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Arquivo Brasileiro de Medicina Veterinária e Zootecnia

Print version ISSN 0102-0935On-line version ISSN 1678-4162

Arq. Bras. Med. Vet. Zootec. vol.71 no.3 Belo Horizonte May/June 2019  Epub June 14, 2019 

Veterinary Medicine

Effects of inspired oxygen fractions in rabbits anesthetized with isoflurane or sevoflurane, maintained on spontaneous ventilation

Efeitos de frações inspiradas de oxigênio em coelhos anestesiados com isoflurano ou sevofluorano, mantidos em ventilação espontânea

1Aluno de pós-graduação ˗ Universidade Estadual Paulista ˗ Jaboticabal, SP

2Universidade Estadual Paulista ˗ Jaboticabal, SP

3Pós-doutoranda - Universidade Estadual Paulista - Jaboticabal, SP


It is important to identify the best inspired fraction of oxygen in a variety of situations, including sevoflurane or isoflurane anesthesia, in spontaneously breathing rabbits. For this, 64 rabbits were assigned to eight groups: GI100 (FiO2= 1,0 + isoflurane), GS100 (FiO2= 1,0 + sevoflurane), GI80 (FiO2= 0,8 + isoflurane), GS80 (FiO2= 0,8 + sevoflurane), GI60 (FiO2= 0,6 + isoflurane), GS60 (FiO2= 0,6 + sevoflurane), GI21 (FiO2= 0,21 + isoflurane), GS21 (FiO2= 0,21 + sevoflurane). The induction was performed with (2.5MAC) of the anesthetic. The vaporizer was setted at 1.5 MAC and FiO2 as attributed for each group. After the induction, the concentration was changed to 1 MAC. Measurements of parameters were performed 30 minutes after induction (T0), and then at 15 minute intervals (from T15 to T60). The arterial partial pressures of oxygen (PaO2), alveolar oxygen partial pressure (PAO2) and alveolar-arterial oxygen gradient [P(A-a)O2] were higher with the use of high FiO2. The GI80 showed higher levels of PaO2 FiO2 ratio and respiratory index (RI). In conclusion, the FiO2 of 0.21 is not indicated, because it causes hypoxemia. The isoflurane determines better ventilation when compared to sevoflurane, but isoflurane associated with 80% of oxygen promotes intrapulmonary shunt increase.

Keywords: rabbit; inhalatory anesthesia; ventilation


Tornou-se importante identificar a melhor fração inspirada de oxigênio em variadas situações, incluindo anestesia pelo sevoflurano ou isoflurano, em coelhos respirando espontaneamente. Para isso, 64 coelhos foram distribuídos em oito grupos: GI100 (FiO 2 = 1,0 + isoflurano), GS100 (FiO 2 = 1,0 + sevoflurano), GI80 (FiO 2 = 0,8 + isoflurano), GS80 (FiO 2 = 0,8 + sevoflurano), GI60 (FiO 2 = 0,6 + isoflurano), GS60 (FiO 2 = 0,6 + sevoflurano), GI21 (FiO 2 = 0,21 + isoflurano) e GS21 (FiO 2 = 0,21 + sevoflurano). A indução foi com 2,5 CAM do anestésico. Ajustou-se o vaporizador para 1,5 CAM, e a FiO 2 foi atribuída a cada grupo. Em seguida, a CAM foi reajustada para 1,0. Iniciaram-se as mensurações 30 minutos após a indução (M0), seguidas em intervalos de 15 minutos (de M15 a M60). As pressões parciais de oxigênio (PaO 2 ), a pressão parcial alveolar de oxigênio (P A O 2 ) e a diferença alvéolo-arterial de oxigênio [P(A-a)O 2 ] foram maiores com o emprego de altas FiO 2 . O GI80 apresentou maiores valores na relação entre PaO 2 e FiO 2 e índice respiratório (IR). Conclui-se que a FiO 2 0,21 não é indicada, pois provoca hipoxemia. No entanto, utilizada com isoflurano, determina melhor ventilação quando comparado ao sevoflurano, porém seu uso, associado a 80% de oxigênio, promove maior formação de shunt intrapulmonar.

