Effective concentration 50 for propofol with and without 67% nitrous oxide

The Effective Blood Concentration (EC) of propofol required to prevent response to surgical incision was determined in 65 ASA I or II female patients breathing either 100% oxygen or 67% N₂O in oxygen. Propofol was administered via a microcomputer-controlled infusion system programmed to maintain the blood propofol concentration at predetermined target values. The blood propofol concentrations predicted by the micro-computer were validated by measurement of whole blood propofol concentration. Predicted and measured concentrations differed during infusion of propofol, but became similar after discontinuing the infusion for at least 90 s, suggesting that equilibration within the central compartment was incomplete during infusion. The response to the initial incision was observed and probit analysis used to determine the predicted blood concentration at which 50% of patients responded. The predicted EC50 for propofol/N₂O/ O₂ and propofol/O₂ was 4.5 μg ml^-1 and 6.0 μg ml^-1 respectively, and the measured EC50 propofol/N₂O/ O₂ and propofol/O₂ was 5.36 μg ml^-1 and 8.1 μg ml^-1, 67% nitrous oxide in oxygen reducing the predicted EC50 by 25% and the measured EC50 of propofol by 33%. The predicted EC may be more representative of the equilibrated concentration in the central compartment and thus reflective of tissue propofol concentrations.     

EEG changes during five minutes of inhalation of a 33% xenon-O2 mixture

The effects on the EEG of inhalation of a 33% Xenon O₂ mixture over a period of 5 minutes were studied in 18 human volunteers. This dosage is similar to that used in xenon CT studies. In 4 subjects no EEG changes were observed during the study. In the 14 other subjects, EEG variations were detected, the most prominent of which was an increase in power. No change was observed in and power. These findings seem to support an early induction (excitation) phase of anaesthetics. All changes disappeared rapidly following the termination of xenon inhalation. The effects reported are minimal and should not impair the clinical value of CBF measurements using the xenon CT method.     

Simulated use of premixed 0.25% isoflurane in 50% nitrous oxide and 50% oxygen

Background. Isoflurane (0.25%) in premixed nitrous oxide andoxygen, 50/50, v/v (IN₂O), has been suggested for pain reliefin labour. Possible phase separation of the mixture was studiedduring simulated administration. Methods. A sinusoidal pump set at stroke volume of 2 litresand a rate of 20–22 bpm and cycling for 1 min in threewas used to simulate breathing during the painful contractionsof labour. Results. The temperature inside a 10-litre capacity cylinderdid not drecrease sufficiently to cause separation of the gasmixture. Temperature in the demand valve decreased to –15.5°Cand this caused a small amount of liquid formation within thevalve. Accordingly, the inspired concentration during the firstbreath of mixture in a cycle could be transiently as high as0.55%. The concentration observed at the patient connectionafter the first breath varied between 0.17 and 0.28%. Conclusions. The system delivered a clinically acceptable performancealthough further development to avoid liquid condensation isneeded. Br J Anaesth 2002; 89: 820–4     

Phase behaviour of premixed 0.25% isoflurane in 50% nitrous oxide and 50% oxygen

Background. Isoflurane (0.25%) in premixed nitrous oxide andoxygen 50/50, v/v, (IN₂O), has been suggested for pain reliefin labour. Methods. Possible phase separation of this mixture was studiedby analysis of samples from pre-filled cylinders as they werecooled. Results. Condensation of isoflurane was found at 3.1°Cin a cylinder, which held 8.7 MPa at 15°C. In a cylinderholding 13.8 MPa, which is the standard filling pressure stipulatedby the National Health Service, the condensation temperaturewas –2.3°C. At the highest cylinder filling pressureinvestigated (14.15 MPa) the separation temperature was evenless, –3.0°C. After exposure of cylinders to –40°Cand complete phase separation of the mixture, complete mixingwas achieved by 24 h storage in the horizontal position at roomtemperature and, either three complete inversions of the cylinderor mechanical rolling at 30 r.p.m. Conclusions. These findings should assist the use and storageof IN₂O. Br J Anaesth 2002; 89: 814–19     

An apparatus for the delivery of 50% premixed nitrous oxide and oxygen on demand or by controlled ventilation

A small, portable and robust apparatus for the administration of 50% premixed nitrous oxide and oxygen mixture for analgesia for hospital and emergency use is described. The equipment can deliver the mixture on demand or by intermittent positive pressure ventilation. It has important advantages over earlier devices particularly in the accident and emergency field in which it has already proved successful.     

