Heart Vessels (2004) 19:225–229 DOI 10.1007/s00380-004-0777-5
© Springer-Verlag 2004
ORIGINAL ARTICLE Hiroyuki Tsukui · Eisei Koh · Shin’ya Yokoyama Mitsugu Ogawa
Which patients can be weaned from inotropic support within 24 hours after cardiac surgery?
Received: July 23, 2003 / Accepted: April 6, 2004
Abstract Inotropic support after cardiac surgery is sometimes employed for a long period without any definite criteria to wean patients from it. There are few reports describing factors influencing the inotropic support period. This study was undertaken to clarify the proper inotropic support period, especially to judge which patients can be weaned from it within 24 h. From January 2000 to December 2001, 151 patients, 88 (58.2%) with ischemic heart disease, 51 (33.8%) with valvular disease, 7 (4.6%) with congenital heart disease, and 5 (3.4%) with other heart disease, underwent cardiac surgery. The mean age was 66.2 ⫾ 10.1 years (range 30–95); 98 patients (65%) were male. The data were analyzed retrospectively. Eighty patients (53%) were weaned from inotropic support within 24 h after cardiac surgery. Univariate analysis showed that intraaortic balloon pumping, blood transfusion, operation time, cardiopulmonary bypass time, and aortic cross-clamping time significantly influenced the inotropic support period. Multivariate analysis indicated that intra-aortic balloon pumping, blood transfusion, and cardiopulmonary bypass time significantly influenced the inotropic support period. Intra-aortic balloon pumping, blood transfusion, and cardiopulmonary bypass time might determine the inotropic support period. Appropriate surgical procedure and methods both reducing cardiopulmonary bypass time (⬍75 min) and minimizing blood loss are the keys to weaning patients from inotropic support within 24 h. Key words Cardiac surgery · Inotropic support · Cardiopulmonary bypass · Blood transfusion
H. Tsukui1 (*) · E. Koh · S. Yokoyama · M. Ogawa Department of Cardiovascular Surgery, Kyoto Second Red Cross Hospital, Kyoto, Japan Present address: 1 Division of Cardiothoracic Surgery, Department of Surgery, University of Pittsburgh, Suite C-700, 200 Lothrop Street, Pittsburgh, PA 15213, USA Tel. ⫹1-412-647-1946; Fax ⫹1-412-647-0754 e-mail:
[email protected]
Introduction Inotropic support after cardiac surgery is sometimes employed for a long period without a definite standard to wean patients from it. Long inotropic support prolongs hospitalization, delays postoperative rehabilitation, and increases the risk of central venous catheter-related infections and inotropic drug-related accidents. Infection of central venous catheters remains a serious source of morbidity and mortality in critically ill patients.1,2 Adal et al. reported that central venous catheters are believed to be responsible for 90% of bloodstream infections. The cumulative risk of acquiring a catheter-related bloodstream infection ranges between 1% and 10% for central venous catheters in general.2,3 The catheter should be removed as soon as inotropic support is no longer necessary, but weaning too early may cause low output syndrome (LOS). Many reports describe factors influencing the period of stay in the intensive care unit (ICU) after cardiac surgery [type of operation, elective/urgent, reoperation, age, sex, left ventricular function, cardiopulmonary bypass (CPB) time, aortic crossclamping (ACC) time, postoperative LOS, volume of blood transfusion (BTF), duration of intubation, 12-h fluid balance, postoperative bleeding, wound infection, pneumonia, arrhythmia, neurologic events, and postoperative infarction].4–11 Michalopoulos et al. demonstrated that the number of inotropic agents administered in the immediate postoperative period (for at least 6 h) was the most important determinant of duration of stay in the ICU, with an overall predictive accuracy of 94.8%, and the most frequent cause of prolonged ICU stay was LOS.7 Prolonged ICU stay increases the overall cost. Early weaning from inotropic support will contribute to a reduction in cost. However, little has been documented about variables influencing the inotropic support period. The aim of this study was to clarify the proper inotropic support, and especially to judge which patients can be weaned from it within 24 h after cardiac surgery.