Palavras-chave: coelhos; anestesia inalatória; oxigenação


The primary function of the cardiovascular and respiratory systems is to meet the metabolic needs of tissues in the body through adequate supply of oxygen (O2) (Romaldini, 1995). Therefore, the maintenance of oxygenation at adequate levels during anesthetic procedures is extremely important. It has been proven that O2 administered at high concentrations or for an extended period of time can induce pulmonary lesions with formation of atelectatic areas (Hartsfield, 1996). However, in Veterinary Medicine, 100% oxygen is still routinely used during anesthetic procedures.

The choice of adequate FiO2 seems to be of great relevance, since the closer to 1.0, the greater the risk of occurrence and serious lesions (Capellier et al., 1999). Hartsfield (1996) stated that, in humans, 100% oxygen should not be administered for more than 12 hours, but in dogs, it should not be offered for more than 24 hours. In contrast, Nelson and Couto (1998) stated that dogs should not be submitted for more than 12 hours to O2 above 50%.

The absence of information regarding the effects of FiO2 lower than those used in the hospital routine on cardiovascular, respiratory and electrolyte balance, in patients during inhalational anesthesia, provides inquiries about the appropriate oxygen concentration to be used in association with isofluorane or sevoflurane, most used halogenated and considered safe for polytrauma patients or with cardiovascular and respiratory problems.

With the research, we aimed to determine among the inspired oxygen fractions of 1.0; 0.8; 0.6 or 0.21, which one was most appropriate in rabbits anesthetized with isofluorane or sevoflurane and maintained under spontaneous respiration. Complementarily, to evaluate the effects of inspired fractions on respiratory variables and comparatively evaluate the effects of sevoflurane and isofluorane on these variables.


Sixty-four New Zealand White rabbits (Approved by the Committee on Ethics and Animal Welfare of the FCAV / UNESP, under protocol No. 023814/11), adult males (n= 32) or females (n= 32) were used, with weight between 3.5 and 4.5kg, coming from specialized producer. The animals were randomly assigned to eight groups with eight rabbits each, differentiated by FiO2 and the inhaled anesthetic. GI100, GI80, GI60 and GI21 animals were given 100%, 80%, 60% and 21% oxygen concentrations (O2), respectively and the anesthesia was maintained with isoflurane. For GS100, GS80, GS60 and GS21 animals, the same methodology was applied, replacing isofluorane by sevoflurane.

For humane and technical reasons, the rabbits have not been subjected to food and water fasting, as this procedure is unnecessary since vomiting is rare in this species (Flecknell and Thomas, 2007). Induction of the anesthesia was performed by means of a sealed naso-oral mask with isoflurane (Isoforine - Cristália, Campinas, SP, Brazil) or sevofluorane (Sevocris - Cristália, Campinas, SP, Brazil) at 2.5 CAM diluted in total flow of 1l/min of oxygen to 100%, provided by anesthetic circuit without gas rebreathing (Mapleson D - Baraka balloon 1/2L - Protec- Cotia / SP), by means of calibrated vaporizer (OHMEDA - ISOTEC mod 5 - Datex Ohmeda- Miami, USA) for the anesthetic agent. The expired anesthetic concentration reading was obtained in a multiparameter monitor (DIXTAL - mod. DX - 2010 LCD - Manaus, AM, Brazil), whose gas analyzer sensor was adapted to the mask during induction. After the laryngotracheal reflex, the animals were intubated with 3.0mm diameter Magill catheter, which was connected to the inhalation anesthesia device. At this time, the gas analyzer sensor was coupled to the proximal end of the orotracheal tube and connected to the anesthetic circuit, the vaporizer being readjusted to 1.5 CAM of isofluorane or sevoflurane.

Afterwards, the animals were placed in the right lateral decubitus position and the right auricular artery was catheterized (Catheter BD Angiocath 22 - Becton, Dickinson Indústria Cirúrgica Ltda - Juiz de Fora / MG - Brazil) with the aim of collecting arterial blood samples for hemogasometry. An incision was made in the skin of the cervical region over the left jugular vein, for its exposure. With the support of a hypodermic needle (40x1,20-Descarpack-São Paulo / SP- Brazil needle), a catheter (PVC urethral catheter No. 04 - Embramed Ind.Com.Ltda - São Paulo / SP-Brasil) was placed in the cranial vena cava, in order to obtain a venous blood sample for hemogasometry.

After completion of these procedures, the anesthetic concentration was readjusted to 1.0 CAM in all groups. The parameters were measured thirty minutes after intubation (T0). The remaining data were collected at 15 minute intervals for a period of 60 minutes (T15, T30, T45 and T60, respectively). The hemogasometric variables were obtained using specific equipment (Hemochrometer - Roche OmiC-Rochi Diagnostics GmbH-Mannheim, Germany), with a volume of 0.3ml for each sample, using 1ml heparinized syringe.

