Dobutamine-induced dissociation between

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Leier CV, Heban PT, Huss P. Comparative systemic and regional hemodynamic effects of dopamine and dobutamine in patients with cardiomyopathic heart ...
British Journal of Anaesthesia 1995; 74: 277-282

Dobutamine-induced dissociation between changes in splanchnic blood flow and gastric intramucosal pH after cardiac surgery I. PARVIAINEN, E. RUOKONEN AND J. TAKALA

Summary

Key w o r d s Heart, dobutamine. Surgery, cardiovascular. Gastrointestinal tract, pH. Oxygen, consumption. Oxygen, delivery.

Patients and methods The study was approved by the Ethics Committee of the hospital and informed consent was obtained from each patient. We studied 28 patients after coronary artery bypass grafting operation. Anaesthesia was standardized with fentanyl 20 |ig kg"1, midazolam 0.07 mg kg-1, and a mixture of alcuronium 0.125 mg kg"1 and pancuronium 0.15 mg kg"1. Anaesthesia was maintained with a continuous infusion of midazolam 0.5 ug kg"1 min"1, fentanyl 0.07 ug kg"1 min~l and alcuronium 1.1 ngkg"1 min"1, and supplemented widi thiopentone and halothane. On admission to the ICU, 22 patients had a cardiac index exceeding 2 litre min"1 nr 2 . They were allocated randomly to receive either dobutamine (mean 4.4 (range 3.5-5.5) ug kg"1 min"1) in order to increase cardiac output by at least 25 % (normal cardiac output and dobutamine group, n = 11) or to serve as a control group (« = 11). The control group received no vasoactive treatment. In six patients cardiac index was less than 2 litre min' 1 m~2 and they received an infusion of dobutamine (mean 4.3 (range ILKKA

PARVIAINEN,

MD, ESKO

RUOKONEN, MD, PHD, JUKKA

TAKALA, MD, PHD, Critical Care Research Program, Department of Intensive Care, Kuopio University Hospital, FIN-70210 Kuopio, Finland. Accepted for publication: October 7, 1994. Correspondence to J.T.

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Gastric intramucosal acidosis, a sign of splanchnic tissue hypoxia, is common after cardiac surgery. We tested the hypothesis that an increase in splanchnic blood flow induced by dobutamine improves splanchnic tissue oxygenation after cardiac surgery. We measured changes in gastric intramucosal pH, splanchnic blood flow and oxygen transport in response to increased systemic flow induced by dobutamine (mean 4.4 (range 3.0-7.0) ug kg"1 min"1) after coronary artery bypass. We studied 22 stable postoperative patients who were allocated randomly to receive dobutamine (n = 11) or to serve as controls (n = 11). Dobutamine was given also to a separate group with a low cardiac index after operation (n = 6). The end-point was to increase cardiac index by at least 25% and to exceed 2 litre min~1 m~2. Dobutamine consistently increased mean splanchnic blood flow (control 0.6 (SD0.2) VS 0.7(0.2) litre min- 1 m-2 ( P < 0 . 0 5 ) ; normal cardiac output and dobutamine 0.7 (0.2) vs 1.1 (0.4) litre min"1 n r 2 ( P < 0 . 0 1 ) ; low cardiac output and dobutamine 0.4(0.1) vs 0.7(0.1) litre min" 1 m~2 (Pc'e Control 12 430 (3870) Normal CO + dobutamine 11470(3140) Low CO + dobutamine 17 910 (2910)+ Femoral vascular resistance index (dyn s cm"5 m2^ Control 64 360 (22 820) Normal CO + dobutamine 65890(18100) Low CO + dobutamine 81420 (17 580)

Second measurement

279

Splanchnic oxygen transport after cardiac surgery

STATISTICAL ANALYSIS

Differences between groups were compared by analysis of variance [13] for repeated measurements using one dependent variable, one grouping factor

(treatment group) and one within-subject factor (time). Significant effects of time, group or timegroup interaction were assessed by Mann-Whitney U test and the Wilcoxon test [14]. Differences between groups in clinical variables were compared by Mann-Whitney U test. Statistical significance was considered at P < 0.05. All results are presented as mean (SD). Results The postoperative course was complicated by mediastinitis in one patient in the control group and by acalculous cholecystitis in one patient with low cardiac output syndrome. All other patients had uneventful recoveries (table 1). Haemodynamic responses are presented in table 2 and blood flow distribution in figure 1. At baseline, splanchnic bloodflowwas reduced in the low cardiac output group. Dobutamine consistently increased 5 i -

4 -

Mil 2-,

Control

Normal CO

Low CO

1.5 -



T

.