226 Table 1. Preoperative diagnosis
Table 2. Surgical procedure No. of patients
Ischemic heart disease AP or MI alone ⫹MR ⫹MR ⫹ TR ⫹LV aneurysm Valvular disease Aortic valve disease AS alone ⫹AP AR alone ⫹DA ⫹MR ASR alone Mitral valve disease MS alone ⫹TR MR alone ⫹TR ⫹AR ⫹AP ⫹IE ⫹IE ⫹ TR ⫹DCM ⫹HCM ⫹post DVR MSR alone ⫹TR Tricuspid valve disease TR ⫹ IE
82 3 1 2
5 1 14 2 1 3 1 1 7 3 2 1 1 1 1 1 1 2 2 1
Congenital heart disease ASD alone ⫹TR MSA
3 3 1
Others Af LA myxoma Rupture of sinus of Valsalva Syphilitic aortitis
2 1 1 1
Af, atrial fibrillation; AP, angina pectoris; AR, aortic regurgitation; AS, aortic stenosis; ASD, atrial septal defect; ASR, aortic stenosis and regurgitation; DA, dissecting aneurysm; DCM, dilated cardiomyopathy; DVR, double valve replacement; HCM, hypertrophied cardiomyopathy; IE, infectious endocarditis; LA, left atrium; LV left ventricle; MI, myocardial infarction; MR, mitral stenosis; MR, mitral regurgitation; MSA, membranous septal aneurysm; MSR, mitral stenosis and regurgitation; TR, tricuspid regurgitation
Materials and methods From January 2000 to December 2001, 151 consecutive patients underwent cardiac surgery at our hospital. The mean age was 66.2 ⫾ 10.1 years and the range 30–95 years; 98 patients (65%) were men and 53 (35%), women. Patients who underwent pediatric cardiac surgery or aortic surgery involving the aortic arch and descending aorta were excluded. The patients’ preoperative profiles are shown in Table 1. All patients received standard anesthesia with propofol/ midazolam, fentanyl citrate, and isoflurane/sevoflurane. Operations were performed through a median sternotomy. Twenty-four patients underwent off-pump coronary artery bypass grafting (CABG) using a heart stabilizer, while 127 patients underwent cardiac surgery on CPB using mild
No. of operations Ischemic heart disease (n ⫽ 85) On-pump CABG Single Double Triple On-pump beating CABG Off-pump CABG Single Double Triple Dor’s procedure
57 5 24 28 2 24 12 10 2 2
Valvular disease (n ⫽ 53) AVR alone ⫹single CABG ⫹double CABG MVR alone ⫹TAP ⫹Maze ⫹TVR ⫹triple CABG ⫹single CABG ⫹ Maze ⫹TAP ⫹ Maze MVP alone ⫹single CABG ⫹TAP DVR alone ⫹Maze TAP alone
21 1 1 11 4 1 1 1 1 1 3 1 1 3 1 1
Congential heart disease (n ⫽ 6) ASD closure alone ⫹TAP
3 3
Others (n ⫽ 7) Bentall Maze alone VSD closure ⫹ TAP ICR
2 2 1 1
Resection of LA myxoma ⫹ single CABG
1
ASD, atrial septal defect; AVR, aortic valve regurgitation; CABG, coronary artery bypass grafting; ICR, intracardiac repair; LA, left atrium; MVP, mitral valve plasty; MVR, mitral valve replacement; TAP, tricuspid annuloplasty; TVR, tricuspid valve replacement; VSD, ventricular septal defect
hypothermia. The heart was arrested with Young’s solution and protected with cold cardioplegia every 30 min in an antegrade fashion. Further operative data are shown in Table 2. After the operation, systolic blood pressure and urine output were maintained for at least more than 100 mmHg and 1 ml/kg per hour, respectively, with proper employment of diuretics, vasodilator agents, and inotropic agents, dopamine hydrochloride, dobutamine hydrochloride, norepinephrine, and milrinone. In patients with a hematocrit value of less than 27%, blood was transfused to raise it to more than 30%. Patients were weaned from inotropic support if systolic blood pressure and urine output were maintained at more than 100 mmHg and 1 ml/kg per hour, respectively. In patients with renal failure, inotropic support was tapered if systolic blood pressure was kept over 100 mmHg. Patients were divided into two groups: group I (n ⫽ 71), which required inotropic support for more than 24 h or reintroduction of inotropic support after discontinuance, and group NI (n ⫽ 80), which required inotropic support for less than 24 h. The two groups were compared
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with respect to 20 preoperative, intraoperative, and postoperative variables; age, sex, body length, body weight, history of atrial fibrillation, hypertension, diabetes mellitus, chronic renal failure requiring hemodialysis, preoperative shock, intra-aortic balloon pumping (IABP), elective or emergent operation, preoperative left ventricular dimension in diastole (LVDd) and systole (LVDs), fractional shortening (FS) revealed by transthoracic echocardiography, operation time, CPB time, ACC time, hematocrit on preoperative and postoperative day 1, and blood transfusion (BTF). Preoperative shock was defined as a preoperative low systolic pressure (⬍60 mmHg). Intra-aortic balloon pumping was employed in patients with an unstable hemodynamic state preoperatively or intraoperatively or with a left main trunk lesion (⬎90% stenosis) preoperatively. Statistical analysis All data were analyzed with the SAS statistical software program (Statview 5.0, SAS Institute, Cary, NC, USA). Univariate analysis of categorical data was carried out with Fisher’s exact test. Univariate analysis of continuous variables was carried out using Student’s t-test, and they were expressed as mean ⫾ SD. Pearson’s correlation coefficient was calculated to assess the univariate association between continuous variables and inotropic support period. Variables with a P value of less than 0.05 in univariate analysis were included in a multiple logistic regression model.
