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Biomedical subjects

F H Sarnquist

Publications and source records attributed to F H Sarnquist.

17 recordsLinked to original sources

Acetazolamide in the treatment of acute mountain sickness: clinical efficacy and effect on gas exchange.

OBJECTIVE: To determine the efficacy of acetazolamide in the treatment of patients with acute mountain sickness and the effect of the drug on pulmonary gas exchange in acute mountain sickness. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: The Denali Medical Research Project high-altitude research station (4200 m) on Mt. McKinley, Alaska. PARTICIPANTS: Twelve climbers attempting an ascent of Mt. McKinley (summit, 6150 m) who presented to the medical research station with acute mountain sickness. INTERVENTION: Climbers were randomly assigned to receive acetazolamide, 250 mg orally, or placebo at 0 (baseline) and 8 hours after inclusion in the study. MAIN OUTCOME MEASURES: An assessment of acute mountain sickness using a symptom score and pulmonary gas exchange measurements was done at baseline and at 24 hours. MAIN RESULTS: After 24 hours, five of six climbers treated with acetazolamide were healthy, whereas all climbers who received placebo still had acute mountain sickness (P = 0.015). Arterial blood gas specimens were obtained from three of the six acetazolamide recipients and all of the placebo recipients. The alveolar to arterial oxygen pressure difference (PAO2-PaO2 difference) decreased slightly over 24 hours in the acetazolamide group (-0.8 +/- 1.2 mm Hg) but increased in the placebo group (+3.3 +/- 2.3 mm Hg) (P = 0.024). Acetazolamide improved PaO2 over 24 hours (+2.9 +/- 0.8 mm Hg) when compared with placebo (-1.3 +/- 2.8 mm Hg) (P = 0.045). CONCLUSION: In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange.

Acetazolamide↗

Anesthesia crisis resource management training: teaching anesthesiologists to handle critical incidents.

The authors have developed a course in Anesthesia Crisis Resource Management (ACRM) analogous to courses in Crew (Cock-pit) Resource Management (CRM) conducted in commercial and military aviation. Anesthesiologists do not typically receive formal training in crisis management although they are called upon to manage life-threatening crises at a moment's notice. Two model demonstration courses in ACRM were conducted using a realistic anesthesia simulation system to test the feasibility and acceptance of this kind of training. Anesthesiologists received didactic instruction in dynamic decision-making, human performance issues in anesthesia, and in the principles of anesthesia crisis resource management. After familiarization with the host institution's operating rooms and with the simulation environment, they underwent a 2-h simulation session followed by a debriefing session which used a videotape of their simulator performance. Participants rated the course as intense, helpful to their practice of anesthesiology, and highly enjoyable. Several aspects of the course were highly rated, including: videotapes of actual anesthetic mishaps, simulation sessions, and debriefing sessions. Scores on written tests of knowledge about anesthesia crisis management showed a significant improvement following the first course (residents) but not the second course (experienced anesthesiologists). Although the ultimate utility of this training for anesthesiologists cannot easily be determined, the course appeared to be a useful method for addressing important issues of anesthesiologist performance which have previously been dealt with haphazardly. The authors believe that ACRM training should become a regular part of the initial and continuing education of anesthesiologists.

Anesthesiology↗

Efficacy and safety of single doses of intramuscular ketorolac tromethamine compared with meperidine for postoperative pain.

Ketorolac tromethamine, a potent nonnarcotic prostaglandin synthetase-inhibiting analgesic, was compared with meperidine for relief of moderate to severe postoperative pain. In a double-blind, randomized study, 125 patients received single intramuscular doses of ketorolac 30 or 90 mg or meperidine 50 or 100 mg. The degree of pain and pain relief were quantified verbally and with visual analog scales at baseline and 30 minutes, then hourly for 6 hours. Ketorolac 30 and 90 mg were significantly superior to meperidine 50 mg in six of nine efficacy measures. The onset of and peak analgesic effect of both doses of ketorolac and of meperidine were equivalent. Compared with both doses of meperidine, the two doses of ketorolac exhibited significantly longer duration of analgesic effect, as measured by the percentage of patients who terminated the study because of inadequate pain relief. The frequency of side effects was not significantly different between the drugs. The prolonged efficacy of intramuscular ketorolac combined with the reduced risk of respiratory depression suggest an important use of this drug for the relief of postoperative pain.