•T0.5H

m 0

Control

Normal CO

Low CO

Normal CO

Low CO

0.3 i

Figure 1 Systemic and regional blood flow (CI = cardiac index, SBF = splanchnic blood flow, FBF = femora] blood flow) (mean, SD) at baseline ( • ) and at the second measurement (D) in the control, and normal and low cardiac output (CO) groups. Analysis of variance: effect of group: CI, P < 0.01, SBF, P < 0.05, FBF, ns; effect of time (baseline vs second measurement): CI, P < 0.001, SBF, P < 0.001, FBF, P < 0.001; group-time interaction: CI, P < 0.01, SBF, P < 0.01, FBF, ns. *P < 0.05 compared with baseline; \P < 0.05 compared with control.

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where Cfv = ICG concentration in the femoral vein. ICG extraction was 76.9 + 8.6% and the coefficients of variation for consecutive bloodflowmeasurements at 20, 25 and 30 min during each infusion of ICG were 4.7 ±2.8% for femoral blood flow and 4.1± 2.7 % for splanchnic blood flow, respectively. Cardiac output was measured by both thermodilution (mean of three measurements) and the Fick principle, and the mean value used for analysis. Regional vascular resistances were calculated by dividing mean arterial pressure by regional blood flow. Arterial oxygen content ( C a ^ was measured by a Co-oximeter (OSM3 Hemoximeter, Radiometer, Copenhagen, Denmark), and systemic and regional oxygen delivery (Z)o2) were calculated as the product of Cao2 and blood flow (thermodilution for systemic and dye dilution for regional blood flow). Regional Vo2 was calculated as the product of regional blood flow and arteriovenous oxygen content difference. Oxygen extraction was derived from measured Vo2 and Do2. Lactate concentrations were measured enzymatically (Boehringer Mannheim GmbH, Mannheim, Germany). Gastric intramucosal pH (pH,) was measured by gastric tonometer (Tonomitor, Tonometrics, Worcester, MA, USA) [5] after 45-60 min of equilibration. In the first 17 patients of the study, saline Pco2 was analysed with the Nova Stat Profile 4 analyser (Nova Biomedical, Waltham, MA, USA). As this analyser was found to underestimate saline Pco2 [11], it was compared with an IL-1302 analyser (Instrumentation Laboratories, Lexington, MA, USA) for measurement of 30 saline samples with Pco2 2.2-5.7 kPa. A correction curve was constructed (Pco2IL = 1.10+1.71 Pco 2Nov ,-0.12Pco2Novm2; r2 = 0.94) and the data corrected accordingly. In the other patients, saline Pco2 was analysed with the IL-1302 blood-gas analyser. Gastric pH, was calculated by a modification of the Henderson-Hasselbalch equation [5]. Based on the reproducibility of the saline Pco2 measurements, a change in pH, exceeding 0.05 pH units was regarded as significant [12]. The correct position of the tonometer was confirmed using fluoroscopy. H2 receptor antagonists were not routinely given. After admission to the ICU, 30-min baseline measurements of haemodynamic variables, oxygen transport and regional blood flow were started. At 20, 25 and 30 min, blood samples were obtained from the catheters for analysis of oxygen saturation, haemoglobin, packed cell volume (PCV), lactate and ICG concentrations. At 30 min of each measurement a saline sample was obtained from the gastric tonometer for analysis of gastric pH,. After the baseline measurement period, vasoactive treatment was started and blood flow measurements were repeated after 90 min. In the control group, the second measurement was performed also 90 min after the baseline measurement.

British Journal of Anaesthesia

280

Table 3 Mean (SD) oxygen transport (consumption (Vo^ and delivery (DO2)) at baseline and at the second measurement in the three groups (see table 1). CO = Cardiac output. *P < 0.05, **P < 0.01 compared with baseline; -\P < 0.05 compared with control. Analysis of variance: effect of group: 'P < 0.05; effect of time (baseline vs second measurement): bP < 0.05, CP < 0.01, d P < 0.001; group-time interaction: CP < 0.05, !P < 0.01, »P < 0.001 Group

cardiac index and splanchnic blood flow; in patients with low cardiac output, flows increased to the same level as in the control patients. The proportion of splanchnic blood flow to cardiac output did not change (control group 25.9 (5.1) m 26.6 (5.6)% (ns); normal cardiac output and dobutamine group 29.4(6.6) vs 29.9(7.0)% (ns); low cardiac output and dobutamine group 25.8(5.4) vs 26.3(5.1)% (ns)). At baseline, there was no difference in femoral blood flow between the groups. Dobutamine increased femoral blood flow. The proportion of femoral blood flow to cardiac output did not change (control group 5.5 (2.5) vs 5.8 (1.8)% (ns); normal cardiac output and dobutamine group 5.2(1.6) vs 5.5 (1.8)% (ns); low cardiac output and dobutamine group 5.7 (1.0) vs 6.1 (1.7)% (ns)). Low cardiac output was associated with low systemic and splanchnic Do2 (P < 0.05) (table 3). Dobutamine increased systemic and splanchnic Do2 in both groups and in the low cardiac output group to the same level as in controls. Baseline systemic and splanchnic Vo2 was similar in all groups. In each group systemic Vo2 increased slightly, but splanchnic Vo2 remained unchanged. Increased blood flow and relatively stable Vo2 were reflected as reduced systemic and regional oxygen extraction in patients

