Toxicology cart for stocking sufficient supplies of poisoning antidotes.

Within a three-month period, the University of New Mexico Health Sciences Center (UNMHSC) encountered three toxicological emergencies in which antidotes were either unavailable or inadequately stocked. Patient A was a patient with ethylene glycol intoxication. The emergency department (ED) physician ordered a 10% ethanol infusion. The pharmacy staff was unable to locate the commercially available solution and had to compound the infusion, resulting in a delay in administration of the antidote. Patient B was a patient at an outside hospital with organophosphate exposure whose transfer to our ED was requested by the other hospital. The pharmacy staff was unable to locate the pralidoxime needed to treat this patient; therefore; the patient was not transferred. It was later discovered that the pralidoxime had been stored in a location inconsistent with the storage policy for this medication. Patient C was a patient with severe rattlesnake envenomation. The pharmacy staff could locate only half of the antivenin needed to treat this patient. In each of these three cases, it was necessary to compound the required medication or to obtain it from other local facilities. These cases underscore the need for pharmacies to stock adequate amounts of poisoning antidotes in one immediately accessible location. A similar problem with understocking of poisoning antidotes exists throughout the United States.

Efficacy of monoclonal antibody against tumor necrosis factor alpha in an endotoxemic baboon model.

Tumor necrosis factor alpha (TNF) has been described as a primary mediator of the pathophysiology associated with bacterial sepsis/endotoxemia. We tested the efficacy and possible mechanisms of protection of a monoclonal antibody against TNF (TNF Mab) in a low mortality (29%), endotoxemic baboon model. A number of parameters were monitored at days 0, 1, 2 and 5-7 after challenge with 2 mg E. coli endotoxin/kg. TNF Mab pretreatment (15 mg/kg) prevented the increase in detectable serum TNF and the early perturbations in cardiovascular function which occurred in the control group. Early metabolic dysfunction was delayed in the TNF MAb group and was attenuated thereafter. Dysfunction of the kidney, liver, and coagulation systems and the increased IL-6 levels were significantly attenuated in the TNF MAb group; neutrophil activation was not affected by TNF MAb. No deaths occurred in the TNF MAb group. These results support the hypothesis that TNF plays a central role in the pathophysiology of endotoxic shock.

Characterization of an endotoxemic baboon model of metabolic and organ dysfunction.

An anesthetized endotoxemic baboon model has been developed by infusing 2.0 mg E. coli endotoxin/kg i.v. over 1 hr (n = 7). Animals were monitored for 5-7 days with analyses of: cardiovascular, metabolic, and organ dysfunction; acid base, hemostatic, and hematological alterations; as well as tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels. Pathophysiologies detected at 2 hr included transient decreases in vascular resistance and blood pressure, a 157% increase in blood lactate, and a 90% decrease in circulating neutrophils. Organ dysfunction was not observed until 24 hr and, although thrombocytopenia was prevalent (-72% at 48 hr), disseminated intravascular coagulation (DIC) was not a major pathology. Hematocrit fell 21% by 24 hr and was -41% at 5-7 days. Serum TNF peaked at 90 min (7.8 +/- 0.2 ng/mL) and was undetectable after 3 hr. IL-6 also increased early, peaked at 3 hr (3872 +/- 846 U/mL) and was still detectable at 24 hr. A low mortality primate model of gram-negative sepsis has been developed that is characterized by early cardiovascular and metabolic dysfunction (2-6 hr), late organ dysfunction (24-48 hr), sub-clinical DIC, a prolonged anemia, and a 29% mortality between 48 and 72 hr.

Airway blood flow distribution and lung edema after histamine infusion in awake sheep.

The present study was designed to evaluate the distribution of bronchial blood flow to major airways and peripheral lung and to quantitate lung edema during a 2-h histamine infusion (2 micrograms.kg-1.min-1) in unanesthetized sheep. By the use of radioactive microspheres, the blood flow to trachea and to tracheal cartilage, smooth muscle, and mucosa/submucosa was determined along with measurements of blood flow to different sized airway segments and the systemic blood flow to lung parenchyma. Histamine greatly increased blood flow to medium-sized (5- to 10-mm-diam) central airways in which blood flow increased 5-10 times base line, whereas in small (1- to 5-mm-diam) central airways the increase was 10-15 times. Blood flow in tracheal mucosa/submucosa increased six times base line, but in tracheal smooth muscle the increase was only three times base line, and in cartilage it remained at base line. Most of the systemic blood flow to the lung perfuses less than 1-mm-diam peripheral airways, and these airways demonstrated less vasodilation during histamine infusion. Mean blood flow to whole-lung parenchyma (whole lung minus trachea) was only two times base line during histamine infusion. Water content of trachea and main stem bronchi was significantly increased after histamine. Histopathologic findings after histamine infusions included congestion and edema of airways with only minor effects noted in alveoli. We conclude that histamine is a potent and selective vasodilator of bronchial vessels and particularly affects blood flow to central airways and to airway mucosal/submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of bronchial blood flow with radioactive microspheres in awake sheep.

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Small-volume resuscitation with hypertonic saline dextran solution.

Small-volume hypertonic resuscitation has been proposed as an effective means for restoration of cardiovascular function after hemorrhage at the scene of an accident. We evaluated the cardiovascular, metabolic, and neurohumoral response of resuscitation after hemorrhage using 200 ml of 2400 mosm sodium chloride, 6% dextran 70. Unanesthetized adult sheep were bled to maintain mean arterial pressure at 50 mm Hg for 3 hours, shed blood volume = 42 +/- 7 ml/kg. The sheep were then treated with a single bolus infusion of hypertonic saline dextran (n = 7) or normal saline solution (control group, n = 7) and then observed for a 30-minute period of simulated patient transport during which no additional fluid was given. Hypertonic saline dextran caused rapid restoration of blood pressure and cardiac output within 2 minutes of infusion. Cardiac output remained at or above baseline level, while both O2 consumption and urine output increased to above baseline level during the 30 minutes of simulated patient transport. By comparison 200 ml of normal saline solution caused only a small increase in blood pressure and no improvement in cardiac output or oxygen consumption. After this 30-minute period, both groups were given lactated Ringer's solution as needed to return and maintain cardiac output at its baseline value. The volume of lactated Ringer's solution required to maintain cardiac output was less in the hypertonic group, 371 +/- 168 ml, only one sixth that of the control group, 2200 +/- 814 ml. In summary after 3 hours of hypovolemia, a small volume of hypertonic saline dextran, about 4 ml/kg, fully restored cardiovascular and metabolic function for at least 30 minutes and significantly lowered the total volume requirements of resuscitation.