Recovery characteristics of propofol anaesthesia, with and without nitrous oxide: a comparison with halothane/nitrous oxide anaesthesia in children

Few studies have examined whether nitrous oxide influences the recovery characteristics of propofol anaesthesia. The present study examined the effect of nitrous oxide on the recovery characteristics of propofol anaesthesia, and compared these data with those for halothane/nitrous oxide anaesthesia. Sixty children aged 3–12 years were assigned at random to receive one of three maintenance regimens: propofol with or without nitrous oxide (70%) or halothane/nitrous oxide (70%). During propofol/N₂O anaesthesia, the infusion rate of propofol (180±39 μg·kg⁻¹·min⁻¹) required to maintain the mean arterial pressure and heart rate within 20% of the baseline values was significantly less than that during propofol/O₂ (220±37 μg·kg⁻¹·min⁻¹; P <0.005). The time from discontinuation of anaesthesia to eye-opening (11±6 min), to response to commands (12±6 min), and to return of full wakefulness (21±10 min) after propofol/N₂O were similar to those after propofol/O₂, but significantly less (by approximately 30%) than those after halothane ( P <0.05). The overall incidence of emesis after propofol/N₂O (53%) was greater than that after propofol/O₂ (17%, P <0.05) and comparable to that after halothane/N₂O (58%). These data suggest that N₂O has little effect on the rate of recovery after propofol, but significantly increases the incidence of postoperative emesis, thereby attenuating one of the main attributes of propofol anaesthesia.     

The influence of the duration of isoflurane anaesthesia on neuromuscular effects of mivacurium

Background: The pharmacodynamic profile of muscle relax-ants is usually changed by volatile anaesthetics. These changes seem to be time-dependent, even though few data are available to substantiate this.
Methods: We studied neuromuscular effects of a single dose of mivacurium (0.2 mg·kg^-1) during short and intermediate duration of isoflurane anaesthesia. Forty-five children 1–10 years of age were randomized to receive 1.5% end-tidal concentration of isoflurane in N₂O/O₂ for 10 or 30 min (groups Iso-10 and Iso-30, respectively) or to receive nitrous oxide in oxygen for 10 min (Group N₂O) before 0.2 mg · kg^-1 of mivacurium was given. Neuromuscular response was recorded by adductor pollicis electromyogram.
Results: The onset time of mivacurium was shorter in Group Iso-30, 1.7 (1.0–2.3) min than in Group Iso-10, 2.3 (1.7-3.3) rnin or Group N₂O, 2.3 (1.7-3.3) min (median with 10–90% percen-tiles) ( P <0.05). In Group Iso-30 the recovery time of the first EMG response was significantly longer than in groups Iso-10 and N₂O ( P <0.0001). Groups Iso-10 and N₂O did not differ from each other.
Conclusions: Our results indicate that the duration of a constant concentration of isoflurane anaesthesia influences significantly the pharmacodynamics of mivacurium. The duration of a volatile anaesthesia is critical when potentiation of NMB is evaluated or compared in neuromuscular studies.     

Propofol reduces emesis after sufentanil supplemented anaesthesia in paediatric squint surgery

Background. Squint surgery is associated with a high incidence of postoperative emesis. The purpose of this prospective study was to examine the influence of propofol and isoflurane anaesthesia on the incidence of postoperative nausea and vomiting in children.
Methods. Ninety children aged 3–10 years were randomly allocated to one of 3 groups. In all groups, children received 2 mg/kg propofol, 0.5 μg/kg sufentanil and 0.5 mg/ kg atracurium for induction of anaesthesia. In group 1, anaesthesia was maintained with 15–20 mg/kg·h propofol and children were ventilated with 30% O₂ in air. In group 2, anaesthesia was maintained with 10–15 mg/kg·h propofol and 30% O₂ in N₂O. In group 3, anaesthesia was maintained with 1.0–1.5 Vol% isoflurane and 30% O₂ in N₂O. The time of extubation, awakening and postoperative surveillance, the incidence and numbers of episodes of postoperative nausea and vomiting were registered as well as requirements of antiemetics. Statistics were made using ANO-VA and Chi-square test or Kruskal-Wallis test with P <0.05 considered as significant.
Results. The overall incidence of nausea ( P =0.0001) and vomiting ( P =0.002) was higher in group 3 (70%;73%) than in group 1 (13%; 23%) and 2 (20%;28%). Episodes of nausea ( P =0.0001) and vomiting ( P =0.0013) were more frequent in group 3 (74%;69%) than in group 1 (13%;15%) and 2 (13%;16%). Antiemetic requirements were higher and the time of postoperative sleep and surveillance was longer in group 3 than in group 1 and 2 ( P =0.04).
Conclusion. Propofol-sufentanil anaesthesia results in less emesis and treatment during the early postoperative phase irrespective of N₂O administration compared with propofol- induced isoflurane anaesthesia and may be recommended in children undergoing squint surgery.     