Second measurement

391 (67) 361 (57) 293 (35)t

399 (93) 495 (57)*t 405(44)*

123(18) 119(14) 111 (28)

140 (27)* 132 (14)* 129 (28)*

102(29) 106(27) 75 (21)f

111(28) 156(47)**f 110(26)*

44(10) 45 (12) 37(9)

49(10) 51(17) 40(9)

22(11) 19(6) 17(5)

24(8) 28(9)* 26 (10)*

8(2) 9(4) 8(3)

10 (3)* 9(3) 9(1)

0.32 (0.06) 0.34 (0.05) 0.38 (0.08)

0.35 (0.05) 0.27 (0.05)**t 0.32 (0.32)*

0.46(0.15) 0.45(0.15) 0.52(0.15)

0.45(0.12) 0.34 (0.04)**t 0.37 (0.07)*

0.40(0.13) 0.46(0.11) 0.51 (0.17)

0.42(0.12) 0.33 (0.08)** 0.39(0.15)*

receiving dobutamine. Gastric pH, did not differ between the groups at baseline, remained unchanged in the control and normal cardiac output groups, but decreased in the low cardiac output group (control group 7.34 (0.05) vs 7.34 (0.04) (ns); normal cardiac output and dobutamine group 7.37 (0.07) vs 7.34 (0.06) (ns); low cardiac output and dobutamine group 7.33 (0.12) vs 7.25 (0.06) (P < 0.05)). Femoral Do2 increased in patients receiving dobutamine, but femoral Vo2 increased only in the control group. Arterial lactate concentrations did not change in any group (control group 1.8(0.8) vs 1.7(0.5)mmol litre"1 (ns); normal cardiac output and dobutamine group 1.7(0.4) vs 1.6 (0.3)mmol litre"1 (ns); low cardiac output and dobutamine group 1.2(0.6) vs 1.3 (0.8) mmol litre"1 (ns)). In patients with low cardiac output, gastric mucosal acidosis (pH, < 7.32) was observed in three patients at baseline and in five during infusion of dobutamine; dobutamine reduced gastric pH, in each case (fig. 2). In patients with a stable haemodynamic state, gastric mucosal acidosis was observed at baseline in three patients and dobutamine decreased gastric pH, infivepatients by more than 0.05 units. The reduction in gastric pH, in response to dobutamine occurred despite a marked increase in

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Systemic Do2 (•*" min"1 m'2^* Control Normal CO + dobutamine Low CO + dobutamine Systemic Vo2 (ml min"1 m'2)6 Control Normal CO + dobutamine Low CO + dobutamine Splanchnic Do2 (ml nun"1 m"2)*ld'f Control Normal CO + dobutamine Low CO + dobutamine Splanchnic Vo2 (ml min"1 m"2)1 Control Normal CO + dobutamine Low CO + dobutamine Femora] Do2 (ml min"1 m" 2 )^ Control Normal CO + dobutamine Low CO + dobutamine Femoral Vo2 (ml min"1 m~2)b Control Normal CO + dobutamine Low CO + dobutamine Systemic oxygen extraction^' Control Normal CO + dobutamine Low CO + dobutamine Splanchnic oxygen extraction'1'1 Control Normal CO + dobutamine Low CO + dobutamine Femoral oxygen extraction0-0 Control Normal CO + dobutamine Low CO + dobutamine

Baseline

Splanchnic oxygen transport after cardiac surgery

281

250

Q.

C/5

50

100

150

200

Splanchnic Do2 (ml min" 1 m" 2

250

50

100

150

200

250

2 Splanchnic Do2 (ml min" m" )

splanchnic Do2 in each case. Gastric pH, was relatively stable in the control group; three patients had gastric mucosal acidosis at baseline and three during the second measurement. Discussion Transient decreases in gastric pH, are common after cardiac surgery [4-6]. We found gastric mucosal acidosis on admission to the ICU in one-third of patients. Visceral tissue hypoxia may be expected in patients with low cardiac output. In contrast, the low gastric pH, found also in one-third of patients with an apparently stable haemodynamic state suggests that transient mismatch between splanchnic oxygen delivery and demand occurs after cardiac surgery without clinically obvious circulatory problems. The most important finding of this study was the marked reduction in gastric pH, in 50 % of patients receiving dobutamine. The decrease in gastric pH, occurred despite major increases in splanchnic Do2 and it was most prominent in patients with low cardiac output. In patients with low cardiac output, dobutamine induced gastric mucosal acidosis in all patients with normal gastric pH, at baseline, and failed to improve mucosal acidosis in patients with initially low gastric pH,. In addition, major reductions in gastric pH,- in response to dobutamine were observed in 50 % of patients with a stable haemodynamic state, despite the increase in splanchnic Do2. As no changes in gastric pH, were observed during the corresponding period in the control patients, it is evident that the reduction in gastric pH, represents dobutamine-induced dissociation be-