Results There were three hospital deaths (2.0%). In group I, one patient who underwent aortic and mitral valve replacement died on postoperative day 1 due to massive hemorrhage, and an other who underwent CABG died of cardiogenic shock on postoperative day 1. In group NI, a patient who underwent aortic valve replacement died on postoperative day 8 because of sudden cardiopulmonary arrest. The median period of inotropic support was 2.4 ⫾ 2.8 days, ranging from 0 to 24 days. Eighty patients (53%) were weaned from inotropic support within 24 h after surgery. Univariate analysis showed significant differences between groups I and NI in three categorical variables: preoperative shock (P ⫽ 0.0096), IABP (P ⫽ 0.0005), and BTF (P ⫽ 0.0011), and three continuous variables: operation time (group NI: 226.8 ⫾ 69.4 min, group I: 276.5 ⫾ 106.8 min; P ⫽ 0.0008), CPB time (group NI: 74.4 ⫾ 50.4 min, group I: 106.5 ⫾ 74.9 minutes; P ⫽ 0.0022), and ACC time (group NI: 58.0 ⫾ 40.4 min, group I: 72.5 ⫾ 43.0 min; P ⫽ 0.0351). All variables subjected to univariate analysis are shown in Tables 3 and 4. Correlations between the significant factors were calculated. There was a strong correlation between operation time and CPB time (Pearson’s correlation coefficient ⫽ 0.652; P ⬍ 0.0001), between CPB time and ACC time (Pearson’s correlation coefficient ⫽ 0.857; P ⬍ 0.0001), and between operation time and ACC time (Person’s correlation coefficient ⫽ 0.546; P ⬍ 0.0001). In a multiple logistic
Table 3. Univariate relations between categorical variables and the inotropic support period Factors Sex Male Female Atrial fibrillation Yes No Hypertension Yes No Diabetes mellitus Yes No Hemodialysis Yes No Preoperative shock Yes No Elective or emergency Elective emergency IABP Yes No BTF Yes No
No. of patients
No. of NI patients (%)
P value
98 53
52 (53) 28 (52)
⬎0.9999
25 126
12 (48) 68 (54)
0.6632
93 58
49 (53) 31 (53)
⬎0.9999
50 101
21 (42) 59 (58)
0.0827
8 143
3 (38) 77 (54)
0.4757
6 145
0 (0) 80 (55)
0.0096
15 136
4 (27) 76 (56)
0.0535
27 124
6 (22) 74 (60)
0.0005
78 73
31 (39) 49 (67)
0.0011
BTF, blood transfusion; IABP, intra-aortic balloon pumping; NI patients, those who required inotropic agents for less than 24 h after surgery
228 Table 4. Univariate relations between categorical variables and the inotropic support period Factors
Inotropic support more than 24 h after surgery No (n ⫽ 80)
Age (years) Body length (cm) Body weight (kg) Operation time (min) CPB time (min) ACC time (min) LVDd (mm) LVDs (mm) FS (%) Preoperative Ht (%) Postoperative Ht (%)
Yes (n ⫽ 71)
P value
Mean
SD
Mean
SD
65.0 159.3 56.9 226.8 74.4 58.0 51.3 32.9 35.9 38.1 30.2
10.2 10.3 11.0 69.4 50.4 40.4 8.1 6.8 6.5 5.1 4.7
67.6 157.8 55.6 276.5 106.5 72.5 51.5 34.8 33.3 36.4 31.1
9.9 8.6 12.0 106.8 74.9 43.0 9.7 9.6 8.7 5.8 4.8
0.1106 0.3376 0.4915 0.0008 0.0022 0.0351 0.9016 0.1872 0.0523 0.0617 0.2779
ACC, aortic cross-clamp; CPB, cardiopulmonary bypass; FS, fractional shortening; Ht, hematocrit; LVDd, left ventricular dimension at diastole; LVDs, left ventricular dimension at systole; SD, standard deviation
Table 5. Multiple logistic regression analysis
IABP BTF CPB time
Odds ratio
95% CI
P value
4.121 2.472 1.007
1.475–11.518 1.226–4.984 1.000–1.013
0.0069 0.0114 0.0365
BTF, blood transfusion; CPB, cardiopulmonary bypass; IABP, intraaortic balloon pumping; CI, confidence interval
regression model, IABP (P ⫽ 0.0069), BTF (P ⫽ 0.0114), and CPB time (P ⫽ 0.0365) significantly influenced the inotropic support period (Table 5).