The Role of Diazepam and Fentanyl in the Production of Balanced Anaesthesia

The effects of diazepam-fentanyl combinations on consciousness, superficial nociception, respiration and circulation during N₂O + O₂ inhalation were studied in 40 premedicated patients during induction of anaesthesia. The balance between antinociception and anaesthesia was closest to the optimum in patients receiving 0.2 mg/kg of diazepam plus 1 μg/kg of fentanyl; the eyelid reflex was negative in all patients and only two out of ten patients reacted to abdominal pinching. When only 0.2 mg/kg of diazepam was given with N₂O + O₂, the eyelid reflex was negative in all patients, but half of them reacted to pinching. When the dose of diazepam was reduced to 0.1 mg/kg and patients received 1 or 2 μg/kg of fentanyl, the balance between anaesthesia and antinociception was good, but 30–50% of patients had a positive eyelid reflex and reacted to pinching. No distinct respiratory depression was observed in patients given 0.2 mg/kg of diazepam, whereas seven patients given 0.1 mg/kg of diazepam plus 2 μg/kg of fentanyl had apnoea lasting more than 60 s associated with a significant (P<0.05–0.001) increase in end-tidal CO₂ and PCO₂ in arterialised venous blood.
No significant changes were observed in blood pressure or heart rate after any of the drugcombinations studied.
It appears that an optimal balance between anaesthesia and antinociception with minimal side-effects during balanced general anaesthesia requires reinforcement of N₂O+O₂ anaesthesia not only with fentanyl but also with hypnotics or sedatives.     

Intravenous propofol vs thiamylal-isoflurane for caesarean section, comparative maternal and neonatal effects

Several studies on propofol (Diprivan) for induction of anaesthesia during caesarean section have demonstrated its safety, however, its safely during maintenance of anaesthesia is not yet fully evaluated.
The present study was undertaken to compare the maternal and neonatal effects of propofol or isoflurane in 74 term parturients undergoing primary or repeat caesarean section. Patients were randomly assigned to two groups, propofol group (n = 37) received propofol 1.5–2.5 mg·kg^-1 for induction followed by a continuous infusion of propofol of 0.05–0.2 mg 4mD kg^-1 · min^-1. The isoflurane group (n=37) received thiamylal 3–4 mg · kg^-1 for induction followed by isollurane 0.25–0.75% for maintenance. All patients had rapid sequence induction using suceinyl-choline and endotracheal intubation, 50% N₂O and O₂ were used in all patients until delivery. After delivery N₂O concentration was increased to 67% and intravenous butorphanol (Stadol) was given as needed. Patients in the propofol group had less hypertension after intubation ( P <0.05) and this was also of shorter duration compared to patients in the isoflurane group (5 min vs 10 min respectively). Maternal blood loss as well as intraoperative awareness and recovery time did not differ significantly between the two groups. Neonatal status as ascertained by Apgar scores, cord acid base status and the neurological and adaptive capacity scores (NACS) was equally good in both groups. It is concluded that propofol used for induction and maintenance of anaesthesia is a safe alternative to thiamylal/isoflurane for patients undergoing caesarean section and is associated with less hypertensive response during laryngoscopy and intubation.     

Comparison of the haemodynamic actions of desflurane/N2O and isoflurane/N2O anaesthesia in vascular surgical patients

