Gastric mucosal blood flow in misoprostol pretreated aspirin-induced ulceration.

To determine whether topical misoprostol (a synthetic PGE analog) pretreatment will increase or prevent a decrease in gastric mucosal blood flow (GMBF) during topical aspirin administration, we studied focal GMBF simultaneously by hydrogen gas clearance in a split canine gastric chamber model with one side as control. In the test chamber, immediately after topical misoprostol, there was a transient and significant increase (18%) in GMBF (55.71 +/- 7.80 to 65.84 +/- 6.12 mL/min/100 g; p less than 0.05). After 15 minutes, GMBF returned to premisoprostol levels and then showed a graded drop throughout the aspirin and postaspirin periods. No grossly visible mucosal lesions were observed. In the control chamber, mucosal lesions were observed 45 minutes after aspirin administration accompanied by a graded drop in GMBF throughout the experiments. Misoprostol neither produced a sustained increase in GMBF nor prevented the subsequent reduction in GMBF induced by aspirin. Therefore, maintenance of GMBF may not be important in cytoprotection by misoprostol. The sustained nonparietal secretion induced by this synthetic PGE1 analog may be important in gastric cytoprotection.     

Prevention of aspiration pneumonia in obstetrical anesthesia with the effervescent combination of cimetidine and sodium citrate

The effect of an oral effervescent formulation combining 200 mg cimetidine and 1.8 g sodium citrate on gastric pH and volume were studied in patients undergoing caesarean section. Seventy-four patients undergoing elective (group 1) or emergency caesarean section (group 2) were included. Before entering the operating theater (5 to 60 min before intubation), they were given the tablet dissolved in 15 ml of water. Induction and maintenance of anaesthesia were carried out with conventional techniques. The patient's gastric content was aspirated just after endotracheal intubation, and before extubation. its pH and volume were measured at both times. Mean pH was similar in the two groups after intubation (6.07 +/- 1.13 in group 1; 5.52 +/- 1.14 in group 2) and before extubation (6.32 +/- 1.08 vs. 5.85 +/- 1.02 respectively). Gastric pH was therefore greater than 2.5 in all 74 patients at both times. Mean volumes of gastric content after intubation were greater in group 2 (32.7 +/- 23.9 ml vs. 21.6 +/- 15.8 ml; p less than 0.02). However, just before extubation, these were similar (15.0 +/- 15.4 ml in group 1, 20.1 +/- 14.9 ml in group 2). The percentage of patients in the 2 groups with gastric volumes greater than 25 ml at the time of intubation were not significantly different (29.7% vs. 45.9% respectively). No patient was at risk of developing pneumonitis in case of aspiration (gastric content pH less than 2.5 and volume greater than 25 ml), either during endotracheal intubation or extubation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cyclosporine on endothelial albumin leakage in rats.

Short-term treatment of rats with cyclosporine (cyclosporine A [CsA]; Sandimmune) results in a marked reduction in intravascular plasma volume, a factor that might contribute to the renal dysfunction associated with this potent immunosuppressant. To examine the role of plasma extravasation in CsA-induced hypovolemia, intravascular plasma volumes (PV), blood volumes, [125I]albumin disappearance, and changes in hematocrit (Hct) were measured in Inactin-anesthetized rats subjected to minimal surgery. The rats were treated for 3 wk with either 25 mg/kg/day of CsA s.c. or vehicle. Plasma creatinine and urea were significantly elevated, and magnesium was reduced in the CsA group (N = 6) as compared with controls (CON) (N = 6). CsA treatment had no effect on urinary protein and albumin excretion. Blood volume was significantly lower in CsA than in CON (8.4 +/- 0.5 versus 10.6 +/- 0.3 mL/100 g body wt) as was PV (4.3 +/- 0.2 versus 5.5 +/- 0.2 mL/100 g body wt). Two hours after injection, plasma [125I]albumin concentration had fallen by 41 +/- 4% in CsA versus 23 +/- 5% in CON. Because Hct, and, hence PV, was unchanged in both groups during these 2 h, these data indicate enhanced endothelial albumin leakage in the CsA group. In two additional groups of six rats each, acute volume expansion with fresh whole blood (2 mL/100 g body wt) resulted in extravasation of plasma. Hct rose by 8.0 +/- 0.2% in CsA versus 3.8 +/- 0.2% in CON after 150 min, corresponding to 27 +/- 3 and 15 +/- 2% decreases in total PV, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Acute Respiratory Acidosis on the Limits of Oxygen Extraction during Hemorrhage

Background: Hypercapnia can impair cells' capacity to maintain energy status anerobically and enhances the risk of hypoxic injury when oxygen availability is reduced. The ability to maintain tissue oxygenation is determined by both bulk blood flow and the efficiency of oxygen extraction. Bulk blood flow is maintained during hypercapnia through increased sympathetic activity. The effect of hypercapnia on oxygen extraction, however, is unknown. This study evaluates the effect of hypercapnia on cells' capacity to adapt to reductions in oxygen availability by increasing oxygen extraction.

