Improving management of ARDS: uniting acute management and long-term recovery.

Acute Respiratory Distress Syndrome (ARDS) is an important global health issue with high in-hospital mortality. Importantly, the impact of ARDS extends beyond the acute phase, with increased mortality and disability for months to years after hospitalization. These findings underscore the importance of extended follow-up to assess and address the Post-Intensive Care Syndrome (PICS), characterized by persistent impairments in physical, cognitive, and/or mental health status that impair quality of life over the long-term. Persistent muscle weakness is a common physical problem for ARDS survivors, affecting mobility and activities of daily living. Critical illness and related interventions, including prolonged bed rest and overuse of sedatives and neuromuscular blocking agents during mechanical ventilation, are important risk factors for ICU-acquired weakness. Deep sedation also increases the risk of delirium in the ICU, and long-term cognitive impairment. Corticosteroids also may be used during management of ARDS, particularly in the setting of COVID-19. Corticosteroids can be associated with myopathy and muscle weakness, as well as prolonged delirium that increases the risk of long-term cognitive impairment. The optimal duration and dosage of corticosteroids remain uncertain, and there's limited long-term data on their effects on muscle weakness and cognition in ARDS survivors. In addition to physical and cognitive issues, mental health challenges, such as depression, anxiety, and post-traumatic stress disorder, are common in ARDS survivors. Strategies to address these complications emphasize the need for consistent implementation of the evidence-based ABCDEF bundle, which includes daily management of analgesia in concert with early cessation of sedatives, avoidance of benzodiazepines, daily delirium monitoring and management, early mobilization, and incorporation of family at the bedside. In conclusion, ARDS is a complex global health challenge with consequences extending beyond the acute phase. Understanding the links between critical care management and long-term consequences is vital for developing effective therapeutic strategies and improving the quality of life for ARDS survivors.

Delirium, depression, and long-term cognition.

OBJECTIVES: We examined whether preadmission history of depression is associated with less delirium/coma-free (DCF) days, worse 1-year depression severity and cognitive impairment. DESIGN AND MEASUREMENTS: A health proxy reported history of depression. Separate models examined the effect of preadmission history of depression on: (a) intensive care unit (ICU) course, measured as DCF days; (b) depression symptom severity at 3 and 12 months, measured by the Beck Depression Inventory-II (BDI-II); and (c) cognitive performance at 3 and 12 months, measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) global score. SETTING AND PARTICIPANTS: Patients admitted to the medical/surgical ICU services were eligible. RESULTS: Of 821 subjects eligible at enrollment, 261 (33%) had preadmission history of depression. After adjusting for covariates, preadmission history of depression was not associated with less DCF days (OR 0.78, 95% CI, 0.59-1.03 p = 0.077). A prior history of depression was associated with higher BDI-II scores at 3 and 12 months (3 months OR 2.15, 95% CI, 1.42-3.24 p = <0.001; 12 months OR 1.89, 95% CI, 1.24-2.87 p = 0.003). We did not observe an association between preadmission history of depression and cognitive performance at either 3 or 12 months (3 months beta coefficient -0.04, 95% CI, -2.70-2.62 p = 0.97; 12 months 1.5, 95% CI, -1.26-4.26 p = 0.28). CONCLUSION: Patients with a depression history prior to ICU stay exhibit a greater severity of depressive symptoms in the year after hospitalization.

An evaluation of single question delirium screening tools in older emergency department patients.