Haemodynamics and Oxygen Consumption in the Dog During High Epidural Block with Special Reference to the Splanchnic Region

High epidural block (Th I-IV) with bupivacaine was carried out in 16 dogs. Mean arterial blood pressure decreased to 52% of control value owing to nearly equal decreases in systemic vascular resistance and cardiac output. Portal venous blood flow decreased from 25.8 ± 8.6 to 16.7 ±7.2 ml/kg b.w. × min^-1 following epidural block, while hepatic arterial blood flow remained unchanged at 9.1 ± 3.1 ml/kg b.w. × min^-1 owing to a reduction in hepatic arterial resistance of 51 %. Hepatic oxygen uptake was maintained during the epidural block through increased oxygen extraction. However, total oxygen uptake decreased by 18 % and, in spite of this, arteriovenous oxygen content difference increased by 25%, indicating circulatory depression.     

Effects of Enflurane-Nitrous Oxide Anaesthesia and Surgical Stimulation on Regional Coronary Haemodynamics in a Patient with LAD Bypass Graft

Central and regional coronary haemodynamics were studied in a patient with a left anterior descending artery (LAD) graft and angiographically visible collaterals from a normal right coronary artery. A three-thermistor thermodilution catheter was used for measuring total coronary sinus blood flow and great cardiac venous blood flow, the latter being a good representative of blood flow through the LAD. Enflurane-nitrous oxide anaesthesia induced marked coronary vasodilatation and redistribution of blood flow from the LAD to other areas draining into the coronary sinus. The most likely mechanism for the redistribution of blood flow in this patient was steal via the collaterals between the LAD and the right coronary artery. During surgical stimulation, the flow through the LAD was further compromised due to pronounced coronary vasoconstriction, probably mediated by catecholamine release.     

The use of 0.25% isoflurane premixed in 50% nitrous oxide and oxygen for pain relief in labour

The addition of 0.25% isoflurane to 50% nitrous oxide in oxygen provides more effective pain relief in labour than 50% nitrous oxide alone. This study was carried out to determine whether self-administration by demand valve of 0.25% isoflurane in 50% nitrous oxide in oxygen premixed in cylinders at 13.7 MPa (IN2O) was practical and safe during labour. Two hundred and twenty-one mothers used IN2O in labour after 50% nitrous oxide had become inadequate for pain relief. Data on IN2O use was recorded during labour and details of the course of labour and opioid usage were taken from the clinical notes. The duration of IN2O use was 0.1-12.35 h (median 2.3). Thirty-two mothers (14.5%) required an epidural and intolerance to IN2O was seen in a maximum of 17 cases (7.7%). One hundred and twenty-six cases were primiparous and 93 parous with 151 deliveries being spontaneous and 70 interventional, of which 12 were by Caesarean section. Maternal blood loss was 20-1500 ml (median 200 ml). Apgar scores at 1 and 5 min were unaffected by IN2O use although a positive correlation was found between the use of opioids and the number of neonates with a 1-min score below 8 and the number requiring resuscitation. Six neonates had an Apgar score below 8 at 5 min, but their condition was adequately explained by factors other than the sedative technique used. Self-administered IN2O was found to be a safe and practical technique for sedation in labour when 50% nitrous oxide alone had become inadequate.     

