European Heart Journal (1992) 13, 1545-1548
Effect of dobutamine on pulmonary gas exchange in patients with severe heart failure H.-H. ERLEMEIER, W. KUPPER AND W. BLEIFELDt
Department of Cardiology, University Hospital Eppendorf, Hamburg, Germany KEY WORDS: Dobutamine, pulmonary gas exchange. Twenty patients (two female, 18 male, mean age 57 ± 11 years) with severe heart failure NYHA IV (7 coronary artery disease, 13 congestive cardiomyopathy) were treated with 8-8±l-7fig .kg~'. min~' of dobutamine. Pulmonary gas exchange was analysed by withdrawal of blood samples from a central venous catheter and a radial artery canula. Dobutamine increased SvO2 from 58-7±11-2% to 72-2±6-3% (P = 00001) and decreased avDO2 from 7-7 ±2-45 Vol% to 4-97 ± 1-34 Vol% (P = 00001). PaO2 and PaCO2 were not changed. Qs/Qt increased slightly from 91 ±8-3% to ll-3±6-4% (P = 0035). Cardiac index increased by 51% (P = 00001), pulmonary capillary wedge pressure decreased by 28% (P = 00001). In patients with severe heart failure, dobutamine improved haemodynamics without detrimental effects on arterial oxygen concentration. Introduction Dobutamine is a beta-adrenoceptor agonist. It works as an inotrope by stimulating myocardial beta-, adrenoceptors. In addition, it decreases peripheral resistance by stimulating arterial beta-2 receptors'1'. In this way, dobutamine has proved to be favourable in the treatment of low cardiac output failure'2'. On the other hand, however, the increase in cardiac output and direct effects of vasoactive compounds on the pulmonary vessels may increase intrapulmonary shunts and deteriorate arterial oxygenation'3"51. Dobutamine may also influence pulmonary shunts, but the results are contradictory*5"10'. It is particularly important that patients with advanced heart failure have sufficient pulmonary gas exchange to supply oxygen to the impaired myocardium. Thus, in the present study, the effects of dobutamine on haemodynamics and pulmonary gas exchange were studied in patients with severe heart failure. Methods PATIENTS
Twenty patients with severe heart failure (NYHA IV) in spite of treatment with diuretics, digitalis, ACE inhibitors and nitrates, were enrolled; their characteristics are presented in Table 1. No patient had concomitant pulmonary disease. All patients gave informed consent prior to study and study protocol was approved by the local Ethics Committee. PROTOCOL
All measurements were studied in the supine position. Transducers for haemodynamic measurements were Submitted for publication on 8 April 1991,andinrcvisedform3January 1992. Supported by a grant from the Deuuche Forschungsgemeinschafl (DFG), Er 1/134. Correspondence: Dr H.-H. Erlemeier, Cardiologist, Ochsenzoller Str. 201, D-2000 Norderstedl, Germany. 0195-668X/92/111545 + 04 $08.00/0
positioned at the mid-chest level. A 7-F thermodilution catheter was floated into the pulmonary artery and the position controlled by a typical pulmonary capillary wedge pressure curve with the inflated balloon and a pulmonary artery curve with the balloon deflated. Arterial pressure was taken from a radial line. After instrumentation, the patients remained as quiet and as comfortable as possible for at least 30min. Registrations were then taken of pulmonary capillary wedge, pulmonary artery, right atrial and arterial pressures. Cardiac output was determined in triplicate by injection of 10 ml of iced saline. Blood samples for blood gas analysis were withdrawn from the arterial canula and pulmonary artery catheter. After the baseline measurements the dobutamine infusion was started at 2-5 ug . k g " ' . min"' and increased in 2-5 ng. kg"' . min"' steps every 15min up to 10 ug. kg"' . min"'. Titration was stopped at the 50 ng. k g " ' . min"' level in two patients because of ventricular premature depolarisation ;> 15 . min"1, at the 7-5 ug. k g " ' . min"' level in four patients because of ventricular premature depolarisation ;> 15 . min"1 and in two patients because of tachycardia ^ 120 beats . min"1. The mean dosage was 8-8± 1-7 ug . kg"1 min"'. The dobutamine infusion was continued at the maximum level tolerated for at least 15 min. Haemodynamic measurements and withdrawal of blood samples were then repeated in the same fashion as at baseline. Derived parameters were calculated using standard formulae'1''. STATISTICS
All values are presented as mean ± standard deviation. Comparison of normally distributed data was performed by Student t-test for paired samples, otherwise, Wilcoxon's test for paired samples was applied. Regression of two parameters was analysed by simple regression analysis and F-test. A probability of at least 005 was considered statistically significant. © 1992 The European Society of Cardiology
