Gastric Mucosal Perfusion in Dogs: Effects of Halogenated Anesthetics and of Hemorrhage

The gastrointestinal tract is one of the first organs affected by hypoperfusion during hemorrhagic shock. The hemodynamics and oxygen transport variables during hemorrhagic shock and resuscitation can be affected by the anesthetics used. In a model of pressure-guided hemorrhagic shock in dogs, we studied the effects of three halogenated anesthetics—halothane, sevoflurane, and isoflurane—at equipotent concentrations on gastric oxygenation. Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of either halothane, sevoflurane, or isoflurane. A gastric tonometer was placed in the stomach to determine mucosal gastric CO₂ (PgCO₂) and for the calculation of gastric-arterial PCO₂ gradient (PCO₂ gap). The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40–50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamics, systemic oxygenation, and PCO₂ gap were measured at baseline, after 45 min of hemorrhage, and at 15 and 60 min after blood resuscitation. Hemorrhage induced reductions of mean arterial pressure and cardiac index, while systemic oxygen extraction increased (p <. 05), without significant differences among groups (p >. 05). Halothane group showed significant lower PCO₂ gap values than the other groups (p <. 05). After 60 min of shed blood replacement, all groups restored hemodynamics, systemic oxygenation, and PCO₂ gap to the prehemorrhage levels (p >. 05), without significant differences among groups (p >. 05). We conclude that halothane is superior to preserve the gastric mucosal perfusion in comparison to isoflurane and sevoflurane, in dogs submitted to pressure-guided hemorrhagic shock at equipotent doses of halogenated anesthetics.     

Splanchnic blood flow during halothane-relaxant anaesthesia in elderly patients

We have previously found that halothane-relaxant anaesthesia in elderly patients causes a change towards a hyperkinetic circulation, with a decrease in the arterial-mixed venous oxygen content difference. This could be attributed to vasodilation. In the present study the splanchnic contribution to these changes was investigated. Nine patients were studied during halothane-relaxant anaesthesia prior to surgery. During anaesthesia splanchnic blood flow was markedly reduced, while splanchnic oxygen uptake decreased only moderately compared with the awake level. This resulted in an increase in splanchnic oxygen extraction. It is concluded that the splanchnic vascular bed does not contribute to the "hyperkinetic" circulation during halothane anaesthesia.     

Intraarterial Perfusion of the Hindlimb with Pyridoxalated Hemoglobin Polyoxyethylene Conjugate Solution in Anesthetized Dogs

Abstract: To evaluate the potential clinical usefulness of a modified hemoglobin, pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), the hindlimb vascular bed was perfused with PHP solution while monitoring tissue oxygen tension (Pto₂) in anesthetized dogs. The hindlimb region was perfused through the external iliac artery with a roller pump at a varying perfusion rate. Pto₂ was measured using a Po₂-monitoring probe inserted into the gra-cial muscle. After surgical preparation for perfusion, the iliac arterial flow rate was 19.9 ± 5.6 ml/min, and baseline Pto₂ was 38.4 ±1.3 mm Hg. Perfusion with autologous arterial blood with the pump increased Pto₂ and perfusion pressure (PP) in a perfusion rate-dependent manner. Perfusion with PHP solution at 20 ml/min decreased Pto₂ from the initial baseline level, but an increase in the flow rate to 40–55 ml/min restored or induced an elevation of Pto₂. Results demonstrated that PHP solution can deliver oxygen to local tissue and maintain tissue oxygen tension at the same level as autologous arterial blood at a high enough flow rate.     

Initial experience of complete switchover to sevoflurane in 1550 children*

A report of our experience with a complete switchover from halothane (HAL) to sevoflurane (SF) in 1550 paediatric cases over a period of 17 months is presented. SF became the sole inhalational anaesthetic in our institution in July 1990. Induction of anaesthesia with SF was performed with the overpressure technique by administering rapid increases of concentration and assisted pulmonary ventilation with a large fresh gas flow (6 l·min^?1 of nitrous oxide and 3 l·min^?1 of oxygen). SF concentration was increased rapidly up to 5 or 7% in increments of 2% in every 2–3 breaths. Induction time as measured in 60 cases (3–6 years) was 50 ± 5 (mean ± SD) sec for loss of eyelash reflex and 119 ± 10 (mean ± SD) sec for loss of movement to venepuncture at 7% SF concentration. No serious complications were observed. Peak serum levels of inorganic fluoride were within a safe range (less than 30 μmol·l^?1) in all 7 cases in which this was studied. The results suggest that SF is a useful anaesthetic agent in paediatric anaesthesia, particularly because of its smooth and rapid inhalation induction.     

