Influence of sepsis on sevoflurane minimum alveolar concentration in a porcine model.

Sevoflurane is widely used in anaesthetic protocols for patients undergoing surgical procedures. However, there are no reports on the influence of sepsis on minimum alveolar concentration of sevoflurane (MAC(SEV)) in animals or in humans. The aim of this study was to test the hypothesis that sepsis could alter the MAC(SEV) in a normotensive septic pig model. Twenty young, healthy pigs were used. After they had received 10 mg kg(-1) of ketamine i.m. for premedication, anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Sevoflurane was used as the sole anaesthetic agent. Baseline haemodynamic recording included electrocardiography, carotid artery blood pressure and a pulmonary thermodilution catheter. Baseline MAC(SEV) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(SEV) was determined using incremental changes in sevoflurane concentration until purposeful movement appeared. Pigs were assigned randomly to two groups: the saline group (n = 10) received a 1-h i.v. infusion of sterile saline solution while the sepsis group (n = 10) received a 1-h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolemic haemodynamic status. In both groups, MAC(SEV) was evaluated 5 h after infusion. Significant increases in mean artery pulmonary pressure, filling, epinephrine and vascular pulmonary resistances occurred in the sepsis group. MAC(SEV) for the saline group was 2.4% [95% confidence interval (CI) 2.1-2.55%] and the MAC(SEV) for the sepsis group was 1.35% (95% CI 1.2-1.45%, P<0.05). These data indicate that MAC(SEV) is significantly decreased in this normotensive septic pig model.

Delayed gastric emptying in ventilated critically ill patients: measurement by 13 C-octanoic acid breath test.

OBJECTIVE: To measure gastric emptying in ventilated critically ill patients with a new noninvasive breath test. DESIGN: Single-center, open study. SETTING: Combined medical and surgical intensive care unit of a university hospital. SUBJECTS: Thirty unselected mechanically ventilated critically ill patients receiving gastric feeding and 22 healthy volunteers. INTERVENTIONS: None. PATIENTS: After 4 hrs without feeding, intragastric infusion of 100 mL of a liquid meal (Ensure) labeled with 100 microL 13C-octanoic acid. End-expiratory breath samples were collected into evacuated tubes from the respirator circuit every 5 mins for the first hour, then every 15 mins for 3 hrs. End-expiratory breath samples were also collected from volunteers studied supine after an overnight fast following an identical infusion via a nasogastric tube. Breath 13CO2 was measured with an isotope ratio mass spectrometer. MEASUREMENTS AND MAIN RESULTS: Performance of the breath test posed no difficulty or interference with patient care. The CO2 level was >1% in 1297/1300 breath samples, indicating satisfactory end-expiratory timing. Data are median and interquartile range. Gastric emptying was slower in patients compared with volunteers: gastric emptying coefficient 2.93 (2.17-3.39) vs. 3.58 (3.18-3.79), p <.001 and gastric half emptying time, derived from the area under the 13CO2 curve, 155 min (130-220) vs. 133 min (120-145), p <.008. Fourteen of the 30 patients had a gastric emptying coefficient <95% of all volunteers and 11 had a gastric half emptying time longer than 95% of all volunteers. The Acute Physiology and Chronic Health Evaluation (APACHE II) score (median 22, range 13-43) either at admission or on the day of the study did not correlate with gastric emptying coefficient. CONCLUSION: Gastric emptying of a calorie-dense liquid meal is slow in 40% to 45% of unselected mechanically ventilated patients in a combined medical and surgical intensive care unit. The 13C-octanoic acid breath test is a novel and useful bedside technique to measure gastric emptying in these patients.

Influence of sepsis on minimum alveolar concentration of desflurane in a porcine model.