The arterial oxygen partial pressure (PaO2) in mmHg, arterial carbon dioxide partial pressure (PaCO2), in mmHg, and oxyhemoglobin saturation in arterial blood (SaO2), in %, were measured. In the venous blood samples were evaluated: the partial pressure of oxygen in the venous blood (PvO2), in mmHg, partial pressure of carbon dioxide in the venous blood (PvCO2) in mmHg and oxyhemoglobin saturation in the venous blood (SvO2), in %. The respiratory dynamics was obtained by means of the calculated variables: Alveolar oxygen partial pressure (PAO2) (PAO2 = [FIO2 x (Pb - 47)] - (PaCO2 / RQ), where: Pb= ambient barometric pressure and RQ: Respiratory coefficient 0.8); Alveolar-arterial oxygen difference (P(A-a) O2 (, this variable was obtained by subtracting PaO2 from PAO2; Respiratory index IR), IR= P(A-a)O2/ PaO2 ; Relation between PaO2 and PAO2, (PaO2 and PAO2 = PaO2 / PAO2); The relationship between PaO2 and FiO2 (PaO2 and FiO2= PaO2 / FiO2) (Haskins, 2007); Differences PaO2 and PAO2 , (PaO2 e PAO2= PaO2/PAO2) (O'flaherty et al., 1994); Arterial oxygen content (CaO2), (CaO2= [1,34 x Hb x (SaO2/100)] + (PaO2 x 0,0031)), where: Hb is the hemoglobin concentration in arterial blood; 1.34 is the oxygen binding coefficient with hemoglobin in mL/g and 0.0031 is the coefficient of solubility of plasma oxygen in mmHg/mL.

At the end of the experiment, each rabbit, before recovering its consciousness, was given antibiotic 30000UI/kg (Multibiótico Reforçado 30000UI/kg - Vitafarma, São Sebastião do Paraíso/MG, Brasil) and tramadol hydrochloride 4mg/kg (Tramadol 50mg/mL - Tramadol hydrochloride 300mg/kg - Vitafarma, São Sebastião do Paraíso, Cristália - Campinas / SP, Brazil), by the intramuscular route.

The data were submitted to statistical analysis by the computer program GraphPad Prism 5 for Windows. Two-way ANOVA was used to detect differences in the means among the groups, followed by the Bonferroni test. For comparison of the time points in each group, one-way ANOVA was used for repeated measurements, followed by the Bonferroni test. Differences were considered significant when P< 0.05.


Evaluating the arterial oxygen partial pressure, it was observed that the mean of this parameter increased as larger FiO2 were used, (Table 1). For the species studied, the values considered normal for PaO2 are between 100 and 137mmHg with O2 at 40%; From 140 to 169mmHg with FiO2= 0.6 and between 228 and 304mmHg with FiO2= 1.0 (Egi et al., 2007), coinciding with the averages recorded in this research. Additionally, the predicted PaO2 was approximately two to three times the percentage of inspired oxygen corroborating Lopes et al. (2011).

Table 1 Mean values and standard deviations ( x¯ ± s) of PaO2 (mmHg), PvO2 (mmHg), PaCO2 (mmHg), PvCO2 (mmHg), SaO2 (%), SvO2 (%),P(A-a)O2 (mmHg), IR, PaO2/PAO2 (mmHg), PaO2/FiO2 (mmHg), CaO2 (mL/dL) in rabbits anesthetized with isoflurane (GI) or sevofluorane (GS) (1 CAM), maintained on spontaneous ventilation and submitted to fraction Inspired oxygen ratio of 1.0, 0.8, 0.6 and 0.21 