Adolescent↗

A prospective, randomized study of the effects of prostacyclin on neuropsychologic dysfunction after coronary artery operation.

This randomized, double-blind study was designed to evaluate the effect of prostacyclin (epoprostenol) on the incidence and severity of postoperative neuropsychologic dysfunction in patients undergoing coronary artery operation. Four days before operation and 1 week after operation, 100 patients having coronary artery bypass grafting underwent detailed neurologic and psychologic examinations and computed tomographic scans of the brain. The psychologic examination was repeated 2 months after operation. During cardiopulmonary bypass, all patients received 300 U/kg of heparin and then either buffer-diluent or prostacyclin (12.5 ng/kg/min from the time of heparinization until onset of cardiopulmonary bypass and 25 ng/kg/min during cardiopulmonary bypass). No deaths or major neurologic complications occurred in this series. Ninety-six patients completed the psychologic and neurologic evaluations 1 week after operation; 74 of these patients were evaluated psychologically 2 months after operation. Psychologic testing demonstrated similar declines in postoperative performance in both the prostacyclin-treated and the control groups; these changes were no longer present in either group 2 months after operation. Results of neurologic examinations and computed tomographic scans of the brain were unchanged. We conclude that the administration of prostacyclin during cardiopulmonary bypass in patients undergoing routine coronary artery operation has no effect on perioperative cognitive changes.

Adult↗

A prospective, randomized study of the effects of prostacyclin on platelets and blood loss during coronary bypass operations.

A randomized, double-blind study was designed to evaluate the therapeutic effect and safety of prostacyclin (epoprostenol) in patients undergoing cardiopulmonary bypass. One hundred patients having isolated coronary bypass grafting received 300 units/kg of heparin and then either prostacyclin (12.5 ng/kg/min from heparinization until cardiopulmonary bypass, 25 ng/kg/min during bypass) or buffer/diluent in a similar manner. Standardized anesthetic, perfusion, and surgical techniques were used. Drug and placebo groups were similar in demographic data and bypass times, and there were no deaths. Activated coagulation time and platelet count were significantly higher during cardiopulmonary bypass in patients receiving prostacyclin. Platelet count remained significantly higher 24 hours after bypass in the active drug group. Immediately after operation, there was significantly less prolongation of bleeding time (1.3 versus 2.9 minutes; p = 0.009) in the patients receiving prostacyclin. Blood loss was significantly reduced during the first 4 hours postoperatively in the prostacyclin group (261 +/- 159 versus 347 +/- 197 ml; p = 0.02). There was no significant difference between the groups when total blood loss was compared (710 +/- 351 versus 869 +/- 498 ml; p = 0.07). Patients receiving prostacyclin required an average of 257 ml less blood transfused in the intensive care unit (p = 0.02). We conclude that the clinical impact of prostacyclin in patients undergoing coronary artery operations was demonstrable, but small. Prostacyclin may provide clinical benefits in patients undergoing cardiopulmonary bypass when there are contraindications to or other difficulties with blood transfusion. With prostacyclin, reduced heparin dose is possible and therefore reduced protamine requirement would offer a potential benefit of less cardiovascular depression immediately after bypass. However, the advantages offered by prostacyclin are not sufficient to recommend its routine use during cardiopulmonary bypass.

Adult↗

Hemodilution of polycythemic mountaineers: effects on exercise and mental function.

