Acta anaesth. scand. 1976, 20, 429-436

The Haemodynamic Effects of Nitrous Oxide Anaesthesia on Systemic and Pulmonary Circulation in Dogs 0. DOTTORI, E. HAGGENDAL, E. LINDER, G. NORDSTROM AND T. SEEMAN Departments of Anaesthesiology and Surgery 11, University of Goteborg, Goteborg, Sweden

The haemodvnamic effects of nitrous oxide in normoxia (200,/, oxygen) and in hyperoxia (50% oxygen) were investigated in 13 dogs. Nitrous oxide in hyperoxia caused a significant rise in total peripheral resistance and a significant decrease in cardiac output, heart rate, myocardial contractility (dP/dt max) and cardiac worl?. On the other hand, nitrous oxide in normoxia seemed to reverse these findings and did not exert any negative inotropic effects on the myocardium. The results indicate that the earlier reported sympathetic activation of the circulation may be related to hyperoxia and not to nitrous oxide as such.

Received 10 April, accepted for publication 15 December 1975

Earlier published studies concerning the cardiovascular effects of nitrous oxide (N,O) contain controversial results. SMITH & CORBASCIO (1 966) could not find any noticeable haemodynamic changes in dogs and nor could STOELTING et al. (1972) in humans, but WYANTet al. (1962), LUNDBORG et al. (1966), HORNBEIN et al. (1969), SMITH et al. (1970), BAHLMAN et al. (1971) and EISELE & SMITH(1972) were able to demonstrate decreased cardiac output and/or myocardial contractility in both animals and humans. THORNTON et al. (1973), who anaesthetized cardiac patients with unsupplemented nitrous oxide in oxygen (1 :1), registered a decrease in cardiac output of 12% and emphasized the possibility that the haemodynamic changes should be attributed to hyperoxia and not to nitrous oxide, as such. The aim of this investigation was, therefore, to investigate whether the earlier reported haemodynamic changes are caused by nitrous oxide, as such, or by high oxygen concentrations in the gas mixtures.

MATERIAL AND METHODS The studies were carried out on a total of 13 mongrel

dogs (20-30 kg) of both sexes. T h e dogs were premedicated with diazepam (Stesolid@,Dumex), 0.4-0.5 mg/kg body weight and atropine, 0.01-0.02 mg/kg body weight. The anaesthesia was induced by 80% nitrous oxide in oxygen using a semi-open, nonrebreathing system. Muscular relaxation was obtained by 2 4 mg/kg body weight suxamethonium, given as a single intravenous injection immediately after induction. After endotracheal intubation with a cuffed Magill tube, the animals were ventilated with an Engstrom respirator with nitrous oxide and oxygen ( 1 :1 or 4 : 1) in a non-rebreathing system. T t e body temperature was measured in the rectum and was kept a t 37-38°C. Muscle relaxation was maintained with intermittent administration of suxamethonium in an average dose of 4 mg/kg b.w./h. The ventilation was adjusted throughout the experiment to give aIveolar normoventilation, and the animals were hyperinsufflated at intervals in order to prevent the development of atelectasis. Four intercostal nerves on either side of the proposed thoracotomy incision were blocked by local injection of 2 cc of bupivacaine (Marcah@,Bofors) 0.5% with adrenaline before the thoracotomy. A left thoracotomy was carried out and the pericardium was incised and sutured to the thoracic wall in order to minimize changes in the position of the heart due to ventilatory movements. Pressures were registered continuously throughout the experimental period via polyethylene or teflon catheters inserted in the common carotid artery, the left atrium, the left ventricle and the main pulmonary artery. These measurements were made with an inductance type transducer and registered on a direct

430

0.DOTTORI, E . HAGGENDAL, E . LINDER, G . NORDSTROM AND T. SEEMAN

writer oscillograph (Mingograf-Elema). Mean blood pressures were obtained by electrical integration. Arterial and mixed venous blood samples were taken from the carotid and pulmonary arteries for blood gas measurements. The cardiac output was determined with an electromagnetic flow meter (Nycotron, Oslo). The flow probe was chosen to fit the vessel snugly, and was placed on the aorta immediately above the aortic valves. Probe calibration was accomplished by perfusing the dog's arteries with blood or 5 N,saline solution. Zero flow for mean blood flow in vivo' was obtained by shutting off the probe magnet instead of inflow occlusion, as the latter was judged to interfere with the experimental condition. The mean flow in the ascending aorta was taken as a n indication of the cardiac output, and the stroke volume was estimated from the peak flow curve. The diastolic ''quiet interval", when no flow except coronary flow occurred in the aorta: was used as a measure of zero for peak flow (SCHENK & DEDICHEN 1967). The peripheral vascular resistance was calculated as the quotient between mean arterial blood pressure in mmHg and cardiac output in l/min, thus ignoring the right atrial pressure. Pulmonary vascular resistance was calculated according to the formula: PAP mmHg- LAP mmHg arb. unit = CO I/min where PAP is the pulmonary arterial pressure, LAP is the left atrial pressure, and CO is the cardiac output. The oxygen tension in arterial and mixed venous blood was estimated according to GLEICHMA" & LUBBERS ( 1960), and carbon-dioxide tension according to the micromethod of SIGGAARD-ANDERSEN (1963).