The effect of sepsis on the minimum alveolar concentration of desflurane (MAC(DES)) in humans and other animals has not been reported previously. The aim of this study was to test the hypothesis that sepsis might alter MAC(DES) in a normotensive septic porcine model. Twenty-four young healthy pigs were premedicated with ketamine 10 mg kg(-1 )i.m and then anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Baseline MAC(DES) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(DES) was determined by changing desflurane concentrations stepwise until purposeful movement appeared. Pigs were randomly assigned to two groups of 12 animals: the saline group received a 1 h i.v. infusion of saline solution while the sepsis group received a 1 h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolaemic haemodynamic status. In both groups, MAC(DES) was evaluated 5 h after infusion. Significant increases in heart rate, cardiac output, mean pulmonary artery pressure and pulmonary vascular resistance occurred in the sepsis group. MAC(DES) was 9.2% (95% confidence interval (CI) 6.8-10.6%) for the saline group and 6.7% (95% CI: 4.7-10.4) for the sepsis group (P<0.05). These data indicate that MAC(DES) is significantly decreased in this normotensive hyperkinetic septic porcine model.

Estimation of cardiac preload changes by systolic pressure variation in pigs undergoing pneumoperitoneum.

BACKGROUND: Variations in systolic pressure arterial waveform (SPV) and its component have been shown to be a reasonable indicator of left ventricular preload. Creation of a pneumoperitoneum (PMOP) by insufflation of CO2 increases intrathoracic pressure, leading to overestimation of preload as assessed by pressure methods. The purpose of this study was to compare SPV with other standard methods in anaesthetized pigs. METHODS: We measured SPV and its DeltaDown component (deltaDown), pulmonary artery occlusion pressure (PAOP) and left ventricular short-axis cross-sectional area using transthoracic echocardiography (TTE) in 7 pigs, at baseline, after 12 mmHg PMOP and after an intravascular load with 10 ml/kg hydroxylethylstarch (HES). RESULTS: PMOP increased SPV from 12.9+/-4.9 to 16.9+/-5.5 mmHg (P<0.05) and decreased pulmonary compliance, with no change in PAOP or end-diastolic area assesssed by TTE. Intravascular volume loading significantly decreased SPV from 16.9+/-5.5 to 11.2+/-4.9 mmHg and deltaDown from 9.9+/-7.1 to 5.2+/-4.5 (P<0.05), and increased PAOP and end-diastolic area. Significant correlation between changes in deltaDown and EDA was noted following HES (r=0.78, P<0.05). CONCLUSION: In anaesthetized pigs, the creation of a PMOP alters SPV, likely by decreasing lung compliance. Once PMOP is established, changes in cardiac preload could be estimated by SPV analysis.

Metabolic acidosis and respiratory acidosis impair gastro-pyloric motility in anesthetized pigs.

UNLABELLED: Acidosis impairs smooth muscle function in various organs. However, the effects of acidosis on the gastroduodenal tract are unknown while its dysfunction has potential perioperative harmful consequences. We investigated the effects of metabolic (MA) and respiratory acidosis (RA) on upper gut motility in tracheally ventilated pigs whose anesthesia was induced with halothane and maintained with alpha-chloralose-urethane administration (IV). Increased dead space and perfusion of hydrochloric acid 1 N (150 mL over 30 min) were used to induce RA and MA, respectively. Measurements of fundic tone using an electronic barostat, antro-pyloroduodenal phasic motility with perfused manometry and antro-duodenal electric control activity by electromyography were used to evaluate gastroduodenal function. Acidosis increased the fundic tone as reflected by a decrease in barostat volumes from 275+/-83 to 194+/-88 mL for MA and from 278+/-93 to 236+/-106 mL for RA. Pyloric and duodenal basal tones were not affected by either acidosis. A decrease in pyloric contraction amplitude from 95+/-24 to 62+/-26 mm Hg during MA and from 94+/-26 to 64+/-20 mm Hg during RA was observed. Both acidosis altered antral control activity that became dysrhythmic. Acidosis could be implicated in perioperative complications, such as gastroparesis, emesis, and regurgitation of gastric contents. IMPLICATIONS: Metabolic and respiratory acidosis mainly affects gastric antral rhythms and has a major effect on fundic tone. Acidosis could be implicated in perioperative complications, such as gastroparesis, emesis, and regurgitation of gastric contents.

Measurements of systolic time intervals using a transoesophageal pulsed echo-Doppler.