Background: The purpose of this study was to compare heart rate and arterial blood pressure response to desflurane/N₂O vs isoflurane/N₂O anaesthesia in a randomised clinical trial performed in patients before vascular surgery.
Methods: To evaluate associated changes in the autonomic nervous system with maintenance of anaesthesia, we used power spectral analysis (PSA) of heart rate and blood pressure and measured plasma catecholamine concentrations. Twenty-five patients whose trachea had been intubated after propofol induction were given either desflurane or isoflurane at 1 and 1.5 MAC in N₂O (60%) in a random manner.
Results: At an anaesthetic depth of up to 1.5 MAC, arterial blood pressure, indices of sympathetic activity derived from PSA, decreased with both anaesthetics, while heart rate and plasma catecholamine concentrations did not significantly change. Plasma renin activity significantly increased at 1.5 MAC anaesthesia in both groups.
Conclusions: We conclude that sympathetic hyperactivity previously reported during desflurane anaesthesia in healthy volunteers is not frequent in clinical practice in elderly vascular surgical patients under desflurane/N₂O anaesthesia, since it occurs at an anaesthetic depth which cannot be reached in these patients because of the lowering arterial blood pressure effects of desflurane, which are similar to those of isoflurane.     

Attenuation of the Cardiovascular Intubation Response with N2O, Halothane or Enflurane

The circulatory intubation response was studied in 75 normotensive, otolaryngological patients after a thiopentone-suxamethonium induction followed by 2 min artificial ventilation with 100% oxygen (control), 70% nitrous oxide in oxygen (N₂O), halothane 2% with N₂O, enflurane 3% with N₂O or enflurane 5% in oxygen. The above study groups (n = 15) were chosen after preliminary experiments performed in 25 different patients with halothane 2% (n = 8) or enflurane 3% (n = 6) in oxygen, which did not prevent the increase of arterial pressure after intubation, or with halothane 3% (n = 11) which attenuated the pressor response but caused cardiac arrhythmias in 55% of patients. Enflurane 5% in oxygen attenuated the increase of systolic arterial pressure by 53%, enflurane 3% with N₂O by 34% and halothane 2% with N₂O by 31 %. The increase in heart rate after intubation was lowest in the halothane 2% with N₂O group, but there were no statistically significant differences between the groups. Cardiac arrhythmias were commonest in the enflurane 3% with N₂O group (20%) and they did not occur in the halothane 2% with N₂O group. Considering the total effect on arterial pressure, heart rate and rate-pressure product, we recommend the combination of halothane 2% with N₂O.     

Occupational exposure to sevoflurane, halothane and nitrous oxide during paediatric anaesthesia Waste gas exposure during paediatric anaesthesia

We report the findings of a study on exposure of operating room staff to sevoflurane, halothane and nitrous oxide during induction and maintenance of anaesthesia in children. Concentrations of anaesthetic agents in the operating theatre were measured directly by highly sensitive, photoacoustic infrared spectrometer during 20 anaesthetics. Samples were taken from the breathing zones of the anaesthetist and the circulating nurse. The operating theatre was of modern design with an air conditioning system providing 20 changes of air each hour. The threshold values of 100 ppm N₂O, 50 ppm isoflurane and 10 ppm halothane recommended by the United Kingdom Committee for Occupational Safety and Health (COSH) were exceeded in several cases for a short time during mask induction. After tracheal intubation, trace concentrations of sevoflurane, halothane and N₂O were mostly under the recommended levels and comparable to levels measured during adult anaesthesia.     

Restoration of Oxygen Uptake and Blood Flow in the Rat Cerebral Cortex after Halothane Anaesthesia

Halothane decreases both the certal blooi Row (CBF) and the cerebral metabolic rate for oxygen (CMRo₂) when given in anaesthetic doses. A recent report (G jedde & H indfelt 1975) suggests that when halothane is administered to rats for 1 hour, CBF and CMRo₂ are depressed by about 30 and 40%, respectively, for as long as 4 hours after discontinuation of the halothane anaesthesia. In the present study rats were anaesthetized with 1% halothane for 1 hour, and CBF and CMRo₂ were measured at the end of a 30 min recovery period, during which 70% N₂O was administered. Comparison with animals maintained on 70% N₂O throughout the entire 90 min period showed that previous halothane anaesthesia had no effects on CBF or CMRo₂.     

Low-flow anaesthesia at a fixed flow rate

Aims and Objectives: This study attempts to assess the safety of low-flow anaesthesia (LFA) at fixed flow rates with particular reference to the incidence of a decline in FiO₂ below safe levels of 0.3 and to determine whether LFA can be used safely in the absence of an FiO₂ monitor.
Methods: A total of 100 patients undergoing procedures under general anaesthesia at fresh gas flows of 300 ml/min of O₂ and 300 ml/min of N₂O were monitored while maintaining the dial setting of isoflurane at 1.5% for 2 h. The changes in gas composition were analysed and even a single recording of FiO₂ of <0.3 was considered sufficient to render the technique unsafe in the absence of gas monitors.
Results: The lowest recorded value of FiO₂ was 31% (v/v%). There was no incidence of adverse events necessitating the conversion from low flows to conventional flows.
Conclusions: We conclude that low flows of 300 ml/min of N₂O and 300 ml/min of oxygen can be used safely for a period of 2 h without the use of monitors for gas analysis of oxygen and agent in adult patients weighing between 40 and 75 kgs.     