OBJECTIVES: To determine the diagnostic performances of several single question delirium screens. To the patient we asked: "Have you had any difficulty thinking clearly lately?" To the patient's surrogate, we asked: "Is the patient at his or her baseline mental status?" and "Have you noticed the patient's mental status fluctuate throughout the course of the day?" METHODS: This was a prospective observational study that enrolled English speaking patients 65 years or older. A research assistant (RA) and emergency physician (EP) independently asked the patient and surrogate the single question delirium screens. The reference standard for delirium was a consultation-liaison psychiatrist's assessment using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. All assessments were performed within 3 h and were all blinded to each other. RESULTS: Of the 406 patients enrolled, 50 (12%) were delirious. A patient who was unable to answer the question "Have you had any difficulty thinking clearly lately?" was 99.7% (95% CI: 98.0%-99.9%) specific, but only 24.0% (95% CI: 14.3%-37.4%) sensitive for delirium when asked by the RA. The baseline mental status surrogate question was 77.1% (95% CI: 61.0%-87.9%) sensitive and 87.5% (95% CI: 82.8%-91.1%) specific for delirium when asked by the RA. The fluctuating course surrogate question was 77.1% (95% CI: 61.0%-87.9%) sensitive and 80.2% (95% CI: 74.8%-84.7%) specific. When asked by the EP, the single question delirium screens' diagnostic performances were similar. CONCLUSIONS: The patient and surrogate single question delirium assessments may be useful for delirium screening in the ED.

Long-term cognitive impairment after critical illness.

BACKGROUND: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. METHODS: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. RESULTS: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. CONCLUSIONS: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

Emergence from general anaesthesia and evolution of delirium signs in the post-anaesthesia care unit.

BACKGROUND: Emergence from anaesthesia is often accompanied by signs of delirium, including fluctuating mental status and inattention. The evolution of these signs of delirium requires investigation since delirium in the post-anaesthesia care unit (PACU) may be associated with worse outcomes. METHODS: Adult patients emerging from anaesthesia were assessed for agitated emergence in the operating room using the Richmond Agitation-Sedation Scale (RASS). The Confusion Assessment Method for the Intensive Care Unit was then used to evaluate delirium signs at PACU admission and during PACU stay at 30 min, 1 h, and discharge. Signs consistent with delirium were classified as hyperactive vs hypoactive based upon a positive CAM-ICU assessment and the concomitant RASS score. Multivariable logistic regression was utilized to assess potential risk factors for delirium during PACU stay including age, American Society of Anesthesiologists classification, and opioid and benzodiazepine exposure. RESULTS: Among 400 patients enrolled, 19% had agitated emergence. Delirium signs were present at PACU admission, 30 min, 1 h, and PACU discharge in 124 (31%), 59 (15%), 32 (8%), and 15 (4%) patients, respectively. In patients with delirium signs, hypoactive signs were present in 56% at PACU admission and in 92% during PACU stay. Perioperative opioids were associated with delirium signs during PACU stay (P=0.02). CONCLUSIONS: A significant proportion of patients develop delirium signs in the immediate postoperative period, primarily manifesting with a hypoactive subtype. These signs often persist to PACU discharge, suggesting the need for structured delirium monitoring in the PACU to identify patients potentially at risk for worse outcomes in the postoperative period.

Insulin-like growth factor-1 and delirium in critically ill mechanically ventilated patients: a preliminary investigation.

BACKGROUND: Delirium occurs frequently in the intensive care unit (ICU), but its pathophysiology is still unclear. Low levels of insulin-like growth factor 1 (IGF-1), a hormone with neuroprotective properties, have been associated with delirium in some non-ICU studies, but this relationship has not been examined in the ICU. We sought to test the hypothesis that low IGF-1 concentrations are associated with delirium during critical illness. METHODS: Mechanically ventilated medical ICU patients were prospectively enrolled, and blood was collected after enrollment for measurement of IGF-1 using radioimmunometric assay. Delirium and coma were identified daily using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale, respectively. The association between IGF-1 and delirium was evaluated with logistic regression. In addition, the association between IGF-1 and duration of normal mental state, measured as days alive without delirium or coma, was assessed using multiple linear regression. RESULTS: Among 110 patients, the median age was 65 years (IQR, 52-75) and APACHE II was 27 (IQR, 22 -32). IGF-1 levels were not a risk factor for delirium on the day after IGF-1 measurement (p = 0.97), at which time 65% of the assessable patients were delirious. No significant association was found between IGF-1 levels and duration of normal mental state (p = 0.23). CONCLUSIONS: This pilot study, the first to investigate IGF-1 and delirium in critically ill patients, found no association between IGF-1 and delirium. Future studies including serial measurements of IGF-1 and IGF-1 binding proteins are needed to determine whether this hormone has a role in delirium during critical illness.