We studied the effects of acute, isovolemic hemodilution on the exercise ability and mental function of four polycythemic mountain climbers (mean hematocrit 58 +/- 1.25%) during the American Medical Research Expedition to Mt. Everest (AMREE). The subjects were studied at 5400 m (PB = 400 mm Hg). Approximately 15% of their blood volume was removed and replaced with an equal volume of 5% human albumin solution. Final hematocrits were 50.5 +/- 1.5%. Before and after hemodilution, the subjects performed psychological and exercise tests. Maximum work level, oxygen uptake, minute ventilation, and blood oxygen saturation did not change. After hemodilution, heart rate increased slightly at all work levels, and there was a small but significant improvement on the psychological tests. It is concluded that this degree of hemodilution was well tolerated and that a hematocrit of greater than 50% conferred no advantage for exercise and may have impaired cerebral function. Although, in these circumstances, isovolemic hemodilution improved cerebration, we feel that this potentially hazardous maneuver is rarely indicated.

Adult↗

Relationship of hypoxic ventilatory response to exercise performance on Mount Everest.

At very high altitude, exercise performance in the human sojourner may depend on a sufficient hypoxic ventilatory response (HVR). To study the relationship of HVR to exercise performance at high altitude, we studied HVR at sea level and 5,400 m and exercise ventilation at sea level, 5,400 m, and 6,300 m in nine members of the American Medical Research Expedition to Everest. The relationship of HVR between individuals was maintained when HVR was repeated after acclimatization to 5,400 m (P less than 0.05). There was a significant correlation in all subjects between HVR and ventilatory equivalent during exercise at sea level (r = 0.704, P less than 0.05). Subjects were then grouped into high (H) and low (L) HVR responders (ventilation increase to end-tidal PO2 of 40 Torr = 21.2 +/- 5.4 and 5.6 +/- 0.9 1 X min-1, respectively. At low and moderate levels of exercise, ventilation at sea level and after acclimatization to 6,300 m was higher in the high HVR group. At 6,300 m blood O2 saturation (Sao2%) decreased from rest to maximum exercise: H = 8.3 +/- 1.8%, L = 20.0 +/- 2.5% (P less than 0.01). HVR correlated inversely in all subjects with the decrease in Sao2 from rest to maximum exercise (P less than 0.05). Climbers with the highest HVR values reached and slept at higher altitudes. We conclude that the relative value of HVR in our group of climbers was not significantly altered after acclimatization; HVR predicts exercise ventilation at sea level and high altitude; the drop in Sao2% that occurs with exercise is inversely related to HVR; and sojourners with high HVR may perform better at extreme altitude.

Altitude↗

Maximal exercise at extreme altitudes on Mount Everest.

Maximal exercise at extreme altitudes was studied during the course of the American Medical Research Expedition to Everest. Measurements were carried out at sea level [inspired O2 partial pressure (PO2) 147 Torr], 6,300 m during air breathing (inspired PO2 64 Torr), 6,300 m during 16% O2 breathing (inspired PO2 49 Torr), and 6,300 m during 14% O2 breathing (inspired PO2 43 Torr). The last PO2 is equivalent to that on the summit of Mt. Everest. All the 6,300 m studies were carried out in a warm well-equipped laboratory on well-acclimatized subjects. Maximal O2 uptake fell dramatically as the inspired PO2 was reduced to very low levels. However, two subjects were able to reach an O2 uptake of 1 l/min at the lowest inspired PO2. Arterial O2 saturations fell markedly and alveolar-arterial PO2 differences increased as the work rate was raised at high altitude, indicating diffusion limitation of O2 transfer. Maximal exercise ventilations exceeded 200 l/min at 6,300 m during air breathing but fell considerably at the lowest values of inspired PO2. Alveolar CO2 partial pressure was reduced to 7-8 Torr in one subject at the lowest inspired PO2, and the same value was obtained from alveolar gas samples taken by him at rest on the summit. The results help to explain how man can reach the highest point on earth while breathing ambient air.

Adult↗

Physicians on Mount Everest. A clinical account of the 1981 American Medical Research Expedition to Everest.

