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Biomedical subjects

D S Prough

Publications and source records attributed to D S Prough.

At least 73 records · Page 4Linked to original sources
PubMed1995

Double-blind, randomized, multicenter study of doxacurium vs. pancuronium in intensive care unit patients who require neuromuscular-blocking agents.

OBJECTIVE: To compare the neuromuscular-blocking and hemodynamic effects of doxacurium vs. pancuronium administered by intermittent bolus to intensive care unit (ICU) patients who required neuromuscular block to facilitate mechanical ventilation for > or = 24 hrs. DESIGN: A multicenter, prospective, double-blind, randomized study comparing doxacurium, a new benzylisoquinolone neuromuscular-blocking agent, with pancuronium. SETTING: ICUs of three tertiary care hospitals. PATIENTS: Forty critically ill patients (29 male, 11 female) with an average age of 52.5 yrs (range 19 to 80). INTERVENTIONS: With approval of our Institutional Review Boards and after obtaining informed consent, 40 critically ill patients were entered into the study. Histories and the results of physical examinations were recorded, laboratory data were collected, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated during the 8 hrs before the start of the study medication. Patients received either doxacurium (initial dose of 0.04 mg/kg) or pancuronium (initial dose of 0.07 mg/kg) by bolus injection with continuous measurement of vital signs every minute for 15 mins. We measured the degree of neuromuscular blockade using a peripheral-nerve stimulator to measure the Train-of-Four count. Patients were rebolused (doxacurium dose of 0.025 mg/kg, pancuronium dose of 0.05 mg/kg) based on clinical criteria, which were substantiated by measurement of the Train-of-Four count. The neuromuscular-blocking drugs were stopped when the patient no longer required paralysis or after 5 days of therapy, whichever came first. Group comparisons were made using repeated measures analysis of variance, Fisher's exact test, and two sample t-tests, when appropriate. Spearman's rank-correction coefficients were calculated to assess the relationship of onset time and recovery time with all baseline laboratory values and the APACHE II scores. A p < .05 was used to establish statistical significance. MEASUREMENTS AND MAIN RESULTS: There were no differences between the two groups with respect to age, gender, or APACHE II scores. There were no differences between groups in terms of adverse experiences, nor with respect to time of onset of block, number of doses, or the duration of neuromuscular blockade (2.6 vs. 2.2 days for doxacurium vs. pancuronium, respectively). There was a statistically significant increase in heart rate after the initial dose of pancuronium (120 +/- 23 vs. 109 +/- 22 beats/min postinjection vs. preinjection, respectively; p < .05) without any differences noted after doxacurium (107 +/- 21 vs. 109 +/- 21 beats/min, respectively). Furthermore, once neuromuscular block was discontinued, the pancuronium group had a more prolonged and variable recovery time (279 +/- 229 mins) compared with the doxacurium group (138 +/- 46 mins, p < .05). CONCLUSIONS: In critically ill patients requiring neuromuscular block for > 24 hrs, doxacurium was well tolerated without evidence of tachycardia and with a relatively prompt recovery profile.

APACHE↗
PubMed1995

Hypertonic acetate dextran achieves high-flow-low-pressure resuscitation of hemorrhagic shock.

OBJECTIVE: For resuscitation of hemorrhagic hypovolemia, we compared the effectiveness of (1) isotonic lactated Ringer's solution (LRS), (2) 2400 mOsm of 7.5% NaCl:6% dextran 70 (HSD), and (3) 2400 mOsm of 7.9% sodium acetate:1.9% NaCl:6% dextran 70 (HAD). DESIGN: In six randomized, blinded experiments for each solution, conscious instrumented adult sheep were hemorrhaged by removing approximately 1.8 L (42 +/- 3 mL/kg) of blood, while maintaining the mean arterial pressure (MAP) at 50 mm Hg for 2 hours. METHODS: Test solutions were infused as needed to restore the cardiac index to baseline. RESULTS: Volume requirements with HAD (236 +/- 29 mL) and HSD (244 +/- 39 mL) were significantly less (p < 0.05) than LRS (3463 +/- 234 mL). Mean arterial pressure was normalized with HSD and LRS, but not with HAD, which resulted in MAPs of 20 to 25 mm Hg less than baseline resulting from a reduced peripheral resistance. Oxygen delivery, however, was significantly higher with HAD during the resuscitation period. Acid-base balance (pH) and oxygen consumption were normalized within 5 minutes of infusion only with HAD. CONCLUSIONS: Small-volume infusion with HAD resulting in "high-flow-low-pressure" resuscitation may offer unique hemodynamic and metabolic advantages for the initial treatment of hemorrhage from trauma.

Acetates↗
PubMed1995

Limiting initial resuscitation of uncontrolled hemorrhage reduces internal bleeding and subsequent volume requirements.

