Natural history and course of acquired lactic acidosis in adults. DCA-Lactic Acidosis Study Group.

STUDY OBJECTIVE: To determine the pathogenesis and clinical course of lactic acidosis in adults receiving standard medical care. DESIGN: Placebo arm of a 5-year prospective, randomized, blinded study comparing placebo and dichloroacetate as specific lactate-lowering therapy. Each patient received intravenous saline placebo in addition to conventional therapy. SETTING: Intensive care units of 10 tertiary care hospitals in North America. PATIENTS: One hundred twenty-six patients with lactic acidosis, defined as arterial blood lactate greater than or equal to 5 mmol/L and either arterial pH of less than or equal to 7.35 or base deficit greater than 6 mmol/L. Patients were followed for up to 6 months. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD demographic entry data for 126 patients included: age 56 +/- 17 years, lactate 10.4 +/- 5.5 mmol/L, pH 7.24 +/- 0.14, calculated base deficit 14.1 +/- 5.4, arterial systolic blood pressure 103 +/- 29 mm Hg, Glasgow Coma score 7.9 +/- 4.9, and APACHE II score 19.2 +/- 8.1. Despite fluids and pressors, 32% of patients had systolic blood pressures of less than or equal to 90 mm Hg in association with sepsis (59%), cardiac failure (18%), or hemorrhage (18%). The most common causes of lactic acidosis in the absence of shock were sepsis (49%), liver disease (15%), and respiratory failure (12%). The median survival was 38.5 hours. Survival at 24 hours was 59%. Arterial pH predicted 24-hour survival better than base deficit or bicarbonate level. Percent survival was 41% at 3 days and 17% at 30 days. Only 21% of patients survived to leave the intensive care unit, and 17% were discharged from the hospital. In patients receiving sodium bicarbonate, neither acid-base nor hemodynamic status improved. CONCLUSIONS: In this first prospective study of the clinical course of acute lactic acidosis in adults, nearly all subjects had both hemodynamic and nonhemodynamic (metabolic) underlying causes, many of which independently predicted survival and most of which were refractory to standard care.

Reflex sympathetic dystrophy following arterial blood gas sampling in the intensive care setting.

A 54-year-old woman developed signs and symptoms consistent with reflex sympathetic dystrophy in her left upper extremity following arterial puncture. Diagnosis was confirmed by bone scan, and sympathetic blockade with intravenous regional bretylium completely relieved her severe, intractable pain.

Pulmonary barotrauma in mechanical ventilation. Patterns and risk factors.

The incidence of mediastinal emphysema (ME) and pneumothorax (PTX) was analyzed to determine the roentgenographic patterns and risk factors for the development of barotrauma in a population of mechanically ventilated patients. The roentgenograms of 139 intubated patients admitted to our medical intensive care unit over a ten-month period were evaluated for the presence of ME and PTX. Barotrauma was diagnosed in 34 of these patients, and ME was the initial manifestation in 24 patients. Of these patients with initial ME, ten subsequently developed PTX, a positive predictive value of 42 percent. The adult respiratory distress syndrome (ARDS) patient population was at highest risk for barotrauma, with an intermediate risk seen in those admitted with COPD or pneumonia. Values of peak inspiratory pressure, positive end-expiratory pressure level, respiratory rate, tidal volume, and minute ventilation were significantly elevated in patients who developed barotrauma as compared with patients who did not develop barotrauma. However, these elevations in part reflect the high incidence of barotrauma in the ARDS population, a patient group in which all of the above parameters were elevated.

The role of bronchoalveolar lavage in patients considered for open lung biopsy.

In summary, BAL should be considered as a diagnostic alternative in many patients for whom open lung biopsy is considered. In the proper clinical setting, several disorders may be adequately confirmed or diagnosed by BAL, with or without transbronchial biopsy, avoiding the morbidity and mortality associated with open lung biopsy. Again in the immune-compromised host with diffuse pulmonary infiltrates, BAL is often the initial procedure of choice. In the future BAL will likely gain a more prominent role in the staging of interstitial and occupational lung diseases, as larger prospective studies are concluded.

Surgical management of chronic pulmonary thromboembolic disease.

Chronic obstruction of the proximal pulmonary arteries appears to be a rare complication of pulmonary thromboembolus. The syndrome, however, may prove to be more common than previously suspected as general awareness of the syndrome increases prompted by the availability of efficacious therapy. Medical management has been ineffective in providing symptomatic or consistent hemodynamic improvement in patients with this syndrome, but a growing body of literature now suggests that surgical relief of obstruction can be undertaken with acceptable surgical risk and with the expectation of dramatic clinical improvement in a selected group of patients. Although no true control groups exist, one might hypothesize that hemodynamic and clinical improvement may translate into improved survival in these patients as well. The most recent series reported by Daily et al7 is the first to include more than 100 patients, and their reported hospital mortality of less than 13% is very encouraging. Whether these results will be reproducible at other centers remains to be seen. It is hoped that future investigation will refine both patient selection and operative technique such that results continue to improve. Pulmonary physicians should be aware of the syndrome and have a high index of suspicion in patients with unexplained pulmonary hypertension or right-sided heart failure. V/Q scans have proved to be useful screening procedures in these patients and can help identify patients at risk who require further more invasive investigation.

Langerhans' cell histiocytosis associated with Hodgkin's disease: a case report.

A patient who developed pulmonary Langerhans' cell histiocytosis after chemotherapy for nodular sclerosing Hodgkin's disease is presented. Twenty-one cases of Langerhans' cell histiocytosis associated with Hodgkin's disease have been reported in the literature. Such an association seems to be more than fortuitous. The possibilities of a common etiological agent inducing both Hodgkin's disease and Langerhans' cell histiocytosis and of a reactive proliferation of Langerhans' cells after radiotherapy or chemotherapy for Hodgkin's disease are discussed.