Parameters Groups Time Points
T0 T15 T30 T45 T60
GI100 254±59A 303±87AE 297±53A 283±82A 331±77A
GS100 340±41Db 349±30Ab 355±35A 376±29Da 358±14A
GI80 154±61Bb 187±73B 212±63BDa 217±36BEa 229±44Ea
PaO2 GS80 242±59AE 267±65E 233±63B 247±58E 247±59E
GI60 168±27B 178±28B 181±50BD 172±47B 169 ±55B
GS60 185±24BE 167±50B 162±53D 157±54B 164±60B
GI21 67±15C 68±21C 64±20C 66±14C 64±24C
GS21 62±12C 57±13C 56±10C 58±9C 56±8C
GI100 74±14A 68±7AE 70±8A 67±8AB 68±9A
GS100 75±20A 74±16A 68±15A 67±12A 67±16A
GI80 55±12BC 59±9BDE 52±9BC 55±10B 56±11A
PvO2 GS80 69±12AB 68±12AE 68±11A 68±13AB 67±11A
GI60 59±9B 57±10E 56±7AB 55±6ABD 55±5A
GS60 59±4B 57±5E 57±4AB 56±4ABD 55±3A
GI21 45±7C 44±9CDE 43±11C 44±6CD 39±9C
GS21 45±8Ca 39±11Cb 41±11C 39±9Cb 39±9Cb
GI100 49±6 51±7 48±8 47±7 46±7B
GS100 43±8 45±11 44±8 47±11 44 ±12B
GI80 42±11 53±11 48±9 44±7 44±9B
PaCO2 GS80 45±14a 54±12 54±21A 57±17A 61±21Ab
GI60 43±6 42±9 38±9B 41±9B 39±8B
GS60 44±10 43±9 44±10 44±10 44±11B
GI21 46±6 47±9 45±7 45±7 47±11B
GS21 36±7 40±6 42±6 40±9B 42±8B
GI100 56±12 59±11 49±18 54±10 54±13B
GS100 52±8 53±8 51±10 53±12 53±14B
GI80 55±5 55±10 54±9 54±6 53±6B
PvCO2 GS80 60±16A 61±12 64±20A 64±19A 70±27A
GI60 50±6a 49±6 44±10Bb 48±8B 47±8B
GS60 52±9 49±8 48±11B 47±11B 53±16B
GI21 50±8 50±12 52±9 51±10 55±13
GS21 42±7Ba 51±7b 50±6b 52±8b 51±11Bb
GI100 99.2±0.5B 99.6±0.5B 99.4±0.7B 99.3±0.8B 99.5±0.6B
GS100 99.9±0.0B 99.9±0.0B 99.9±0.0B 99.9±0.0B 99.9±0.0B
GI80 96.9±4.0B 98.2±2.2B 99.2±0.9B 99.6±0.1B 99.7±0.1B
SaO2 GS80 99.6±0.3B 99.6±0.3B 99.6±0.1B 99.7±0.1B 99.5±0.4B
GI60 98.9±0.6B 98.9±0.5B 98.3±1.5B 98.3±1.4B 97.8±1.6B
GS60 99.5±0.2B 99.5±1.2B 99.2±1.0B 98.7±2.1B 98.9±1.4B
GI21 88.4±6.0A 87.2±10.0A 85.7±9.8A 88.3±6.1A 83.1±12.0A
GS21 91.8±0.5Aa 92.7±0.3Cb 90.7±0.4Ccd 90.9±0.5Ac 89.9 ±0.6Cde
GI100 84.8±6.7BC 83.2±3.8BCD 86.4±7.7BC 86.1±7.3BC 88.9 ±5.9B
GS100 93.0±3.4Ba 92.9±2.7C 92.0±2.7B 91.3±2.4B 90.2±3.8Bb
GI80 84.7±11.9BC 82.4±10.3BD 81.9±12.0BC 84.2±9.6BC 84.7±10.2B
SvO2 GS80 90.0±2.3BDa 88.6±3.9BC 87.8±5.7BC 88.2±4.8BC 87.0±4.7Bb
GI60 78.3±5.8AC 78.2±7.5AD 79.3±7.1C 80.8±6.8AC 83.2±4.2B
GS60 86.3±3.6BC 85.7±3.8BCD 83.2±8.0BC 83.0±6.6BC 83.9±6.0B
GI21 73.0±7.8A 70.9±16.9A 68.4 ±18.2A 72.3±8.2A 62.3±18.5A
GS21 82.1±2.4ACD 81.5±1.8BD 82.5±2.8BC 81.4±2.3AB 81.5±2.6B
GI100 352±61A 301±88A 312±49A 328±84A 284±79A
GS100 277±37Ba 265±28ABa 261±31AB 236±31BCb 258±21AB
GI80 334±59Aa 287±69A 269±62ABb 269±38ABb 256±45ABb
P(A-a)O2 GS80 245±53B 208±53BC 242±65BD 225± 49BD 220±39BD
GI60 177±28C 170±28C 173±45C 179±39C 185± 55C