1546 H.-H. Erlemeier et al.
Table 1 Patient characteristics Mean dosage/day (nig) n
Sex Age
Diagnosis LA diameter LVED diameter Concomitant medication furosemide digoxin digitoxin captopril cnalapril ISDN IS5MN Dobutamine doses
20
2 female 18 male 57 ± 11 years 7 CAD 13CMP 50 ±8 mm 74 ± 10 mm 20 patients 12 patients 7 patients 14 patients 3 patients 4 patients 6 patients 8-8±l-7ng.kg-'.min-'
124±59 0-2 ±01 008 ±002 67 ±40 8±3 110±20 42 ±4
LA = left atrium; LVED = left ventricular end-diastolic; CAD = coronary artery disease; CMP = cardiomyopathy; ISDN = isosorbidc dinitrate; IS5MN = isosorbide 5 mononitrate.
Results HAEMODYNAMIC DATA
Dobutamine, at an average dose of 8-8 ug. kg" 1 . min"1, increased heart rate by 9% (/> = 0-0001). Mean arterial blood pressure showed no significant change, but right atrial pressure and pulmonary capillary wedge pressure dropped by 38% and 28% respectively (/> = 0-0001). Cardiac index and stroke volume index increased markedly, while systemic vascular resistance decreased by 30% (f = 0-004). Pulmonary vascular resistance and mean pulmonary artery pressure showed no clear changes (Table 2). OXYMFTRY
Arterial oxygen pressure (PaO2) did not change under dobutamine, and arterial carbon dioxide pressure (PaCO2) remained constant. Mixed venous oxygen saturation (SvO2) increased significantly under dobutamine. The arterio-venous difference in oxygen pressure (avDO2) decreased, while the alveolo-arterial difference in oxygen pressure (AaDO2) did not change significantly under dobutamine. Intrapulmonary shunt (Qs/Qt) increased slightly, and the change was statistically significant (/> = 0035)(Table3). REGRESSION ANALYSIS
Stable or changing pulmonary capillary wedge pressure did not influence arterial PO2; the corresponding data after transformation to categorical values are shown in Table 4. No relationship was evident between intrapulmonary shunts or changes in intrapulmonary shunts and changes in cardiac index or absolute values of cardiac index. A weak positive correlation was found between changes of Qs/Qt and SvO2 (P < 0-1) (Fig. 1).
In the individual patient, PaO2 did not deteriorate under dobutamine in patients with low baseline values (Fig. 2). Discussion In patients with acute cardiac failure and impaired haemodynamics, dobutamine increases cardiac index and decreases filling pressures. Therefore it is widely used in the treatment of acute cardiac failure'1-212131. However, therapy with an inotrope or a vasodilator may lead to a decrease in arterial oxygen concentration due to the opening of intrapulmonary shunts which may result in a detrimental effect on impaired left ventricular function'3"6'9'. The results of previous studies concerning pulmonary perfusionduringdobutamine treatment are contradictory: a decrease, an increase or no changes in intrapulmonary shunts have been described'5"101. Furthermore, in most of the studies either animals or patients with normal cardiac function were investigated and most studies were carried out under non-physiological conditions, e.g. under mechanical ventilation'12', during lung surgery*5'6' or experimentally during artificial pulmonary oedema induced by injection of oleic solution in one pulmonary arter/ 7 ' 8 ' In the present study, we investigated the effects of dobutamine on blood gases in conscious patients with end-stage heart failure. Our attention was focused on changes in arterial oxygen pressure. Surprisingly, PaO2 was not influenced by pulmonary capillary wedge pressure either at baseline or during dobutamine infusion (Table 4): in contrast with systemic perfusion, the thin-walled collapsible pulmonary vessels only become patent when hydrostatic pressure exceeds alveolar pressure'14151. However, our investigations were performed in the supine position: such gravitational
Effect ofdobutamine on pulmonary gas exchange 1547
Table 2
Haemodynamic changes