Adaptation and Validation of a Chart-Based Delirium Detection Tool for the ICU (CHART-DEL-ICU).

OBJECTIVE: To adapt and validate a chart-based delirium detection tool for use in critically ill adults. DESIGN: Validation study. SETTING: Medical-surgical intensive care unit (ICU) in an academic hospital. MEASUREMENTS: A chart-based delirium detection tool (CHART-DEL) was adapted for use in critically ill adults (CHART-DEL-ICU) and compared with prospective delirium assessments (i.e., clinical assessments (reference standard) by a research nurse trained by a neuropsychiatrist and routine delirium screening tools Confusion Assessment Method (CAM-ICU)) and (Intensive Care Delirium Screening Checklist (ICDSC)). The original CHART-DEL tool was adapted to include physician-reported ICDSC score (for probable delirium) and Richmond-Agitation Sedation Scale score (for altered level of consciousness and agitation). Two trained chart abstractors blinded to all delirium assessments manually abstracted delirium-related information from medical charts and electronic medical records and rated if delirium was present (four levels: uncertain, possible, probable, definite) or absent (no evidence). RESULTS: Charts were manually abstracted for delirium-related information for 213 patients who were included in a prospective cohort study that included prospective delirium assessments. The CHART-DEL-ICU tool had excellent interrater reliability (kappa = 0.90). Compared to the reference standard, the sensitivity was 66.0% (95% CI = 59.3-72.3%) and specificity was 82.1% (95% CI = 78.0-85.7%), with a cut-point that included definite, probable, possible, and uncertain delirium. The AUC of the CHART-DEL-ICU alone is 74.1% (95% CI = 70.4-77.8%) compared with the addition of the CAM-ICU and ICDSC (CAM-ICU/CHART-DEL-ICU: 80.9% (95% CI = 77.8-83.9%), P = .01; ICDSC/CHART-DEL-ICU: 79.2% (95% CI = 75.9-82.6%), P = .03). CONCLUSION: A chart-based delirium detection tool has improved diagnostic accuracy when combined with routine delirium screening tools (CAM-ICU and ICDSC), compared to a chart-based method on its own. This presents a potential for retrospective detection of delirium from medical charts for research or to augment routine delirium screening methods to find missed cases of delirium.

The CAM-ICU-7 and ICDSC as measures of delirium severity in critically ill adult patients.