Discussion From this study we concluded that IABP, BTF, and CPB time were definitive factors indicating whether patients can be weaned from inotropic support within 24 h. It is not surprising that patients requiring IABP need a prolonged inotropic support period after cardiac surgery. In our study, patients with IABP required inotropic support for 4.63 ⫾ 4.97 days. We concluded that BTF influenced the inotropic support period. Patients with BTF required inotropic support for 3.30 ⫾ 3.56 days, whereas patients without BTF required it for 1.63 ⫾ 1.23 only days (P ⬍ 0.0002). There were no differences in hematocrit values on the preoperative day and postoperative day 1 between group I and group NI. These results indicate that anemia developed during or after operation and BTF was introduced to maintain hemodynamics. Weiskopf et al. demonstrated that an acute isovolemic reduction in the hemoglobin concentration decreased systemic vascular resistance.12 In other words, BTF itself might not prolong the inotropic support period, but severe anemia requiring BTF might prolong it. It is important for reducing the inotropic support period to perform a
Fig. 1. Correlation between cardiopulmonary bypass time and the inotropic support period. Inotropic support period (days) ⫽ 1.738 ⫾ 0.008, r 2 ⫽ 0.037
proper surgical procedure and to avoid an extended operation to minimize blood loss. To achieve cardiac surgery without BTF, some authors have proposed various strategies: preoperative autologous blood storage with erythropoietin (recombinant human erythropoietin) injection,13,14 and the use of aprotinin.15 However, BTF should be performed when it is necessary. Carson et al. reported that operative blood loss increases the risk of death or serious morbidity more in patients with cardiovascular disease than in those without. The decision to give BTF should take account of the cardiovascular status and operative blood loss.16 Cardiopulmonary bypass time can significantly influence the inotropic support period. Also, as prolonged ACC time takes place under prolonged CPB time, there was a significant correlation between these two variables. In the multivariate analysis ACC time dropped out, and CPB time appeared to have a more important impact on the inotropic support period (Fig. 1); it was significantly shorter in the
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patients who underwent off-pump CABG (1.04 ⫾ 0.37 days) than in those who underwent cardiac surgery on CPB (4.13 ⫾ 3.43 days) in our study (P ⬍ 0.0001). Michalopoulos et al. reported that CPB and ACC time longer than 120 and 90 min, respectively, increased the risk for a prolonged stay in the ICU.7 Appropriate surgical technique and methods are mandatory to decrease the CPB time. In our study, the inotropic support period was significantly shorter in patients with a CPB time of less than 75 min (1.90 ⫾ 1.88 days) than in those with CPB time of longer than 75 min (2.85 ⫾ 3.22 days) (P ⬍ 0.05). Based on Table 3, a CPB time of less than 75 min may be an indicator that patients can be weaned from inotropic support easily within 24 h. On the other hand, a CPB time of longer than 110 min may be an index indicating that it is difficult for patients to be weaned from it within 24 h. Therefore, they should be weaned carefully. In our study, there was no relationship in preoperative cardiac function indicated by LVDd, LVDs, and FS between group I and group NI. Zaroff et al. showed that although a low preoperative ejection fraction is a known predictor of a poor immediate postoperative outcome after cardiac surgery, not all patients with a low preoperative ejection fraction required inotropic support.17 In some highrisk cases, there may be great improvement in left ventricular function after operation as a result of successful revascularization. Weintraub et al. demonstrated that the factors related to prolonged hospital stay could not be predicted from preoperative variables alone.9 They emphasized that serious intraoperative complications such as myocardial ischemia or infarction, inadequate myocardial revascularization, and inadequate myocardial protection during CPB were responsible for prolonging the length of stay after coronary artery bypass grafting surgery. In conclusion, appropriate surgical procedure concomitant with both reducing blood loss and CPB time, hopefully to less than 75 min, are keys to shortening the inotropic support period after cardiac surgery. Limitations of this study The number of patients in our study may have been too small to make a valid conclusion, but our data suggest that some factors, i.e., IABP, BTF, and CPB time, may be indicators for smooth weaning from inotropic support. Further research is required to assess their predictive value.
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