Effects of Enflurane on Coronary Haemodynamics in Patients with Ischaemic Heart Disease

The effects of enflurane with and without nitrous oxide on coronary haemodynamics and myocardial oxygenation were investigated in 11 patients with generalised atherosclerotic disease. Enflurane decreased systemic blood pressure (-50%) mainly by systemic vasodilation (SVR -41%) and to a lesser degree by impairment of cardiac performance (CO —27%). A change from 1MAC enflurane-nitrogen-oxygen (70/30) to 1MAC enflurane-mtrous oxide-oxygen (70/30) decreased blood pressure and cardiac output further (-16% and -14%). Enflurane-nitrogen-oxygen decreased coronary blood flow (-29%) and perfusion pressure (-47%). Coronary vascular resistance fell (-20%) along with decreases in myocardial oxygen consumption and extraction (— 40% and — 16%). Regional coronary blood flow measurements in four of the patients revealed maldistribution of blood flow. During enflurane-nitrous oxide-oxygen, myocardial oxygen consumption and extraction decreased further (-29% and -12%) without change in coronary blood flow or resistance. Myocardial ischaemia was observed in four patients during enflurane-nitrogen. During enflurane-nitrous oxide, ischaemia disappeared in two of the previously ischaemic patients and appeared in two not previously ischaemic. The regional blood flow maldistribution was abolished with nitrous oxide. It is concluded that enflurane is a powerful coronary vasodilator and in this respect slightly less potent than isoflurane. Enflurane may induce myocardial ischaemia by redistributing coronary blood flow and/or by producing hypotension. Nitrous oxide added to enflurane depresses cardiac function and augments the coronary vasodilatory effect of enflurane to a level at which coronary blood flow becomes totally pressure dependent.     

The effect of nitrous oxide on cerebral blood flow velocity in children anesthetized with propofol

BACKGROUND: Propofol for maintenance of anesthesia by continuous infusion is gaining popularity for use in pediatric patients. Nitrous oxide (N2O) has been shown to increase cerebral blood flow velocity (CBFV) in both children and adults. To determine the effects of N2O on middle cerebral artery blood flow velocity (Vmca) during propofol anesthesia in children, Vmca was measured with and without N2O using transcranial Doppler (TCD) sonography. METHODS: Thirty ASA I or II children aged 18 months to 6 years undergoing elective urological surgery were enrolled. Anesthesia comprised propofol aimed at producing an estimated steady-state serum concentration of 3 micro g.ml-1 and a caudal epidural block. A transcranial Doppler probe was used to measure middle cerebral artery blood flow velocity. Each patient was randomized to receive a sequence of either Air/N2O/Air or N2O/Air/N2O in 35% oxygen. Fifteen min after each change in the N2O concentration, three measurements of cerebral blood flow velocity, blood pressure and heart rate were recorded. Ventilatory parameters and EtCO2 were kept constant throughout the study period. RESULTS: CBFV increased by 12.4% when air was replaced by N2O, and returned to baseline when N2O was subsequently removed. There was a 14% decrease in CBFV when N2O was replaced with air, which increased to baseline when air was subsequently replaced with N2O. Mean heart rate and blood pressure remained constant throughout the study period. CONCLUSION: The effects of nitrous oxide on CBFV are preserved in children during propofol anesthesia.     

Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and quantified electroencephalography (EEG) under two sets of conditions: 1) 1.7% end-tidal concentration of isoflurane in air/oxygen; 2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N2O)/oxygen. The object was to study the effects of N2O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N2O in the anaesthetic gas mixture caused a 43% (P less than 0.05) increase in CBF during normocarbic conditions but no significant change during hypocapnia. CMRO2 was not significantly altered by N2O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N2O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear.     

O2 and N2O analysis with a single intravascular catheter electrode

The simultaneous measurement of O2 and N2O in liquid, using a single polarographic catheter electrode, is described. It is shown that commercial PO2 intravascular electrodes, with silver cathodes, produce separate and distinct polarograms for O2 and N2O, and that these electrodes can be used for the measurement of both PO2 and PN2O.     

Nitrous oxide reduces inspired oxygen fraction but does not compromise circulation and oxygenation during hemodilution in pigs

