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Simultaneous Evaluation of Cardiorespiratory and Analgesic Effects of Nitrous Oxide-Oxygen Inhalation Analgesia
S im u lta n e o u s e v a lu a tio n o f c a r d io r e s p ir a to r y a n d a n a lg e s ic e f fe c t s o f n itr o u s o x id e -o x y g e n in h a la tio n a n a lg e s ia
G a ith e r B. E v e r e tt, D D S G e ra ld D. A lle n , M D , S e a ttle
A s tu d y w a s m a d e t o e v a lu a te th e c a r d io r e s p ir a t o r y a n d a n a lg e s ic e f f e c ts o f n it r o u s o x id e -o x y g e n a n a l g e s ia in te n h e a lt h y v o lu n t e e r s w h o w e re n o t u n d e r g o in g o p e r a t io n . C o r r e la tio n o f f in d in g s w ith th o s e fr o m o x y g e n in h a la tio n a lo n e s h o w e d t h a t p h y s io lo g ic c h a n g e s d u r in g n it r o u s o x id e -o x y g e n a n a lg e s ia p a r a lle l th o s e o f in h a la t io n o f 1 0 0 % o x y g e n . T h e s a fe ty o f n it r o u s o x id e -o x y g e n in h a la tio n a n e s th e s ia , w h e n u s e d f o r r e lie f o f a n x ie ty a n d te n s io n , w a s d e m o n s tr a te d .
The ra p id and w idespread acceptance o f nitrous oxide-oxygen analgesia has prom pted th e in tro d u c tion o f postgraduate courses devoted to instruction ini analgesia for dentistry. T he em phasis in these program s has been on the technique o f ad m in istra tion. Instruction in nitrous oxide-oxygen analgesia has stressed th e inherent safety o f th e tech n iq u e.1 How ever, som e studies indicate th at nitrous oxide is a cardiorespiratory depressant.2-3 T he studies o f cardiovascular responses, however, were n o t relate4 to th e use o f nitrous oxide in analgesia. T h e re fore, th e present study was undertaken to evaluate thfc cardiorespiratory and analgesic effects o f n i trous oxide-oxygen analgesia, and to confirm the pi|rp o rted lack o f deleterious physiologic effects.
¡Methods and materials Ten volunteer subjects, eight men and two wom en, 23 to 34 years o f age and free from disease, w ere
studied. The purpose o f the study was fully ex plained to the subjects and inform ed consents were obtained. T he subjects were brought to the r e search area in a fasting and unprem edicated state where, under local anesthesia, Teflon and polyvi nyl catheters w ere inserted percutaneously into the brachial artery and basilic vein and advanced into the subclavian artery and superior vena cava, r e spectively. A rterial and venous pressures w ere m easured with Statham strain gauges, P 2 3 d b and P23B C , r e spectively, and recorded continuously on a Gilson G M E polygraph; the electrocardiogram was record ed continuously. A fter a 3 0 -m inute perio d o f rest in the supine position, the subjects w ere seated in a standard dental chair th at h a d been converted to contour chair configuration. A dditional 30 m in utes o f rest in the sitting position w ere allowed, during which tim e control values w ere obtained with an algesimeter for tibial pressure, and a B ur ton V italom eter for tooth stim ulation.4 O utput from the tibial pressure algesim eter was recorded on the G M E polygraph with three readings taken at each period and averaged. C ontrol m easurem ents were m ade o f m ean arterial pressure, central venous pressure, cardiac rate, and cardiac output. Cardiac o utput was determ ined by the indicator-dilution technique using indocyanine green. A rterial blood was sam pled anaerobically for determ ination o f P a 0 2 and pH , using a m odified C larke electrode and an A strup p H electrode, respectively. P aC O z was calculated by the tonom etric m ethod o f A strup. Stroke volum e was determ ined from cardiac o u t p u t and cardiac rate, and total p eripheral resist ance, stroke work, and m inute w ork w ere calculat ed. Cardiovascular m easurem ents, with the excep tion o f central venous pressure, w ere converted to percent change from control values. A ll other paJADA, Vol. 83, July 1971 ■ 129
NS NS * «* #*-P
NS
Fig 1 ■ Mean arterial pressure and mean percent change from control. Note the statistically significant, but clin ica lly nonsignificant, rise in mean arterial pressure with increasing delivered nitrous oxide concentrations. CARDIAC OUTPUT O-------- O TOTAL PERIPHERAL RESISTANCE A------- 4
-2CH----------- ------------ 1 10% 20% ## C.O. tftt* ** T.RR. KM* *MK'P
#»-R
i----------- 1------------1 40% 30% 10" * NS NS ** *K * *» P « X 0 5
N S-N st tlgntficant
Fig 2 ■ Mean percent change from control for cardiac out put and total peripheral resistance. Decrease in cardiac out put is noted as is an increase in total peripheral resistance, both parameter changes relating to the high oxygen concen trations delivered. CARDIAC RATE STROKE VOLUME
O--------O A-------- A
10-,
C.R. S.V.