Heart rate (beats . min~') Cardiac index (1. min~'. m"2) Mean arterial pressure (mmHg) Mean pulmonary artery pressure (mmHg) Pulmonary capillary wedge pressure (mmHg) Right atrial pressure (mmHg) Systemic vascular resistance (dyn . s. cm"5) Pulmonary arteriolar resistance (dyn . s . cm *)
While taking dobutamine
91 ± 17 I 99±0-61 82±12 34± 10 25±9 12 1 ±7 2 1596 ±628 226 ±200
99±18 30l±0-71 83±12 32±9 18±8 7-5 ±4-6 1122 + 368 204±139
Changes in parameters of gas exchange
140 130
Baseline
dobutamine 120
PaO2 (mmHg) PaCO 2 (mmHg) SvO2 (%) avDO 2 (Vol%) AaDO 2 (mmHg) Qs/Qt(%)
85-4 ±22 5 34-8±4-4 58-7± 11 2 7-70±2-45 23-7±20-7 9 1 ±8 3
85-5± 12-4 34-5±2-6 72-2±6-3 4-97 ±1-34 24-2± 12-3 11-3±6-4
NS NS 00001 00001 NS 0035
0003 00001 NS NS 00001 00001 0004 NS
1 1 1 1
Table 3
Baseline
: "A
I 10
\>
100 90
~^~— Jk •r J -~r
80
^
Table 4 Pulmonary capillary wedge pressure and arterial PO2 Low vs high (NS) Pulmonary capillary wedge pressure
p
low, high, While taking dobutamine low, high,
£ 2 4 mmHg > 24 mmHg ^ 17 mmHg > 17 mmHg
60
~ 2
83-3 ± 2 7 1 mmHg 86-9 ± 19-2 mmHg 83-9 ± 13-9 mmHg 87O± 11-3 mmHg
35
• :
30 :
25
•
\
Effect of dobutamine on pulmonary gas exchange in patients with severe heart failure H.-H. ERLEMEIER, W. KUPPER AND W. BLEIFELDt
Department of Cardiology, University Hospital Eppendorf, Hamburg, Germany KEY WORDS: Dobutamine, pulmonary gas exchange. Twenty patients (two female, 18 male, mean age 57 ± 11 years) with severe heart failure NYHA IV (7 coronary artery disease, 13 congestive cardiomyopathy) were treated with 8-8±l-7fig .kg~'. min~' of dobutamine. Pulmonary gas exchange was analysed by withdrawal of blood samples from a central venous catheter and a radial artery canula. Dobutamine increased SvO2 from 58-7±11-2% to 72-2±6-3% (P = 00001) and decreased avDO2 from 7-7 ±2-45 Vol% to 4-97 ± 1-34 Vol% (P = 00001). PaO2 and PaCO2 were not changed. Qs/Qt increased slightly from 91 ±8-3% to ll-3±6-4% (P = 0035). Cardiac index increased by 51% (P = 00001), pulmonary capillary wedge pressure decreased by 28% (P = 00001). In patients with severe heart failure, dobutamine improved haemodynamics without detrimental effects on arterial oxygen concentration. Introduction Dobutamine is a beta-adrenoceptor agonist. It works as an inotrope by stimulating myocardial beta-, adrenoceptors. In addition, it decreases peripheral resistance by stimulating arterial beta-2 receptors'1'. In this way, dobutamine has proved to be favourable in the treatment of low cardiac output failure'2'. On the other hand, however, the increase in cardiac output and direct effects of vasoactive compounds on the pulmonary vessels may increase intrapulmonary shunts and deteriorate arterial oxygenation'3"51. Dobutamine may also influence pulmonary shunts, but the results are contradictory*5"10'. It is particularly important that patients with advanced heart failure have sufficient pulmonary gas exchange to supply oxygen to the impaired myocardium. Thus, in the present study, the effects of dobutamine on haemodynamics and pulmonary gas exchange were studied in patients with severe heart failure. Methods PATIENTS
Twenty patients with severe heart failure (NYHA IV) in spite of treatment with diuretics, digitalis, ACE inhibitors and nitrates, were enrolled; their characteristics are presented in Table 1. No patient had concomitant pulmonary disease. All patients gave informed consent prior to study and study protocol was approved by the local Ethics Committee. PROTOCOL
All measurements were studied in the supine position. Transducers for haemodynamic measurements were Submitted for publication on 8 April 1991,andinrcvisedform3January 1992. Supported by a grant from the Deuuche Forschungsgemeinschafl (DFG), Er 1/134. Correspondence: Dr H.-H. Erlemeier, Cardiologist, Ochsenzoller Str. 201, D-2000 Norderstedl, Germany. 0195-668X/92/111545 + 04 $08.00/0