Methods: In three groups of paralyzed, mechanically ventilated dogs that were anesthetized with alpha-chloralose, the concentration of carbon dioxide in the inhaled gas mixture was adjusted to achieve normocapnia, moderate hypercapnia (PaCO2 = 72 +/- 3 [SE] mmHg) or severe hypercapnia (PaCO2 = 118 +/- 4 [SE] mmHg). Stepwise hemorrhage was induced until each dog's blood pressure was destabilized. At each stage in the hemorrhage protocol, the oxygen delivery, oxygen consumption, and oxygen extraction ratios (ratio of arteriovenous oxygen content difference to arterial oxygen content) were determined.

Results: At the point of onset of delivery dependence of oxygen consumption, the oxygen delivery rate (critical oxygen delivery) was 7.8 +/- 1.5 (SE) ml [dot] kg sup -1 [dot] min sup -1 and the oxygen extraction ratio (critical oxygen extraction ratio) was 0.72 +/- 0.04 (SE) in the normocapnic dogs. Moderate hypercapnia had no effect on these parameters. In the severely hypercapnic dogs, the critical values for oxygen delivery and extraction ratios were 12.5 +/- 1.8 (SE) ml [dot] kg sup -1 [dot] min sup -1 and 0.54 +/- 0.035 (SE), respectively (P < 0.05 for differences from the normocapnic dogs).     

Effect of metoclopramide on gastric fluid volumes in diabetic patients who have fasted before elective surgery

BACKGROUND: Diabetes-induced gastroparesis is believed to increase fasting gastric fluid volume before elective surgery. Metoclopramide is routinely administered preoperatively to reduce gastric fluid volume in these patients. This study compared nondiabetic controls to non-insulin-dependent and insulin-dependent diabetics to determine the effect of metoclopramide, administered before surgery, on gastric volumes in patients who fasted before surgery. METHODS: Control and diabetic patients fasted preoperatively before receiving either placebo or 10 mg intravenous metoclopramide 20 min before induction of anesthesia. After intubation, a gastric tube was placed, and stomach contents were aspirated with volumes compared among the groups. RESULTS: Both groups of diabetic patients were older than the control group, and insulin-dependent patients had a higher incidence of comorbidities compared with the non-insulin-dependent group. Fasting blood sugar and hemoglobin A1C values were higher in both insulin-dependent and non-insulin-dependent patients. Gastric fluid volumes were similar in control, non-insulin-dependent, and insulin-dependent patients (8.0 +/- 2.6 vs. 9.6 +/- 4.1 vs. 17.7 +/- 2.5 ml, respectively). In insulin-dependent diabetic patients, metoclopramide decreased gastric volume compared with placebo treatment (17.7 +/- 2.5 vs. 7.8 +/- 2.9 ml; P = 0.027). After stratification, a subpopulation of patients with poorly controlled diabetes, regardless of type, were identified to have increased gastric residual volumes. CONCLUSION: In elective surgical patients who have fasted before surgery, gastric volumes are minimal, even in diabetics with severe neuropathic symptoms. Metoclopramide prophylaxis to reduce gastric volumes seems to be unnecessary unless the patient has a prolonged history of poor blood glucose control.     

Brain bioenergetics during cardiopulmonary resuscitation in dogs.