In vivo assessment of airway inflammation.

Chronic obstructive pulmonary disease (COPD) and asthma are chronic inflammatory diseases which cause considerable morbidity and mortality. A number of in vivo methods have been developed to assess airway inflammation both to study mechanistic factors leading to airway inflammation as well as to assess disease activity. These have included non-invasive tests such as pulmonary function testing, bronchial provacation testing and nuclear medicine scans. Bronchoalveolar lavage and bronchoscopic derived biopsies of the airways have provided information regarding cell populations and inflammatory mediators involved in the pathogenesis of chronic airway and lung inflammation. Induced sputum may become a less invasive means to sample the lower respiratory tract in patients with these disorders.

Fear of success, fear of failure, and the imposter phenomenon: a factor analytic approach to convergent and discriminant validity.

A sample of 104 mid-level managers completed measures of fear of success, fear of failure, and the imposter phenomenon. First- and second-order factor analyses indicated that the instruments tapped two personality domains, lack of self-confidence and the competitive neurosis. Results are discussed in terms of the most appropriate use of the instruments employed in the analysis and the need to avoid redundancy in the development and popularization of new psychological constructs.

Intrapulmonary bronchogenic cyst: spontaneous dissolution?

A well-demarcated, non-calcific, solitary pulmonary nodule was initially discovered 3 v2 years ago on a chest radiograph in a 43-year-old woman with recurrent acute bronchitis. The nodNle had been stationary with minimal change in size until the last radiographic examination which showed total disappearance of the nodule. A thin-walled, air-filled cyst was, however, demonstrated by computed tomography at the same location. The nodule was believed to be an intrapulmonary bronchogenic cyst which developed communication with airway with discharge of its watery content, leading to its pseudo resolution.

Clinical risk factors for pulmonary barotrauma: a multivariate analysis.

Previous investigations have suggested that elevated airway pressures increase the risk of ventilator-induced pneumothorax. However, risk factor analysis using multivariate techniques has not been done. We investigated the hypothesis that airway pressures would not independently correlate with pneumothorax when underlying disease was considered. All ventilated patients over a 1 yr period in the Hohenburg Critical Care Unit at the University of Alabama were followed until death or discharge from the ICU. Ventilator data were collected daily and the presence of pneumomediastinum and pneumothorax determined by review of chest radiographs. Maximal values of airway pressures, minute ventilation, tidal volume, and respiratory rate, as well as age, sex, and underlying disease, were entered into logistic regression analysis. A total of 168 patients was studied, and 20 experienced pneumothorax. Multivariate analysis of the entire ventilated population revealed that only the presence of ARDS independently correlated with pneumothorax. A similar analysis performed on the ARDS population revealed independent correlation only with male sex. Trends toward elevation in airway pressures were seen that did not reach statistical significance. We conclude that development of pneumothorax is most closely correlated with underlying disease, specifically ARDS, and that the associations previously noted between airway pressures and barotrauma largely relate to the occurrence of high airway pressures in ARDS.

Pulmonary complications of transplantation.

Improved immunosuppressive regimens, advances in surgical proficiency and techniques, and improved supportive medical care have translated into dramatic increases in graft survival in organ transplantation and in patient outcome in bone marrow transplantation. Though effective immunosuppression has also led to an increase in infectious complications, several recent advances, including the development of effective surveillance protocols and antiviral therapy and the use of prophylactic antibiotics, appear to have made a significant positive impact on the management of infections and survival of transplant recipients. In addition, a clearer understanding of noninfectious pulmonary complications, such as bronchiolitis obliterans, and continued improvement in techniques for evaluating a host of posttransplant pulmonary disorders will likely further enhance posttransplant therapy and survival.

A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group.

BACKGROUND: Mortality is very high in lactic acidosis, and there is no satisfactory treatment other than treatment of the underlying cause. Uncontrolled studies have suggested that dichloroacetate, which stimulates the oxidation of lactate to acetyl-coenzyme A and carbon dioxide, might reduce morbidity and improve survival among patients with this condition. METHODS: We conducted a placebo-controlled, randomized trial of intravenous sodium dichloroacetate therapy in 252 patients with lactic acidosis; 126 were assigned to receive dichloroacetate and 126 to receive placebo. The entry criteria included an arterial-blood lactate concentration of > or = 5.0 mmol per liter and either an arterial-blood pH of < or = 7.35 or a base deficit of > or = 6 mmol per liter. The mean (+/- SD) arterial-blood lactate concentrations before treatment were 11.6 +/- 7.0 mmol per liter in the dichloroacetate-treated patients and 10.4 +/- 5.5 mmol per liter in the placebo group, and the mean initial arterial-blood pH values were 7.24 +/- 0.12 and 7.24 +/- 0.13, respectively. Eighty-six percent of the patients required mechanical ventilation, and 74 percent required pressor agents, inotropic drugs, or both because of hypotension. RESULTS: The arterial-blood lactate concentration decreased 20 percent or more in 83 (66 percent) of the 126 patients who received dichloroacetate and 45 (36 percent) of the 126 patients who received placebo (P = 0.001). The arterial-blood pH also increased more in the dichloroacetate-treated patients (P = 0.005). The absolute magnitude of the differences was small, however, and they were not associated with improvement in hemodynamics or survival. Only 12 percent of the dichloroacetate-treated patients and 17 percent of the placebo patients survived to be discharged from the hospital. CONCLUSIONS: Dichloroacetate treatment of patients with severe lactic acidosis results in statistically significant but clinically unimportant changes in arterial-blood lactate concentrations and pH and fails to alter either hemodynamics or survival.