positioned at the mid-chest level. A 7-F thermodilution catheter was floated into the pulmonary artery and the position controlled by a typical pulmonary capillary wedge pressure curve with the inflated balloon and a pulmonary artery curve with the balloon deflated. Arterial pressure was taken from a radial line. After instrumentation, the patients remained as quiet and as comfortable as possible for at least 30min. Registrations were then taken of pulmonary capillary wedge, pulmonary artery, right atrial and arterial pressures. Cardiac output was determined in triplicate by injection of 10 ml of iced saline. Blood samples for blood gas analysis were withdrawn from the arterial canula and pulmonary artery catheter. After the baseline measurements the dobutamine infusion was started at 2-5 ug . k g " ' . min"' and increased in 2-5 ng. kg"' . min"' steps every 15min up to 10 ug. kg"' . min"'. Titration was stopped at the 50 ng. k g " ' . min"' level in two patients because of ventricular premature depolarisation ;> 15 . min"1, at the 7-5 ug. k g " ' . min"' level in four patients because of ventricular premature depolarisation ;> 15 . min"1 and in two patients because of tachycardia ^ 120 beats . min"1. The mean dosage was 8-8± 1-7 ug . kg"1 min"'. The dobutamine infusion was continued at the maximum level tolerated for at least 15 min. Haemodynamic measurements and withdrawal of blood samples were then repeated in the same fashion as at baseline. Derived parameters were calculated using standard formulae'1''. STATISTICS
All values are presented as mean ± standard deviation. Comparison of normally distributed data was performed by Student t-test for paired samples, otherwise, Wilcoxon's test for paired samples was applied. Regression of two parameters was analysed by simple regression analysis and F-test. A probability of at least 005 was considered statistically significant. © 1992 The European Society of Cardiology
1546 H.-H. Erlemeier et al.
Table 1 Patient characteristics Mean dosage/day (nig) n
Sex Age
Diagnosis LA diameter LVED diameter Concomitant medication furosemide digoxin digitoxin captopril cnalapril ISDN IS5MN Dobutamine doses
20
2 female 18 male 57 ± 11 years 7 CAD 13CMP 50 ±8 mm 74 ± 10 mm 20 patients 12 patients 7 patients 14 patients 3 patients 4 patients 6 patients 8-8±l-7ng.kg-'.min-'
124±59 0-2 ±01 008 ±002 67 ±40 8±3 110±20 42 ±4
LA = left atrium; LVED = left ventricular end-diastolic; CAD = coronary artery disease; CMP = cardiomyopathy; ISDN = isosorbidc dinitrate; IS5MN = isosorbide 5 mononitrate.
Results HAEMODYNAMIC DATA
Dobutamine, at an average dose of 8-8 ug. kg" 1 . min"1, increased heart rate by 9% (/> = 0-0001). Mean arterial blood pressure showed no significant change, but right atrial pressure and pulmonary capillary wedge pressure dropped by 38% and 28% respectively (/> = 0-0001). Cardiac index and stroke volume index increased markedly, while systemic vascular resistance decreased by 30% (f = 0-004). Pulmonary vascular resistance and mean pulmonary artery pressure showed no clear changes (Table 2). OXYMFTRY
Arterial oxygen pressure (PaO2) did not change under dobutamine, and arterial carbon dioxide pressure (PaCO2) remained constant. Mixed venous oxygen saturation (SvO2) increased significantly under dobutamine. The arterio-venous difference in oxygen pressure (avDO2) decreased, while the alveolo-arterial difference in oxygen pressure (AaDO2) did not change significantly under dobutamine. Intrapulmonary shunt (Qs/Qt) increased slightly, and the change was statistically significant (/> = 0035)(Table3). REGRESSION ANALYSIS
Stable or changing pulmonary capillary wedge pressure did not influence arterial PO2; the corresponding data after transformation to categorical values are shown in Table 4. No relationship was evident between intrapulmonary shunts or changes in intrapulmonary shunts and changes in cardiac index or absolute values of cardiac index. A weak positive correlation was found between changes of Qs/Qt and SvO2 (P < 0-1) (Fig. 1).