The effects of wound infiltration with bupivacaine versus saline on postoperative pain and opioid requirements after herniorrhaphy

In a prospective, double-blind, placebo-controlled study, twenty-eight healthy, male patients, aged 20–69 years, scheduled for unilateral elective inguinal herniorrhaphy ad modum Bassini were randomized to receive postoperative infiltration of the surgical wound with either bupivacaine 0.25%, or isotonic saline. General anaesthesia was induced with thiopentone 3–5 mg·kg^-1 and alfentanyl 10 μg·kg^-1, and maintained with alfentanyl 5 μg·kg^-1 15 min and N₂O/O₂. After herniorrhaphy, the internal fascia was infiltrated with bupivacaine 0.25% or saline, 10 ml. After closure of the external fascia, the subcutaneous tissue was infiltrated with bupivacaine 0.25% or saline, 15 ml on both sides of the surgical wound. Pain at rest, during mobilisation and during cough was significantly decreased in patients receiving bupivacaine compared to placebo. Median time to first request for morphine was increased from 25 min to 135 min, and the consumption of supplementary morphine during the 24 h study period reduced from four to two doses of 0.1 mg·kg^-1 iv or 0.125 mg·kg^-1 im, in patients who received bupivacaine compared to placebo.     

Comparison of Halothane and Enflurane Anaesthesia for Tonsillectomy in Adults

Halothane and enflurane in combination with N₂O/O₂ were compared in 103 adults undergoing tonsillectomy. Anaesthesia was induced with thiopental, and intubation was facilitated with suxamethonium. During halothane anaesthesia the mean heart rate ranged from 91 to 106 beats/min and the mean systolic arterial pressure from 111 to 127 mmHg. The values did not diifer significantly from the corresponding values during enflurane anaesthesia. Electrocardiographic changes occurred in 56% and 31% of the patients anaesthetized with halothane or enflurane, respectively. The incidence of junctional rhythm, the most common ECG change, was 46% in the halothane group and 29% in the enflurane group. 19% of the patients in the halothane group and 31% in the enflurane group responded to surgical stimulus by swallowing or coughing. The responses were mostly short-lasting and did not much disturb the surgeon. The incidence of laryngospasm was 6% after halothane and 2% after enflurane anaesthesia. The mean total recovery score (0—10) was 6.1 after halothane and 6.3 after enflurane at arrival in the recovery room and 9.8 in both groups 30 min later. After halothane, nausea and vomiting occurred in 8 and 12% of the patients, respectively. The corresponding figures after enflurane were 2 and 8%. It is concluded that both halothane and enflurane arc suitable anaesthetics for tonsillectomy in adults. The most striking difference between the anaesthetics was the significantly more common occurrence of ECG changes during halothane than enflurane anaesthesia.     

Effect of Combinations of Topical Anaesthesia, Fentanyl, Halothane or N2O on Circulatory Intubation Response in Normo- and Hypertensive Patients

Attenuation of the circulatory intubation response was studied using the following combinations: oropharyngeal topical anaesthesia (OTA) + fentanyl 2μg/kg (F2), OTA+2% halothane with 70% nitrous oxide (H2N₂O) or F₂ + H2N₂O. Firstly, it was observed in 48 normotensive patients that the combinations of OTA + F₂ or F₂ + H2N₂O totally prevented the intubation response; OTA + H2N₂O, on the other hand, was less effective. Secondly, the effect of OTA+F₂ was studied in 26 hypertensive patients and their 26 normotensive controls of the same age group. The combination prevented the circulatory intubation response also in the hypertensive patients, whose circulatory reactions did not differfrom those of the normotensive patients. Nitrous oxide had no beneficial effect on the intubation response.     