Cardiac arrest causes a rapid loss of cerebral adenosine triphosphate [corrected] (ATP) and a decrease in cerebral intracellular pH (pHi). Depending on the efficacy of cardiopulmonary resuscitation (CPR), cerebral blood flow levels (CBF) ranging from near zero to near normal have been reported experimentally. Using 31P magnetic resonance spectroscopy, the authors tested whether experimental CPR with normal levels of cerebral blood flow can rapidly restore cerebral ATP and pHi despite the progressive systemic acidemia associated with CPR. After 6 min of ventricular fibrillation in six dogs anesthetized with fentanyl and pentobarbital, ATP was reduced to undetectable concentrations and pHi decreased from 7.11 +/- 0.02 to 6.28 +/- 0.09 (+/- SE) as measured by 31P magnetic resonance spectroscopy. Application of cyclic chest compression by an inflatable vest placed around the thorax and infusion of epinephrine (40 micrograms/kg bolus plus 8 micrograms/kg/min, intravenously) maintained cerebral perfusion pressure greater than 70 mmHg for 50 min with the dog remaining in the magnet. Prearrest cerebral blood flows were generated. Cerebral pHi recovered to 7.03 +/- 0.03 by 35 min of CPR, whereas arterial pH decreased from 7.41 +/- 0.4 to 7.08 +/- 0.04 and cerebral venous pH decreased from 7.29 +/- 0.03 to 7.01 +/- 0.04. Cerebral ATP levels recovered to 86 +/- 7% (+/- SE) of prearrest concentration by 6 min of CPR. There was no further recovery of ATP, which remained significantly less than control. Therefore, in contrast to hyperemic reperfusion with spontaneous circulation and full ATP recovery, experimental CPR may not be able to restore ATP completely after 6 min of global ischemia despite restoration of CBF and brain pHi to prearrest levels.     

Effect of Metoclopramide on Gastric Fluid Volumes in Diabetic Patients Who Have Fasted before Elective Surgery

Background: Diabetes-induced gastroparesis is believed to increase fasting gastric fluid volume before elective surgery. Metoclopramide is routinely administered preoperatively to reduce gastric fluid volume in these patients. This study compared nondiabetic controls to non-insulin-dependent and insulin-dependent diabetics to determine the effect of metoclopramide, administered before surgery, on gastric volumes in patients who fasted before surgery.

Methods: Control and diabetic patients fasted preoperatively before receiving either placebo or 10 mg intravenous metoclopramide 20 min before induction of anesthesia. After intubation, a gastric tube was placed, and stomach contents were aspirated with volumes compared among the groups.

Results: Both groups of diabetic patients were older than the control group, and insulin-dependent patients had a higher incidence of comorbidities compared with the non-insulin-dependent group. Fasting blood sugar and hemoglobin A1C values were higher in both insulin-dependent and non-insulin-dependent patients. Gastric fluid volumes were similar in control, non-insulin-dependent, and insulin-dependent patients (8.0 +/- 2.6 vs. 9.6 +/- 4.1 vs. 17.7 +/- 2.5 ml, respectively). In insulin-dependent diabetic patients, metoclopramide decreased gastric volume compared with placebo treatment (17.7 +/- 2.5 vs. 7.8 +/- 2.9 ml; P = 0.027). After stratification, a subpopulation of patients with poorly controlled diabetes, regardless of type, were identified to have increased gastric residual volumes.     

The Comparative Pharmacodynamics of Remifentanil and Its Metabolite, GR90291, in a Rat Electroencephalographic Model

Background: The purpose of this study was to investigate the in vivo pharmacodynamics and the pharmacodynamic interactions of remifentanil and its major metabolite, GR90291, in a rat electroencephalographic model.

Methods: Remifentanil and GR90291 were administered according to a stepwise infusion scheme. The time course of the electroencephalographic effect (0.5-4.5 Hz) was determined in conjunction with concentrations of the parent drug and the metabolite in blood.

Results: Administration of remifentanil resulted in concentrations of remifentanil and GR90291 in the ranges 0-120 ng/ml and 0-850 ng/ml, respectively. When the metabolite was administered, concentrations of the metabolite in the range 0-220 [micro sign]g/ml and no measurable concentrations of remifentanil were observed. The mean +/- SE values of the pharmacokinetic parameters clearance and volume of distribution at steady state were 920 +/- 110 ml [middle dot] min-1 [middle dot] kg-1 and 1.00 +/- 0.931/kg for remifentanil and 15 +/- 2 ml [middle dot] min-1 [middle dot] kg-1 and 0.56 +/- 0.08 1/kg for GR90291. The relative free concentrations in the brain, as determined on the basis of the cerebrospinal fluid/total blood concentration ratio at steady state, were 25 +/- 5% and 0.30 +/- 0.11% for remifentanil and GR90291, respectively. Concentration-electroencephalographic effect relations were characterized on the basis of the sigmoidal Emax pharmacodynamic model. The mean +/- SE values for the maximal effect (Emax), the concentration at which 50% of the maximal effect is obtained (EC50), and Hill factor for remifentanil were 109 +/- 12 [micro sign]V, 9.4 +/- 0.9 ng/ml, and 2.2 +/- 0.3, respectively (n = 8). For GR90291, the mean +/- SE values for EC50 and the Hill factor were 103,000 +/- 9,000 [micro sign]g/ml and 2.5 +/- 0.4, respectively (n = 6).     