The American Medical Research Expedition to Everest had a wide variety of medical problems, ranging from leech bites to high-altitude pulmonary edema. Preventive measures, however, such as careful attention to ingesting only pure water and food at the lower elevations and adequate personal hydration, nutrition and rest at extremely high altitude minimized the morbidity suffered by the group. Prophylactic administration of doxycycline was effective in reducing the severity of diarrheal illness in the group. Every member of the expedition suffered upper respiratory tract infections and many other infections, some of which were resistant to all therapy until the patient moved down from high altitude. Despite careful acclimatization, several cases of acute mountain sickness occurred and required descent to a lower altitude for treatment. Frostbite was avoided entirely.

Altitude Sickness↗

Elevation of cerebrospinal fluid lactate with aging in subjects with normal blood oxygen saturations.

It has been hypothesized that cerebral oxidative glucose metabolism may become impaired with age and lead to deterioration of neuronal function. One marker of impaired cerebral oxidative glucose metabolism is increased cerebrospinal fluid (CSF) lactate. Prior studies have found an increase in CSF lactate in aged normals, but these studies have not controlled for the possibility that decreased respiratory function with age may lead to hypoxemia and increased CSF lactate. The current study measured peripheral blood oxygen saturations in 11 subjects during collection of CSF and documented that the increase in CSF lactate observed was not due to peripheral hypoxemia. Thus, increased CSF lactate with age appears to be of central origin.

Adult↗

A bioassay for a water-soluble benzodiazepine against sodium thiopental.

The authors performed a bioassay of midazolam maleate, an investigational, water-soluble benzodiazepine; to determine the duration of sleep after a single intravenous dose. Sodium thiopental was the standard against which the midazolam maleate was assayed. Prior to operation 60 surgical patients were randomly given one of five doses of drugs, either thiopental, 180 or 270 mg, or midazolam maleate, 6.6, 10, or 15 mg. The designated drug was infused intravenously over 20 sec in a double-blind fashion. Sleep was defined as commencing when the patients stopped counting, and ending when they could respond appropriately to verbal commands. Midazolam maleate, 10 mg (9--12 mg represents 95 per cent confidence limits), was found to be equivalent to thiopental, 200 mg, in the duration of sleep induced. Apnea following the infusion was less frequent and of shorter duration after midazolam maleate than after thiopental. It is concluded that midazolam maleate is a satisfactory agent for the induction of anesthesia, and that it is about 20 times as potent as thiopental.

Adolescent↗

Phase I 1/2 evaluation and methodology of RO 20-2230 in postoperative patients.

This report presents the rationale and methodology of our "phase 1 1/2" model for drug evaluation and reports the results of a typical study. We found that Ro 20-2230, and investigational agonist-antagonist analgesic, was well tolerated in therapeutic doses, with 15 mg intramuscular Ro 20-2230 approximately equivalent to 10 mg intramuscular morphine sulfate.

Adult↗

Ketorolac tromethamine absorption, distribution, metabolism, excretion, and pharmacokinetics in animals and humans.

Ketorolac tromethamine (KT), a potent non-narcotic analgesic, with cyclooxygenase inhibitory activity, was administered (14C-labeled and unlabeled) intravenously (iv), orally (po), and intramuscularly (im) in solution to humans, cynomolgus monkeys, rabbits, rats, and mice. KT was absorbed rapidly (Tmax less than 1.0 hr) and efficiently (greater than 87%) following po and im doses in all species. The plasma half-life of ketorolac (K) ranged from 1.1 hr (rabbits) to 6.0 hr (humans). The protein binding of K ranged from 72.0% (mouse) to 99.2% (humans). Linear pharmacokinetics of K was observed in the mouse after single oral doses of KT ranging from 0.25 to 16 mg/kg. Radioactivity was excreted predominantly into urine, ranging from 78.9% (mouse) to 102% (monkey) following iv doses. The dose was excreted into urine primarily as K conjugates, K, and p-hydroxy-K in humans. The monkey was similar to humans with respect to kinetics, but did not form the p-hydroxy metabolite. The rabbit was unusual in that it exhibited substantial presystemic metabolism (50%). The rat excreted a much higher percentage of radioactivity into the feces and formed an additional unidentified metabolite. The most comparable species with respect to humans metabolically was the mouse. The metabolism and excretion of K was similar following iv, po, and im doses within each species studied.

Administration, Oral↗