GS60 165±25C 184±49C 189±47CD 194±56CD 187±52CD
GI21 14±18D 11±24D 17±25E 16±20E 14±33E
GS21 31±14D 31±14D 30±10E 29±09E 29±10E
GI100 1.46±0.60B 1.13±0.66 1.09±0.38 1.32±0.74C 0.95±0.51
GS100 0.84±0.26BCa 0.77±0.14BC 0.75±0.18 0.63±0.14BCb 0.72±0.08
GI80 2.88±2.15Aa 2.02±1.50AC 1.52±1.04B 1.30±0.45 1.19±0.46b
IR GS80 1.12±0.56BC 0.88±0.54BC 1.15±0.53 0.99±0.41 0.97±0.39
GI60 1.08±0.40BC 0.99±0.38BC 1.09±0.67 1.18±0.69 1.35±1.01
GS60 0.92±0.26BC 1.43±1.36C 1.55±1.44B 1.66 ±1.50AC 1.54±1.40A
GI21 0.27±0.34C 0.28±0.46BC 0.40±0.48A 0.31±0.34B 0.41±0.57B
GS21 0.55±0.34BC 0.65±0.56B 0.58±0.31 0.53 ±0.23BC 0.55±0.28
GI100 0.42±0.09BC 0.50±0.14BC 0.49 ±0.08BC 0.46 ±0.13BC 0.53±0.12B
GS100 0.54±0.06CDa 0.56±0.04BCa 0.57 ±0.05BC 0.61±0.04b 0.58±0.02B
GI80 0.31±0.12B 0.39±0.15B 0.44±0.12B 0.44±0.07B 0.47±0.09B
PaO2/PAO2 GS80 0.49±0.12BCD 0.55±0.12BC 0.49 ±0.12BC 0.52 ±0.11BC 0.52±0.10B
GI60 0.49±0.08BCD 0.51±0.08BC 0.51 ±0.13BC 0.49 ±0.12BC 0.47±0.15B
GS60 0.52±0.06CD 0.47±0.14BC 0.45 ±0.14BC 0.44±0.15B 0.46±0.15B
GI21 0.83±0.22AD 0.88±0.35A 0.80 ±0.31AC 0.81 ±0.24AC 0.87±0.50A
GS21 0.67±0.14D 0.64±0.14C 0.65±0.11C 0.66±0.09C 0.65±0.10B
GI100 261.2±59.6 308.9±87.4 301.5±52.7 287.6±82.3 331.9±77.5
GS100 339.8±40.6Ba 349.2±29.9Ba 355.6±35.1 376.1±29.3Ab 357.9±14.5
GI80 192.5±77.0Aa 234.5±91.3A 265.9±78.3b 271.6±45.1Bb 287.0±54.6b
PaO2/FiO2 GS80 302.5±73.5B 334.5±81.0B 291.7±78.7 309.2±73.2 308.8±73.9
GI60 288.6±46.9B 301.7±47.4 306.0±80.9 290.8±75.4 282.4±90.1
GS60 308.5±40.1B 279.8±83.2 270.2±89.0 261.9 ±89.8B 273.9±99.6
GI21 320.5±72.2B 323.9±99.0 306.5±98.7 315.0±68.8 307.7±117.4
GS21 296.3±56.8B 270.7±63.4 267.6±49.0 278.8 ±45.7B 269.8±40.7
GI100 20.0±10.8A 16.6±10.1 13.7±14.1 11.4±11.2 10.0±10.0
GS100 12.9±9.3 12.9±12.5 7.7±9.7 8.3±12.8 7.3±14.0
GI80 11.5±17.0 23.1±18.4A 15.3±10.7 8.7±6.9 8.2±5.4
P(a-ET)CO2 GS80 5.2±17.9B 10.0±14.8 7.7±13.8 7.8±7.6 8.9±8.0
GI60 14.4±10.0 14.6±10.9 9.2±12.8 11.3±10.5 10.1±9.9
GS60 17.5±11.2 15.5±11.1 14.9±13.8 13.1±10.0 15.4±13.0
GI21 13.9±6.9 15.3±10.0 12.9±10.4 13.6±8.9 15.3±12.4
GS21 4.4±4.8B 5.6±4.1B 4.7±5.7 2.4±9.3 2.7±6.6
GI100 14.7±3.1AC 14.7±2.4BCD 15.2±1.6 14.4±1.5AC 14.7±1.8
GS100 16.9±2.6C 17.0±2.5CD 17.9±2.1AC 17.6±1.7BC 17.4±2.6ACD
GI80 15.1±1.3AC 15.5±1.2D 16.2±1.7C 16.0±2.2C 16.2±1.7D
CaO2 GS80 15.6±1.5 15.1±2.2 14.7±1.0BC 15.9±2.1C 15.9±2.0D
GI60 14.2±2.1AC 14.2±1.9BCD 13.5±3.1BC 11.8±5.2A 13.8±2.5BD
GS60 18.0±2.1BC 17.9±2.2ACD 17.7±2.2AC 17.5±2.3BC 17.7±2.1CD
GI21 13.1±1.5A 13.2±1.7BD 13.0±0.9B 13.6±1.6AC 12.6±1.7B
GS21 13.0±1.2A 12.5±1.8B 13.4±1.5B 12.6±1.6A 12.1±1.9B