tween splanchnic Do2 and gastric mucosal tissue oxygenation. As regional Do2 and Vo2 are mathematically coupled, small changes in regional Vo2 in response to Do2 should be interpreted with caution. Nevertheless, two distinct patterns of response to dobutamine were observed. A marked increase in splanchnic Vo2 was observed infivepatients and gastric pH, was unchanged in all except one of these patients. In contrast, decreased gastric pH,, unchanged splanchnic Vo2 and markedly increased splanchnic Do2 were found in 50 % of patients receiving dobutamine, and especially in patients with low cardiac output. This strongly suggests inappropriate distribution of blood flow within the splanchnic region. The reduction in gastric pH, could have resulted from either diversion of bloodflowaway from the mucosa or an increase in mucosal metabolic demand. If gastric mucosal tissue hypoxia developed as a result of splanchnic blood flow redistribution, improved perfusion of other tissues within the splanchnic region would be likely, as splanchnic Vo2 remained unchanged. The splanchnic region is a complex system of tissues with heterogeneous metabolic demands and perfusion. The method we used assessed global splanchnic blood flow, Do2 and Vo2 and was insensitive to regional defects in oxygenation within the splanchnic region. On the other hand, the dissociation between splanchnic Do2 and gastric pH, suggests that while gastric pH, reflects tissue oxygenation in the stomach wall, it does not necessarily correlate with changes in the global splanchnic region. After hypothermic cardiopulmonary bypass both core and peripheral temperatures increase during the

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Figure 2 A: Relationship between splanchnic oxygen delivery {Do^ and consumption (KO2) at baseline and at the second measurement. B: Relationship between splanchnic oxygen delivery (DoJ and gastric pH, at baseline and at the second measurements. Patients with cardiac index > 2 litre min"1 m"2 treated with dobutamine (top; solid arrow); patients with cardiac index < 2 litre min"1 m~2 treated with dobutamine (top; open arrow) and control patients (bottom).

282

Acknowledgement This study was supported in part by the senior clinical researcher's grant 1945/3015/92 from the Academy of Finland to J.T.

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immediate postoperative period. This leads to spontaneous haemodynamic responses and changes in tissue oxygenation. In the control group, a decrease in systemic and regional vascular resistances contributed to minor increases in blood flow and Do2. The marked increases in regional blood flow induced by dobutamine did not further modify regional Vo2. This suggests that the minor increases in systemic and regional Vo2 in both groups mainly reflect increased metabolic demand caused by rewarming. The changes in gastric pH, in the control patients were within the range of variability of the method of measurement, but in patients receiving dobutamine there were major reductions in gastric pH,. In healthy volunteers the use of H2 receptor antagonists reduced the variance of gastric pH, [15], but in a recent study H2 receptor antagonists had no influence on pH, values in critically ill patients [16]. The effects of dobutamine on splanchnic blood flow in humans have not been well documented. In chronic congestive heart failure dobutamine had no consistent effect on total splanchnic blood flow [17]. In contrast, the only available study in ICU patients indicated that dobutamine induced a marked, consistent increase in splanchnic bloodflowafter cardiac surgery [7]. This was also confirmed in the present study. Experimental studies have suggested that the sympathomimetic amines may redistribute splanchnic blood flow both between organs and within the microcirculation [18]. Our results suggest that dobutamine may actually induce a mismatch between splanchnic oxygen supply and demand, despite increased total splanchnic Do2. Also, in the study by Silverman and Tuma in septic patients, infusion of fluids and inotropes reduced gastric pH, in some patients [19]. Dobutamine has been found to magnify histological liver damage in experimental peritonitis [20] and dopamine to impair gut mucosal perfusion despite an increase in total intestinal blood flow [18]. The effects of dobutamine on regional blood flow may have been modified by endothelial damage and impaired vasoregulation after open heart surgery and extracorporeal circulation. The well-maintained gastric pH, in the control group suggests that appropriate vasoregulation and tissue oxygen extraction were well preserved. This suggests that under these circumstances dobutamine may interfere with normal vasoregulation. The results indicated that the effects of commonly used vasoactive drugs on regional blood flow and oxygen transport cannot be predicted from their basic pharmacological properties.

British Journal of Anaesthesia