T he m ethod o f study involved the introduction o f the Ohio nasal m ask to the volunteer and ex planation o f its purpose. T he m ask was then placed over the volunteer’s nose and m aintained in p o si tion throughout the study by the investigator a d m inistering analgesia. T he exhalation valve was m aintained in the fully open position, and the air dilution valve rem ained closed throughout the study, enabling adm inistration o f known concentra tions o f nitrous oxide-oxygen. G ases were deliv ered via a Q uantiflex anesthesia m achine equipped w ith calibrated rotam eter flowm eters. T he anal gesia circuit used was a standard M agill system with a five-liter reservoir bag. A 10% nitrous oxide concentration in oxygen with a total flow o f 10 liters was adm inistered for ten m inutes. C ardiorespiratory m easurem ents were then m ade and the tooth V italom eter and tibial pressure values recorded. Evaluation at the 20 % nitrous oxide, 30 % nitrous oxide, and 4 0 % nitrous oxide concentration levels was m ade with the same ten-m inute equilibration period allowed at each concentration;5 cardiorespi rato ry and analgesic m easurem ents w ere carried o u t in a like m anner. A fter m easurem ents were m ade at the 40 % n i trous oxide concentration, the nasal m ask was r e m oved and the subject was allow ed to breathe room air for an additional ten-m inute period. T he B ender face-hand te s t6 w as then adm inistered as an index o f recovery. I f results w ere positive, card io respiratory and analgesia m easurem ents w ere con ducted at this time.
Results
t0% NS *K*
*M*>P
20% NS ft* M*'P<0.0l
40% 30% NS NS ** NS NS-Not significant
10" NS NS
Fig 3 ■ Mean percent change from control for cardiac rate and stroke volume. Cardiac rate maintains a near control val ue, and stroke volume decreases as a consequence o f a de creased cardiac output.
ram eters w ere converted to m ean change from m ean o f control. T he significance o f th e change was determ ined by th e use o f Student’s t test for p aired values. 130 ■ JADA, Vol. 83, July 1971
M ean arterial pressure showed a progressive rise, paralleling the rise in nitrous oxide concentration, th at was significant at the 30% nitrous oxide and 4 0 % nitrous oxide concentrations ( P < 0 .0 5 to P < 0 .01) (Fig 1). C entral venous pressure changes w ere nonsignif icant. Cardiac ou tp u t significantly decreased ( P < 0 .0 5 to P < 0.001) soon after the adm inistration o f n i trous oxide-oxygen was begun. A s the concentra tion o f nitrous oxide was increased, cardiac output increased, and although it rem ained below control values, the change at the 4 0 % nitrous oxide concen tration was nonsignificant (Fig 2). T otal peripheral resistance progressively in creased ( P < 0 .0 1 to P < 0.0 0 1 ) throughout nitrous oxide-oxygen adm inistration (Fig 2).
STROKE WORK MINUTE WORK
S.W M.W #*P<0.05
* *
NS »
O--------O A------- A
NS NS
NS NS
NS NS 11UU
NS.Not significant
Fig 4 ■ Mean percent change from control for stroke work and minute work. Minute and stroke work decrease in itially in consequence of a lessened demand on the heart, attributa ble to the higher in itial oxygen concentrations delivered.
C ardiac ra te changes w ere nonsignificant (Fig 3). Stroke volum e decreased ( P < 0.0 0 1 ) soon after adm inistration o f analgesia h a d begun and then rose gradually as nitrous oxide concentration in creased; how ever, it rem ained below control v a l ues at all tim es (Fig 3). M inute w ork and stroke w ork showed only slight decreases ( P < 0 .0 5 ) a t th e 10% and 2 0% n i trous oxide concentrations and then rose to n o n significant levels throughout th e rem ainder o f c o n centration changes (Fig 4). P a 0 2 rose as expected to significant levels ( P < 0.00 1 ) a t all concentrations o f nitrous oxide b e cause o f th e high concentration o f delivered oxy gen (Fig 5, top). P a C 0 2 decreased slightly w ith only scattered sig nificant periods (Fig 5, center); p H changes m ir rored the change in P a C 0 2, indicating a slight re s pirato ry alkalosis (Fig 5, bottom ). T ooth V italom eter (sensitivity) changes w ere m i nor, showing statistically significant decrease ( P < 0.01) only at th e 4 0 % nitrous oxide concentration (Fig 6, top). T ibial pressure progressively increased after the 20% n itro u s oxide concentration h ad been reached; significant ( P < 0 .0 5 to P < 0 .0 0 1 ) levels showed at the higher concentrations (Fig 6, bottom ). T he B ender face-hand test was positive in all volunteers after they h ad breathed room air for ten minutes.
