Effects of propofol containing EDTA on mineral metabolism in medical ICU patients with pulmonary dysfunction.

OBJECTIVE: To determine whether the addition of disodium edetate (EDTA) to propofol significantly alters mineral metabolism, adverse events, and outcome in critically ill medical patients with acute pulmonary dysfunction. DESIGN: Multicentre, double-randomised, double-blind, comparative trial. SETTING: Medical intensive care units of 5 health centres. PATIENTS: A total of 85 haemodynamically stable men and women aged 18-81 years who had pulmonary dysfunction or adult respiratory distress syndrome as a primary diagnosis or complication and who were expected to require at least 48 hours of sedation and mechanical ventilation. INTERVENTIONS: Patients were randomised to receive propofol with or without EDTA and then to 1 of 2 sedation levels: light (Modified Ramsay Sedation Scale [MRSS] score of 2 to 3) or deep (MRSS score of 4 to 5). Propofol was administered by continuous infusion at an initial rate of 5 microg/kg per min and titrated as needed. MEASUREMENTS AND RESULTS: Approximately 63 % of patients had a high severity of illness as indicated by an Acute Physiology and Chronic Health Evaluation II score > or = 19. As expected, these patients had a higher mortality rate but did not require a higher dose of propofol or propofol with EDTA. Extensive evaluation of cation homeostasis showed that ionised calcium and magnesium concentrations remained remarkably stable during treatment. Total calcium concentration was low as a result of hypoalbuminemia. Parathyroid hormone (PTH) concentration was elevated in both study groups at baseline, on day 4, and at the end of sedation. There were no significant differences in electrolyte levels and no progression to renal dysfunction. There were also no significant differences in haemodynamic or adverse-event profiles. Treatment-related adverse events occurred in 5 patients in each group; 4 of these (in 3 patients receiving propofol and 1 patient receiving propofol with EDTA) were considered serious. Because a large percentage of patients experienced a change in sedation level, no analyses were performed using sedation level. CONCLUSIONS: The addition of EDTA to propofol does not alter calcium and magnesium homeostasis in critically ill patients with acute pulmonary dysfunction. The reason for the elevation in PTH concentrations in such patients is not known.

Isolated transient loss of consciousness is an indicator of significant injury.

OBJECTIVE: To determine if isolated transient loss of consciousness is an indicator of significant injury. SETTING: University-based level I trauma center. DESIGN AND PATIENT: Phase 1 retrospective case series of all patients with trauma admitted directly from the emergency department to the operating room or an intensive care unit who had transient loss of consciousness as their only trauma triage criterion. Phase 2 prospective case series of all trauma patients transported by emergency medical system personnel with transient loss of consciousness as their only trauma triage criterion. MAIN OUTCOME MEASURES: Emergency operation and intensive care unit admission. RESULTS: Phase 1: From January 1, 1992, to March 31, 1995, we admitted 10255 patients with trauma. Three hundred seven (3%) met the enrollment criteria and were admitted to the operating room (n = 168) or intensive care unit (n = 139). Of these, 58 (18.9%) were taken to the operating room emergently to manage life-threatening injuries: 11 (4%) had craniotomies and 47 (15%) had non-neurosurgical operations. Phase 2: From July 1 to December 31, 1996, 2770 trauma patients were transported to our facility; 135 (4.9%) met the enrollment criteria. Forty-one (30.4%) of these required admission, and 6 (4.4%) were taken emergently to the operating room from the emergency department (1 [1%] for a craniotomy, 3 [2.2%] for intra-abdominal bleeding, and 2 [1.5%] for other procedures). Two (1.5%) of the 135 patients died. CONCLUSIONS: Patients with isolated transient loss of consciousness are at significant risk of critical surgical and neurosurgical injuries. These patients should be triaged to trauma centers or hospitals with adequate imaging, surgical, and neurosurgical resources.

Intrathoracic neoplasms other than bronchogenic carcinoma.

Intrathoracic neoplasms other than bronchogenic carcinoma comprise a disparate group of tumors that have in common an anatomic location within the thorax. For the purposes of this review, they are divided into three categories: pulmonary metastases from locations other than the thorax, mediastinal neoplasms, and unusual primary lung neoplasms. This article reviews the recent literature; discusses evolving strategies for imaging, diagnosis, and treatment; and presents promising research developments.