Racemic Ketamine Decreases Muscle Sympathetic Activity but Maintains the Neural Response to Hypotensive Challenges in Humans

Background: Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent sympathetic nerve activity have not been performed in humans. The authors tested the hypothesis that racemic ketamine increases efferent muscle sympathetic activity (MSA) and maintains the muscle sympathetic response to hypotensive challenges.

Methods: Muscle sympathetic activity was recorded by microneurography in the peroneal nerve of six healthy subjects before and during anesthesia with racemic ketamine (2 mg/kg intravenously plus 30 [mu]g [middle dot] kg-1 [middle dot] min-1). Catecholamine plasma concentrations, heart rate, and blood pressure were also determined. Muscle sympathetic neural responses to a hypotensive challenge were assessed by injection of sodium nitroprusside (2-10 [mu]g/kg) before and during ketamine anesthesia. In the final step, increased arterial pressure observed during ketamine anesthesia was adjusted to preanesthetic baseline by sodium nitroprusside infusion (1-6 [mu]g [middle dot] kg-1 [middle dot] min-1).

Results: Ketamine significantly decreased MSA burst frequency (mean +/- SD, 18 +/- 9 bursts/min to 9 +/- 8 bursts/min) and burst incidence (26 +/- 11 bursts/100 heart beats to 9 +/- 6 bursts/100 heart beats). However, when increased mean arterial pressure (85 +/- 8 mmHg to 121 +/- 20 mmHg) was normalized to the awake baseline by sodium nitroprusside, MSA recovered (25 +/- 18 bursts/min; 23 +/- 14 bursts/100 heart beats). During ketamine anesthesia, both epinephrine (15 +/- 10 pg/ml to 256 +/- 193 pg/ml) and norepinephrine (250 +/- 105 pg/ml to 570 +/- 270 pg/ml) plasma concentrations significantly increased, as did heart rate (67 +/- 13 beats/min to 113 +/- 15 beats/min). Hypotensive challenges similarly increased MSA both in the awake state and during ketamine anesthesia.     

Alterations in Canine Left Ventricular-arterial Coupling and Mechanical Efficiency Produced by Propofol

Background: Propofol reduces blood pressure by decreasing left ventricular (LV) afterload and myocardial contractility. This investigation tested the hypothesis that propofol preserves LV-arterial coupling and mechanical efficiency because of these simultaneous hemodynamic actions.

Methods: Experiments were conducted in open-chest dogs (n = 8) instrumented for measurement of aortic and LV pressure, dP/dtmax, and LV volume. Myocardial contractility was assessed with the slope (E sub es) of the LV end systolic pressure-volume relationship. Effective arterial elastance (Ea; the ratio of end systolic arterial pressure to stroke volume), stroke work (SW), and pressure-volume area (PVA) were determined from the LV pressure-volume relationships. Dogs were studied 30 min after instrumentation and after 15-min intravenous infusions of propofol at 5, 10, 20, and 40 mg [center dot] kg sup -1 [center dot] h sup -1.

Results: Propofol caused dose-dependent decreases in Ees (4.7 +/- 0.9 during control to 2.7 +/- 0.5 mmHg/ml during the high dosage) and dP/dtmax, indicating a direct negative inotropic effect. Ea increased at the 10 mg [center dot] kg sup -1 [center dot] h sup -1 dose of propofol but decreased at higher dosages. Propofol decreased the ratio of Ees to Ea (0.88 +/- 0.13 during control to 0.56 +/- 0.10 during the high dosage), consistent with impairment of LV-arterial coupling. Propofol also reduced the ratio SW to PVA (0.54 +/- 0.03 during control to 0.45 +/- 0.03 during the 20 mg [center dot] kg sup -1 [center dot] h sup -1), suggesting a decline in LV mechanical efficiency. SW and PVA recovered toward baseline values at the 40 mg [center dot] kg sup -1 [center dot] h sup -1 dose.     