Discussion N itrous oxide-oxygen analgesia has as its objective the relief o f th e psychic overtones related to the dental experience w ith m inim al upset to the p a-
###-P
*
UMU KKW
WWW Knn
WWW nnn
IIÉ
WO
NS-Not significant
NS
NS
#
NS
# ■PC003 NS«Not significant
K*P<0.05
NS>Not significant
Fig 5 ■ PaC02 mean change from mean o f control. PaC02 shows a significant increase due to the high oxygen concen trations delivered (top). PaC02 showsa slight decrease, prob ably due to the concentration effect of nitrous oxide (center). The pH shows a slight increase, paralleling the decrease in PaC02 (bottom).
tien t’s physiology. R esults o f the study support this contention. Physiologic changes seen during our studies w ere generally o f a m inor degree an d generally o f a progressive nature, paralleling changes in nitrous oxide concentration. H owever, in a previous sim i lar study volunteers who were given 100% oxygen to breathe for five m inutes showed cardiovascular Everett—Allen: NITROUS OXIDE-OXYGEN ANESTHESIA ■ 131
Table ■ Comparativecardiorespiratoryeffectsof 100% oxy gen versus increasing concentrations of nitrous oxide in oxy gen.
100% 0 2
* # # *P < O .O I
NS *-P < 0 .0 5
NS
##
*
N S 'N o t significant
MAP
CO
CR
SV
TPR
PaC02
5.4 ±1.7
-5.7± 3.3
-1.0 ± 2 .2
-4 .l± 2 .7
16.4 ± 4 2
33.3 ±1.4
10% N 2 0
2.1
± 2.2
H0.6 ±2.2 -1.0 ±1.9
-97 ±1.8
14.7 ±3.1
34.1
20% N 20
2.8 ± 2 .4
HOO ±1.2 -1.2 ±IB
-8.7 ±1.8
14.2 ±2.0
34.4 ±0.9
2
± 2 .4
-8.6 ±2.9 -3 3 ±2.1
-5 9 ±2.7
16.6 ±3.9
334
2
±2J
-8.4
-7.3 ±2.0
19.7 ±4.7
34.4 ±0.7
30% N O 58
4 0 % N O 82
±4.1 -0.8 ± 4.2
±1.2
±1.2
Mean percent change from control and standard error of the mean are shown. All changes are nonsignificant statistically, as determined by Student’s t test. MAP, mean arterial pres sure; CO, cardiac output; CR, cardiac rate; SV, strokevolume; TPR, total peripheral resistance; and PaC02, partial pressure of carbon dioxide in arterial blood.
NS
##**P
-#**P
*
* *
* ■ P<0.05
*# *
NS
N S • Not significant
Fig6 ■ ToothVitalometerandtibialpressurereadings,mean change from mean of control. Tooth v ita lity readings show clin ica lly nonsignificant changes at all delivered nitrous oxide concentrations studied (top). Tibial pressure analgesia shows progressive increase in relation to nitrous oxide con centration delivered (bottom).
c h a n g e s th a t w ere n o t sta tistica lly d iffe re n t fro m th o se in th e p re se n t study (T a b le ).7 S tatistical c o m p a ris o n o f th e re su lts o f th is stu d y w ith re su lts o f p a tie n ts b re a th in g 100% oxygen in d ic ates n o n s ig n ific a n t d iffe ren ce s an d su p p o rts th e co n te n tio n th a t th e p h ysiologic ch an g es a re a co n seq u e n ce o f th e h ig h d e liv e re d oxygen co n c en tra tio n s. T h e u ltim a te goal o f c a rd io re sp ira to ry fu n ctio n is th e su p p ly to b o d y tissues o f oxygen a n d th e r e m o v a l o f c a rb o n dioxide. A n in c re a se d p a rtia l p re ssu re o f oxygen in th e b lo o d p la ce s a le ssen ed d e m a n d o n th e ca rd io v a sc u la r system in th is su p p ly system , an d , th e re fo re , th e d ec reases in c a rd ia c o u t p u t a n d stro k e v o lu m e c o u ld b e p re d ic te d o n a p h y sio lo g ic b asis. P hysiologic co m p en sa tio n fo r th e d e c re a se in c a rd ia c o u tp u t is re fle c te d in th e i n c re a s e d to ta l p e rip h e ra l resistan c e. In c re a se in m e an a rte ria l p re ssu re c a n b e re la te d to th e in c re a se in to ta l p e rip h e ra l re sista n c e an d , th e re fo re , u ltim a te ly re la te d to th e in c re a se in PaC>2. C h a n g e s in stro k e w ork a n d m in u te w o rk show th a t w ith a le ssen ed d em an d o n ca rd io v a sc u la r fu n ctio n , th e re is a lessened w o rk e x p e n d itu re b y th e h e a rt. 132 ■ JADA, Vol. 83, July 1971
F u n ctio n o f th e re sp ira to ry system , as re fle c te d in th e b lo o d g a s p ic tu re , is c o n siste n t w ith a h ig h o xygen c o n c e n tra tio n ; sp ecifically an in c re a se d P a 0 2. T h e slig h t d ec rease in PaC C >2 w ith a c o n c o m ita n t in c re a se in p H w o u ld b e co n siste n t w ith th e c o n c e n tra tio n effect o f n itro u s o x id e .8 T h e a c tu a l an alg esic effects o f n itro u s o x id e a re re v e a le d w h en th e effects o f in c re ase s o f tib ia l p r e s su re a re stu d ied . T h e in c reasin g p re ssu re re q u ire d to elicit a re sp o n se c le a rly show s th a t p e rio ste a l an a lg e sia ex ists a n d in c re ase s w ith co n c e n tra tio n . T h e re la tiv e ly m in o r c h a n g es in to o th V ita lo m e te r re a d in g s in d ic a te th a t th e re is little effect o n to o th sen sitiv ity ; th e se fin d in g s a re sim ilar to th o se in a p re v io u s stu d y .9 T h e e x p e rim en tal p a in a n d th e te c h n iq u e o f ev a lu a tio n a re d iffe re n t fro m th a t u se d in a p re v io u s e x p e rim en tal s tu d y .10 V o lu n te e rs in th is stu d y re p o rte d e u p h o ria a n d c o m p le te o r n e a r c o m p le te re la x a tio n a t levels o f n itro u s o x id e in th e ra n g e o f 3 0 % to 4 0 % .
