Failure and Cardiogenic Shock - Daniel Sedehi, Venu Menon* Right Ventricular Failure - Joshua Sternbach, Francois Haddad, John E. Arbo, Anne-Sophie Beraud*Hypertensive Crises - Anand Swaminathan, Michael P. Jones*Controversies in Arrhythmia Management - Sam Senturia*Left Ventricular Assist Devices - Joseph Hsu, Rachel Dotson*Management of the Post-Cardiac Arrest Patient - Cappi Lay Section 6 Neurological Critical Care *Acute Ischemic Stroke - Mohamed Teleb, Paul Sing*Subarachnoid and Intracerebral Hemorrhage - Airton Leonardo de Oliveira Manoel, David Turkel-Parrella, Cappi Lay, Albert Goffi, Joshua Stillman*Seizure and Status Epilepticus - Brandon Foreman, Anil Mendiratta*Myasthenic Crisis and Peripheral Neuromuscular Disorders - Christina Ulane Section 7 Gastrointestinal and Hematological Critical Care *Gastrointestinal Hemorrhage - Parvathi Myer, Shai Freidland*Acute Liver Failure and Hepatic Encephalopathy - Robert Wong, Glen Lutchman*Pancreatitis - Susan Quan, Walter Park*Leukemia - Martina Trinkaus,*Sickle Cell Disease - Richard Ward*Platelet Disorders and Hemostatic Emergencies - Shawn Kaku, Catherine T. Jamin*Transfusion Therapy - Michael P. Jones, John E. Arbo Section 8 Sepsis and Septic Shock *Sepsis - Michael Scott, Michael Winters*Vasopressors and Inotropes - Matthew Strehlow*Principles of Antimicrobial Therapy - Chanu Rhee, Michael Klompas*Infections in the Immunocompromised Host - Maria Cristina Vazquez-Guillamet, Joshua Mooney, Joseph Hsu*Burns and Soft Tissue Infections - Carla M. Carvalho, Paul Maggio*Biomarkers in Sepsis - David M. Maslove Section 9 Disorders of Acid-Base, Electrolytes, and Fluid Balance *Acid-Base Disorders - Tara Scherer, Corey Slovis*Electrolytes Disorders - Katy Deljoui, Michael McCurdy*Rhabdomyolysis - Audrey Wagner, Deborah M. Stein*Acute Kidney Injury and Renal Replacement Therapy - Emilee Ruth Willhem-Leen, Glen Chertow Section 10 Endocrine Critical Care *Glycemic Control in the Critically Ill - Daniel Runde, Jarone Lee*Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State - Catherine T. Jamin, Jeffrey Manko*Adrenal Insufficiency - Thomas B. Perera*Thyroid Storm and Myxedema Coma - James Lantry III, John E. Arbo Geoffrey K. Lighthall Section 11 Toxicological Critical Care *Cardiotoxins - Nicholas Connor, Silas W. Smith*Pulmonary Toxins - Hong Kim, Rama B. Rao*Toxicologic Hyperthermic Syndromes - Mai Takematsu, Rama B. Rao*Metabolic Inhibitors - Lauren Shawn, Lewis S. Nelson*Caustics - Payal Sud, Mark Su*Anticoagulants - Betty Chen, Lewis S. Nelson*Drugs of Abuse - Rana Biary, Jane Marie Prosser*Alcohol Withdrawal - Nicole Bouchard Section 12 Environmental Critical Care *Hypothermia - Morgan Eutermoser, Jay Lemery*Altitude Emergencies - Zina Semenovskaya, Christopher Davis, Jay Lemery*Drowning and Dive-Related Emergencies - Samuel Gerson, Jose Evangelista III Section 13 Sedation and Delirium *Delirium - Jin H. Han, Eduard E. Vasilevsis, E. Wesley Ely*Sedation of the Agitated Patient - Randall Wood, Jin H. Han*Induction of Intubation and Sedation of the Mechanically Ventilated Patient - Jin H. Han, Pratik Pandharipande Section 14 Geriatrics and Palliative Care *The Geriatric Patient - Mary Mulcare, Alexis Halpern, Michael Stern*Palliative Care in the Emergency Department - Lawrence Ho, J. Randall Curtis Section 15 The ED-ICU Transfer of Care *Emergency Department Evaluation of the Critical Ill Patient - Geoffrey K. Lighthall, John E. Arbo*Severity of Illness Scores and Prognostication - David Maslove*Indications for Contact and Respiratory Isolation - Chanu Rhee, Michael Klompas Epilogue - Scott Weingart
Rationale: Patients with refractory Mycobacterium avium complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates versus GBT alone by Month 6. Limited data are available regarding >6-month treatment in a refractory population.Objectives: Evaluate 12-month safety, tolerability, and efficacy of ALIS+GBT.Methods: Adults with refractory MAC lung disease not achieving culture conversion by CONVERT Month 6 could enroll in this open-label extension (INS-312) to receive 590 mg once-daily ALIS+GBT for 12 months. Two cohorts enrolled: the "ALIS-naive" cohort included patients randomized to GBT alone in CONVERT, and the "prior-ALIS" cohort included those randomized to ALIS+GBT in CONVERT. Safety and tolerability of ALIS over 12 months (primary endpoint) and culture conversion by Months 6 and 12 were assessed.Results: In the ALIS-naive cohort, 83.3% of patients (n = 75/90) experienced respiratory treatment-emergent adverse events (TEAEs), and 35.6% (n = 32) had serious TEAEs; 26.7% (n = 24) achieved culture conversion by Month 6 and 33.3% (n = 30) by Month 12. In the prior-ALIS cohort, 46.6% of patients (n = 34/73) experienced respiratory TEAEs, and 27.4% (n = 20) had serious TEAEs; 9.6% (n = 7) achieved culture conversion by Month 6 (≤14 mo ALIS exposure) and 13.7% (n = 10) by Month 12 (≤20 mo ALIS exposure). Nephrotoxicity-related TEAEs and measured hearing decline were infrequent in both cohorts.Conclusions: In up to 20 months of ALIS use, respiratory TEAEs were common, nephrotoxicity and hearing decline were infrequent, and culture conversion continued beyond 6 months of therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02628600).
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