Gastric fluid pH and volume in gynaecologic out-patients. Influences of cimetidine and cimetidine-sodium citrate combination

Eighty consecutive ASA physical status 1 women scheduled for day-case gynaecological laparoscopy under general anaesthesia were randomly allocated during the pre-operative visit to receive one of four premedication regimes. Patients in group 1 received hydroxyzine 100 mg; patients in group 2 received hydroxyzine 100 mg and cimetidine 400 mg; patients in group 3 received hydroxyzine 100 mg and effervescent cimetidine (cimetidine 200 mg + sodium citrate 1.8 g). All were given orally in 30 ml of water, 90 min before anaesthetic induction. Patients in group 4 received effervescent cimetidine orally in 30 ml of water 5 min before anaesthetic induction. Following induction of anaesthesia, gastric pH and residual volume (phenol red dilution technique) were measured. Gastric pH was higher (P < 0.05) in groups 2, 3 and 4 (medians: 5.71, 4.84, 6.07, respectively) than in group 1 (2.18). No patient had a gastric pH < or = 2.5 in group 4 compared with 13/14 n group 1, 1/15 in group 2 and 2/14 in group 3 (P < 0.0001). Mean gastric volumes were higher (P < 0.05) in group 4 (30.4 +/- 23.2 ml) than in groups 1, 2 and 3 (11.8 +/- 6.4, 15.8 +/- 11.2, 17.2. +/- 24.4 ml, respectively). Nine of the 19 patients in group 4 had a volume higher than 25 ml. Only one patient in group 1 had both gastric pH < or = 2.5 and volume > or = 25 ml. The administration of effervescent cimetidine 5 min prior to anaesthetic induction seems to be an easy and effective method of decreasing the acidity of gastric contents in day surgery.     

Extrarenal clearance of oxalate increases with progression of renal failure in the rat.

Oxalic acid is an end product of metabolism, and no significant degradation of oxalate occurs in mammals. The sole route of oxalate excretion is believed to be via the kidney. The extrarenal clearance of oxalate in control rats (N = 16) and in 5/6 nephrectomized rats (N = 25) with renal insufficiency was investigated. [14C]oxalic acid, approximately 2 microCi/day, was infused sc by a mini osmotic pump over 4 days. Excretion of 14C was measured in urine, in feces, and in expired CO2. The 14C content of kidney, heart, liver, muscle and bone was also determined at the time the animals were killed. Plasma oxalate was determined by an enzymatic method and by an isotopic dilution procedure. Creatinine clearance in the controls was 1.82 +/- 0.1 mL/min (mean +/- SE) compared with 0.31 +/- 0.04 mL/min (P < 0.0005) in the nephrectomized rats. Plasma oxalate was 5.6 +/- 0.6 mumol/L in controls and 27.0 +/- 3.9 (mean +/- SE; N = 24) in nephrectomized animals (P < 0.0005). The total 14C recovered in urine, feces, and CO2 combined was similar in both groups. The 14C excreted in the feces over the 4-day period was 27.8 +/- 1.5% (of the 14C recovered) in rats with renal failure and 6.5 +/- 0.5% in controls (P < 0.0005). Percent fecal 14C excretion in nephrectomized rats was inversely correlated with creatinine clearance (r = 0.80; P < 0.0001) and directly correlated with plasma oxalate (r = 0.66; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of clonidine and dopamine on gastric tone

BACKGROUND AND OBJECTIVE: The effects of clonidine and dopamine, both alone and together, on gastric tone were studied using an electronic barostat. This enabled volume changes to be measured in an intragastric bag with a constant preset pressure. METHODS: Nine healthy male volunteers were each studied on two occasions in a randomized order. During each study period, a continuous infusion of dopamine was given, starting with a dose of 2.5 microg kg(-1) min(-1), and then increasing at 15-min intervals to 5.0 and 7.5 microg kg(-1) min(-1). Clonidine 150 microg intravenously was given on one occasion during the infusion of dopamine (7.5 microgkg(-1) min(-1)) and on the other occasion 15 min before the dopamine infusion started. RESULTS: During dopamine infusion, the intragastric bag volume increased (gastric tone therefore decreasing) in a dose-related manner (total increase 290 +/- 114 mL). Clonidine given either during or before dopamine infusion did not influence the bag volume. When the dopamine infusion started 15 min after clonidine, the bag volume did not change until the infusion of dopamine reached 7.5 microg kg(-1) min(-1) (total increase 205 +/- 156 mL). CONCLUSIONS: Dopamine reduced gastric tone in a dose-related manner, and clonidine did not influence gastric tone per se. If clonidine is given before dopamine, the effects of dopamine are reduced.     