Conclusions N itro u s o x id e-o x y g en an alg esia fo r th e re lie f o f p sy ch ic o v e rto n e s a tte n d a n t to th e d e n ta l e x p e ri en c e c a n b e r e a d ily a c h iev ed w ith m in im a l u p se t to th e p h y sio lo g ic m a k e u p o f th e p a tie n t. P o sitiv e e v i d en c e o f a c tu a l to o th an a lg e sia a t levels o f n itro u s o x id e su fficie n t fo r psy ch ic re la x a tio n w as n o t o b ta in ed . I t is co n c lu d e d , th e re fo re , th a t w hen n i tro u s o x id e-o x y g en is u se d fo r sed atio n , th e a d d i
tion o f a local anesthetic m ay be necessary to o b tain ideal operating conditions. H ow ever, p erio ste al pain relief, as indicated by an increase in tibial pressure, w ould suggest th at operations on th e g in gival and m ucosal tissues o f the oral cavity m ay be possible by th e use o f nitrous oxide-oxygen a n a l gesia alone. Analgesic effects, being related to nitrous oxide concentrations, have been shown to proceed in a progressive m anner, and we conclude, therefore, th a t to adm inister analgesia in a scientific m anner one m ust know the delivered concentration. T he use o f an air dilution valve will elim inate any know ledge o f delivered concentration, and its use is to be discouraged. Physiologic changes attendant to nitrous oxideoxygen adm inistration are closely related to a d m inistration o f oxygen alone. H ow ever, as has been shown previously, oxygen alone has no effect on analgesia.11
Summary The cardiorespiratory and analgesic effects o f n i trou s oxide-oxygen inhalation analgesia were in vestigated in healthy volunteers not undergoing operation. D ecreases in cardiac output, stroke v o l um e, m ean arterial pressure, stroke work, and m i n u te work, and an increase in total peripheral r e sistance were noted. C orrelation o f findings w ith oxygen inhalation alone revealed th at physiologic changes during nitrous oxide-oxygen analgesia parallel those o f inhalation o f 100% oxygen. E v i dence o f analgesia to tibial pressure was shown; however, little tooth analgesia existed at the tim e o f euphoria and relaxation. T he safety o f nitrous oxide-oxygen inhalation analgesia, when used solely for relief o f anxiety
and tension, has been dem onstrated. T he question regarding dental operation on the teeth when the p atient is under nitrous oxide-oxygen analgesia, w ithout benefit o f local anesthesia, has n o t been fully clarified; further scientific clinical studies are needed.
This study was supported in part by NI DR Grant No. DEO 2419-04. Doctor Everett isassistant professor, departments of com m unity dentistry and anesthesiology; Doctor Allen is associ ate professor, departments of anesthesiology and oral sur gery; Anesthesia Research Center, University of Washington Schools of Medicine and Dentistry, Seattle.
1. Langa, H. Relative analgesia in dental practice. Phila delphia, W. B. Saunders Co., 1968. 2. Bloch, M. Some systemic effects of nitrous oxide. Brit J Anaesth 35:631 Oct 1963. 3. Bloch, M. Systemic effects of nitrous oxide when used with halothane and oxygen anaesthesia at normal body tem perature. Brit J Anaesth 38:119 Feb 1966. 4. Freedman, G.L., and Allen, G.D. Comparison of d iffe r ing modalities of experimental pain in man. J Dent Res 49: 378 March-April 1970. 5. Kety, S.S., and Schmidt, C.F. The determination o f cer ebral blood flow in man by the use of nitrous oxide in low con centrations. Amer J Physiol 143:53 Jan 1945. 6. Jaffe, J., and Bender, M.B. Perceptual patterns during recovery from general anaesthesia. J Neurol Neurosurg Psychiat 14:316 Nov 1951. 7. Allen, G.D., and others. Cardiovascular responses during general anesthesia of dental outpatients. J Oral Ther 1:602 May 1965. 8. Eastwood, D.W., (ed.). Nitrous oxide. (Clinical anesthe sia series.) Philadelphia, F. A. Davis Co., 1964. 9. Haugen, F.P.; Coppock, W.J.; and Berquist, H.C. N i trous oxide hypalgesia in trained subjects. Anesthesiology 20:321 May-June 1959. 10. Persson, P.A. Nitrous oxide hypalgesia in man. Acta Odont Scand 9:9 (Suppl 7), 1951. 11. Sonnenschein, R.R., and others. A study on the mech anism of nitrous oxide analgesia. J Appl Physiol 1:254 Sept 1948.