We tested the hypothesis that full or "standard resuscitation" (SR) with lactated Ringer's solution (LRS) results in increased bleeding in uncontrolled hemorrhagic shock, compared with a "limited prehospital resuscitation" (LPR) regimen and a control group of "no resuscitation" (NR). Cardiac output was used as physiological endpoint for resuscitation. Twenty swine had 25 mL/kg of blood withdrawn during a 30-minute controlled hemorrhage, followed by a 20-minute "prehospital" resuscitation regimen was conducted in three groups: the SR group (n = 6), LRS infused as needed to restore cardiac index (CI) to 100% baseline; the LPR group (n = 8), with resuscitation using LRS to 60% of baseline CI, with volume limited to 10 mL/kg; and the NR group (n = 6). After aortotomy repair, intraoperative resuscitation was continued for 120 minutes using LRS to achieve and maintain 80% of baseline mean arterial pressure. Blood pressure and cardiac index were greatly reduced, to 34% and 39% of baseline, respectively, by hemorrhage. During prehospital resuscitation, the SR group required 48.8 +/- 6.5 mL/kg of LRS, whereas the LPR group received 9.4 +/- 0.6 mL/kg (p < 0.05). Mean arterial pressure increased in all three groups during prehospital resuscitation (p < 0.05). Pulse pressures increased in the SR and LPR groups only (p < 0.05). The increment in oxygen delivery was significantly greater in the SR group, compared with the LPR group (p < 0.05), which in turn was significantly greater than the NR group (p < 0.05). Peritoneal blood volume was significantly higher in the SR group (20.6 +/- 5.6 mL/kg), versus the LPR (7.3 +/- 1.3 mL/kg; p < 0.05) and NR groups (3.0 +/- 0.9 mL/kg; p < 0.05). Crystalloid and whole blood requirements during the intraoperative resuscitation phase were significantly higher in the SR group (193 +/- 16.0 and 9.0 +/- 2.5 mL/kg), than in LPR (111.8 +/- 15.6 and 4.5 +/- 1.8 mL/kg; p < 0.05) and NR groups (128.5 +/- 32.3 and 3.9 +/- 2.3 mL/kg; p < 0.05). In the presence of uncontrolled hemorrhagic shock, LPR and NR can significantly reduce internal hemorrhage and subsequent intraoperative crystalloid and blood requirements.

Animals↗
PubMed1995

Enhanced vulnerability to secondary ischemic insults after experimental traumatic brain injury.

Both experimental traumatic brain injury and clinical traumatic brain injury appear to render the brain more vulnerable to a second ischemic insult. The mechanisms of enhanced vulnerability to subsequent ischemia appear to include a reduced ability to increase cerebral blood flow in response to hypotension, hypoxemia, or acute anemia and increased tissue sensitivity to ischemia. Although numerous mediators may be involved in increased tissue sensitivity, those that particularly merit investigation include oxygen free radicals, glutamate, arachidonate metabolites, calcium ions, and protein kinase C.

Animals↗
PubMed1995

Fluid management in patients with traumatic brain injury.

Movement of water between the brain and the intravascular space is dependent on osmotic gradients, which may be established by the acute administration of either hyper- or hypo-osmolar solutions. Mannitol, a hypertonic crystalloid solution, is commonly used to decrease brain water content and reduce intracranial pressure (ICP). Hypertonic saline solutions also decrease brain water and ICP while temporarily increasing systolic blood pressure and cardiac output. Hypo-osmolar solutions, such as 5% dextrose in water, reduce serum sodium and increase brain water and ICP. Colloid solutions exert little influence on either variable. Fluid restriction minimally affects cerebral edema and, if pursued to excess, may result in episodes of hypotension, which may increase ICP and are associated with worse neurologic outcome. Although there is no single best fluid for patients with traumatic brain injury, isotonic crystalloids are widely used and can be justified on a scientific basis.

Brain Edema↗
PubMed1994

Cardiopulmonary bypass impairs vascular endothelial relaxation: effects of gaseous microemboli in dogs.