In the individual patient, PaO2 did not deteriorate under dobutamine in patients with low baseline values (Fig. 2). Discussion In patients with acute cardiac failure and impaired haemodynamics, dobutamine increases cardiac index and decreases filling pressures. Therefore it is widely used in the treatment of acute cardiac failure'1-212131. However, therapy with an inotrope or a vasodilator may lead to a decrease in arterial oxygen concentration due to the opening of intrapulmonary shunts which may result in a detrimental effect on impaired left ventricular function'3"6'9'. The results of previous studies concerning pulmonary perfusionduringdobutamine treatment are contradictory: a decrease, an increase or no changes in intrapulmonary shunts have been described'5"101. Furthermore, in most of the studies either animals or patients with normal cardiac function were investigated and most studies were carried out under non-physiological conditions, e.g. under mechanical ventilation'12', during lung surgery*5'6' or experimentally during artificial pulmonary oedema induced by injection of oleic solution in one pulmonary arter/ 7 ' 8 ' In the present study, we investigated the effects of dobutamine on blood gases in conscious patients with end-stage heart failure. Our attention was focused on changes in arterial oxygen pressure. Surprisingly, PaO2 was not influenced by pulmonary capillary wedge pressure either at baseline or during dobutamine infusion (Table 4): in contrast with systemic perfusion, the thin-walled collapsible pulmonary vessels only become patent when hydrostatic pressure exceeds alveolar pressure'14151. However, our investigations were performed in the supine position: such gravitational
Effect ofdobutamine on pulmonary gas exchange 1547
Table 2
Haemodynamic changes
Heart rate (beats . min~') Cardiac index (1. min~'. m"2) Mean arterial pressure (mmHg) Mean pulmonary artery pressure (mmHg) Pulmonary capillary wedge pressure (mmHg) Right atrial pressure (mmHg) Systemic vascular resistance (dyn . s. cm"5) Pulmonary arteriolar resistance (dyn . s . cm *)
While taking dobutamine
91 ± 17 I 99±0-61 82±12 34± 10 25±9 12 1 ±7 2 1596 ±628 226 ±200
99±18 30l±0-71 83±12 32±9 18±8 7-5 ±4-6 1122 + 368 204±139
Changes in parameters of gas exchange
140 130
Baseline
dobutamine 120
PaO2 (mmHg) PaCO 2 (mmHg) SvO2 (%) avDO 2 (Vol%) AaDO 2 (mmHg) Qs/Qt(%)
85-4 ±22 5 34-8±4-4 58-7± 11 2 7-70±2-45 23-7±20-7 9 1 ±8 3
85-5± 12-4 34-5±2-6 72-2±6-3 4-97 ±1-34 24-2± 12-3 11-3±6-4
NS NS 00001 00001 NS 0035
0003 00001 NS NS 00001 00001 0004 NS
1 1 1 1
Table 3
Baseline
: "A
I 10
\>
100 90
~^~— Jk •r J -~r
80
^
Table 4 Pulmonary capillary wedge pressure and arterial PO2 Low vs high (NS) Pulmonary capillary wedge pressure
p
low, high, While taking dobutamine low, high,
£ 2 4 mmHg > 24 mmHg ^ 17 mmHg > 17 mmHg
60
~ 2
83-3 ± 2 7 1 mmHg 86-9 ± 19-2 mmHg 83-9 ± 13-9 mmHg 87O± 11-3 mmHg
35
• :
30 :
25
•
\