Measurement of systolic time intervals (STI), an index of left ventricular (LV) systolic function, is usually labour intensive and requires considerable expertise to perform accurately. We have evaluated the accuracy of an automated, continuous and non-invasive STI measurement technique using a descending aortic blood velocity Doppler signal obtained using a transoesophageal echo-Doppler system (TEDS) and an ECG signal. STI were measured in adult pigs using a transoesophageal probe (4 x 4 mm pulsed wave Doppler transducer, 5-MHz frequency and a 3 x 3 mm echo transducer, 10-MHz frequency) associated with an ECG recorder. Measurements were performed at baseline and after injection of esmolol and dobutamine. TEDS data were compared with those obtained by one-line recordings of the electrocardiogram and the central aortic arterial pressure wave. Similar mean values were observed for pre-ejection period (PEPI), LV ejection time (LVET) and PEP/LVET with the two methods. Agreement between the methods (Bland and Altman's test) was excellent with 95% confidence intervals for PEP, LVET and PEP/LVET of -7.17 to +1.37 ms, -12.64 to +0.24 ms and -0.033 to +0.028, respectively. We conclude that the combination of descending aorta blood velocity Doppler and ECG signal is an alternative technique for non-invasive and objective measurement of STI, allowing continuous monitoring of LV systolic function.

Lower oesophageal sphincter tone increases after induction of anaesthesia in pigs with full stomach.

PURPOSE: The lower oesophageal sphincter (LOS) is the man mechanism that prevents gastro-oesophageal regurgitation during anaesthesia. The aim of this study was to assess the effect on lower oesophageal sphincter pressure (LOSP) of rapid sequence induction in pigs with full stomachs. METHODS: Lower oesophageal sphincter pressure and oesophageal barrier pressure (BrP = LOSP minus gastric pressure) were measured using a water-perfused manometric catheter method in 12 pigs after gastric filling with 500 ml of liquid nutrient mixture. Six pigs were randomly allocated to receive 5 mg.kg-1 propofol and 3 mg.kg-1 succinylcholine i.v. and six pigs received 8 mg.kg-1 thiopentone and 3 mg.kg-1 succinylcholine i.v. RESULTS: After induction, mean LOSP increased during the period with fasciculations from 19 +/- 4 mmHg to 28 +/- 5 mmHg in the propofol-succinylcholine group and from 23 +/- 6 mmHg to 36 +/- 7 mmHg in the thiopentone-succinylcholine group. The LOSP remained elevated after the fasciculations. LOSP and BrP were not different between the groups. CONCLUSIONS: Induction of anaesthesia with propofol-succinylcholine or thiopentone-succinylcholine increases LOSP and, consequently, BrP in pigs with a full stomach. This increase begins before fasciculations and remains elevated for the period when intubation would occur.

Overestimation of low cardiac output measured by thermodilution.

We have investigated the influence of a cold water bolus (CWB) injection on overestimation of cardiac output (CO) in low CO states in anaesthetized dogs. CO was measured using three methods: (1) thermodilution (TD), (2) electromagnetic (EM) flow meter placed on the pulmonary artery and (3) transoesophageal echo-Doppler (OD) placed on the descending aorta. Measurements of CO were obtained before (steady state) and after induction of a low CO state with thiopentone 5 mg kg-1 i.v. After CWB injection, mean CO measured by EM and OD increased by 26% and 27%, respectively (P < 0.05) during steady state, and by 85% and 75% (P < 0.05) during the low CO state. This transient increase was produced by an increase in stroke volume, while heart rate did not change. Frank Starling's law may explain this variation by a sudden increase in preload produced by CWB injection. These results indicate that thermodilution overestimated CO during low CO states when CWB injection was used.

Cricoid cartilage pressure decreases lower esophageal sphincter tone.