Gaseous microemboli during hypothermic cardiopulmonary bypass (CPB) may injure the vascular endothelium and interfere with intrinsic vasomotion. We tested whether gaseous microemboli reduced the vasodilator response to acetylcholine (ACh, 10(-9)-10(-6) M) and potentiated the vasoconstrictor response to norepinephrine (NE, 3 x 10(-8)-10(-4) M). Arteries from 18 dogs were excised before and after 120 min 28 degrees C CPB using membrane (n = 9) and bubble (n = 9) oxygenators to produce microemboli, which were quantitated by Doppler. Five nonbypassed dogs were controls. In isolated vessel rings, the 50% effective dose (ED50) values for ACh (10(-8) M) and NE (10(-7) M) responses were calculated. Mean microemboli count per minute was 0 +/- 0 in the control group, 1.0 +/- 0.4 in the membrane group (P < 0.05 vs. controls), and 46.9 +/- 8.4 in the bubble group (P < 0.05 vs. control and membrane groups). ACh ED50 values did not change in controls but increased in the membrane group from 4.01 +/- 1.52 to 5.66 +/- 1.39 (P < 0.05) and in the bubble group from 2.32 +/- 0.56 to 7.21 +/- 1.90 (P < 0.05). The change in ED50 was greater for bubble than for membrane animals (P < 0.05) but did not correlate with microemboli number (bubble: r = 0.392, P = 0.297; membrane: r = 0.058, P = 0.802). NE responses were similar in all groups. Hypothermic CPB reduces ACh-induced dilation of the canine femoral artery independent of the incidence of gaseous microemboli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Arterial microsphere concentrations in cats are not affected by changes in hematocrit.

BACKGROUND AND PURPOSE: Acute anemia may lead to erroneously low arterial reference sample concentrations of radioactive microspheres, depending on the sampling rate and the size of the artery from which the reference samples are withdrawn. Because this error would lead to falsely high cerebral blood flow values in studies involving hemodilution caused by hemorrhage and fluid resuscitation, we studied the effects of hematocrit, withdrawal rate, and vessel location and size on arterial microsphere concentrations in anesthetized adult cats. METHODS: Cats were anesthetized with ketamine, isoflurane, and nitrous oxide; both brachial arteries were cannulated with polyethylene tubing, as was the abdominal aorta through the femoral artery. Sequential left atrial microsphere injections were made using several doses of each of five isotopes. The rate of reference sample withdrawal from the three sampling catheters was randomized to 1.03 mL.min-1 or 2.06 mL.min-1. We analyzed the ratio of the number of microspheres in paired reference samples using the factors hematocrit, rate of withdrawal, and site. A ratio less than 1 indicates an underestimation of arterial microsphere concentration, which would lead to erroneously high cerebral blood flow values. The procedure was repeated after isovolemic hemodilution with 10% hetastarch to hemoglobin levels approximating 85%, 70%, 55%, and 40% of baseline. RESULTS: No significant effects of hematocrit on ratios of microsphere concentrations existed at any withdrawal rate or site. Ratios of microsphere concentrations in reference samples withdrawn slowly (1.03 mL.min-1) from the aorta and ratios of microsphere concentrations withdrawn either rapidly (2.06 mL.min-1) or slowly from the brachial arteries were significantly (P < .001) less than 1. CONCLUSIONS: Hemodilution did not affect microsphere concentrations in arterial reference samples at any withdrawal site or rate and therefore does not affect the accuracy of microsphere blood flow determinations. However, slow withdrawal from a large vessel may underestimate actual microsphere concentrations.

Animals↗
PubMed1994

Phenylephrine does not reduce cerebral perfusion during canine cardiopulmonary bypass.

Gaseous microemboli during cardiopulmonary bypass (CPB) could injure the blood-brain barrier so that cerebral vasoconstriction would result from infusing alpha-agonist drugs, such as phenylephrine. Cerebral blood flow (radioactive microspheres) and metabolism were measured in seven dogs after rewarming from 150 min hypothermic CPB with bubble oxygenators used to produce gaseous microemboli. Phenylephrine (40 micrograms/min) was infused directly into the brachiocephalic artery so that aortic pressure before (80 +/- 2 mm Hg) and during (79 +/- 3 mm Hg) the infusion did not change. Neither blood flow to the cerebral hemispheres (P = 0.960), cerebellum (P = 0.854), and brainstem (P = 0.694) nor the cerebral metabolic rate for oxygen (P = 0.862) differed when values obtained before and after 30 min of phenylephrine infusion were compared. Cerebral vascular resistance was also unchanged by phenylephrine, being 1.22 +/- 0.10 mm Hg.mL-1.min-1 x 100 g-1 before infusion and 1.25 +/- 0.17 mm Hg.mL-1.min-1 x 100 g-1 during infusion (P = 0.849). Phenylephrine does not cause cerebral vasoconstriction after rewarming from hypothermic CPB, a finding which suggests that the blood-brain barrier is preserved during bypass.

Animals↗
PubMed1994

The effects of carrier gas composition on the performance of the Tec 6 desflurane vaporizer.