Blood samples were collected without exposure to air and were stored a t 0°C (ice water). The correction factor was calculated according to KELMAN& NU" (1966) for temperature and for oxygen consumed during the interval between sampling and analysis. Dissolved oxygen was calculated using 0.0235 as the solubility cofficient of oxygen in blood. I n the determination of oxygen content, the amount of physically dissolved oxygen was included in both arterial and venous blood samples. The total oxygen consumption was calculated from determinations of arterio-venous oxygen difference and cardiac output. Left ventricular work (LVW) was calculated using the formula: kpm/min = 0.0135 x cardiac output in l/min x mean aortic blood pressure in mmHg Left ventricular stroke work (LVSW) was calculated using the formula :

J=-

1 O0

x

stroke volume in m l x (mean arterial blood pressure mmHg- left atrial pressure in mmHg)

In addition, the product of the arterial systolic blood pressure and the heart rate was calculated (BPs x H R ) , and presented as a measure of cardiac work. The effects of nitrous oxide-oxygen anaesthesia were studied a t different oxygen concentrations (1 : 1 or 4 : l ) , and comparedwith the effects of ventilation with nitrogen-oxygen a t the same oxygen concentrations. Nitrous oxide-oxygen and nitrogenoxygen were compared in the ratio 1 : 1 in four dogs

Table 1 Summary of investigations. ~~

N20-02 vs NzOz

Mixtures compared

80% - 20%

Concentrations

NZO-02 vs NzO,-diazepam 80%

- 20%

NzO-02 vs N~OZ 50% - 50%

N20-02-Nz vs N,O,-diazepam

50% - 20% - 30% vs

80% - 20% Pressures Sr flow Systemic O2 consumption No. of Pressures & observations flow Systemic O2 consumption

No. of dogs

* Same experimental

dogs.

4

5*

4

5*

4

5

-

5

18

15

10

15

6

5

-

5

NITROUS OXIDE ANAESTHESIA AND PULMONARY CIRCULATION

and nitrous oxide-oxygen and nitrogen-oxygen in the ratio 4:1 were compared in another four dogs. I n five other dogs, unsupplemented nitrous oxideoxygen in the ratio 4 : 1 and nitrous oxide-oxygennitrogen in the ratio 2:0.80 : 1.20 were compared to nitrogen-oxygen supplemented by 5-1 0 mg diazepam at the same oxygen concentrations (Table 1). After any change in the ventilated gas mixture, no measurements were performed until a period of 7-10 min had passed, in order to obtain equilibrium. Each measurement period lasted 8-10 min. The values obtained during nitrogen-oxygen ventilation were used as control values, and the changes which were registered during nitrous oxide-oxygen ventilation are given in per cent of these values. Thus each animal represented its own control. Statistical analyses of all data were performed according to the formula: Rn - Ud

I n order to compare the results obtained in the four dogs ventilated with nitrous oxide a t 1 : 1 with

those ventilated with nitrous oxide at the ratio

2 :0.80 : 1.20, the flows were reported in ml/kg body weight, because of the large differences of weight in the two groups. For this comparison the t-test for independent means was also used for statistical analysis. T h e changes after the hyperoxic nitrous oxide ventilation were thus assumed as control values. The level of significance chosen was P < 0.05.

RESULTS Figure 1 (A) summarizes the effects of 50% nitrous oxide in oxygen on systemic circulation, as compared to the control period when the animals were ventilated with nitrogen a t the same oxygen concentrations. No significant changes were registered for any parameter. I n Figure 1 (B), the results obtained in dogs ventilated with nitrous oxide in oxygen at the ratio 1: 1 were compared to those

C

B

A

431

CHANGES Nz(50%) “ $ W O W IN I PER CENT 02(50%)

I0 (50%) I

I I

co

120

HR

100

80 140

-

120

MAP

80 6 0 ,F

I

0 L

PsO. 05

NS

Fig. 1. Changes in certain circulatory parameters during ventilation with hyperoxic (A and B) and normoxic (C) nitrous oxide gas mixtures, as compared with measurements during ventilation with hyperoxic nitrogen, normoxic nitrous oxide gas mixture and air, respectively. Definitions of abbreviations: HR = heart rate, CO = cardiac output, SV = stroke volume, MAP = mean arterial blood pressure, LAP = left atrial pressure, TPR = total peripheral resistance, PVR = pulmonary vascuIar resistance, LVW = left ventricular work, LVSW = left ventricular BPs = arterial stroke work, systolic blood pressure, dP/dt pressure max = maximum change versus time, A-Vo2 = arterio-venous oxygen difference, Vo, = systemic oxygen consumption.

432

0.DOTTORI, E. HAGGENDAL, E. LINDER, G. NORDSTROM AND T. SEEMAN

obtained when the dogs were ventilated with 50% nitrous oxide and a reduced oxygen concentration. Significant decreases in heart rate of 11% (from 175.7f21.9 to 159.5f13.8 beats/min) and in cardiac output of 23% (from 105.2f 47.9 to 86.5 & 16.5 ml/min/b.w.) were registered. The total peripheral resistance increased significantly (38%), as did the mean arterial blood pressure (from 1.14.1f30.4 to 151.6f37.2 mrnHg), while the cardiac work did not show any changes. The myocardial contractility expressed as the maximum pressure change verws time (dP/dt max) decreased about 50% in the hyperoxic nitrous oxide group. I n the same Figure 1 (C), it is shown that

I

I

I

I

14 0

no significant changes were registered when the oxygen concentration in the nitrous oxide-oxygen mixture was reduced from 50 to 20%, when compared with the dogs medicated with diazepam and ventilated with air, except a small though significant increase in the heart rate (from 182.3f 19.5 to 188.0$- 18.4 beats min). Pulmonary haemodynamics and total oxygen consumption were investigated only in the normoxic nitrous oxide group. As seen in Figure 1 (C), no significant differences were found between studies with air and with normoxic nitrous oxide (50 :30 :20). In the normoxic nitrous oxide group the oxygen tension in the pulmonary artery decreased about 10% as compared with the

~

LVSW

100

-

80

-

LAP TPR PVR

PVR

140 120

B

b 0

P