Fentanyl remaining in a transdermal system following three days of continuous use.

OBJECTIVE: To determine whether there was a sufficient amount of fentanyl remaining in a patch that had been used continuously for 3 days to warrant establishment of disposal policies to prevent diversion of fentanyl. DESIGN: Nine patches were applied and removed by hospice nurses after 3 days of continuous use on hospice patients with cancer. Patches were analyzed for the remaining fentanyl contents using the Coat-A-Count Fentanyl radioimmunoassay. Five 2.5-mg patches and four 10.0-mg patches were opened, solubilized with methanol, diluted with water, and analyzed in duplicate. An unused 2.5-mg patch also was analyzed as a control and showed a 94% recovery of fentanyl. A methanol blank was negative for fentanyl. MAIN OUTCOME MEASURES: The study determined the amount of fentanyl in milligrams remaining in a used patch. Using pharmacokinetics principles, this quantity was compared with a potential lethal dose of fentanyl. RESULTS: Analysis showed 0.7-1.22 mg remaining in the 2.5-mg patches and 4.46-8.44 mg remaining in the 10.0-mg patches. These numbers represent 28-84.4% of the original contents. Using the pharmacokinetic values of the volume of distribution of 4L/kg and a potential lethal blood concentration of 3.7 micrograms/L, one can calculate the potential lethal dose for a 70-kg person to be 1036 micrograms. This is well within the amount remaining in the patch. This study also demonstrated that a wide patient variability exists in the absorption of fentanyl from the patch. CONCLUSIONS: There is a sufficient amount of fentanyl available for abuse and misuse after 3 days of therapeutic use. Adequate disposal policies currently are not established and need to be implemented.

Developing guidelines for biotechnology drug use: experience with antithrombin III.

Development of institutional guidelines for use of high-cost biotechnology drugs, such as antithrombin III, is a valuable tool in formulary management. This article describes the process by which the University of California Davis Medical Center used an ad hoc committee to the P & T Committee to develop guidelines for antithrombin III use. Performing an objective analysis of available literature to address the appropriate role of a biotechnology agent is necessary to develop consensus guidelines. Approval of use guidelines by the P & T Committee provides the necessary structure for optimal use of biotechnology agents, such as antithrombin III.

Intrathoracic neoplasms other than bronchogenic carcinoma.

Intrathoracic neoplasms other than lung cancer represent a diverse group of diseases. This review focuses on the recent literature addressing mediastinal neoplasms, unusual primary lung neoplasms, and pulmonary metastases from other locations. Advances in classification, imaging, diagnosis, surgical issues, and treatment issues shown in case series and individual case reports are presented and discussed.

The pharmacology and toxicology of three new biologic agents used in pulmonary medicine.

Biological agents have played an important role in the evolution of modern medical therapeutics. Recent advances in biologicals have in part been stimulated by the biotechnology revolution seen over the last several years. Toxicologists need to be aware of the proposed mechanisms and approved and experimental uses of these new biologic agents. Further, controversies about their use, efficacy, cost issues and potential toxicities should be known. Often these drugs are designed for small patient populations thus limiting the availability of human toxicological data bases. This paper reviews the pharmacology and toxicology of three new biologics (recombinant human DNase I, alpha 1-protease inhibitor, and nitric oxide). These agents appear to have important roles in treating specific diseases or disease states seen in pulmonary medicine.

Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome.

OBJECTIVE: To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS). DESIGN: A prospective, double-blind, placebo-controlled, randomized, parallel, multicenter pilot clinical trial. PATIENTS: A total of 51 patients with sepsis-induced ARDS were entered into the study within 18 hours of developing sepsis or sepsis syndrome. INTERVENTION: Patients were randomized into four treatment groups in a 2:1:2:1 ratio, as follows: 12 hours of surfactant per day, 12 hours of 0.6% saline per day, 24 hours of surfactant per day, and 24 hours of 0.6% saline per day. Surfactant or saline was aerosolized continuously for up to 5 days using an in-line nebulizer that aerosolized only during inspiration. MAIN OUTCOME MEASURES: Ventilatory data, arterial blood gases, and hemodynamic parameters were measured at baseline, every 4 or 8 hours during the 5 days of treatment, 24 hours after treatment, and 30 days after treatment, at which time mortality was also assessed. Safety was evaluated throughout the 30 days of the study. RESULTS: Surfactant was administered safely in ventilated patients when given continuously throughout the 5 days using the nebulizer system. Although there were no differences in any physiological parameters between the treatment groups, there was a dose-dependent trend in reduction of mortality from 47% in the combined placebo group to 41% and 35% in the groups treated with 12 hours and 24 hours of surfactant per day, respectively. CONCLUSIONS: Aerosolized surfactant was well tolerated when administered on a continuous basis for up to 5 days; however, at the doses given, it did not result in significant improvements in patients with sepsis-induced ARDS.