Effects of Prenalterol and Volume Loading with Dextran on Haemodynamics and Oxygen Consumption in Dogs During High Epidural Block with Special Reference to the Splanchnic Region

High lumbar epidural block was induced in seven dogs, causing a fall in mean arterial blood pressure (AP) from 24.5 +/- 2.9 to 12.0 +/- 3.1 kPa owing to reductions in cardiac output (QT) and systemic vascular resistance (SVR) to 67% and 68% of the pre-epidural values. Volume loading with dextran 10 ml X kg-1 b.w. increased QT nearly to the pre-epidural value. SVR decreased further to 61% of the pre-epidural value and AP was only slightly increased to 14.9 +/- 2.7 kPa. Subsequent administration of prenalterol 20 micrograms X kg-1 b.w. caused a further increase in QT to 17% above the pre-epidural value due to an increase in heart rate of 51 beats/min. AP did not change since SVR decreased further to 49% of the pre-epidural value. The hepatic arterial blood flow (QHA) was essentially unchanged during epidural block as well as during volume loading, while the portal venous blood flow (Qpv) was changed concurrently with (QT). In spite of the decrease in SVR, the preportal and hepatic arterial vascular resistances were not diminished following prenalterol. The increase in OT must therefore have favoured other vascular beds. Hepatic and pre-portal tissue oxygen uptakes were unchanged during the experimental procedure, while whole-body oxygen uptake decreased by 20% following the epidural block and increased nearly to the pre-epidural level following volume loading in combination with prenalterol.     

Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass

BACKGROUND: Phosphodiesterase (PDE) III inhibitors have both an inotropic and a peripheral vasodilatory effect, and also inhibit the activation of macrophages. Thus a newly developed PDE III inhibitor, olprinone, could modify gastric intramucosal pH (pHi), systemic oxygen consumption, and systemic inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: We studied 23 patients. In 15 patients, olprinone (0.1 or 0.2 microg x kg(-1) x min(-1)) was administered from the commencement of CPB until their admission to the ICU. The other 8 patients received placebo. The pHi and regional CO2 tension (PrCO2) were assessed by a capnometric air tonometry. Systemic inflammatory responses were evaluated by serum interleukin-6 (IL-6), IL-10, and leucocyte counts. RESULTS: The pHi and PCO2-gap, the difference between PrCO2 and arterial CO2 tension (PaCO2), showed a transient decrease and an increase after CPB, respectively. Although olprinone did not affect pHi, olprinone at 0.2 microg x kg(-1) x min(-1) significantly lessened post-CPB increase in PCO2-gap. Olprinone at 0.2 microg x kg(-1) x min(-1) significantly increased IL-10 and reduced the extent of leucocytosis, while it did not affect IL-6 levels. At the same dosage, olprinone also lessened the surge in systemic oxygen uptake index (VO2) and augmented the increase in mixed oxygen saturation (SvO2) both of which occurred after CPB. At 0.1 microg x kg(-1) x min(-1), however, olprinone did not show any significant effect. CONCLUSION: Our results suggest that olprinone at 0.2 microg x kg(-1) x min(-1) suppresses gastric intramucosal acidosis and systemic inflammation following CPB.     