Impaired free fatty acid uptake in skeletal muscle but not in myocardium in patients with impaired glucose tolerance: studies with PET and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid.

Free fatty acids (FFAs) are an important substrate for myocardial and skeletal muscle metabolism, and increased availability and oxidation of FFA are suggested to be associated with insulin resistance. This study was undertaken to assess whether myocardial or muscle uptake of FFA is altered in patients with impaired glucose tolerance (IGT). Eight healthy men (control group; age 48+/-1 years, BMI 25+/-1 kg/m2, mean +/- SE) and eight men with IGT (glucose-intolerant group; age 49+/-1 years, BMI 29+/-1 kg/m2) were studied in the fasting state. Myocardial oxygen consumption and blood flow and myocardial and femoral muscle FFA uptake rates were measured with positron emission tomography (PET) and [15O]O2, [15O]H2O, [15O]CO, and 14(R, S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA), a fatty acid tracer trapped into the cell after undergoing initial steps of beta-oxidation. Serum glucose and insulin concentrations were higher in the glucose-intolerant group during the PET study, but FFA concentrations were comparable between the groups. No differences between the groups were observed in the myocardial blood flow, oxygen consumption, fractional FTHA uptake rates, or FFA uptake indices (5.6+/-0.4 vs. 5.2+/-0.4 pmol x 100 g(-1) x min(-1), glucose-intolerant versus control, NS). In the femoral muscle, fractional FTHA uptake (0.0062+/-0.0003 vs. 0.0072+/-0.0003 min(-1), P = 0.044) and FFA uptake indices (0.30+/-0.02 vs. 0.43+/-0.04 min(-1), P = 0.020) were significantly lower in the glucose-intolerant group than in the control group. In conclusion, when studied at the fasting state and normal serum FFA concentrations, subjects with IGT have similar myocardial but lowered femoral muscle FFA uptake. This finding argues against the hypothesis that an increased oxidation of serum FFA, via the competition of glucose and FFA as fuel sources, is the primary cause for impaired peripheral glucose utilization and insulin resistance commonly observed in IGT.     

Efficacy of Intraoperative Cooling Methods

Background: Patients may require perioperative cooling for a variety of reasons including treatment of a malignant hyperthermia crisis and induction of therapeutic hypothermia for neurosurgery. The authors compared heat transfer and core cooling rates with five cooling methods.

Methods: Six healthy volunteers were anesthetized with desflurane and nitrous oxide. The cooling methods were 1) circulating water (5 [degree sign] Celsius, full-length mattress and cover), 2) forced air (10 [degree sign] Celsius, full-length cover), 3) gastric lavage (500 ml iced water every 10 min), 4) bladder lavage (300 ml iced Ringer's solution every 10 min), and 5) ice-water immersion. Each method was applied for 40 min or until the volunteers' core temperatures approached 34 [degree sign] Celsius. The volunteers were rewarmed to normothermia between treatments. Core cooling rates were evaluated using linear regression.

Results: The first volunteer developed abdominal cramping and diarrhea after gastric lavage. Consequently, the technique was not again attempted. Bladder lavage increased heat loss 10 [nearly =] 10 W and decreased core temperature 0.8 +/- 0.3 [degree sign] Celsius/h (r2 = 0.99 +/- 0.002; means +/- SD). Forced-air and circulating-water cooling comparably increased heat flux, [nearly =] 170 W. Consequently, core cooling rates were similar during the two treatments at 1.7 +/- 0.5 [degree sign] Celsius/h (r2 = 0.99 +/- 0.001) and 1.6 +/- 1.1 [degree sign] Celsius/h (r2 = 0.98 +/- 0.02), respectively. Immersion in an ice water slurry increased heat loss [nearly =] 600-800 W and decreased core temperature 9.7 +/- 4.4 [degree sign] Celsius/h (r sup 2 = 0.98 +/- 0.01). Immersion cooling was associated with an afterdrop of [nearly =] 2 [degree sign] Celsius.     

Gastric emptying in trauma patients.