Everett—Allen: NITROUS OXIDE-OXYGEN ANESTHESIA ■ 133
G a ith e r B. E v e r e tt, D D S G e ra ld D. A lle n , M D , S e a ttle
A s tu d y w a s m a d e t o e v a lu a te th e c a r d io r e s p ir a t o r y a n d a n a lg e s ic e f f e c ts o f n it r o u s o x id e -o x y g e n a n a l g e s ia in te n h e a lt h y v o lu n t e e r s w h o w e re n o t u n d e r g o in g o p e r a t io n . C o r r e la tio n o f f in d in g s w ith th o s e fr o m o x y g e n in h a la tio n a lo n e s h o w e d t h a t p h y s io lo g ic c h a n g e s d u r in g n it r o u s o x id e -o x y g e n a n a lg e s ia p a r a lle l th o s e o f in h a la t io n o f 1 0 0 % o x y g e n . T h e s a fe ty o f n it r o u s o x id e -o x y g e n in h a la tio n a n e s th e s ia , w h e n u s e d f o r r e lie f o f a n x ie ty a n d te n s io n , w a s d e m o n s tr a te d .
The ra p id and w idespread acceptance o f nitrous oxide-oxygen analgesia has prom pted th e in tro d u c tion o f postgraduate courses devoted to instruction ini analgesia for dentistry. T he em phasis in these program s has been on the technique o f ad m in istra tion. Instruction in nitrous oxide-oxygen analgesia has stressed th e inherent safety o f th e tech n iq u e.1 How ever, som e studies indicate th at nitrous oxide is a cardiorespiratory depressant.2-3 T he studies o f cardiovascular responses, however, were n o t relate4 to th e use o f nitrous oxide in analgesia. T h e re fore, th e present study was undertaken to evaluate thfc cardiorespiratory and analgesic effects o f n i trous oxide-oxygen analgesia, and to confirm the pi|rp o rted lack o f deleterious physiologic effects.
¡Methods and materials Ten volunteer subjects, eight men and two wom en, 23 to 34 years o f age and free from disease, w ere
studied. The purpose o f the study was fully ex plained to the subjects and inform ed consents were obtained. T he subjects were brought to the r e search area in a fasting and unprem edicated state where, under local anesthesia, Teflon and polyvi nyl catheters w ere inserted percutaneously into the brachial artery and basilic vein and advanced into the subclavian artery and superior vena cava, r e spectively. A rterial and venous pressures w ere m easured with Statham strain gauges, P 2 3 d b and P23B C , r e spectively, and recorded continuously on a Gilson G M E polygraph; the electrocardiogram was record ed continuously. A fter a 3 0 -m inute perio d o f rest in the supine position, the subjects w ere seated in a standard dental chair th at h a d been converted to contour chair configuration. A dditional 30 m in utes o f rest in the sitting position w ere allowed, during which tim e control values w ere obtained with an algesimeter for tibial pressure, and a B ur ton V italom eter for tooth stim ulation.4 O utput from the tibial pressure algesim eter was recorded on the G M E polygraph with three readings taken at each period and averaged. C ontrol m easurem ents were m ade o f m ean arterial pressure, central venous pressure, cardiac rate, and cardiac output. Cardiac o utput was determ ined by the indicator-dilution technique using indocyanine green. A rterial blood was sam pled anaerobically for determ ination o f P a 0 2 and pH , using a m odified C larke electrode and an A strup p H electrode, respectively. P aC O z was calculated by the tonom etric m ethod o f A strup. Stroke volum e was determ ined from cardiac o u t p u t and cardiac rate, and total p eripheral resist ance, stroke work, and m inute w ork w ere calculat ed. Cardiovascular m easurem ents, with the excep tion o f central venous pressure, w ere converted to percent change from control values. A ll other paJADA, Vol. 83, July 1971 ■ 129
NS NS * «* #*-P
NS
Fig 1 ■ Mean arterial pressure and mean percent change from control. Note the statistically significant, but clin ica lly nonsignificant, rise in mean arterial pressure with increasing delivered nitrous oxide concentrations. CARDIAC OUTPUT O-------- O TOTAL PERIPHERAL RESISTANCE A------- 4
-2CH----------- ------------ 1 10% 20% ## C.O. tftt* ** T.RR. KM* *MK'P
#»-R
i----------- 1------------1 40% 30% 10" * NS NS ** *K * *» P « X 0 5
N S-N st tlgntficant
Fig 2 ■ Mean percent change from control for cardiac out put and total peripheral resistance. Decrease in cardiac out put is noted as is an increase in total peripheral resistance, both parameter changes relating to the high oxygen concen trations delivered. CARDIAC RATE STROKE VOLUME
O--------O A-------- A
10-,
C.R. S.V.