Among groups: averages followed by upper case letters in the column differ from each other (P< 0.05).

Among time points: averages followed by different lowercase letters in the line differ among them (P< 0.05).

In this study, at different times, there were differences between groups submitted to the same concentration of O2, in the G100 and G80, and the animals anesthetized with sevoflurane had averages higher than those anesthetized with isoflurane. It is known that, in rats, the response to hypoxia is higher with isofluorane than with sevoflurane, the latter having lower depressant potency (Karanovic et al., 2010). Therefore, it is believed that in the animals submitted to FiO2 of 1.0 or 0.8, the lower depressant effect of sevoflurane may have contributed to the higher PaO2, since the hypoxemia, characterized by PaO2< 60mmHg and SaO2< 90%, (Cortopassi, 2002) was not observed in the groups that received these concentrations of O2.

However, in GI21 and GS21, hypoxemia was observed, according to the means of PaO2 and PaO2 (Table 1), and no differences were recorded between them. Such an event may be justified by the greater response to hypoxia with the use of isoflurane as described by Karanovic et al. (2010).

The value of PvO2 considered normal is 40 to 50mmHg, for animals breathing in ambient air (Haskins, 2004). With the exception of GI21 and GS21, in the other groups PvO2 was greater than 50mmHg. Such a difference can be attributed to the inspired concentration of oxygen. Thus, in this study, PvO2 behaved in a similar way to PaO2, presenting higher mean values, the higher the FiO2 used (Table 1). This same relation between PvO2 and FiO2 was observed by O'Neill et al. (1995), when studying oxygen therapy (100%, 50% and 30%) in rabbits submitted to anesthesia with halothane and by Borges et al. (2011), with the same species, anesthetized with propofol, maintained under controlled ventilation with different FiO2 and induced to hypovolemia. In GS21, there was a decrease in PvO2 in T15, T45 and T60 in relation to T0, with mean values below 40mmHg (Table 1). PvO2 represents the overall balance between the oxygen consumed (VO2) and its release, and is therefore dependent on (VO2) and hemoglobin concentration. However, hemoglobin averages were within the normal range for species, ranging from 9.4 to 17.4g/dL (Suckow and Douglas, 1996).

PaCO2 can be used to measure early respiratory changes. The normal range of PaCO2 in rabbits is from 20 to 46mmHg (Suckow and Douglas, 1996), and these values were observed in groups that received oxygen at 21%, 60%, and GS100. In GI100, GI80 and GS80, PaCO2 was greater than 46mmHg at most time points, characterizing hypercapnia (Table 1). This is commonly related to pulmonary abnormalities (Jefferies, 1994), and means above 60mmHg may be associated with the presence of hypoxemia and respiratory acidosis. In dogs anesthetized with propofol and maintained in spontaneous ventilation, Lopes et al. (2007) observed higher PaCO2 values with the use of FiO2 of 1.0 and 0.8. These authors attributed this clinical change to the occurrence of atelectasis due to the use of high concentrations of O2. However, in the study that was the object of this discussion, the clinical differences between the PaCO2 values were not relevant, as observed by the aforementioned authors.

Increasing levels of PaCO2 may be correlated with the administration of anesthetics, which alter the response of central and peripheral chemoreceptors to carbon dioxide and oxygen, occurring in a dose-dependent manner (McDonell and Kerr, 2007). The hypercapnia found must not be related to the anesthetic administered or both determine elevation of PaCO2 in the same manner, since the finding was similar with the use of sevoflurane or isofluorane.