BACKGROUND/AIM: The aim of this study was to obtain quantitative data on gastric emptying following trauma. METHODS: In order to assess gastric emptying for early enteral feeding, we evaluated the absorption of an amino acid, L-[1-(13)C]phenylalanine, within 24 h of admission and 7 days later in 14 trauma patients (injury severity score 36 +/- 2). Following nasogastric administration of 100 mg L-[1-(13)C]phenylalanine, the plasma L-[1-(13)C]phenylalanine enrichment at 30 and 60 min and the expired (13)CO(2) for 1 h in the breath were used to measure the degree of gastric emptying. RESULTS: The plasma L-[1-(13)C]phenylalanine enrichment concentration at 30 min was 0.53 +/- 0.23 mmol/l during the first study and 2.46 +/- 0. 62 mmol/l during the second study (p = 0.006, a fivefold increase). The L-[1-(13)C]phenylalanine plasma level in historic controls was 4. 57 +/- 1.48 mmol/l. The percent of the dose oxidized and expired as (13)CO(2) in 1 h was 0.51 +/- 0.17 during the first 24-hour study compared to the second study of 3.37 +/- 0.68 (p = 0.0008) 7 days later (an over sixfold increase). The percent of the dose oxidized in 1 h in 37 normal historic controls was 7.08 +/- 0.33. CONCLUSION: These data indicate delayed gastric emptying with limited recovery in 1 week. We conclude that gastric feeding should not be employed, and the route for early nutritional intervention should be transpyloric for the trauma patient.     

Effect of Flumazenil on Ventilatory Drive during Sedation with Midazolam and Alfentanil

Background: Patients who receive a combination of a benzodiazepine and an opioid for conscious sedation are at risk for developing respiratory depression. While flumazenil effectively antagonizes the respiratory depression associated with a benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and an opioid has not been established. This study was designed to determine whether flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in the presence of an opioid.

Methods: Twelve healthy volunteers completed this randomized, double-blind, crossover study. Ventilatory responses to carbon dioxide and to isocapnic hypoxia were determined during four treatment phases: (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil infusions, and (4) combined alfentanil, midazolam, and "study drug" (consisting of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6 weeks later to receive the alternate study drug.

Results: Alfentanil decreased the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/- 0.19 l [dot] min sup -1 [dot] mmHg sup -1 (x +/- SE, P < 0.05), and decreased the minute ventilation at PET CO2 = 50 mmHg (V with dotE 50) from 19.7 +/- 1.2 to 14.8 +/- 0.9 l [dot] min sup -1 (P < 0.05). Midazolam further reduced these variables to 0.87 +/- 0.17 l [dot] min sup -1 [dot] mmHg sup -1 (P < 0.05) and 11.7 +/- 0.8 l [dot] min sup -1 (P <0.05), respectively. With addition of flumazenil, slope and V with dot sub E 50 increased to 1.47 +/- 0.37 l [dot] min sup -1 [dot] mmHg sup -1 (P < 0.05) and 16.4 +/- 2.0 l [dot] min sup -1 (P < 0.05); after placebo, the respective values of 1.02 +/- 0.19 l [dot] min sup -1 [dot] mmHg sup -1 and 12.5 +/- 1.2 l [dot] min sup -1 did not differ significantly from their values during combined alfentanil and midazolam administration. The effect of flumazenil differed significantly from that of placebo (P < 0.05). Both the slope and the displacement of the hypoxic ventilatory response, measured at PET CO2 = 46 +/- 1 mmHg, were affected similarly, with flumazenil showing a significant improvement compared to placebo.     

Recruitment Maneuvers after a Positive End-expiratory Pressure Trial Do Not Induce Sustained Effects in Early Adult Respiratory Distress Syndrome

Background: Recruitment maneuvers performed in early adult respiratory distress syndrome remain a matter of dispute in patients ventilated with low tidal volumes and high levels of positive end-expiratory pressure (PEEP). In this prospective, randomized controlled study the authors evaluated the impact of recruitment maneuvers after a PEEP trial on oxygenation and venous admixture (Qs/Qt) in patients with early extrapulmonary adult respiratory distress syndrome.

Methods: After a PEEP trial 30 consecutive patients ventilated with low tidal volumes and high levels of PEEP were randomly assigned to either undergo a recruitment maneuver or not. Data were recorded at baseline, 3 min after the recruitment maneuver, and 30 min after baseline. Recruitment maneuvers were performed with a sustained inflation of 50 cm H2O maintained for 30 s.