T he m ethod o f study involved the introduction o f the Ohio nasal m ask to the volunteer and ex planation o f its purpose. T he m ask was then placed over the volunteer’s nose and m aintained in p o si tion throughout the study by the investigator a d m inistering analgesia. T he exhalation valve was m aintained in the fully open position, and the air dilution valve rem ained closed throughout the study, enabling adm inistration o f known concentra tions o f nitrous oxide-oxygen. G ases were deliv ered via a Q uantiflex anesthesia m achine equipped w ith calibrated rotam eter flowm eters. T he anal gesia circuit used was a standard M agill system with a five-liter reservoir bag. A 10% nitrous oxide concentration in oxygen with a total flow o f 10 liters was adm inistered for ten m inutes. C ardiorespiratory m easurem ents were then m ade and the tooth V italom eter and tibial pressure values recorded. Evaluation at the 20 % nitrous oxide, 30 % nitrous oxide, and 4 0 % nitrous oxide concentration levels was m ade with the same ten-m inute equilibration period allowed at each concentration;5 cardiorespi rato ry and analgesic m easurem ents w ere carried o u t in a like m anner. A fter m easurem ents were m ade at the 40 % n i trous oxide concentration, the nasal m ask was r e m oved and the subject was allow ed to breathe room air for an additional ten-m inute period. T he B ender face-hand te s t6 w as then adm inistered as an index o f recovery. I f results w ere positive, card io respiratory and analgesia m easurem ents w ere con ducted at this time.
Results
t0% NS *K*
*M*>P
20% NS ft* M*'P<0.0l
40% 30% NS NS ** NS NS-Not significant
10" NS NS
Fig 3 ■ Mean percent change from control for cardiac rate and stroke volume. Cardiac rate maintains a near control val ue, and stroke volume decreases as a consequence o f a de creased cardiac output.
ram eters w ere converted to m ean change from m ean o f control. T he significance o f th e change was determ ined by th e use o f Student’s t test for p aired values. 130 ■ JADA, Vol. 83, July 1971
M ean arterial pressure showed a progressive rise, paralleling the rise in nitrous oxide concentration, th at was significant at the 30% nitrous oxide and 4 0 % nitrous oxide concentrations ( P < 0 .0 5 to P < 0 .01) (Fig 1). C entral venous pressure changes w ere nonsignif icant. Cardiac ou tp u t significantly decreased ( P < 0 .0 5 to P < 0.001) soon after the adm inistration o f n i trous oxide-oxygen was begun. A s the concentra tion o f nitrous oxide was increased, cardiac output increased, and although it rem ained below control values, the change at the 4 0 % nitrous oxide concen tration was nonsignificant (Fig 2). T otal peripheral resistance progressively in creased ( P < 0 .0 1 to P < 0.0 0 1 ) throughout nitrous oxide-oxygen adm inistration (Fig 2).
STROKE WORK MINUTE WORK
S.W M.W #*P<0.05
* *
NS »
O--------O A------- A
NS NS
NS NS
NS NS 11UU
NS.Not significant
Fig 4 ■ Mean percent change from control for stroke work and minute work. Minute and stroke work decrease in itially in consequence of a lessened demand on the heart, attributa ble to the higher in itial oxygen concentrations delivered.
C ardiac ra te changes w ere nonsignificant (Fig 3). Stroke volum e decreased ( P < 0.0 0 1 ) soon after adm inistration o f analgesia h a d begun and then rose gradually as nitrous oxide concentration in creased; how ever, it rem ained below control v a l ues at all tim es (Fig 3). M inute w ork and stroke w ork showed only slight decreases ( P < 0 .0 5 ) a t th e 10% and 2 0% n i trous oxide concentrations and then rose to n o n significant levels throughout th e rem ainder o f c o n centration changes (Fig 4). P a 0 2 rose as expected to significant levels ( P < 0.00 1 ) a t all concentrations o f nitrous oxide b e cause o f th e high concentration o f delivered oxy gen (Fig 5, top). P a C 0 2 decreased slightly w ith only scattered sig nificant periods (Fig 5, center); p H changes m ir rored the change in P a C 0 2, indicating a slight re s pirato ry alkalosis (Fig 5, bottom ). T ooth V italom eter (sensitivity) changes w ere m i nor, showing statistically significant decrease ( P < 0.01) only at th e 4 0 % nitrous oxide concentration (Fig 6, top). T ibial pressure progressively increased after the 20% n itro u s oxide concentration h ad been reached; significant ( P < 0 .0 5 to P < 0 .0 0 1 ) levels showed at the higher concentrations (Fig 6, bottom ). T he B ender face-hand test was positive in all volunteers after they h ad breathed room air for ten minutes.
Discussion N itrous oxide-oxygen analgesia has as its objective the relief o f th e psychic overtones related to the dental experience w ith m inim al upset to the p a-
###-P
*
UMU KKW
WWW Knn
WWW nnn
IIÉ
WO
NS-Not significant
NS
NS
#
NS
# ■PC003 NS«Not significant
K*P<0.05
NS>Not significant
Fig 5 ■ PaC02 mean change from mean o f control. PaC02 shows a significant increase due to the high oxygen concen trations delivered (top). PaC02 showsa slight decrease, prob ably due to the concentration effect of nitrous oxide (center). The pH shows a slight increase, paralleling the decrease in PaC02 (bottom).
tien t’s physiology. R esults o f the study support this contention. Physiologic changes seen during our studies w ere generally o f a m inor degree an d generally o f a progressive nature, paralleling changes in nitrous oxide concentration. H owever, in a previous sim i lar study volunteers who were given 100% oxygen to breathe for five m inutes showed cardiovascular Everett—Allen: NITROUS OXIDE-OXYGEN ANESTHESIA ■ 131
Table ■ Comparativecardiorespiratoryeffectsof 100% oxy gen versus increasing concentrations of nitrous oxide in oxy gen.