According to Lopes et al. (2007), in dogs submitted to two and a half hours of general anesthesia, by continuous infusion of propofol, pulmonary collapse can be found in animals breathing 80 to 100% oxygen. Therefore, the presence of atelectasis was not observed in this study, since, at most times in the G100, PaCO2 remained within the range of normality (Capellier et al., 1999). With this, it can be deduced that, in this study, the duration of the anesthesia of one hour and thirty minutes was not sufficient for the formation of atelectasis areas. Observing the values in the GS80, it was possible to verify that this group presented the highest averages, coinciding with the high values observed in the variable and PVCO2. However, the means observed in GS80 remained below 60mmHg.

According to Luna (2002), the partial pressure of carbon dioxide in the venous blood is 5 to 10mmHg higher than PaCO2, therefore, the values found remained within the physiological limits, except in T0, GS80. In which the difference between the carbon dioxide partial pressure in the venous and arterial blood (ΔPCO2) exceeded 15mmHg (Table 1). In addition, it was observed that PvCO2 remained unchanged compared to the different FiO2, a fact already observed by Cole and Bishop (1963), who did not observe alterations of this variable with the use of FiO2 of 1.0; 0.5 and 0.21 in sedated humans and maintained under pressure-controlled ventilation. Although there was stability of PVCO2, it is proposed that in GS80, in T0, cardiac output was not sufficient to meet the global metabolic needs (Lamia et al., 2006).

SaO2 is an index measuring the lungs' ability to deliver O2 to blood (Haskins, 2004). In rabbits, values above 94% are considered normal. In this study, GI21 and GS21 showed SaO2 < 94%, probably due to the lower concentration of O2 supplied to these animals, indicating that the lungs were not able to properly distribute oxygen to the blood. These results corroborate those found by Lopes et al. (2007), who obtained values below 90% in dogs anesthetized with propofol and maintained on spontaneous ventilation with FiO2= 0.21, in addition to observing the presence of cyanosis. In this study, although the mucous membranes were not cyanotic, PaO2 < 60mmHg and SaO2 < 90% were observed, characterizing hypoxemia (Cortopassi, 2002) in GI21 and GS21 (Table 1).

The values considered normal for SvO2 are between 68% and 77%, indicating a normal balance between supply and demand for oxygen, provided by normal distribution of peripheral blood flow. According to Marx and Reinhart (2006), SvO2 > 75% indicates normal extraction with O2 supply greater than consumption, averages between 50 and 75% show the occurrence of compensatory extraction, due to increased consumption or decreased supply. The means found in the groups that received FiO2 of 1.0, 0.8 and 0.6 remained above 75%, providing a normal distribution of O2 to the tissues. In this study, GI21 presented values below 75%, confirming that there was not a good supply of oxygen. The low mean recorded indicates hypoxemia, which is in agreement with the data obtained in the SaO2 variable that remained below 90%.

Elevations in P(A-a) O2 occur mainly due to the presence of increased ventilation / perfusion (V/Q) imbalance, decreased pulmonary capillary perfusion and increased FiO2 (Carvalho and Schiettino, 1997). In this study, the higher the FiO2 used, the higher were the means found between the groups (Table 1). Thus, the groups that received FiO2 of 0.21, presented the lowest values. In addition, differences were found between GI100 and GS100 and between GI80 and GS80. This difference was characterized by higher averages found in animals receiving isoflurane. As discussed above, high P(A-a)O2 values may be related to a V/Q imbalance or a decrease in pulmonary capillary perfusion.

The respiratory index is a more specific quantifier of lung dysfunction than P(A-a)O2 and correlates more closely with the shunt (Terzi and Dragosvac, 2006). Values of 0.1 to 0.37 are considered adequate (Siggaard-Andersen et al., 1990). However et al. (1993) defined that RI <0.4 would be normal, but its increase would indicate worsening of intrapulmonary shunt. Thus, in this study, in T0 and T15, GI80 presented greater intrapulmonary shunt than the other groups, since it presented the highest respiratory indexes (Table 1). In addition, in GI80, it was observed that in some moments the RI was higher than 2.0, which may indicate refractory hypoxemia and elevated pulmonary shunt (Lundstrom, 2011). As hypoxemia refractory to oxygen administration is demonstrated by PaO2/FiO2 <200mmHg (Fioretto et al., 2006), which was not observed in this study, it is suggested that this value may be associated with increased shunt.