BACKGROUND: In clinical practice, a dichotomous approach to delirium identification may no longer be relevant when existing delirium screening tools measure a range of scores. The objective of this study was to compare the Confusion Assessment Method for the Intensive Care Unit 7-item (CAM-ICU-7) and the Intensive Care Delirium Screening Checklist (ICDSC) as measures of the spectrum of delirium severity in critically ill adult patients. METHODS: In this cross-sectional study, 218 patients underwent 641 paired assessments by bedside nurses (ICDSC, as per usual care) and trained research assistants (CAM-ICU-7). Correlation between the CAM-ICU-7 and ICDSC scores was evaluated. Logistic regression was used to explore associations between CAM-ICU-7 or ICDSC score and length of ICU stay and mechanical ventilation (receipt, ≥96 hours). RESULTS: Delirium prevalence evaluated by the CAM-ICU-7 and ICDSC were 46.3% (95% CI:39.7-53.0) and 34.4% (95% CI:28.3-41.0). Prevalence of less than clinical threshold symptoms of delirium evaluated by the CAM-ICU-7 (score: 1-2) and ICDSC (score: 1-3) were 30.3% (95%CI:24.5-36.7) and 50.9% (95%CI:44.3-57.6). The CAM-ICU-7 and ICDSC had significant positive correlation (0.58, p<0.001). Agreement between the tools as measures of delirium was moderate (kappa = 0.51) and as measures of less than clinical threshold symptoms of delirium was fair (kappa = 0.21). Less than clinical threshold symptoms of delirium identified by the ICDSC, not CAM-ICU-7, were associated with prolonged length of ICU stay (≥7 days) in patients <65 years of age [Odds Ratio (OR) 9.2, 95% CI:2.5-34.0] and mechanical ventilation (receipt: OR 2.8, 95% CI:1.3-6.4; ≥96 hours: OR 6.6, 95% CI:1.9-22.9), when compared to patients with no delirium. CONCLUSIONS: The CAM-ICU-7 and ICDSC are measures of the spectrum of delirium severity that are closely correlated. Less than clinical threshold symptoms of delirium measure by the ICDSC is a better predictor of outcomes, when compared with the CAM-ICU-7.

Feasibility and acceptability of family administration of delirium detection tools in the intensive care unit: a patient-oriented pilot study.

BACKGROUND: Family-administered delirium detection tools may serve as valuable diagnostic adjuncts because family caregivers may be better able than providers to detect changes in patient cognition and behaviour from pre-illness levels of functioning. The aim of this pilot study was to assess the feasibility and acceptability of family-administered tools to detect delirium in critically ill patients. METHODS: In this single-centre pilot tool validation study conducted in August and September 2017, eligible family caregivers used the Family Confusion Assessment Method (FAM-CAM) and the Sour Seven questionnaire to detect delirium during the patient's intensive care unit (ICU) stay. We calculated descriptive statistics for all study variables. Patients and family caregivers were involved as research partners throughout the study. A patient-orient research approach was taken, engaging patients and family caregivers as full partners. RESULTS: Of 141 patients admitted to the ICU, 75 were eligible, of whom 53 were approached; 21 patients (40%), 23/38 family caregivers (60%) and 17/38 dyads (i.e., patient and family caregiver enrolled together) (45%) consented to participate. The most common reason for nonenrolment was refusal by the family, who commonly reported feeling overwhelmed. The completion rate for the FAM-CAM and Sour Seven questionnaire was 74% (17/23). Among 13 dyads, family caregivers detected delirium in 5 patients (38%) using the FAM-CAM, and delirium or possible delirium in 8 patients (62%) using the Sour Seven questionnaire, whereas trained research assistants detected delirium in 8 patients (62%) using the Confusion Assessment Method for the Intensive Care Unit 7 and the Richmond Agitation-Sedation Scale (κ coefficient for agreement between the former and the FAM-CAM and Sour Seven questionnaire 0.62 and 0.85, respectively). INTERPRETATION: Administration of the FAM-CAM and Sour Seven questionnaire by family caregivers to detect delirium in the ICU is feasible and acceptable, although, as with most family engagement strategies, it was not desired by all. Results from this pilot study support a definitive study with a larger sample to enable calculation of inferential statistics, but additional recruitment strategies are necessary to improve the response rate. Trial registration: Clinicaltrials.gov, no. NCT03379129.

Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study.