100% 0 2
* # # *P < O .O I
NS *-P < 0 .0 5
NS
##
*
N S 'N o t significant
MAP
CO
CR
SV
TPR
PaC02
5.4 ±1.7
-5.7± 3.3
-1.0 ± 2 .2
-4 .l± 2 .7
16.4 ± 4 2
33.3 ±1.4
10% N 2 0
2.1
± 2.2
H0.6 ±2.2 -1.0 ±1.9
-97 ±1.8
14.7 ±3.1
34.1
20% N 20
2.8 ± 2 .4
HOO ±1.2 -1.2 ±IB
-8.7 ±1.8
14.2 ±2.0
34.4 ±0.9
2
± 2 .4
-8.6 ±2.9 -3 3 ±2.1
-5 9 ±2.7
16.6 ±3.9
334
2
±2J
-8.4
-7.3 ±2.0
19.7 ±4.7
34.4 ±0.7
30% N O 58
4 0 % N O 82
±4.1 -0.8 ± 4.2
±1.2
±1.2
Mean percent change from control and standard error of the mean are shown. All changes are nonsignificant statistically, as determined by Student’s t test. MAP, mean arterial pres sure; CO, cardiac output; CR, cardiac rate; SV, strokevolume; TPR, total peripheral resistance; and PaC02, partial pressure of carbon dioxide in arterial blood.
NS
##**P
-#**P
*
* *
* ■ P<0.05
*# *
NS
N S • Not significant
Fig6 ■ ToothVitalometerandtibialpressurereadings,mean change from mean of control. Tooth v ita lity readings show clin ica lly nonsignificant changes at all delivered nitrous oxide concentrations studied (top). Tibial pressure analgesia shows progressive increase in relation to nitrous oxide con centration delivered (bottom).
c h a n g e s th a t w ere n o t sta tistica lly d iffe re n t fro m th o se in th e p re se n t study (T a b le ).7 S tatistical c o m p a ris o n o f th e re su lts o f th is stu d y w ith re su lts o f p a tie n ts b re a th in g 100% oxygen in d ic ates n o n s ig n ific a n t d iffe ren ce s an d su p p o rts th e co n te n tio n th a t th e p h ysiologic ch an g es a re a co n seq u e n ce o f th e h ig h d e liv e re d oxygen co n c en tra tio n s. T h e u ltim a te goal o f c a rd io re sp ira to ry fu n ctio n is th e su p p ly to b o d y tissues o f oxygen a n d th e r e m o v a l o f c a rb o n dioxide. A n in c re a se d p a rtia l p re ssu re o f oxygen in th e b lo o d p la ce s a le ssen ed d e m a n d o n th e ca rd io v a sc u la r system in th is su p p ly system , an d , th e re fo re , th e d ec reases in c a rd ia c o u t p u t a n d stro k e v o lu m e c o u ld b e p re d ic te d o n a p h y sio lo g ic b asis. P hysiologic co m p en sa tio n fo r th e d e c re a se in c a rd ia c o u tp u t is re fle c te d in th e i n c re a s e d to ta l p e rip h e ra l resistan c e. In c re a se in m e an a rte ria l p re ssu re c a n b e re la te d to th e in c re a se in to ta l p e rip h e ra l re sista n c e an d , th e re fo re , u ltim a te ly re la te d to th e in c re a se in PaC>2. C h a n g e s in stro k e w ork a n d m in u te w o rk show th a t w ith a le ssen ed d em an d o n ca rd io v a sc u la r fu n ctio n , th e re is a lessened w o rk e x p e n d itu re b y th e h e a rt. 132 ■ JADA, Vol. 83, July 1971
F u n ctio n o f th e re sp ira to ry system , as re fle c te d in th e b lo o d g a s p ic tu re , is c o n siste n t w ith a h ig h o xygen c o n c e n tra tio n ; sp ecifically an in c re a se d P a 0 2. T h e slig h t d ec rease in PaC C >2 w ith a c o n c o m ita n t in c re a se in p H w o u ld b e co n siste n t w ith th e c o n c e n tra tio n effect o f n itro u s o x id e .8 T h e a c tu a l an alg esic effects o f n itro u s o x id e a re re v e a le d w h en th e effects o f in c re ase s o f tib ia l p r e s su re a re stu d ied . T h e in c reasin g p re ssu re re q u ire d to elicit a re sp o n se c le a rly show s th a t p e rio ste a l an a lg e sia ex ists a n d in c re ase s w ith co n c e n tra tio n . T h e re la tiv e ly m in o r c h a n g es in to o th V ita lo m e te r re a d in g s in d ic a te th a t th e re is little effect o n to o th sen sitiv ity ; th e se fin d in g s a re sim ilar to th o se in a p re v io u s stu d y .9 T h e e x p e rim en tal p a in a n d th e te c h n iq u e o f ev a lu a tio n a re d iffe re n t fro m th a t u se d in a p re v io u s e x p e rim en tal s tu d y .10 V o lu n te e rs in th is stu d y re p o rte d e u p h o ria a n d c o m p le te o r n e a r c o m p le te re la x a tio n a t levels o f n itro u s o x id e in th e ra n g e o f 3 0 % to 4 0 % .