Assessment of splanchnic perfusion by gastric tonometry in patients with acute hypovolemic burn shock

OBJECTIVE: To compare the changes in pHi and intramucosal-arterial CO(2)-gap with invasive haemodynamic and global perfusion measurements during hypovolemic burn shock and to evaluate the sensitivity of these parameters as an early predictor of mortality in patients with extensive burns. DESIGN: Prospective, controlled, clinical study. SETTING: An eight-bed intensive burn care unit in a university-affiliated hospital. PATIENTS: Fifty severely burned patients with TBSA burned >25% BSA. METHODS: During the first 48h after burn, gastric intramucosal CO(2) was measured every 8h using automated air tonometry. pHi and intramucosal-arterial CO(2)-gap were calculated. Simultaneously invasive haemodynamic data were registered by the transpulmonary thermodilution technique, using the mean of triplicate injections. The intramucosal-arterial CO(2)-gradient and pHi were compared with haemodynamic and global perfusion data by regression analysis. Mean pHi and CO(2)-gap values at 8 and 24h after injury were compared between survivors and non-survivors to evaluate the prognostic significance of this parameter. RESULTS: Regression analyses revealed no or a negligible correlation between intramucosal and haemodynamic or perfusion data, even during the critical low flow-high resistance phase of resuscitation. Mean pHi and PCO(2)-gap at 8 and 24h did not differ significantly between survivors and non-survivors. CONCLUSION: Gastric tonometry is a poor indicator of splanchnic perfusion in patients with burn shock, even when all precautions are taken to prevent methodological errors. The intramucosal-arterial PCO(2)-gap and pHi do not distinguish survivors from non-survivors. Therefore, gastric tonometry does not seem to improve the ability to anticipate and avert regional anaerobic metabolism during burn shock and its routine use in these patients cannot be recommended.     

Sevoflurane versus halothane: effect of oxycodone premedication on emergence behaviour in children

BACKGROUND: Clinical studies have provided conflicting conclusions about whether the frequency of emergence agitation is increased in children following sevoflurane anaesthesia. The purpose of the study was to determine a frequency and duration of agitation with halothane and sevoflurane anaesthesia and whether oxycodone premedication affected the incidence of emergence agitation in children. METHODS: We measured and compared halothane and sevoflurane recovery in 130 patients using a 5-point scale measuring emergence behaviour every 10 min during the first 60 min of recovery or until discharge. RESULTS: We used this 5-point scale to assess the presence or absence of emergence agitation and found a frequency of emergence agitation of more than 40% in children who received halothane and sevoflurane anaesthesia. CONCLUSIONS: Oxycodone reduced the frequency of agitation in children who received halothane, but not in the children who received sevoflurane anaesthesia.     

A comparison of sevoflurane to halothane in paediatric surgical patients: results of a multicentre international study

Induction, emergence and recovery characteristics were compared during sevoflurane or halothane anaesthetic in a large (428) multicentre, international study of children undergoing elective inpatient surgical procedures. Two hundred and fourteen children in each group underwent inhalation induction with nitrous oxide/oxygen and sevoflurane or halothane. Incremental doses of either study drug were added until loss of eyelash reflex was achieved. Steady state concentrations of anaesthesia were maintained until the end of surgery when anaesthetic agents were terminated simultaneously. Time variables were recorded for induction, emergence and the first need for analgesia in the recovery room. In addition, in 86 of the children in both groups, venous blood samples were drawn for plasma fluoride levels during and after surgery. There was a trend toward smoother induction (induction of anaesthesia without coughing, breath holding, excitement laryngospasm, bronchospasm, increased secretion, and vomiting) in the sevoflurane group with faster induction (2.1 min vs 2.9 min, P= 0.037) and rapid emergence times (10.3 min vs 13.9 min, P= 0.003). Among the children given sevoflurane, 2% developed bradycardia compared with 11% in the halothane group. Postoperatively, 46% of the children in the halothane group developed nausea and or vomiting versus 31% in the sevoflurane group (P= 0.002). Two children in the halothane group developed cardiac dysrhythmia and were dropped from the study. In addition, a child in the halothane group developed malignant hyperthermia, received dantrolene, and had an uneventful recovery. Mean maximum inorganic fluoride concentration was 18.3 μM˙l^?1. The fluoride concentrations peaked within one h of termination of sevoflurane anaesthetic and returned rapidly to baseline within 48 h. This study suggests that sevoflurane may be the drug of choice for the anaesthetic management of children.     