Haemodynamics during inhalation of a 50% nitrous-oxide-in-oxygen mixture with and without hypovolaemia

Background: Inhalation of a gas mixture containing 50% nitrous oxide in oxygen (N₂O/O₂) is widely used for pain relief in emergency situations, which may also be associated with blood loss. The aim of this study was to evaluate the haemodynamic effects of this gas mixture in normo- and hypovolaemic subjects.
Methods: Six healthy males were studied during inhalation of N₂O/O₂ before and after withdrawal of 900 ml of blood. On each occasion, we measured systemic and pulmonary arterial pressures, cardiac output, blood gases, extravascular lung water, and the blood flow and oxygen consumption in the whole body, liver and kidneys.
Results: Inhalation of N₂O/O₂ reduced the stroke volume and increased peripheral resistance. Oxygen uptake decreased in the liver (-30%) and in the whole body (-23%). Blood withdrawal reduced the pulmonary arterial and central venous pressures (-30 to -50%) and further decreased stroke volume and the blood flows to the liver and the kidney (-15%). The extravascular lung water tended to increase both during inhalation of N₂O/O₂ and during hypovolaemia.
Conclusion: N₂O/O₂ aggravated the hypokinetic circulation induced by hypovolaemia. However, the oxygen consumption decreased only during inhalation of N₂O/O₂. This opens up the possibility that the cardiodepression associated with N₂O/O₂ is caused by a change in metabolic demands.     

Comparison of the respiratory and systemic kinetics of nitrous oxide in the sheep

Background. To determine whether discrepancies in views on the kinetics of nitrous oxide (N₂O) may have a methodological basis, we compared its kinetics, simultaneously, in the respiratory system and systemic circulation.
Methods. Six merino ewes (40–50 Kg) were previously prepared with catheters in the pulmonary artery and aorta. The animals were anaesthetised with thiopentone then ventilated on a mixture of 70% N₂O, 1% halothane in oxygen for 4 h. Simultaneous serial arterial and pulmonary arterial blood samples were assayed for N₂O by gas chromatography and respiratory gases were monitored continuously by mass spectrometry.
Results. Marked differences were observed between the respiratory and systemic kinetics of N₂O uptake. While the expired/inspired N₂O concentration ratio rose within 30 min to a value close to unity, the pulmonary arterial/arterial blood N₂O concentration ratio did not reach unity during the 4 h of each study, but approached a constant rate of uptake shown by the mean ratio of 0.94 (SD 0.01) from about 2 h onward.
Conclusions. Discrepancies in fluid flow between respiratory gas and the cardiovascular systems, a concentration effect of N₂O in the lungs, the relative solubility of N₂O in blood and tissues, and ventilation/perfusion inequalities all may contribute to the observed differences. The ongoing uptake is consistent with persistent extrapulmonary losses. There remains a need for experimental data on the pharmacokinetics of N₂O. Unequivocal studies on the disposition of N₂O can be undertaken only by using direct measurement of fluxes of N₂O across relevant organs or tissues.     

Peroperative adenosine infusion reduces isoflurane concentrations during general anesthesia for shoulder surgery

Background: Adenosine (ADO), and stable analogs thereof, have been shown to exert antinociceptive action under experimental conditions in animals and in humans. The aim of this randomized double-blind placebo-controlled study was to evaluate if a low dose of intravenous (i.v.) ADO could reduce isoflurane requirements during joint-associated surgery, as an indication of antinociception in deep somatic pain.
Methods: Thirty-two patients, age 19–62 years, ASA I and II, scheduled for shoulder joint surgery, were assigned to receive an i.v. infusion of either adenosine, 80 μg kg^-1 min^-1, or placebo, during the surgical procedure. Anesthesia was maintained with isoflurane/N₂O/O₂ inhalation.
Results: The peroperative isoflurane concentration was significantly reduced at 50 minutes of surgery in the group receiving adenosine infusion. Also, the systolic blood pressure level was peroperatively more stable during adenosine infusion than during placebo. Other clinical parameters, such as pain, postoperative analgesic requirements and nausea, were not different between groups.
Conclusion: A peroperative infusion of a low dose of adenosine during shoulder joint surgery may reduce the peroperative isoflurane requirement.     

Effect of nitrous oxide and volatile anaesthetics on platelet function in man

Twelve otherwise healthy male volunteers scheduled for arthroscopy of the knee were studied. The influence in vivo of nitrous oxide (N₂O) per se and the addition of a halogenated volatile anaesthetic (halothane or isoflurane) on ADP–induced platelet aggregation and release of beta–thromboglobulin into plasma was evaluated. All measurements were made before surgery. We found that N₂O increased platelet aggregation. Adding a halogenated anaesthetic reversed the relative hyperaggregation induced by N_aO. The concentrations in plasma of the platelet release product beta thromboglobulin were not influenced by the anaesthetics.     