BACKGROUND: Delirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment. METHODS: In this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study. We assessed patients at least once a day for delirium using the Confusion Assessment Method-ICU and identified a priori-defined, non-mutually exclusive phenotypes of delirium per the presence of hypoxia, sepsis, sedative exposure, or metabolic (eg, renal or hepatic) dysfunction. We considered delirium in the absence of hypoxia, sepsis, sedation, and metabolic dysfunction to be unclassified. 3 and 12 months after discharge, we assessed cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We used multiple linear regression to separately analyse associations between the duration of each phenotype of delirium and RBANS global cognition scores at 3-month and 12-month follow-up, adjusting for potential confounders. FINDINGS: Between March 14, 2007, and May 27, 2010, 1048 participants were enrolled, eight of whom could not be analysed. Of 1040 participants, 708 survived to 3 months of follow-up and 628 to 12 months. Delirium was common, affecting 740 (71%) of 1040 participants at some point during the study and occurring on 4187 (31%) of all 13 434 participant-days. A single delirium phenotype was present on only 1355 (32%) of all 4187 participant-delirium days, whereas two or more phenotypes were present during 2832 (68%) delirium days. Sedative-associated delirium was most common (present during 2634 [63%] delirium days), and a longer duration of sedative-associated delirium predicted a worse RBANS global cognition score 12 months later, after adjusting for covariates (difference in score comparing 3 days vs 0 days: -4·03, 95% CI -7·80 to -0·26). Similarly, longer durations of hypoxic delirium (-3·76, 95% CI -7·16 to -0·37), septic delirium (-3·67, -7·13 to -0·22), and unclassified delirium (-4·70, -7·16 to -2·25) also predicted worse cognitive function at 12 months, whereas duration of metabolic delirium did not (1·14, -0·12 to 3·01). INTERPRETATION: Our findings suggest that clinicians should consider sedative-associated, hypoxic, and septic delirium, which often co-occur, as distinct indicators of acute brain injury and seek to identify all potential risk factors that may impact on long-term cognitive impairment, especially those that are iatrogenic and potentially modifiable such as sedation. FUNDING: National Institutes of Health and the Department of Veterans Affairs.

A research algorithm to improve detection of delirium in the intensive care unit.

INTRODUCTION: Delirium is a serious and prevalent problem in intensive care units (ICU). The purpose of this study was to develop a research algorithm to enhance detection of delirium in critically ill ICU patients using chart review to complement a validated clinical delirium instrument. METHODS: Prospective cohort study of 178 patients 60 years and older admitted to the Medical ICU. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and a validated chart review method for delirium were performed daily. We assessed the diagnostic accuracy of the chart-based delirium method using the CAM-ICU as the gold standard. We then used an algorithm to detect delirium first using the CAM-ICU ratings, then chart review when the CAM-ICU was unavailable. RESULTS: When using both the CAM-ICU and the chart-based review the prevalence of delirium was 143/178 (80%) patients or 929/1457 (64%) of patient-days. Of these, 292 patient-days were classified as delirium by the CAM-ICU, and the remainder (n=637 patient-days) were classified as delirium by the validated chart review method when the CAM-ICU was missing due to weekends or holidays (404 patient-days), when CAM-ICU was not performed due to stupor or coma (205 patient-days), and when the CAM-ICU was negative (28 patient-days). Sensitivity of the chart-based method was 64% and specificity was 85%. Overall agreement between chart and the CAM-ICU was 72%. CONCLUSIONS: Eight of 10 patients in this cohort study developed delirium in the ICU. Although use of a validated delirium instrument with frequent direct observations is recommended for clinical care, this approach may not always be feasible, especially in a research setting. The algorithm proposed here comprises a more comprehensive method for delirium detection in a research setting taking into account the fluctuation that occurs with delirium, a key component to accurately determining delirium status. Improving delirium detection is of paramount importance first to advance delirium research and, subsequently to enhance clinical care and patient safety.

Neutrophil release of arachidonic acid, oxidants, and proteinases: causally related or independent.