BACKGROUND: Cricoid cartilage pressure induced to prevent pulmonary aspiration from regurgitation of gastric contents has been recommended, and its efficacy requires a force greater than 40 Newtons. For regurgitation to occur, both an increase in gastric pressure and relaxation of the lower esophageal sphincter (LES) are necessary. However, the effect of cricoid cartilage pressure on the LES is unknown. This study evaluated the effects of cricoid cartilage pressure on LES in human volunteers. METHODS: Lower esophageal sphincter and esophageal barrier pressures (which equals LES pressure-gastric pressure) were measured using a manometric method in eight unanesthetized volunteers (4 men, 4 women) classified as American Society of Anesthesiologists physical status 1. The force applied to the cricoid cartilage was measured continuously, and LES pressure was recorded at a cricoid force of 20 and 40 Newtons. RESULTS: Cricoid pressure decreased LES pressure from 24 +/- 3 mmHg to 15 +/- 4 mmHg at a force of 20 Newtons (P < 0.05) and to 12 +/- 4 mmHg with a force of 40 Newtons (P < 0.01). CONCLUSIONS: These findings may explain the occurrence of pulmonary aspiration before tracheal intubation despite application of cricoid cartilage pressure.

Effect of halothane, isoflurane and desflurane on lower oesophageal sphincter tone.

We have studied the effects of volatile anaesthetics on lower oesophageal sphincter (LOS) tone in three groups of eight pigs allocated randomly to receive end-tidal concentrations of 0.5, 1.0 and 1.5 MAC of desflurane, isoflurane or halothane for 15 min. LOS and oesophageal barrier pressures (BrP = LOSP - gastric pressure) were measured using a manometric method. The decrease in BrP paralleled the decrease in LOS pressure and was significant at 0.5 MAC for isoflurane and at 1.0 MAC for halothane. At 1.5 MAC, BrP values were approximately 62% of baseline values for halothane, 37% for isoflurane and 83% for desflurane. Inter-group comparisons showed that BrP did not differ at baseline and at 0.5 MAC. At 1.0 MAC the effect of isoflurane on BrP was significantly different from desflurane (P < 0.001) and halothane (P < 0.02) whereas the effect of desflurane on BrP was not significantly different from halothane. At 1.5 MAC the effect of isoflurane on BrP was significantly different from desflurane (P < 0.01) and halothane (P < 0.05) whereas the effect of desflurane on BrP was not significantly different from halothane. We conclude that desflurane maintained BrP and this may be clinically important in patients at high risk of regurgitation.

Extradural clonidine combined with sufentanil and 0.0625% bupivacaine for analgesia in labour.

We have studied the use of clonidine combined with low doses of sufentanil and bupivacaine in 45 parturients requiring extradural analgesia for the first stage of labour, in a double-blind, randomized study. We gave 0.0625% bupivacaine 10 ml containing 1:200,000 adrenaline and sufentanil 10 micrograms (1 ml) to which was added 0.9% saline, or clonidine 100 or 150 micrograms (1 ml). We compared the quality (VAS scores) and duration of analgesia, motor block, maternal haemodynamic state (mean arterial pressure and heart rate) and fetal and maternal side effects. Mean duration of anaesthesia was prolonged slightly: 105 (SD 21) min without clonidine, 130 (26) min with clonidine 100 micrograms (P < 0.05 vs control) and 144 (40) min with clonidine 150 micrograms (P < 0.01 vs control, ns vs 100 micrograms). There were no differences in VAS scores, onset times, heart rate, ventilatory frequency, motor block, sedation, pruritus or bradycardia between the groups. Analgesia was associated with a reduction in mean arterial pressure with clonidine. However, these adverse side effects were of minor clinical importance regardless of the extradural clonidine dose, except for a high incidence of fetal heart tracing abnormalities when clonidine 150 micrograms was used. These effects associated with a limited effect on analgesia may curtail the widespread use of clonidine as an adjunct to extradural 0.0625% bupivacaine with sufentanil 10 micrograms during labour.

Calcium homeostasis during i.v. infusion of 1.5% glycine in anaesthetized pigs.