Enkephalinase Inhibition Prevented Tolerance to Nitrous Oxide Analgesia in Rats

Tolerance to nitrous oxide (N₂O) antinociception was studied in rats in accordance with the Randall-Selitto pressure nociception test. Both N₂O (70% in 30% O₂) and the relatively selective enkephalinase inhibitor phosphoramidon (350 μg i.c.v.), which blocks the biotransformation of enkephalins, were administered. They both induced a significant analgesic effect which vanished within 45 min. The rapidly developed tolerance to N₂O analgesia does not affect the anaesthetic state since the animals remained motionless for the duration of exposure lasting 3 h. In the animals treated with the enkephalinase inhibitor phosphoramidon, no development of tolerance to N₂O-antinociception occurred during the exposure lasting 3 h. The results indicate that tolerance to N₂O analgesia can be abolished by activation of the enkephalinergic system, which might suggest a possible insufficiency of this system during tolerance to N₂O.     

Cisatracurium during halothane and balanced anaesthesia in children

Cisatracurium, 51W89, is one of the ten stereoisomers of Tracrium^® which, unlike atracurium, has been reported to have a lack of histamine mediated cardiovascular effects at doses as high as 8×ED₉₅ in adults. We compared the time-course of neuromuscular effects of 80 μg·kg⁻¹ or 100 μg·kg⁻¹ cisatracurium during N₂O-O₂-halothane or N₂O-O₂-opioid anaesthesia, respectively, in 32 children 2–12 years old. Neuromuscular function was monitored by evoked adductor pollicis EMG. Even-numbered patients ( n =16) were allowed to obtain full spontaneous recovery of neuromuscular function and odd-numbered patients ( n =16) received neostigmine 45 μg·kg⁻¹ together with glycopyrrolate at the time of 25% EMG recovery. Data are expressed as median with 10th to 90th percentile range. Cisatracurium had an onset time (time from administration to maximal effect) of 2.2 (1.7–3.8) or 2.3 (1.8–4.9) min, a clinical duration (time to 25% EMG recovery) of 34 (22–40) or 27 (24–33) min, and a spontaneous 25–75% recovery time (time from 25 to 75% EMG recovery) of 11 (9–13) or 11 (7–12) min during halothane or balanced anaesthesia, respectively (NS). Train-of-four ratio recovered to 0.70 in 2.5 (1.8–3.0) or 3.2 (2.1–4.3) min following neostigmine during halothane or balanced anaesthesia, respectively (NS). Changes in blood pressure or heart rate following cisatracurium were negligible. We regard cisatracurium as a safe and promising intermediate duration muscle relaxant the effects of which can easily be reversed with neostigmine.     

The interaction between nitrous oxide and isoflurane on suppression of learning: a study using classical conditioning in rabbits

Background: Nitrous oxide (N₂O) is commonly combined with a volatile agent for administration of general anesthesia. We studied the effects of N₂O and isoflurane on learning of the rabbit nictitating membrane responses (NMRs).
Methods: Classical conditioning of the NMR was accomplished by presenting a 400 ms tone conditioned stimulus before the presentation of a 100 ms shock unconditioned stimulus over 6 daily training sessions. The percentages of conditioned responses (CRs) were calculated for animals treated with 0% (n=10), 33% (n=11), 67% (n=11), and 75% (n=7) N₂O and for those treated with 0% (n=8), 0.2% (n=7), 0.4%, (n=13) and 0.8% (n=9) isoflurane separately. ED-50 for suppression of learning for each drug were calculated. Percentages of CRs were calculated for treatments with combinations of 0.2% isoflurane with either 32 or 48% N₂O (n=14, for each).
Results: Isobolographic analysis demonstrated that the combination of the two drugs exerted no greater effect than that seen with either agent administered alone; for well-established CRs (mean of days 5 and 6), the estimated concentrations corresponding to a rate of 70% CRs were 0.31% isoflurane with no N₂O, 65.3% N₂O with no isoflurane, and 0.2% isoflurane combined with 32.4% N₂O.
Conclusions: N₂O and isoflurane interact additively on suppression of learning.