Background: The use of nitrous oxide (N₂O) during hemodilution has been questioned. Nitrous oxide reduces the inspired oxygen fraction (F₁O₂), depresses myocardial function and may reduce cardiac output (CO) and systemic oxygen delivery (DO_2SY). The aim of this study was to evaluate the importance of the effects of nitrous oxide on systemic and myocardial circulation and oxygenation during extreme, acute, normovolemic hemodilution. Methods: Ten midazolam-fentanyl-pancuronium anesthetized pigs were exposed to 65% N₂O before and after extreme isovole-mic hemodilution (hematocrit 33±1% and 10±1%, respectively). Systemic and myocardial hemodynamics, oxygen delivery and consumption and blood lactate were measured before (at FrO₂ 1.0 and 0.35) and during N₂O exposure. Results: Hemodilution caused an increase in CO from 137±43 to 229±32 ml kg^-1 min^-1 (P< 0.01), a decrease in systemic vascular resistance (from 42±14 to 20±4 mmHg L^-1 min^-1, P < 0.05), a decrease in mean arterial blood pressure (from 119±19 to 100±26 mmHg, P<0.05) and a decrease in DO_2SY from 21.1 ±6.9 to 13.7±2.1 ml kg^-1 min^-1 (P < 0.01). Cardiac venous blood flow increased by 135% (P < 0.01) and cardiac venous saturation from 25±6 to 41±5% (P < 0.05). After hemodilution, changing F_IO₂ from 1.0 to 0.35 reduced arterial blood oxygen content from 59.4±3.7 to 52.3±5.1 ml L^-1 (P < 0.01), mixed venous saturation (SvO₂) from 75±9 to 47±7% (P < 0.05) and DO_2SY from 13.7±2.1 to 11.9+2.3 ml kg^-1 - min^-1 (P < 0.05). Dissolved oxygen at F₁O₂=1.0 and F₁O₂=0.35 constituted 25.4±3.1% and 10.1 ±1.5%, respectively, of systemic oxygen delivery after hemodilution, compared with 10.7±1.2% and 3.9±0.5% before hemodilution (P < 0.01). Left ventricular oxygen delivery and consumption were unchanged. Exposure to N₂O did not affect mean arterial blood pressure or systemic vascular resistance before or after hemodilution. After hemodilution during N₂O-exposure, CO and DO_2SY decreased by 9% (P < 0.01 and P < 0.05, respectively), but no changes in SvO₂, systemic oxygen uptake or arterial lactate were observed. The effect of N₂O on myocardial oxygenation was similar before and after hemodilution; cardiac venous blood flow, left ventricular oxygen delivery and uptake decreased, but no animals showed left ventricular lactate production. Conclusion: Nitrous oxide did not compromise systemic and myocardial circulation and oxygenation during acute normovolemic hemodilution in pigs. Possible adverse effects from the use of nitrous oxide during hemodilution seem to be related to a reduced F_IO₂, reducing the safety margin for systemic oxygen delivery.     

Intraoperative measurement of graft blood flow - a necessity in liver transplantation

Abstract Portal venous and hepatic arterial flow was measured intraop-eratively in the 70 most recent patients undergoing liver transplantation in our institution. Impaired graft flow due to vascular abnormalities was detected in six patients. One patient suffered from arterial steal due to stenosis of the recipient celiac trunk with blood shunting from the hepatic to the splenic artery. Ligation of the recipient hepatic artery restored the arterial graft flow. In two patients we found reduced portal venous flow due to large portosystemic collaterals. The collaterals accountable for the impaired portal flow were identified and ligated, which restored portal venous graft flow. Excessive sensitivity of the portal venous flow to the position of the graft was found in a 6-month-old boy. Portal venous flow varied considerably, depending upon the position of the graft, and intraoperative flow measurement allowed the best position of the graft to be identified. Two patients developed arterial thrombosis in the early postoperative course. Immediate laparatomy with thrombectomy resulted in good, palpable pulsation in the graft artery in both patients. Intraoperative flow measurement demonstrated satisfactory arterial flow in one patient, whereas there was no net flow in the other patient's graft artery. Pulsation in this patient was caused by blood oscillating in and out of the liver. In conclusion, we find that causes of primary graft dysfunction due to technically flawed reperfusion of the graft can be identified and alleviated by intraoperative measurement of the flow in the graft vessels.     