Greenfield inferior vena cava filter dislodged during central venous catheter placement.

Two cases of a Greenfield inferior vena cava (IVC) filter being dislodged during central venous catheter placement are described. This event appears to be related to J-tip guidewire use during venous catheterization. To our knowledge, this occurrence previously has not been reported. One of the two filters was dislodged from the IVC to a new position in the right atrium. Dislodging of the filter in these two particular cases did not give rise to clinical signs or symptoms.

Inhalation abuse of fentanyl patch.

A 36-year-old male became intoxicated from fentanyl by heating and inhaling the contents from a fentanyl patch. He collapsed immediately after one inhalation with a respiratory rate of 6/m, heart rate of 120 bpm, and unobtainable blood pressure. He responded to a naloxone injection. Inhalation abuse of fentanyl base is a novel phenomenon. In two studies of nebulized fentanyl at doses of 64-318 micrograms of fentanyl base, analgesia was achieved with these doses, and small decreases in respiratory rate occurred with the larger dose. The greater absorption expected from inhaling the volatilized product, the large quantity of fentanyl available in a patch, and the high potency of fentanyl produces a high potential for abuse and overdose.

Survival of patients undergoing Nd:YAG laser therapy compared with Nd:YAG laser therapy and brachytherapy for malignant airway disease.

Brachytherapy in combination with Nd:YAG laser therapy may add to the duration of survival of the palliative period when compared with laser alone. A retrospective study of patients with inoperable squamous cell carcinoma (SCC) was undertaken to determine if there was a difference in survival between those patients treated with Nd:YAG laser alone and those treated with Nd:YAG laser and brachytherapy. Twenty-two patients were treated with brachytherapy for malignant airway disease at our institution of which 13 had SCC. All patients had previously received treatment with Nd:YAG laser for exophytic disease. Survival was compared with those patients treated with Nd:YAG laser alone for SCC involving the airway. There was no statistical difference between the two groups with regard to age. The duration of survival of patients with SCC of the airway from the first Nd:YAG laser treatment was determined. A significant difference between those patients treated with Nd:YAG laser alone and those patients treated with combined therapy was found (p < 0.001). Brachytherapy may potentiate the duration of survival in patients with SCC involving the airway compared to palliation with Nd:YAG laser alone.

The effect of morphine and naloxone on cocaine toxicity.

The effect of morphine and naloxone on acute cocaine toxicity was studied. Male Sprague-Dawley rats were pretreated intraperitoneally (ip) with saline, morphine sulfate 25 mg/kg, or naloxone 1.0 mg/kg 15 minutes prior to challenge by cocaine. After pretreatment, each group was challenged with one of three doses of cocaine (35, 50, or 75 mg/kg ip). Each of the nine drug combinations was tested on at least 10 animals. Animals were observed for behavior, seizures, and death. The animals pretreated with saline and challenged with cocaine (35, 50, or 75 mg/kg) had seizure incidences of 0%, 40%, and 100%, respectively, after increasing doses. Pretreatment with morphine resulted in cocaine-induced seizures of 20%, 80% and 100%, respectively (p less than or equal to 0.05 with cocaine 35 and 50 mg/kg). Time to seizures in these groups did not differ significantly compared to the saline groups. Pretreatment with naloxone resulted in cocaine-induced seizures of 0%, 50%, and 60% (p less than or equal to 0.05 at the 75 mg/kg dose). The incidence of death was significantly increased by pretreatment with morphine in animals that received cocaine 50 or 75 mg/kg. The time to death was not significantly different compared to saline controls. The death rate in naloxone pretreated animals was not significantly different from the saline groups. In additional studies, high-dose naloxone pretreatment (10 mg/kg) also failed to provide protection from acute cocaine toxicity. In conclusion, cocaine toxicity is potentiated by morphine and does not appear to be altered by naloxone.