Conclusions N itro u s o x id e-o x y g en an alg esia fo r th e re lie f o f p sy ch ic o v e rto n e s a tte n d a n t to th e d e n ta l e x p e ri en c e c a n b e r e a d ily a c h iev ed w ith m in im a l u p se t to th e p h y sio lo g ic m a k e u p o f th e p a tie n t. P o sitiv e e v i d en c e o f a c tu a l to o th an a lg e sia a t levels o f n itro u s o x id e su fficie n t fo r psy ch ic re la x a tio n w as n o t o b ta in ed . I t is co n c lu d e d , th e re fo re , th a t w hen n i tro u s o x id e-o x y g en is u se d fo r sed atio n , th e a d d i
tion o f a local anesthetic m ay be necessary to o b tain ideal operating conditions. H ow ever, p erio ste al pain relief, as indicated by an increase in tibial pressure, w ould suggest th at operations on th e g in gival and m ucosal tissues o f the oral cavity m ay be possible by th e use o f nitrous oxide-oxygen a n a l gesia alone. Analgesic effects, being related to nitrous oxide concentrations, have been shown to proceed in a progressive m anner, and we conclude, therefore, th a t to adm inister analgesia in a scientific m anner one m ust know the delivered concentration. T he use o f an air dilution valve will elim inate any know ledge o f delivered concentration, and its use is to be discouraged. Physiologic changes attendant to nitrous oxideoxygen adm inistration are closely related to a d m inistration o f oxygen alone. H ow ever, as has been shown previously, oxygen alone has no effect on analgesia.11
Summary The cardiorespiratory and analgesic effects o f n i trou s oxide-oxygen inhalation analgesia were in vestigated in healthy volunteers not undergoing operation. D ecreases in cardiac output, stroke v o l um e, m ean arterial pressure, stroke work, and m i n u te work, and an increase in total peripheral r e sistance were noted. C orrelation o f findings w ith oxygen inhalation alone revealed th at physiologic changes during nitrous oxide-oxygen analgesia parallel those o f inhalation o f 100% oxygen. E v i dence o f analgesia to tibial pressure was shown; however, little tooth analgesia existed at the tim e o f euphoria and relaxation. T he safety o f nitrous oxide-oxygen inhalation analgesia, when used solely for relief o f anxiety
and tension, has been dem onstrated. T he question regarding dental operation on the teeth when the p atient is under nitrous oxide-oxygen analgesia, w ithout benefit o f local anesthesia, has n o t been fully clarified; further scientific clinical studies are needed.
This study was supported in part by NI DR Grant No. DEO 2419-04. Doctor Everett isassistant professor, departments of com m unity dentistry and anesthesiology; Doctor Allen is associ ate professor, departments of anesthesiology and oral sur gery; Anesthesia Research Center, University of Washington Schools of Medicine and Dentistry, Seattle.
1. Langa, H. Relative analgesia in dental practice. Phila delphia, W. B. Saunders Co., 1968. 2. Bloch, M. Some systemic effects of nitrous oxide. Brit J Anaesth 35:631 Oct 1963. 3. Bloch, M. Systemic effects of nitrous oxide when used with halothane and oxygen anaesthesia at normal body tem perature. Brit J Anaesth 38:119 Feb 1966. 4. Freedman, G.L., and Allen, G.D. Comparison of d iffe r ing modalities of experimental pain in man. J Dent Res 49: 378 March-April 1970. 5. Kety, S.S., and Schmidt, C.F. The determination o f cer ebral blood flow in man by the use of nitrous oxide in low con centrations. Amer J Physiol 143:53 Jan 1945. 6. Jaffe, J., and Bender, M.B. Perceptual patterns during recovery from general anaesthesia. J Neurol Neurosurg Psychiat 14:316 Nov 1951. 7. Allen, G.D., and others. Cardiovascular responses during general anesthesia of dental outpatients. J Oral Ther 1:602 May 1965. 8. Eastwood, D.W., (ed.). Nitrous oxide. (Clinical anesthe sia series.) Philadelphia, F. A. Davis Co., 1964. 9. Haugen, F.P.; Coppock, W.J.; and Berquist, H.C. N i trous oxide hypalgesia in trained subjects. Anesthesiology 20:321 May-June 1959. 10. Persson, P.A. Nitrous oxide hypalgesia in man. Acta Odont Scand 9:9 (Suppl 7), 1951. 11. Sonnenschein, R.R., and others. A study on the mech anism of nitrous oxide analgesia. J Appl Physiol 1:254 Sept 1948.
Everett—Allen: NITROUS OXIDE-OXYGEN ANESTHESIA ■ 133