Increased synthesis of nitric oxide in rat brain cortex due to halogenated volatile anesthetics confirmed by EPR spectroscopy

BACKGROUND: Halogenated volatile anesthetics (HVAs) are considered to be inhibitors of nitric oxide synthase (NOS). On other hand, NO mediates the vasodilation produced by HVAs. Thus, both increase and decrease of NO concentration in brain tissues are possible during anesthesia. Previously, we have observed an increase of NO content in rat brain cortex under halothane anesthesia. The goal of this study was to determine whether the observed phenomenon was general for this anesthetic group, if it was specific for brain cortex, and if the NO increase was due changes in NOS activity. METHODS: NO scavengers were injected to adult rats 30 min prior to anesthesia. Rats were anesthetized by inhalation of an O2 mixture with volatile anesthetics (1.5% for halothane; 1% for isoflurane, 2% for sevoflurane). After 30 min of anesthesia, rats were decapitated and brain cortex, cerebellum, liver, heart, kidneys and testes were dissected, frozen in liquid nitrogen and subjected to EPR spectroscopy. Nitric oxide content was determined quantitatively based on the intensity of the NO-Fe-DETC complex spectrum and its comparison with the calibration curve. RESULTS: In rats anesthetized with HVAs, we observed a greater than twofold increase of NO content in brain cortex as compared to the nonanesthetized animals. No significant changes were detected in other organs. The NOS inhibitor N(omega)-nitro-L-arginine abolished the increase of NO content in brain produced by volatile anesthetics. CONCLUSION: The action of volatile anesthetics is coupled with an increase of NO content in the cortex dependent on NOS activity.     

Effects of halothane and sevoflurane on QT dispersion in paediatric patients

BACKGROUND: The QT dispersion (QTd) of the ECG is an indirect measure of heterogeneity of ventricular repolarization which may contribute to complex ventricular arrhythmias. We compared the effects of halothane and sevoflurane on QTd, and heart-rate corrected QT dispersion (QTcd). METHODS: Fifty ASA physical status I patients, aged 5-15 years, undergoing general anaesthesia were studied. A control ECG recording was printed before induction of anaesthesia. In the halothane group, anaesthesia was induced with halothane 4% in 2 : 1 ratio of air : O2 mixture and in the sevoflurane group with sevoflurane 8% in 2 : 1 ratio of air : O2 mixture. The ECG was recorded 1 and 3 min after induction of anaesthesia, 1 and 3 min after the administration of vecuronium 0.08 m.kg(-1) intravenous and 1 and 3 min after the tracheal intubation. All ECGs were analysed by two cardiologists blinded to the anaesthetic. RESULTS: Although QTd increased in both groups following intubation, this difference was not statistically significant when compared with control values. Following intubation five patients in the halothane group had ventricular arrhythmias of short duration, whereas no arrhythmias were recorded in the sevoflurane group (P = 0.052). Following intubation, QTd (45 +/- 15 ms vs 40 +/- 14 ms) and QTcd (60 +/- 17 ms vs 55 +/- 16 ms) values in the halothane group were significantly greater than the sevoflurane group (P < 0.05). CONCLUSION: Neither sevoflurane nor halothane caused a significant increase in QTd compared with control values before induction. Only QTd following intubation was significantly greater in the halothane group than the sevoflurane group.     

Effects of simulated hypovolaemia on haemodynamics, left ventricular function, mesenteric blood flow and gastric Pco2