Lidocaine potentiation of cocaine toxicity.

STUDY HYPOTHESIS: The toxic effects of cocaine are enhanced in the presence of lidocaine. STUDY POPULATION: Male Sprague-Dawley rats weighing 200 to 300 g. METHODS: Animals received intraperitoneal injections of cocaine (10, 20, 35, or 50 mg/kg), lidocaine (30 or 40 mg/kg), or a combination of all doses of cocaine given simultaneously with 30 or 40 mg/kg lidocaine. The incidence and time to seizure and death were recorded in these groups and compared by chi 2 and analysis of variance analyses, respectively. RESULTS: At doses of 30 or 40 mg/kg, lidocaine does not induce seizures or death. The effect of simultaneous injection of both cocaine and lidocaine was to dramatically increase the incidence of both seizures and death over that of cocaine alone. The incidence of seizures in animals receiving 35 mg/kg cocaine alone was 10%; this increased to 50% and 80% with the addition of 30 and 40 mg/kg lidocaine, respectively (P less than or equal to .05; P less than or equal to .01). Death did not occur in animals receiving 35 mg/kg cocaine alone; the addition of 30 and 40 mg/kg lidocaine resulted in death in 30% and 60% of animals, respectively (P less than or equal to .01 each group). Similarly, in rats receiving 50 mg/kg cocaine, the incidence of death increased from 0% to 60% and 80% with 30 and 40 mg/kg lidocaine, respectively (P less than or equal to .01). CONCLUSION: In the rat, overall toxicity of cocaine is significantly increased with simultaneous exposure to lidocaine.

Nd:YAG laser bronchoscopy. Rigid or fiberoptic mode?

One hundred twenty four Nd:YAG laser procedures were performed on 79 patients (age range, 25 to 89 years) over a five-year period at our institution. Over 90 percent of patients had malignant tumors. The fiberoptic bronchoscope (FOB group) was used exclusively during the first two years (61 cases, 32 patients). All except four of these cases utilized conscious sedation and local anesthesia. Subsequent to this, the rigid bronchoscope (RB group) was used as the primary instrument under general anesthesia (51 cases, 42 patients). Twelve cases combined both bronchoscopic modalities (combined group, 12 patients). The percentage improvement in proximal airway lumen diameter post-Nd:YAG laser therapy was significantly greater using the RB (p less than 0.05). For distal lesions, the FOB was superior (p less than 0.05). There was no difference in the complication or survival rates between the groups. Our data suggest that whenever possible, the RB should be used to treat proximal lesions, and the FOB should be used for distal lesions. Both bronchoscopes are often used together. Hence, laser bronchoscopists should be proficient in both bronchoscopic techniques.

Pressure controlled inverse ratio ventilation in severe adult respiratory failure.

Thirty-one patients with severe respiratory failure who were failing volume controlled conventional ratio ventilation were placed on pressure controlled inverse ratio ventilation (PC-IRV) for a total of 4,426 patient-hours. The PC-IRV resulted in a reduction of minute ventilation from 22 +/- 1.0 L/min (mean +/- SEM) to 15 +/- 0.7 L/min. Peak inspiratory pressure (PIP) was reduced from 66 +/- 2.3 cm H2O to 46 +/- 1.6 cm H2O and positive end expiratory pressures (PEEP) from 15 +/- 1.0 cm H2O to 2.5 +/- 0.5 cm H2O. Mean airway pressure increased from 30 +/- 1.7 cm H2O to 35 +/- 1.7 cm H2O. Oxygenation (PaO2) improved from 69 +/- 4.0 mm Hg to 80 +/- 4.5 mm Hg. The PaCO2 and arterial pH were not significantly changed. There were no significant changes in mean hemodynamic pressures. A lung compromise index (FIO2.PIP.10/PaO2) retrospectively distinguished between successful and unsuccessful PC-IRV episodes. These data suggest that PC-IRV can be successfully and safely implemented in critically ill patients with severe respiratory failure over prolonged periods of time resulting in significant improvement in oxygenation at lower minute volume, peak airway pressure and PEEP requirements.