We have examined changes in plasma concentrations of calcium in seven anaesthetized pigs during i.v. infusion of irrigating fluid containing 1.5% glycine. Volumes infused were 875 ml at 20 min (22 ml kg-1), 1475 ml at 40 min and 2075 ml at 60 min (75 ml kg-1). Plasma concentrations of sodium decreased from 134.5 (SD 3.4) to 112.8 (6.7) mmol litre-1 at 60 min and correlated with the volume of glycine infused (r2 = 0.73; P < 0.0001). Changes in total calcium concentrations were not statistically significant. A decrease in ionized calcium concentration was observed at 40 min (1.12 (0.05) vs 1.24 (0.04) mmol litre-1; P < 0.05) and reached 1.11 (0.05) mmol litre-1 at 60 min (P < 0.01). However, when corrected for pH, this decrease was not statistically significant. These results suggest that changes in plasma concentrations of sodium rather than changes in calcium homeostasis are probably more important in the development of transurethral prostatic syndrome.

Cricoid pressure decreases lower oesophageal sphincter tone in anaesthetized pigs.

PURPOSE: Previous studies have shown a decrease of lower oesophageal sphincter (LOS) tone during stimulation of the upper oesophageal sphincter. Therefore, we hypothesized that during anaesthesia, cricoid pressure could result in a decrease in LOS pressure. METHODS: The LOS and oesophageal barrier pressures (BrP = LOSP minus gastric pressure) were obtained in 11 anaesthetized pigs with intraabdominal pressure of 15 mmHg using a manometric method (perfused catheters) before and during firm application of cricoid pressure. Reflux was assessed with concomitant recording of the lower oesophageal pH. RESULTS: Cricoid pressure decreased LOSP from 31.0 +/- 14.5 mmHg to 26.1 +/- 12.7 mmHg (P < 0.001) leading to a 35% reduction of oesophageal barrier pressure (9 +/- 10.3 mmHg vs 13.7 +/- 12.4 mmHg; P < 0.001). No episodes of reflux were recorded. CONCLUSIONS: This study shows that cricoid pressure decreases LOS tone in anaesthetized pigs. Although no gastrooesophageal reflux was recorded, this study suggests that, if cricoid pressure does not completely occlude the oesophagus, the decrease of oesophageal barrier pressure induced could favour the appearance of pulmonary aspiration.

The effect of increase in end-tidal carbon dioxide on lower esophageal sphincter tone.

The lower esophageal sphincter is composed of smooth muscles and is the main barrier against regurgitation during anesthesia. As smooth muscles are usually sensitive to CO2, we investigated the response of lower esophageal sphincter pressure to varying concentrations of CO2 in six anesthetized pigs using a manometric method. CO2 was increased by increasing the dead space at the Y piece of the ventilator. Basal values for ETCO2 were 35 +/- 2 mm Hg, reaching 62 +/- 1 mm Hg at the end of the study (P < 0.03). In response to the increase in ETCO2, no change in lower esophageal sphincter pressure was noted (12 +/- 3 mm Hg vs 13 +/- 4 mm Hg). These findings indicate that the lower esophageal sphincter is not affected by CO2 in the range usually encountered in clinical practice.

Effect of pneumoperitoneum and Trendelenburg position on gastro-oesophageal reflux and lower oesophageal sphincter pressure.

We have measured the effect of pneumoperitoneum and the Trendelenburg position on lower oesophageal sphincter (LOSP) and barrier pressures (BrP) in 11 anaesthetized pigs while measuring the incidence of gastro-oesophageal reflux with a pH electrode. Propofol in combination with sufentanil had no effect on LOSP or BrP. Adoption of the Trendelenburg position with a pneumoperitoneum of 15 mm Hg resulted in a significant increase in LOSP (P < 0.002) and BrP (P < 0.001). However, in two of 11 pigs who had the lowest LOSP before induction, there was regurgitation.

[Effects of anesthesia on the lower sphincter of the esophagus]. / Répercussions de l'anesthésie sur le sphincter inférieur de l'oesophage.

The lower oesophageal sphincter (LOS) is the most important structure preventing regurgitation of gastric contents, with the risk of tracheobronchial aspiration, as it occurs in cases of laryngeal incompetence in connection with general anaesthesia. This article reviews anatomical data, means of assessment of the sphincter function, as well as the effects of anaesthetic agents and situations carrying a high risk of regurgitation and tracheobronchial aspiration.