This investigation examined the concept that arachidonic acid (AA) serves as a second messenger in stimulation of the respiratory burst and degranulation of polymorphonuclear neutrophils (PMN). The main support for this idea is from observations that reagent AA, added to cell suspensions, stimulates the respiratory burst and degranulation and these events are blocked by PLA2 inhibitors. We verified that exogenously-added AA stimulated release of O2-, myeloperoxidase (MPO), and lysozyme (LZ), but this required amounts of AA which approximated the critical micellar concentration. This suggested that such administration of AA might act as an extracellular agonist, similar to particulate stimuli, rather than acting as a second messenger as might occur following mobilization of AA from cellular membranes. To investigate the role of fatty acids released by hydrolysis of cellular phospholipids, exogenously-added group I, II or III PLA2's were used to mobilize fatty acids from cellular membranes. Mole quantities of cell-associated free fatty acids were measured by negative ion chemical ionization gas chromatography/mass spectrometry. AA mobilization in response to exogenous PLA2 was dose- (0.1 to 10 U/ml PLA2) and time-dependent (peak at 1 to 2 min with a reduction by 4 min). Resting neutrophils contained < 10 pmol free AA/10(7) PMN; the receptor-mediated agonist N-formyl-methionyl-leucyl-phenylalanine (fMLP) alone did not increase these values. Exogenously-added PLA2 generated large quantities of free AA in control and fMLP-treated cells (462 +/- 122 and 2097 +/- 176 pmol/10(7) PMN, respectively); however, this did not induce O2-, nor did it augment the level of O2- stimulated by fMLP. Also, PLA2 caused no degranulation and did not alter degranulation induced by fMLP. PLA2 also did not alter O2- or degranulation responses in primed PMN. The data indicate that mobilization of AA from cellular phospholipids neither stimulates nor modulates the respiratory burst or degranulation of PMN.

Alpha-2 agonists: can they modify the outcomes in the Postanesthesia Care Unit?

While most patients recover uneventfully from the effects of anesthesia and surgery, for a small percentage of patients the immediate postoperative period can be a period of significant physiological stress. Hence the goal for a Post Anesthesia Care Unit (PACU) is to provide a safe environment for a patient to recover, while avoiding the undesirable side effects of pain, nausea, vomiting and shivering, and to monitor for potentially life threatening hemodynamic and respiratory complications that may require admission into the intensive care unit (ICU). Anesthetic techniques in the operating room are extremely important as these may have significant bearing on the post-operative course. The type of surgery, the patients' co morbid conditions, anticipated extubation and recovery of the patient, as well as the sophistication of the PACU and the expertise of its staff, all influence the choice of anesthetic technique. These agents, however, may themselves contribute to some of the complications and unpleasant events encountered in the PACU. Therefore, evaluation of newer and safer agents, which promote a smoother PACU transition, are warranted. Alpha 2 agonists are increasingly being used as adjuvant therapeutic agents in the perioperative period because of their ability to block the sympathetic stress response, complete with their anesthetic and analgesic sparing properties, lack of respiratory depression and low and predictable side effect profile.

Cryptococcal pneumonia complicating pregnancy.

