Discontinuation Of N2O Research Articles

Does Nitrous Oxide Affect Bispectral Index and State Entropy When Added to a Propofol Versus Sevoflurane Anesthetic?

In earlier studies, nitrous oxide (N2O) did not affect bispectral index (BIS) or state entropy (SE) when administered as the sole anesthetic agent. We investigated the effect of adding N2O to sevoflurane or propofol anesthesia on BIS and SE. A total of 28 patients were randomized to receive general anesthesia using either 2% sevoflurane or 120 mcg/kg/min propofol during surgery. After 20 minutes of stable anesthetic and surgical conditions (baseline), 60% N2O was added for 20 minutes. Another 20 minutes was allowed for washout after N2O was discontinued. Sevoflurane concentration was closely monitored using the standard end-tidal gas analysis and vaporizer output was constantly adjusted to offset the second-gas effect caused by the addition and discontinuation of N2O. Mean values for BIS and SE were calculated for the last 5 minutes of the baseline, nitrous oxide, and washout periods. In the propofol group, BIS and SE values in baseline versus N2O periods were 40±10 versus 39±10 and 43±11 versus 43±12, respectively (mean±SD, P>0.05). In the sevoflurane group, addition of N2O decreased both BIS (36±7 to 32±7, P<0.001) and SE (37±10 to 31±11, P=0.001). The magnitude of change from the baseline in BIS and SE in the sevoflurane group was 3.6±3.8 (95% CI: 0.8-6.5) and 6.1±5.5 (95% CI: 3.7-8.6), respectively. Average baseline and washout values of BIS and SE were not different in both groups (P>0.05). N2O decreased both BIS and SE when added to sevoflurane, but not propofol. The observed changes in the sevoflurane group were not clinically significant. Decreases in BIS and SE in the sevoflurane group could result from a true additive effect and second-gas effect of N2O that was unaccounted for despite a meticulous titration of sevoflurane using end-tidal gas monitoring.

Regional cerebral metabolic rate (positron emission tomography) during inhalation of nitrous oxide 50% in humans

Recent studies in man have shown that cerebral blood flow increases during inhalation of nitrous oxide (N2O), a finding which is believed to be a result of an increased cerebral metabolic rate (CMR). However, this has not previously been evaluated in man. Regional CMR(glu) (rCMR(glu)) was measured three dimensionally with positron emission tomography (PET) after injection of 2-(18F)fluoro-2-deoxy-D-glucose in 10 spontaneously breathing men (mean age 31 yr) inhaling either N2O 50% in O2 30% or O2 30% in N2. Global CMR(glu) in young men was 27 (3) micromol 100 g(-1) min(-1) [mean (SD)]. Inhalation of N2O 50% did not change global CMR(glu) [30 (5) micromol 100 g(-1) min(-1)] significantly, but it changed the distribution of the metabolism in the brain (P<0.0001 analysis of variance). Compared with inhalation of O2 30% in N2, N2O 50% inhalation increased the metabolism in the basal ganglia [14 (17)%, P<0.05] and thalamus [22 (23) %, P<0.05]. There was a prolonged metabolic effect of N2O inhalation seen on a succeeding PET scan with oxygen-enriched air (P<0.0001) performed 1 h after the N2O administration. Inhalation of N2O 50% did not change global CMR(glu), but the metabolism increased in central brain structures, an effect that was still present 1 h after discontinuation of N2O.

Nitrous Oxide Decreases Substance P Receptor Binding in The Rat Spinal Cord

Synaptic transmission of substance P (SP) in the spinal cord during nitrous oxide (N2O) exposure was examined in rats. In the analgesia study, 75% N2O significantly increased tail-flick latency by 57% during the first 2-h N2O exposure and by 19% after a second 2-h N2O exposure, suggesting development of acute tolerance. In the SP content study, SP in the dorsal part of the spinal cord significantly increased by 120% at the end of first N2O exposure, but returned to the control level by the end of second N2O exposure. In the receptor binding study, N2O significantly decreased the [I]Bolton-Hunter-SP ([I]BH-SP) binding (SP-P) in laminae I-II of the dorsal horn by 19, 18, and 18% at the end of first N2O exposure, at the end of the second N2O exposure, and at 4 h after the second N2O exposure, respectively, as compared to the control. This decrease in the [I]BH-SP binding became statistically insignificant by 12 h after the second N2O exposure. In contrast, [I]Bolton-Hunter-eledoisin binding (SP-E) remained unchanged. In the equilibrium binding study, the number of SP-P receptor (Bmax) in laminae I-II of the dorsal horn significantly decreased by 24, 38, and 30% at the end of the first and at the end of the second N2O exposure, and at 4 h after the second N2O exposure, respectively, without significant changes in the affinity (Ka). The present study demonstrated that tolerance to N2O analgesia occurred during the two repeated N2O exposures. SP receptor binding decreased and remained decreased 4 h after discontinuation of N2O. This evidence is the first demonstration of the functional changes caused by N2O in SP synaptic transmission of the spinal cord.