The new Tec 6 desflurane vaporizer is an electrically heated, pressurized, electromechanically coupled dual-circuit blender. We hypothesized that carrier gas viscosity should affect the electromechanical coupling of the fresh gas and vapor circuits, and that desflurane output should vary with different carrier gases. In the first portion of the study, the performance of eight vaporizers was evaluated using a constant dial setting of 10% desflurane with four different carrier gases and three different fresh gas flow rates. In the second portion of the study, the carrier gas flow rate was maintained at 1, 5, or 10 L/min, and vaporizer output was analyzed at all integer dial settings from 1% to 18%. Vaporizer output was highest when oxygen was the carrier gas and lowest when nitrous oxide was the carrier gas. This effect was accentuated at low fresh gas flow rates and correlated with carrier gas viscosity. At a flow rate of 1.0 L/min with a constant dial setting of 10%, the averaged output from vaporizers was 10.3 +/- 0.66, 9.4 +/- 0.58, 8.7 +/- 0.52, and 8.1 +/- 0.44 vol% for 100% oxygen, air, 30% oxygen plus 70% nitrous oxide, and 100% nitrous oxide, respectively. With 100% nitrous oxide as the carrier gas at a flow rate of 1.0 L/min, the vaporizer delivered 2 vol% less than the dial setting at dial settings in excess of 12%. Differences between the analyzed concentration and the dial setting were most pronounced with high concentrations of nitrous oxide at low fresh gas flow rates.

Anesthetics↗
PubMed1993

Significance of gaseous microemboli in the cerebral circulation during cardiopulmonary bypass in dogs.

BACKGROUND: Gaseous microemboli during cardiac surgery may damage the brain by reducing cerebral blood flow (CBF). We examined whether the incidence of gaseous microemboli during 150-minute hypothermic (28 degrees C) cardiopulmonary bypass (CPB) adversely affects CBF (radioactive microspheres). METHODS AND RESULTS: Thirty anesthetized dogs were placed on CPB using bubble oxygenators with 50% O2 (n = 10) or 100% O2 (n = 10) to produce a wide range in the number of gaseous microemboli or membrane oxygenators with 50% O2 (n = 10) to avoid microemboli. The number of carotid artery microemboli occurring in a 1-minute interval was counted using a 5-MHz Doppler probe every 15 minutes for the duration of CPB, which lasted 258 +/- 5 minutes. With bubbled 100% O2, the number of microemboli averaged 4.1 +/- 1.7 emboli per minute on normothermic bypass and increased with cooling to 18.3 +/- 4.9 emboli per minute (P < .001). With bubbled 50% O2, the microemboli number was greater on normothermic bypass (19.8 +/- 9.8 emboli per minute, P = .0653 compared with bubbled 100% O2) and increased with cooling (100.3 +/- 18.7 emboli per minute, P < .001) to a greater extent than with bubbled 100% O2 (P < .001). In contrast, with membrane 50% O2, the emboli number was small (0.6 +/- 0.1 emboli per minute) and did not change with CPB temperature. CBF values were not reduced after termination of CPB, even when compared with prebypass values, being 48.3 +/- 7.5 mL/min per 100 g (bubbled 50% O2), 49.6 +/- 4.1 mL/min per 100 g (bubble 100% O2), and 44.5 +/- 2.8 mL/min per 100 g (membrane 50% O2, P = .7581). Similarly, regional perfusion to the cerebellum, hippocampus, and caudal brainstem was not adversely affected by microemboli. After CPB, cortical biopsies demonstrated no difference among groups with respect to lactate (P = .1753), energy charge (P = .5179), and brain water content (P = .939). Retinal histopathology indicated no differences among groups. CONCLUSIONS: These results indicate that: (1) the incidence of gaseous microemboli during hypothermia increases when a bubble oxygenator is used, and (2) global CBF and regional brain perfusion are not adversely affected by numerous gaseous microemboli.

Animals↗
PubMed1992

Regional cerebrovascular responses to progressive hypotension after traumatic brain injury in cats.

We investigated the effects of hypotension on cerebral blood flow (CBF) after traumatic brain injury (TBI) in cats. Isoflurane-anesthetized cats were prepared for TBI and for microsphere measurements of total (T) and regional (r) CBF. Four groups were studied: sham injury (group I, n = 6); TBI (group II, n = 6); isoflurane anesthesia, no TBI or hypotension (group III, n = 4); and isoflurane and TBI, no hypotension (group IV, n = 8). After TBI or sham trauma, mean arterial pressure (MAP) was reduced to 80, 60, and 40 mmHg by hemorrhage. Group I TCBF did not change significantly from baseline until MAP reached 40 mmHg, but rCBF was more dependent on MAP in anterior hemispheric than in brain stem regions. Group II TCBF was significantly lower than baseline, and group I TCBF at all levels of hypotension and autoregulation was impaired at higher MAP levels in anterior than in posterior brain regions. Groups III and IV indicated that decreases in TCBF were not due to duration of the preparation or to TBI in the absence of hemorrhagic hypotension. We conclude that global and regional autoregulation are absent in response to hemorrhagic hypotension after TBI.

Anesthesia↗