In the present report we describe 4 previously healthy women who developed cryptococcal pneumonia during pregnancy, and 1 pregnant woman with cryptococcal meningitis. These cases illustrate a previously uncharacterized spectrum of cryptococcal disease. We also discuss 24 patients previously reported who had cryptococcal meningitis during pregnancy. Finally, we review the available data for each therapeutic option and present an algorithm for management based on appraisals of disease severity and risk to the unborn fetus. This report emphasizes the need for heightened awareness of cryptococcosis in the differential diagnosis of pneumonia, chest pain, and hypoxemia in the pregnant patient, but at present, there are insufficient epidemiologic data to determine whether incidences of pulmonary or disseminated cryptococcosis actually increase during pregnancy. The risk of congenital cryptococcosis to the unborn fetus is low, and the most likely mechanism whereby neonates acquire invasive fungal pulmonary infection is through aspiration. While it is unclear whether there is any real increased risk of spontaneous abortion or premature labor, the data indicate that overall fetal outcome depends on effective treatment of maternal infection. For patients with dense air-space consolidation, progressive pulmonary disease, or dissemination, antifungal therapy is necessary. Optimal treatment is determined by the acuity and severity of the clinical presentation. Amphotericin B (approximately 1 g) with or without flucytosine represents the choice for initial treatment of the more acutely ill patient with disseminated or progressive pulmonary cryptococcosis who requires hospitalization (whether during or after pregnancy). Oral fluconazole appears to be safe and effective alternative therapy after delivery for the less severely ill patient who can be managed on an outpatient basis. While the use of fluconazole during pregnancy generally appears safe in terms of fetal outcome (49, 58), the class C status and single report of fetal malformation (62) preclude confident recommendation for its use during pregnancy. The risks and benefits of this effective and generally less toxic drug should be discussed with the parents and weighed against the use of amphotericin B. For pregnant women with limited pulmonary cryptococcosis (segmental or nodular infiltrates) and no evidence of dissemination, we recommend close follow-up without antifungal therapy similar to the recommendation for normal hosts with minimal disease. However, it is important to note that there is no extensive experience upon which to base this recommendation for pregnant individuals (45, 55, 103, 108). It is prudent to use frequent physical examinations (for example, every 1-2 months), combined with chest roentgenograms and serum cryptococcal antigens to monitor progression and/or development of disease in both the mother and child for approximately 6 months postpartum. In conclusion, cryptococcosis during pregnancy presents a special challenge to the clinician. A balanced therapeutic approach holds great promise for successful maternal and fetal outcomes.

Warehouse workers' headache: emergency evaluation and management of 30 patients with carbon monoxide poisoning.

BACKGROUND: Carbon monoxide (CO) is the leading cause of fatal toxic inhalation in the United States, but the medical literature contains few reports of mass exposures. Warehouse workers' headache (WWH) is an infrequently reported form of CO poisoning due to industrial exposure. METHODS: We describe 30 persons who developed WWH after inhaling exhaust from a propane-fueled forklift, their emergency medical management at a small community hospital, and their long-term courses. RESULTS: Workers with more direct exposures to vented exhaust had significantly higher expired CO levels (21.1 +/- 0.7% versus 8.4 +/- 4.8%, P < 0.0001) and higher acute symptom scores (9.0 +/- 2.2 versus 4.7 +/- 3.3, P = 0.01) than persons with less direct exposures. Work location, expired CO levels, and acute symptom scores did not correlate with symptom scores 2 years after exposure. Workers experiencing acute difficulty concentrating or confusion had higher expired CO levels than persons with neither of these symptoms (16.3 +/- 6.7% versus 8.4 +/- 5.2%, P = 0.005) and developed higher chronic symptom scores (3.9 +/- 3.0 versus 1.1 +/- 1.5, P = 0.04), suggesting that this subgroup may require closer follow-up for long-term complications. CONCLUSION: With earlier recognition of ongoing CO toxicity, this disaster would likely have been averted. Since CO exposures are more common than is often recognized, general internists must be familiar with the manifestations of CO toxicity, its timely evaluation, management, and prevention.

Thoracic complications of dental surgical procedures: hazards of the dental drill.

CASE REPORTS: Dental surgical procedures occasionally result in intrathoracic complications that may subsequently be encountered by clinicians. We report four patients with such complications, including pneumomediastinum, fatal descending necrotizing mediastinitis, and Lemierre's syndrome. In each of these patients, the commonly used dental handpiece with exhausted air directed to the working drill point was an important, but unrecognized, predisposition to their intrathoracic complication. CONCLUSION: Clinicians should be aware of the spectrum of these problems and, in particular, of the potential hazards of pressurized nonsterile air blown into open surgical sites by the dental drill.

Pulmonary veno-occlusive disease: a case series and new observations.