The effect of nitrous oxide on cerebral blood flow velocity in children anaesthetised with desflurane

The aim of this study was to determine the effect of nitrous oxide on cerebral blood flow velocity in children anaesthetised with desflurane. Eighteen healthy children scheduled for elective surgery were enrolled into the study. Anaesthesia was induced using sevoflurane, and a caudal block was performed following tracheal intubation. Anaesthesia was maintained with 1 age-adjusted MAC desflurane. A transcranial Doppler probe was used to measure middle cerebral artery blood flow velocity. Each patient was randomised to receive a sequence of either air/nitrous oxide/air or nitrous oxide/air/nitrous oxide in 30% oxygen. Fifteen minutes after each change in the nitrous oxide concentration, three measurements of cerebral blood flow velocity, blood pressure and heart rate were recorded. Neither the addition nor removal of nitrous oxide caused any significant changes in middle cerebral artery blood flow velocity, heart rate or blood pressure. This may be due to a more potent cerebral vasodilatory effect of desflurane in children.     

Use of a tourniquet with and without adrenaline reduces blood loss during liposuction for lymphoedema of the arm

Sixty-two patients with lymphoedema of the arm after mastectomy and with hypertrophy of the adipose tissue were consecutively treated by liposuction in three different ways. The first group was operated on without the use of a tourniquet. In the second group, liposuction extended up to the distal edge of the tourniquet, and then into the proximal upper arm previously covered by the tourniquet using the ‘dry’ technique. Treatment of the third group was identical to that of the second one, but the area covered by the tourniquet was treated by the tumescent technique. Eighteen patients who did not have lymphoedema either treated or not treated with adrenaline served as a reference group to see how blood transfusions varied with various volumes of aspirate. Using a tourniquet significantly reduced blood loss and the number of transfusions, which was further reduced by tumescence. In the historical reference group, the number of blood transfusions increased as the volume of aspirate increased, and further if no adrenaline was added.     

Intraoperative measurement of graft blood flow — a necessity in liver transplantation

Portal venous and hepatic arterial flow was measured intraoperatively in the 70 most recent patients undergoing liver transplantation in our institution. Impaired graft flow due to vascular abnormalities was detected in six patients. One patient suffered from arterial steal due to stenosis of the recipient celiac trunk with blood shunting from the hepatic to the splenic artery. Ligation of the recipient hepatic artery restored the arterial graft flow. In two patients we found reduced portal venous flow due to large portosystemic collaterals. The collaterals accountable for the impaired portal flow were identified and ligated, which restored portal venous graft flow. Excessive sensitivity of the portal venous flow to the position of the graft was found in a 6-month-old boy. Portal venous flow varied considerably, depending upon the position of the graft, and intraoperative flow measurement allowed the best position of the graft to be identified. Two patients developed arterial thrombosis in the early postoperative course. Immediate laparatomy with thrombectomy resulted in good, palpable pulsation in the graft artery in both patients. Intraoperative flow measurement demonstrated satisfactory arterial flow in one patient, whereas there was no net flow in the other patient's graft artery. Pulsation in this patient was caused by blood oscillating in and out of the liver. In conclusion, we find that causes of primary graft dysfunction due to technically flawed reperfusion of the graft can be identified and alleviated by intraoperative measurement of the flow in the graft vessels.     

Effect of nitrous oxide on the bispectral index and the 95% spectral edge frequency of the electroencephalogram during surgery

We studied the effect of nitrous oxide on the bispectral index and 95% spectral edge frequency of the electroencephalogram in 20 patients undergoing lumbar surgery under general anaesthesia combined with epidural administration of 5 mg morphine. Anaesthesia was induced with propofol and sufentanil, and maintained with sevoflurane in air/oxygen adjusted to keep the bispectral index between 40 and 60. One and a half hours after the start of surgery, nitrous oxide was administered in a randomised sequence of concentrations (20, 40 and 60% end-expired). Under steady-state conditions, mean (SD) bispectral index and spectral edge frequency decreased as end-tidal concentration of nitrous oxide increased, from 47.7 (4.3) and 15.6 (1.3) at 0% nitrous oxide to 39.8 (6.3) and 14.3 (1.8) at 60% nitrous oxide. A negative correlation was found between nitrous oxide concentration and bispectral index (r = -0.48; p < 0.01) and spectral edge frequency (r = -0.39; p < 0.05). We conclude that this dose-dependent decrease in bispectral index and spectral edge frequency induced by nitrous oxide may reflect the level of analgesia associated with the anaesthetic regimen.