Results: Compared with baseline the ratio of the arterial oxygen partial pressure to the fraction of inspired oxygen (Pao2/Fio2) and Qs/Qt improved significantly at 3 min after the recruitment maneuver (Pao2/Fio2, 139 +/- 46 mm Hg versus 246 +/- 111 mm Hg, P < 0.001; Qs/Qt, 30.8 +/- 5.8% versus 21.5 +/- 9.7%, P < 0.005), but baseline values were reached again within 30 min. No significant differences in Pao2/Fio2 and Qs/Qt were detected between the recruitment maneuver group and the control group at baseline and after 30 min (recruitment maneuver group [n = 15]: Pao2/Fio2, 139 +/- 46 mm Hg versus 138 +/- 39 mm Hg; Qs/Qt, 30.8 +/- 5.8% versus 29.2 +/- 7.4%; control group: [n = 15]: Pao2/Fio2, 145 +/- 33 mm Hg versus 155 +/- 52 mm Hg; Qs/Qt, 30.2 +/- 8.5% versus 28.1 +/- 5.4%).     

Does selective vagotomy prevent delayed gastric emptying and altered myoelectric activity following Roux-en-Y gastrojejunostomy?

Delayed gastric emptying occurs frequently following Roux-en-Y gastrojejunostomy. The role of vagal denervation in the etiology of this "Roux-stasis syndrome" is controversial. This study evaluates the effect of selective vagotomy on gastric emptying and motility following Roux-en-Y. Four dogs underwent control gastric emptying studies. The animals then underwent selective vagotomy, antrectomy, and Billroth II gastrojejunostomy, with placement of serosal electrodes. Gastric emptying was assessed with simultaneous myoelectric recordings, and the animals were converted to Roux-en-Y, followed by repeat studies. Gastric emptying was unchanged following selective vagotomy, antrectomy, and Billroth II gastrojejunostomy (T 1/2: 132 +/- 18 min [SEM] versus 118 +/- 14 min control) but was markedly delayed following Roux-en-Y diversion (T 1/2: 286 +/- 44 min; p less than 0.01). All animals went into the fed pattern following Billroth II gastrojejunostomy (migrating myoelectric complex [MMC] interval: 326 +/- 6 min postprandial versus 92 +/- 5 min fasting; p less than 0.01), but no fed pattern was recognized in three of four animals following Roux-en-Y diversion (MMC interval: 68 +/- 12 min postprandial versus 62 +/- 1.5 min fasting; p = NS). In a canine model, selective vagotomy does not prevent delayed gastric emptying or myoelectric alterations following Roux-en-Y.     

Recruitment maneuvers after a positive end-expiratory pressure trial do not induce sustained effects in early adult respiratory distress syndrome

BACKGROUND: Recruitment maneuvers performed in early adult respiratory distress syndrome remain a matter of dispute in patients ventilated with low tidal volumes and high levels of positive end-expiratory pressure (PEEP). In this prospective, randomized controlled study the authors evaluated the impact of recruitment maneuvers after a PEEP trial on oxygenation and venous admixture (Qs/Qt) in patients with early extrapulmonary adult respiratory distress syndrome. METHODS: After a PEEP trial 30 consecutive patients ventilated with low tidal volumes and high levels of PEEP were randomly assigned to either undergo a recruitment maneuver or not. Data were recorded at baseline, 3 min after the recruitment maneuver, and 30 min after baseline. Recruitment maneuvers were performed with a sustained inflation of 50 cm H2O maintained for 30 s. RESULTS: Compared with baseline the ratio of the arterial oxygen partial pressure to the fraction of inspired oxygen (Pao2/Fio2) and Qs/Qt improved significantly at 3 min after the recruitment maneuver (Pao2/Fio2, 139 +/- 46 mm Hg versus 246 +/- 111 mm Hg, P < 0.001; Qs/Qt, 30.8 +/- 5.8% versus 21.5 +/- 9.7%, P < 0.005), but baseline values were reached again within 30 min. No significant differences in Pao2/Fio2 and Qs/Qt were detected between the recruitment maneuver group and the control group at baseline and after 30 min (recruitment maneuver group [n = 15]: Pao2/Fio2, 139 +/- 46 mm Hg versus 138 +/- 39 mm Hg; Qs/Qt, 30.8 +/- 5.8% versus 29.2 +/- 7.4%; control group: [n = 15]: Pao2/Fio2, 145 +/- 33 mm Hg versus 155 +/- 52 mm Hg; Qs/Qt, 30.2 +/- 8.5% versus 28.1 +/- 5.4%). CONCLUSION: In patients with early extrapulmonary adult respiratory distress syndrome who underwent a PEEP trial, recruitment maneuvers failed to induce a sustained improvement of oxygenation and venous admixture.