BACKGROUND: Compensated clinically silent hypovolaemia may lead to low cardiac output, hypoperfusion and ischaemia. We investigated the cardiovascular effects of simulated hypovolaemia to determine whether it caused mesenteric ischaemia detectable by gastric tonometry. METHODS: Thirteen healthy volunteers, aged 21-36 years, were investigated. Lower body negative pressure (LBNP) was used to simulate normotensive hypovolaemia. Cardiovascular parameters were measured using echocardiography. Mesenteric blood flow was investigated using Doppler sonography of the superior mesenteric artery (SMA). Gastric Pco(2) (P(g)co(2)) was measured using gas tonometry. Data were collected at baseline, LBNP and during a recovery period. RESULTS: Normotensive hypovolaemia was induced successfully in 11 volunteers. There were no significant differences in mean arterial pressure between the three data points (91 +/- 6, 93 +/- 10 and 95 +/- 9 mmHg, respectively). With the induction of LBNP, the heart rate increased from 64 +/- 16 to 73 +/- 16 beats/min (P < 0.001), the cardiac index decreased from 2.7 +/- 1.0 to 1.8 +/- 0.6 l/min/m(2) (P= 0.002) and the systemic vascular resistance increased from 1535 +/- 445 to 2270 +/- 550 dyn s/cm(5) (P < 0.001). The SMA mean flow velocity decreased from 53 +/- 18 to 37 +/- 20 cm/s (69 +/- 20%) (P= 0.007), and increased to 56 +/- 34 cm/s (106 +/- 38%) (P= 0.001) during reperfusion. The SMA resistance increased from 92 +/- 30 to 174 +/- 110 mmHg/l/min (P= 0.004). These changes were reversible after termination of LBNP. By contrast, there were no significant differences in P(g)co(2) between the three data points. CONCLUSIONS: In these volunteers, the mesenteric vascular bed contributed importantly to the maintenance of arterial pressure during normotensive hypovolaemia. However, this compensated hypovolaemia did not compromise the mesenteric perfusion sufficiently to increase P(g)co(2) and to allow detection by tonometry.     

Serum glutathione S-transferase alpha as a measure of hepatocellular function following prolonged anaesthesia with sevoflurane and halothane in paediatric patients

We studied the effects of prolonged anaesthesia (4.3-7.7 h) with sevoflurane and halothane on hepatic function in 14 paediatric patients. Hepatic function was assessed using serum concentrations of liver-specific glutathione S-transferase alpha (GSTA) before and 0, 3 and 15 h after the end of anaesthesia. A transient significant increase in GSTA over baseline was observed in the sevoflurane group, but not in the halothane group, and the difference between the groups was not significant. These data suggest that, although statistically insignificant, the use of sevoflurane for prolonged anaesthesia in paediatric patients is more likely than halothane to be involved in damage to hepatic function.     

Epicardial ultrasound in a case of myocardial bridge and apical hypertrophic cardiomyopathy

A 59-year-old male with a history of unstable angina was diagnosed with a myocardial bridge of the left anterior descending artery (LAD) and apical variant hypertrophic cardiomyopathy (AHCM). He underwent unroofing of the myocardial bridge and a left ventricular apical myectomy. Intraoperatively, epicardial ultrasound was used to identify the myocardial bridge with systolic compression of the LAD and confirm resolution of this compression postoperatively. Furthermore, epicardial ultrasound was used for guiding the degree of apical resection of the decompressed heart. This novel use of intraoperative epicardial ultrasound can help guide surgeons preoperatively and confirm results immediately after an operation.     

Effects of halothane, isoflurane, and sevoflurane on lipid peroxidation following experimental closed head trauma in rats

Background: In a rat closed head trauma model we examined both the time course of lipid peroxidation and the effects of halothane, isoflurane, and sevoflurane on it by analysis of malondialdehyde (MDA) formation.
Methods: Animals were divided randomly into five groups: sham-operated (SO), n =18; control-closed head trauma to left frontal pole, n =18; closed head trauma model+halothane, n =18; closed head trauma model+isoflurane, n =18; and closed head trauma model+sevoflurane, n =18. Halothane, isoflurane, or sevoflurane were applied 15 min after trauma for 30 min. Rats were euthanized 1,3, and 5 h after the inhalation agents. Brain tissue samples were taken 5 mm from the left and right frontal poles. MDA was considered to reflect the degree of lipid peroxidation.
Results: MDA concentrations were greater in the control, halothane, sevoflurane, and isoflurane groups than in SO animals ( P <0.001). No statistical difference between the hemispheres was found between the halothane, isoflurane, or sevoflurane groups, but MDA levels were lower with isoflurane than in the halothane, sevoflurane, and control groups at 1, 3, and 5 h ( P <0.001). MDA levels were higher as compared with the halothane and sevoflurane groups at 1 h but not at 3 or 5 h ( P <0.001).
Conclusion: MDA levels with the isoflurane group were lower than in the other trauma groups, which suggest that isoflurane, given after closed head trauma, might be protective against lipid peroxidation of cerebral injury.