STUDY OBJECTIVES: The aim of this study was to describe our experience at one institution with pulmonary veno-occlusive disease (PVOD) during the past 10 years, with particular reference to new findings and long-term outcome. SETTING: Tertiary care, academic medical center. PATIENTS AND METHODS: Eleven patients who were evaluated and treated for PVOD at our institution were retrospectively studied. Included were all available clinical, radiographic, hemodynamic, and pathologic data. RESULTS: All 11 patients in our series had at least one symptom or clinical finding that, in conjunction with known pulmonary hypertension, suggested the diagnosis of PVOD. Digital clubbing, not previously reported in PVOD, was found in 5 patients, rales in 6, and increased interstitial markings on chest radiograph in 10. Half of the 10 patients who underwent acute vasodilator testing exhibited a decrease in pulmonary artery pressure of > 20%, although one patient died shortly after receiving IV calcium-channel blockers. Three patients have demonstrated sustained clinical improvement with therapy, which includes calcium-channel blockers, epoprostenol, and lung transplantation in one patient each. However, outcome was generally poor, with a 72% mortality within 1 year of diagnosis. CONCLUSION: The diagnosis of PVOD requires a high clinical suspicion. However, both physical examination findings and radiographic studies often provide clues to the diagnosis, which may obviate the need for lung biopsy in the majority of cases. Although there may be patients who respond to medical therapy, the use of vasoactive medications in patients with PVOD should be undertaken with great caution. Long-term survival is poor, and lung transplantation remains the only proven therapy.

Portable chest radiographs identify mechanical ventilator-associated hyperinflation.

OBJECTIVE: Portable chest radiographs (CRs) are obtained routinely in mechanically ventilated patients, but little is known about relationships between CR findings and ventilator parameters. It is unclear whether radiographically apparent hyperinflation correlates with tidal volume (VT), body weight (BW), VT/kg, or levels of peak airway pressure (PAP), positive end-expiratory pressure (PEEP), or pressure support (PS). DESIGN: Prospective comparison of CR and ventilator parameters in 62 mechanically ventilated patients in surgical and medical intensive care units of a university hospital. PATIENT SELECTION: All mechanically ventilated adults with portable CR on four separate dates. METHODS: Chest radiographs were classified by subjective assessments as hyperinflated (H+) or nonhyperinflated (H-), independent of knowledge of patients or their mechanical ventilation. Chest radiographs were reclassified independently as H+, H-, or indeterminate by a radiologist using objective criteria. Ventilator parameters recorded at the time of the CR were obtained and compared. RESULTS: Patients with CRs classified subjectively as H+ compared with patients with CRs classified as H- had a larger VT/kg (12.0 +/- 0.4 ml/kg [mean +/- SEM] vs 10.2 +/- 0.4; p = 0.004), lower BW (70.8 +/- 2.9 kg vs 81.5 +/- 3.8; p = 0.03), higher PEEP (6.5 +/- 0.5 cm H2O vs 5.0 +/- 0.4; p = 0.01), and higher PAP (38.2 +/- 2.1 cm H2O vs. 33.4 +/- 1.8; p = 0.06). Using objective CR classifications, patients with H+ CRs had a VT/kg of 12.6 +/- 0.4, larger than in the indeterminate (11.1 +/- 0.8) and H- (9.9 +/- 0.3) groups (p < 0.001). The BW differed among objectively classified groups (66.5 +/- 2.7 H+, 68.9 +/- 5.1 indeterminate, and 85.2 +/- 3.7 H-; p < 0.001), but other ventilator parameters did not correlate univariately with the degree of inflation on CR. Multivariate analysis showed that higher VT was predictive of H+ after adjusting for BW in subjective (p = 0.076) and objective (p = 0.017) classifications. PEEP (p = 0.004) and older age (p = 0.021) were also associated with H+ in multivariate analysis. Four of 25 (16 percent) patients with objectively H+ CRs developed barotrauma, while no patient with H- CR had this complication (p = 0.037). CONCLUSIONS: In mechanically ventilated patients, hyperinflation seen on portable CR is associated with higher VT, VT/kg, and lower BW, and may help predict subsequent barotrauma.