As the use of high FiO2 for long periods is related to the formation of pulmonary collapse (Magnusson and Spahn, 2003), it is believed that in this study, the time of anesthesia was short, one hour and thirty minutes, to observe the presence of atelectasis and its consequences.

However, differences were found between GI80 and GS80, in T0 and T15, with higher IRs recorded in GI80 (Table 1). Thus, it is suggested that, for these two groups that received the same FiO2, the animals submitted to sevoflurane anesthesia, the shunt was smaller. This hypothesis corroborates the claim that isoflurane provides deficient gas and V/Q changes when compared to sevofluorane (Terzi and Dragosvac, 2006). Thus, the hypothesis of shunt increase by the use of isoflurane in the test species strengthens.

The relation between PaO2 and PAO2 is also a pulmonary disturbance quantifier and the normal value of this variable is 0.75 to 0.9 (Terzi and Dragosvac, 2006). When their value is less than 0.75, there is evidence of inadequate ventilation / perfusion or diffuse pulmonary dysfunction, while means below 0.6 indicate ineffective gas exchange, which was found in the groups submitted to FiO2 of 1.0, 0.8 and 0.6 (Table 1). In GI21 and GS21 the values remained higher. In addition, in GI21, the means were higher than in GS21 (in T15 and T60), which again can be attributed to the better isoflurane response to pulmonary hypoxia, observed in animals submitted to FiO2 of 21% when compared to sevoflurane (Karanovic et al., 2010). This is because in cases of hypoxia blood is diverted from poorly ventilated areas to better ventilated areas of the lung, characterizing hypoxic vasoconstriction, more effectively with the use of isofluorane when compared to sevofluorane (Ishibe et al., 1993).

The relationship between PaO2 and FiO2 reflects shunt or arteriovenous mixture, with values considered normal above 400 (Terzi and Dragosvac, 2006). In this study, GI80 obtained the lowest values, close to 200, in T0 and T15, indicating that these values were inadequate (Table 1). Thus, it was noted that PaO2/FiO2 behaved in a manner similar to IR. In T0 and T15, GI80 presented greater intrapulmonary shunt than the other groups, because it had the lowest means of PaO2/FiO2 and higher mean of IR.

The difference between PaCO2 and ETCO2 indicates the alveolar dead space index and ranges from 2 to 3mmHg (O'flaherty et al., 1994). This variable is also considered a good indicator of the quality of the V/Q relation (Carvalho and Schiettino, 1997). In addition, large differences between the ETCO2 and PaCO2 parameters generally occur as a result of the absence of gas exchange, which may suggest that there is no adequate pulmonary perfusion or that the alveoli are not adequately ventilated or even during prolonged anesthesia in which they may cause changes in the exchange (O'flaherty et al., 1994). In this study, P (a-ET)CO2 was greater than 3mm Hg in all groups, probably due to changes in V/Q. In T0 and T15, in GS21 smaller averages were recorded (Table 1). However, GI21, who also received FiO2= 0.21, presented high values for P(a-ET)CO2, although not statistically significant.

CaO2 represents the amount of oxygen transported in arterial blood through binding to hemoglobin or dissolved in the blood, and its normal value is 17 to 20ml/dL (Espada and Carmona, 1995). In this study, this variable remained within the expected values only in GS100 and GS60 (Table 1). Hemoglobin is the most important factor contributing to oxygen content (Haskins, 2007); however, the low result cannot be justified by changes in hemoglobin, since the values found for Hb were within the normal range, 9.4 to 17.4g/dL (Suckow and Douglas, 1996).


Based on the results obtained with the proposed methodology, the inspired fractions of oxygen interfere in the respiratory variables. It was possible to verify the greater formation of intrapulmonary shunt in the groups that received FiO2 0.8. In addition, isofluorane determined better ventilation compared to sevoflurane when administered in a 21% oxygen atmosphere. Therefore, it is suggested that the best FiO2 for rabbits anesthetized with sevoflurane or isofluorane is close to the fractions 0.6 and 0.21.


The authors thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and the Post-Graduation Program in Veterinary Surgery of Faculdade de Ciências Agrárias e Veterinárias - FCAV.


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Received: December 18, 2017; Accepted: July 02, 2018

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