Nitrous Oxide

Two-dimensional and pulsed Doppler echocardiography were used to measure cardiovascular function in 31 unmedicated infants and small children. In 15 patients, the cardiovascular effects of equipotent levels of halothane were compared with and without N2O. In 16 patients, the cardiovascular effects of isoflurane with and without N2O were compared. Prior to anesthesia induction, cardiovascular measurements of heart rate (HR), mean blood pressure (MBP), and two-dimensional and pulsed Doppler echocardiography were recorded. The echocardiographic measurements were used to determine cardiac output (CO), stroke volume (SV), ejection fraction (EF), and left ventricular end-diastolic and end-systolic volume (LVEDV and LVESV). Twenty minutes after mask inhalation induction with halothane or isoflurane with N2O and O2 (3:2 liters/min), cardiovascular measurements were repeated with end-expired halothane or isoflurane maintained at 0.9 MAC. A third set of cardiovascular data was collected 10 minutes after the discontinuation of N2O, with inspired isoflurane or halothane levels in O2 (5 liters/min) increased to maintain 1.5 MAC end-expired levels. Ventilation was controlled throughout the study period and the study was completed before intubation and the start of elective surgery. Heart rate and MBP decreased to similar degrees below awake levels in both patient groups during N2O with halothane or isoflurane. When N2O was discontinued and end-expired levels of halothane or isoflurane increased, MBP remained at levels observed during N2O-O2 with halothane or isoflurane. Heart rate increased during isoflurane in O2. Cardiac output decreased significantly and similarly below awake levels during both halothane of isoflurane with and without N2O.

Plasma concentrations of alfentanil required to supplement nitrous oxide anesthesia for general surgery.

To design an efficient infusion regimen from pharmacokinetic data, it is necessary to know the alfentanil plasma concentrations required for satisfactory anesthesia. In 37 patients about to undergo lower abdominal gynecologic, upper abdominal, or breast surgery, anesthesia was induced with alfentanil 150 micrograms/kg iv and 66% N2O in oxygen. Thereafter, N2O anesthesia was supplemented with a continuous infusion of alfentanil that was varied between 25 and 150 micrograms X kg-1 X h-1, as indicated by the patient's responses to surgical stimulation. Small bolus doses of alfentanil 7 or 14 micrograms/kg were administered and the infusion rate increased to suppress precisely defined somatic, autonomic, and hemodynamic responses. Arterial plasma concentrations of alfentanil were measured during the operation when the patient did and did not respond to noxious stimulation. Logistic regression was used to determine plasma concentration-effect curves for different stimuli. Plasma alfentanil concentrations required along with 66% N2O to obtain responses to single episodes of stimulation in 50% of the 37 patients (Cp50 +/- SE) were: 475 +/- 28 ng/ml for tracheal intubation, 279 +/- 20 ng/ml for skin incision, and 150 +/- 23 ng/ml for skin closure. Between skin incision and closure, multiple determinations of response/no response were made for each patient and an individual Cp50 was estimated. The Cp50 (mean +/- SD) for the three surgical procedures were: breast, 270 +/- 63 ng/ml (n = 12); lower abdominal, 309 +/- 44 ng/ml (n = 14); and upper abdominal, 412 +/- 135 ng/ml (n = 11). The Cp50 for satisfactory spontaneous ventilation after the discontinuation of N2O was 223 +/- 13 ng/ml. These data demonstrate that different perioperative stimuli require different alfentanil concentrations to suppress undesirable responses. Thus, the alfentanil infusion rate should be varied according to the patient's responsiveness to stimulation in order to maintain satisfactory anesthetic and operative conditions and to provide rapid recovery of consciousness and spontaneous ventilation.

Time Course of Mental and Psychomotor Effects of 30 per cent Nitrous Oxide during Inhalation and Recovery

Two experiments were conducted testing the duration of action of nitrous oxide on human performance. In the first experiment, 11 subjects inhaled 30 per cent nitrous oxide for two periods of 40 min each, 45 min apart. Their mental and psychomotor skills were measured using free recall, tapping board, arithmetic and flicker fusion tests before and 2, 12, 22 and 32 min after establishing and end-tidal concentration of N2O of 30 per cent. Recovery was tested using the same tests 2, 12, 22 and 32 min after discontinuation of N2O. Eleven additional subjects inhaled oxygen only and served as a control group. In the second experiment, 8 subjects received both 30 per cent N2O and oxygen in cross-over fashion, and their flicker fusion threshold was measured. When compared to baseline or oxygen administration, N2O significantly impaired tapping rate, number of words recalled, and performance in arithmetic tests. The effects of N2O were maximal at 2 min and remained similar throughout the entire administration. In flicker fusion tests, the effects of N2O were similar to those of stimulant drugs; N2O improved the subjects' ability to discriminate the fusion of flickering light. Recovery was complete in 22 min. The effects of, and recovery from the second administration of N2O were similar to those of the first experiment. There was no evidence of development of tolerance to mental and psychomotor effects of the drug.

Time course of mental and psychomotor effects of 30 per cent nitrous oxide during inhalation and recovery.

Two experiments were conducted testing the duration of action of nitrous oxide on human performance. In the first experiment, 11 subjects inhaled 30 per cent nitrous oxide for two periods of 40 min each, 45 min apart. Their mental and psychomotor skills were measured using free recall, tapping board, arithmetic and flicker fusion tests before and 2, 12, 22 and 32 min after establishing and end-tidal concentration of N2O of 30 per cent. Recovery was tested using the same tests 2, 12, 22 and 32 min after discontinuation of N2O. Eleven additional subjects inhaled oxygen only and served as a control group. In the second experiment, 8 subjects received both 30 per cent N2O and oxygen in cross-over fashion, and their flicker fusion threshold was measured. When compared to baseline or oxygen administration, N2O significantly impaired tapping rate, number of words recalled, and performance in arithmetic tests. The effects of N2O were maximal at 2 min and remained similar throughout the entire administration. In flicker fusion tests, the effects of N2O were similar to those of stimulant drugs; N2O improved the subjects' ability to discriminate the fusion of flickering light. Recovery was complete in 22 min. The effects of, and recovery from the second administration of N2O were similar to those of the first experiment. There was no evidence of development of tolerance to mental and psychomotor effects of the drug.