Bispectral EEG Index Monitoring of High-Dose Nitrous Oxide: RESULTS

1 Dec 2009

Demographic characteristics of the 22 subjects appear in Table 2. The ratio of males to females was 12 to 10, with a mean age of 29 ± 7 years and average weight of 159 ± 36 lb. Data for vital signs appear in Table 3, expressed as means ± standard errors for the combined control periods, nitrous oxide sessions, and low-dose sevoflurane sessions. There were no statistically significant changes in systolic and diastolic BP, MAP, P, RR, Temp, and Sp02 observed at any dosage of either gas compared with the combined control sessions and with each subject acting as his/her own control. No subjects experienced nausea or vomiting during the study.

Table 2. Demographics and Gas Preferences

Ages	Men	Women	Gas Preferences
20-25	4	4	4 N20, 4 sevo
26-30	7	3	6 N20, 2 sevo, 2 split
31-40	1	1	1 N20, 1 sevo
41-50	0	2	1 N20, 1 split
Totals	12	10	12 N20, 7 sevo, 3 split

Table 3. Vital Signs (Mean Values ± Standard Errors)

Group

Respiration (BPM)

Sp02 (% Saturation)

Temp. (°F)

Pulse (BPM)

Systolic (mm Ид)

Diastolic (mm big)

MAP (mm Ид)

Control ± SE N20 ± SE Sevo ± SE

13 ± 1

12 ± 0.4

13 ± 0.5

99 ± 0.5 99 ± 0.3 99 ± 0.2

94.4 ± 0.4 94.2 ± 0.2 94.6 ± 0.2

69 ± 3 69 ± 2 68 ± 2

106 ± 2 109 ± 2 106 ± 2

59 ± 2 61 ± 2 58 ± 2

74 ± 2 77 ± 2 74 ± 2

Figure 3 (a through d) shows the dose-response curves for ET N20 and ET sevoflurane versus BIS and OAA/S composite (responsiveness, speech, facial expression, and eyes rated on 1-5 scales). With the exception of 1 unusually sensitive subject (subject 114), who passed very rapidly and smoothly through a momentary excitement stage into what appeared to be plane 1 of stage 3 of general anesthesia with loss of lid reflex from an administered concentration of 70% N20 (registered ET N20 = 56%) while exhibiting a BIS depression from the mid-90s to the mid-70s, there was no correlation between nitrous oxide dosage and BIS. Even though 70% (16/22) of these ASA 1 subjects seemed to tolerate an administered concentration of 70% N20 for a full 15-minute period, this corresponded to a registered ET N20 of 50% or greater in only 30% (6/22). Six of the 22 participants had maximal NzO inspired dosage reduced—4 to 60% and 2 subjects who could not tolerate more than 50% N20. All test subjects tolerated the maximal administered dose of 0.8% sevoflurane. Both N20 and sevoflurane generated a near linear dose-response curve with OAA/S at ET concentrations of 33-58% and 0.4-0.7%, respectively (Spearman’s rho, P < .01). EMG readings demonstrated a statistically significant difference from control values only at the 0.7% ET concentration of sevoflurane (Figure 4). Viagra Super Active

Table 4. Amenesia/Memory Scores

Inspired Gas

Picture Recall Testing (% Correct)

Picture Recognition Testing (% Correct)

Auditory Word Recall (% Correct)

Dosage

Comb.

F-M

Comb.

F-M

F Comb.

F-M

Study Control

100% o2

18*

14*

30% N20

100*

-10*

100*

100

N/A

40% N20

80*

82*

-5

100*

91*

-9*

100

10*

50% N20

81*

13*

91*

60% N20

31*

55*

45*

24*

100

-1

62*

64*

70% N20

10*

54*

40*

44*

60*

68*

65*

20*

36*

25*

16*

0.2% Sevo

10*

100*

14*

N/A

0.4% Sevo

60*

89*

80*

29*

73*

100*

85*

27*

71*

100

85*

29*

0.6% Sevo

58*

78*

67*

20*

75*

100

86*

25*

58*

100

76*

42*

0.8% Sevo

22*

15*

13*

36*

67*

50*

31*

33*

16*

33*

Average

totals

16*

11*

19*

* Indicates statistically significant differences of male (M), female (F), and combined male + female (comb.), memory testing vs study controls with female minus male (F-M) difference P > chi-square .05 or less.

Figure 5 illustrates the near linear relationship between BIS and OAA/S composite scores less than or equal to 3 for sevoflurane sessions, with statistical significance as indicated. These OAA/S composite scores corresponded to sevoflurane ET concentrations of 0.4-0.7%. viagra jelly

Figure 3. (a) BIS versus ET-N20. (b) OAA/S versus ET-N20. (c) BIS versus ET-sevoflurane. (d) OAA/S composite versus ET-sevoflurane. The asterisk indicates statistically significant differences compared with control (P < .05).

Amnesia results in Table 4 indicate memory loss was associated with both gases beginning at administered concentrations of 40-70% N20 and 0.4-0.8% sevoflurane. Memory scores were 10-20% poorer in male versus female subjects (likelihood ratio chi-square < .004). These gas doses corresponded to ET concentrations of 25-58% N20 and 0.4-0.7% sevoflurane that correlated with OAA/S composite scores of 2.75-4.25 for N20 and 3.0-4.25 for sevoflurane. A maximal administered dosage of 70% N20 typically resulted in registered ET concentrations of 37-58%, OAA/S composite scores of 2.75-3.0, and male plus female combined average memory loss/amnesia ranging from 35 (picture recognition) to 75% (audio recall). A maximal administered dosage of 0.8% sevoflurane resulted in ET concentrations of 0.6-0.7%, OAA/S composite scores of 3.0-3.5, and memory loss ranging from 50% (picture recognition) to 85% (picture recall) along with a BIS depression of 10%. Study control testing resulted in combined male and female correct recall of 87% (13% loss) of the pictures and correct recognition of 94% (6% loss) of the pictures used in this research. Memory scores after the sessions were also assessed with 24-hour questionnaires. The results were consistent with the intras-tudy data demonstrating that sevoflurane was associated with slightly more amnesia than N20 and that female subjects attained higher memory scores than males.
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Figure 4. EMG versus ET-sevoflurane. The asterisk indicates statistically significant differences compared with control (P < .01).

Sevoflurane did show statistically significant BIS depression (P < .01, 2-tailed) according to the Spearman correlation and P < .001 using Friedman’s test, beginning with a threshold ET concentration of 0.7%. Almost 80% of test subjects exhibited BIS depression of approximately 10 points at an inhaled dosage of 0.8% sevoflurane when an ET concentration of 0.7% was reached, regardless of age, sex, and weight.

Figure 5. Sevoflurane BIS versus OAA/S composite. The asterisk indicates statistically significant differences compared with control (P < .01).

Poststudy questionnaire results indicated that approximately 55% of subjects preferred nitrous oxide, 30% favored sevoflurane, and 15% were equivocal (see Table 2). Although 27% (6/22) of the subjects answered that the smell of sevoflurane bothered them, only 10% (2/ 22) responded that they would not use it. Over 90% of the subjects felt that both gases produced adequate sedation/relaxation and would like to use both agents for their future patients. Written comments from subjects combined with subject feedback during poststudy debriefing universally described sevoflurane as a straight depressant/downer compared with nitrous oxide, which combined more noticeable stimulatory/upper and sedative/downer subjective symptoms. strattera medication